WorldWideScience

Sample records for adhl regulation progress

  1. A genetic analysis of Adhl regulation. Progress report, June 1991--May 1993

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-12-01

    Several separate but related studies are reported on the mechanism of alcohol dehydrogenase (Adh-1) are reported. A study of a deletion mutation in the TATA box region which resulted in an increase from 6--60% of wildtype Adh-1 expression in the revertant has led to a focus on trans-acting protein factors that bind the TATA box. Analysis of another revertant has led to study of cis-acting sequences in Adh-1 expression. Screening efforts aimed at defining different mutants affecting Adh-1 expression are reported.

  2. A genetic analysis of Adhl regulation

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-01-01

    Several separate but related studies are reported on the mechanism of alcohol dehydrogenase (Adh-1) are reported. A study of a deletion mutation in the TATA box region which resulted in an increase from 6--60% of wildtype Adh-1 expression in the revertant has led to a focus on trans-acting protein factors that bind the TATA box. Analysis of another revertant has led to study of cis-acting sequences in Adh-1 expression. Screening efforts aimed at defining different mutants affecting Adh-1 expression are reported.

  3. Progress toward risk informed regulation

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, K.C.

    1997-01-01

    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  4. (Regulation of teopene metabolism). Progress report. [Mentha piperita

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1985-01-01

    Progress in elucidating the biosynthesis of several monoterpenes in the peppermint is described. Tracer studies were performed to clarify metabolic pathways involved. Several growth regulators were screened for their influence on monoterpene composition and yield in peppermint and sage. (DT)

  5. [Regulation of terpene metabolism.] Progress report

    International Nuclear Information System (INIS)

    This research program represents a very broad-based approach to understanding the biochemistry of the monoterpene and sesquiterpene constituents of the essential oils. This program includes basic research on the pathways, enzymes and mechanisms of terpene biosynthesis and catabolism, on the physiology of essential oil production, and on the morphology and development of oil glands, as well as practical approaches to manipulating essential oil composition and yield. As a natural extension of research on monoterpene biosynthesis and catabolism in sage and peppermint we have explored some aspects of possible regulatory mechanisms. Tentative evidence has been obtained for developmental regulation of the levels of biosynthetic and catabolic enzymes. 10 refs., 8 figs

  6. (Regulation of terpene metabolism. ) Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1984-01-01

    This research program represents a very broad-based approach to understanding the biochemistry of the monoterpene and sesquiterpene constituents of the essential oils. This program includes basic research on the pathways, enzymes and mechanisms of terpene biosynthesis and catabolism, on the physiology of essential oil production, and on the morphology and development of oil glands, as well as practical approaches to manipulating essential oil composition and yield. As a natural extension of research on monoterpene biosynthesis and catabolism in sage and peppermint we have explored some aspects of possible regulatory mechanisms. Tentative evidence has been obtained for developmental regulation of the levels of biosynthetic and catabolic enzymes. 10 refs., 8 figs.

  7. [Regulation of terpene metabolism]. Progress report

    International Nuclear Information System (INIS)

    Studies on the regulation of monoterpene metabolism in M. piperita were conducted. All of the steps from the acyclic precursor geranyl pyrophosphate to the various menthol isomers have been demonstrated. The first intermediate to accumulate in vivo is d-pulegone. The emphasis has been on the demonstration, partial purification and characterization of the relevant enzymes in the pathway. The studies on the isopiperitenol dehydrogenase and isopiperitenone isomerase have been completed. We are not studying the endocyclic double-bond reductase (NADPH-dependent) and, based on substrate specificity studies and the previously demonstrated isomerization of cis- isopulegone to pulegone, are now virtually convinced that the major pathway to menthol(s) in peppermint involves reduction of isopiperitenone to isopulegone and isomerication of isopulegone to pulegone. 16 refs., 1 fig

  8. Progression of Financial Reporting in Czech Republic and its Regulation

    OpenAIRE

    Ištvánfyová, Jana; Mejzlík, Ladislav; Pelák, Jiří

    2010-01-01

    The development of a national accounting framework presents unique issues. A strong accounting system needs sufficient time to evolve. The influence of IFRS and of existing tax objectives of Czech accounting system increase the complexity and costs of implementing and monitoring the accounting rules. Given the short time between abandoning an economy based on public ownership and joining the European Union, Czech Republic made significant progress in development of its accounting regulation. ...

  9. 76 FR 81942 - Federal Acquisition Regulation; Information Collection; Progress Payments (SF-1443)

    Science.gov (United States)

    2011-12-29

    ... Regulation; Information Collection; Progress Payments (SF-1443) AGENCIES: Department of Defense (DOD... ``Progress Payments,'' contractors are required to request progress payments on Standard Form (SF) 1443... information, reasonably requested by the Contracting Officer. The contractual requirement for submission of...

  10. Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress

    Science.gov (United States)

    Olsovska, Katarina; Kovar, Marek; Brestic, Marian; Zivcak, Marek; Slamka, Pavol; Shao, Hong Bo

    2016-01-01

    Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID:27551283

  11. Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress.

    Science.gov (United States)

    Olsovska, Katarina; Kovar, Marek; Brestic, Marian; Zivcak, Marek; Slamka, Pavol; Shao, Hong Bo

    2016-01-01

    Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID:27551283

  12. Daxx regulates mitotic progression and prostate cancer predisposition.

    Science.gov (United States)

    Kwan, Pak Shing; Lau, Chi Chiu; Chiu, Yung Tuen; Man, Cornelia; Liu, Ji; Tang, Kai Dun; Wong, Yong Chuan; Ling, Ming-Tat

    2013-04-01

    Mitotic progression of mammalian cells is tightly regulated by the E3 ubiquitin ligase anaphase promoting complex (APC)/C. Deregulation of APC/C is frequently observed in cancer cells and is suggested to contribute to chromosome instability and cancer predisposition. In this study, we identified Daxx as a novel APC/C inhibitor frequently overexpressed in prostate cancer. Daxx interacts with the APC/C coactivators Cdc20 and Cdh1 in vivo, with the binding of Cdc20 dependent on the consensus destruction boxes near the N-terminal of the Daxx protein. Ectopic expression of Daxx, but not the D-box deleted mutant (DaxxΔD-box), inhibited the degradation of APC/Cdc20 and APC/Cdh1 substrates, leading to a transient delay in mitotic progression. Daxx is frequently upregulated in prostate cancer tissues; the expression level positively correlated with the Gleason score and disease metastasis (P = 0.027 and 0.032, respectively). Furthermore, ectopic expression of Daxx in a non-malignant prostate epithelial cell line induced polyploidy under mitotic stress. Our data suggest that Daxx may function as a novel APC/C inhibitor, which promotes chromosome instability during prostate cancer development.

  13. Regulation's future: progress or oblivion

    Energy Technology Data Exchange (ETDEWEB)

    Cudahy, R.D.

    1978-11-09

    A former state utility regulator, now a practicing attorney, Mr. Cudahy reflects on the changing character of public utility regulation: the rapidly emerging new concerns with which it is most-frequently confronted and the standards and mental processes most appropriate for meeting them. He indicates the possibility of a strand of continuity and permanence. He recommends against hiring consultants to answer regulatory questions and suggests that regulators emphasize standards rather than give specific directions. A cautionary note is added against assuming that irreconcilable interests can be balanced by opening up the regulatory process.

  14. 77 FR 19287 - Federal Acquisition Regulation; Submission for OMB Review; Progress Payments (SF-1443)

    Science.gov (United States)

    2012-03-30

    ... Register at 76 FR 81942, on December 29, 2011. No comments were received. Public comments are particularly... Regulation; Submission for OMB Review; Progress Payments (SF-1443) AGENCY: Department of Defense...

  15. Regulation of prostate cancer progression by the tumor microenvironment.

    Science.gov (United States)

    Shiao, Stephen L; Chu, Gina Chia-Yi; Chung, Leland W K

    2016-09-28

    Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. PMID:26828013

  16. The Role of pH Regulation in Cancer Progression.

    Science.gov (United States)

    McIntyre, Alan; Harris, Adrian L

    2016-01-01

    Frequently observed phenotypes of tumours include high metabolic activity, hypoxia and poor perfusion; these act to produce an acidic microenvironment. Cellular function depends on pH homoeostasis, and thus, tumours become dependent on pH regulatory mechanisms. Many of the proteins involved in pH regulation are highly expressed in tumours, and their expression is often of prognostic significance. The more acidic tumour microenvironment also has important implications with regard to chemotherapeutic and radiotherapeutic interventions. In addition, we review pH-sensing mechanisms, the role of pH regulation in tumour phenotype and the use of pH regulatory mechanisms as therapeutic targets. PMID:27557536

  17. Regulation of cell division in higher plants. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, T.W.

    1992-07-01

    Cell division is arguably the most fundamental of all developmental processes. In higher plants, mitotic activity is largely confined to foci of patterned cell divisions called meristems. From these perpetually embryonic tissues arise the plant`s essential organs of light capture, support, protection and reproduction. Once an adequate understanding of plant cell mitotic regulation is attained, unprecedented opportunities will ensue for analyzing and genetically controlling diverse aspects of development, including plant architecture, leaf shape, plant height, and root depth. The mitotic cycle in a variety of model eukaryotic systems in under the control of a regulatory network of striking evolutionary conservation. Homologues of the yeast cdc2 gene, its catalytic product, p34, and the cyclin regulatory subunits of the MPF complex have emerged as ubiquitous mitotic regulators. We have cloned cdc2-like and cyclin genes from pea. As in other eukaryotic model systems, p34 of Pisum sativum is a subunit of a high molecular weight complex which binds the fission yeast p13 protein and displays histone H1 kinase activity in vitro. Our primary objective in this study is to gain baseline information about the regulation of this higher plant cell division control complex in non-dividing, differentiated cells as well as in synchronous and asynchronous mitotic cells. We are investigating cdc2 and cyclin expression at the levels of protein abundance, protein phosphorylation and quaternary associations.

  18. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L;

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone...... chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  19. (Regulation of terpene metabolism). Progress report. [Mentha piperita

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1986-01-01

    Studies on the regulation of monoterpene metabolism in M. piperita were conducted. All of the steps from the acyclic precursor geranyl pyrophosphate to the various menthol isomers have been demonstrated. The first intermediate to accumulate in vivo is d-pulegone. The emphasis has been on the demonstration, partial purification and characterization of the relevant enzymes in the pathway. The studies on the isopiperitenol dehydrogenase and isopiperitenone isomerase have been completed. We are not studying the endocyclic double-bond reductase (NADPH-dependent) and, based on substrate specificity studies and the previously demonstrated isomerization of cis- isopulegone to pulegone, are now virtually convinced that the major pathway to menthol(s) in peppermint involves reduction of isopiperitenone to isopulegone and isomerication of isopulegone to pulegone. 16 refs., 1 fig.

  20. Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

    Science.gov (United States)

    Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin; Tellides, George; Simons, Michael

    2016-01-01

    The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2α led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high-fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFβ activity, and increased disease severity. These results identify SMC FGF/TGFβ signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth. PMID:27189169

  1. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  2. [Regulation of terpene metabolism]. Annual progress report, March 15, 1988--March 14, 1989

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-12-31

    Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

  3. Social Possible Selves, Self-Regulation, and Social Goal Progress in Older Adulthood

    Science.gov (United States)

    Ko, Han-Jung; Mejía, Shannon; Hooker, Karen

    2014-01-01

    Lifespan development involves setting and pursuing self-guided goals. This study examines how in the social domain, possible selves, a future-oriented self-concept, and self-regulation, including self-regulatory beliefs and intraindividual variability in self-regulatory behavior, relate to differences in overall daily social goal progress. An…

  4. Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

    Directory of Open Access Journals (Sweden)

    Anna Klimaszewska

    2011-11-01

    Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

  5. Assembly and interrogation of Alzheimer's disease genetic networks reveal novel regulators of progression.

    Directory of Open Access Journals (Sweden)

    Soline Aubry

    Full Text Available Alzheimer's disease (AD is a complex multifactorial disorder with poorly characterized pathogenesis. Our understanding of this disease would thus benefit from an approach that addresses this complexity by elucidating the regulatory networks that are dysregulated in the neural compartment of AD patients, across distinct brain regions. Here, we use a Systems Biology (SB approach, which has been highly successful in the dissection of cancer related phenotypes, to reverse engineer the transcriptional regulation layer of human neuronal cells and interrogate it to infer candidate Master Regulators (MRs responsible for disease progression. Analysis of gene expression profiles from laser-captured neurons from AD and controls subjects, using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe, yielded an interactome consisting of 488,353 transcription-factor/target interactions. Interrogation of this interactome, using the Master Regulator INference algorithm (MARINa, identified an unbiased set of candidate MRs causally responsible for regulating the transcriptional signature of AD progression. Experimental assays in autopsy-derived human brain tissue showed that three of the top candidate MRs (YY1, p300 and ZMYM3 are indeed biochemically and histopathologically dysregulated in AD brains compared to controls. Our results additionally implicate p53 and loss of acetylation homeostasis in the neurodegenerative process. This study suggests that an integrative, SB approach can be applied to AD and other neurodegenerative diseases, and provide significant novel insight on the disease progression.

  6. Progress in the Regulation of Radiation Environmental Safety in the Utilization of Mineral Resources in China

    International Nuclear Information System (INIS)

    In the paper, the background to the progress made in the regulation of radiation environmental safety in the utilization of mineral resources other than uranium (thorium) ores in China is first introduced. The regulatory experience of radiation environmental safety in the utilization of mineral resources in international organizations and industrial countries (e.g. International Commission on Radiological Protection, IAEA, European Union and United States of America) is surveyed and analysed. Finally, the scope and requirements of regulation on the radiation environmental safety in the utilization of mineral resources in China are stated. (author)

  7. SON controls cell-cycle progression by coordinated regulation of RNA splicing.

    Science.gov (United States)

    Ahn, Eun-Young; DeKelver, Russell C; Lo, Miao-Chia; Nguyen, Tuyet Ann; Matsuura, Shinobu; Boyapati, Anita; Pandit, Shatakshi; Fu, Xiang-Dong; Zhang, Dong-Er

    2011-04-22

    It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.

  8. Progression to impaired glucose regulation and diabetes in the population-based Inter99 study

    DEFF Research Database (Denmark)

    Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine;

    2009-01-01

    prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity......Objective: To estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population-based Inter99 study and in a high-risk subpopulation, separately. Research Design and Methods: From a population-based primary......, or having impaired glucose tolerance). High-risk individuals (57.1%) were examined with an oral glucose tolerance test at 1- and 3-year, and all the participants were re-examined at 5-year follow-up. Person-years at risk were calculated. Progression rates to impaired glucose regulation and diabetes were...

  9. Akt Inhibitor A-443654 Interferes with Mitotic Progression by Regulating Aurora A Kinase Expression

    Directory of Open Access Journals (Sweden)

    Xuesong Liu

    2008-08-01

    Full Text Available Both Akt and Aurora A kinase have been shown to be important targets for intervention for cancer therapy. We report here that Compound A (A-443654, a specific Akt inhibitor, interferes with mitotic progression and bipolar spindle formation. Compound A induces G2/M accumulation, defects in centrosome separation, and formation of either monopolar arrays or disorganized spindles. On the basis of gene expression array studies, we identified Aurora A as one of the genes regulated transcriptionally by Akt inhibitors including Compound A. Inhibition of the phosphatidylinositol 3-kinase (PI3K/Akt pathway, either by PI3K inhibitor LY294002 or by Compound A, dramatically inhibits the promoter activity of Aurora A, whereas the mammalian target of rapamycin inhibitor has little effect, suggesting that Akt might be responsible for up-regulating Aurora A for mitotic progression. Further analysis of the Aurora A promoter region indicates that the Ets element but not the Sp1 element is required for Compound A-sensitive transcriptional control of Aurora A. Overexpression of Aurora A in cells treated with Compound A attenuates the mitotic arrest and the defects in bipolar spindle formation induced by Akt inhibition. Our studies suggest that that Akt may promote mitotic progression through the transcriptional regulation of Aurora A.

  10. Investigating the regulation of stem and progenitor cell mitotic progression by in situ imaging.

    Science.gov (United States)

    Gerhold, Abigail R; Ryan, Joël; Vallée-Trudeau, Julie-Nathalie; Dorn, Jonas F; Labbé, Jean-Claude; Maddox, Paul S

    2015-05-01

    Genome stability relies upon efficacious chromosome congression and regulation by the spindle assembly checkpoint (SAC). The study of these fundamental mitotic processes in adult stem and progenitor cells has been limited by the technical challenge of imaging mitosis in these cells in situ. Notably, how broader physiological changes, such as dietary intake or age, affect mitotic progression in stem and/or progenitor cells is largely unknown. Using in situ imaging of C. elegans adult germlines, we describe the mitotic parameters of an adult stem and progenitor cell population in an intact animal. We find that SAC regulation in germline stem and progenitor cells is distinct from that found in early embryonic divisions and is more similar to that of classical tissue culture models. We further show that changes in organismal physiology affect mitotic progression in germline stem and progenitor cells. Reducing dietary intake produces a checkpoint-dependent delay in anaphase onset, and inducing dietary restriction when the checkpoint is impaired increases the incidence of segregation errors in mitotic and meiotic cells. Similarly, developmental aging of the germline stem and progenitor cell population correlates with a decline in the rate of several mitotic processes. These results provide the first in vivo validation of models for SAC regulation developed in tissue culture systems and demonstrate that several fundamental features of mitotic progression in adult stem and progenitor cells are highly sensitive to organismal physiological changes.

  11. Deciphering the spatio-temporal regulation of entry and progression through mitosis.

    Science.gov (United States)

    Gheghiani, Lilia; Gavet, Olivier

    2014-02-01

    Mitosis has been studied since the early 1880s as a key event of the cell division cycle where remarkable changes in cellular architecture take place and ultimately lead to an equal segregation of duplicated chromosomes into two daughter cells. A detailed description of the complex and highly ordered cellular events taking place is now available. Many regulators involved in key steps including entry into mitosis, nuclear envelope breakdown, microtubule (MT) spindle formation, and chromosome attachment, as well as mitotic exit and cytokinesis, have also been identified. However, understanding the precise spatio-temporal contribution of each regulator in the cell reorganization process has been technically challenging. This review will focus on a number of recent advances in our understanding of the spatial distribution of protein activities and the temporal regulation of their activation and inactivation during entry and progression through mitosis by the use of intramolecular Förster resonance energy transfer (FRET)-based biosensors. PMID:24421267

  12. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

    Science.gov (United States)

    Mura, M; Hopkins, T G; Michael, T; Abd-Latip, N; Weir, J; Aboagye, E; Mauri, F; Jameson, C; Sturge, J; Gabra, H; Bushell, M; Willis, A E; Curry, E; Blagden, S P

    2015-09-24

    RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression. PMID:25531318

  13. Plac8 Links Oncogenic Mutations to Regulation of Autophagy and Is Critical to Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Conan Kinsey

    2014-05-01

    Full Text Available Mutations in p53 and RAS potently cooperate in oncogenic transformation, and correspondingly, these genetic alterations frequently coexist in pancreatic ductal adenocarcinoma (PDA and other human cancers. Previously, we identified a set of genes synergistically activated by combined RAS and p53 mutations as frequent downstream mediators of tumorigenesis. Here, we show that the synergistically activated gene Plac8 is critical for pancreatic cancer growth. Silencing of Plac8 in cell lines suppresses tumor formation by blocking autophagy, a process essential for maintaining metabolic homeostasis in PDA, and genetic inactivation in an engineered mouse model inhibits PDA progression. We show that Plac8 is a critical regulator of the autophagic machinery, localizing to the lysosomal compartment and facilitating lysosome-autophagosome fusion. Plac8 thus provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression.

  14. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    Science.gov (United States)

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-05-30

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.

  15. An Emerging Model for BAP1’s Role in Regulating Cell Cycle Progression

    OpenAIRE

    Eletr, Ziad M.; Wilkinson, Keith D.

    2011-01-01

    BRCA1-associated protein-1 (BAP1) is a 729 residue, nuclear-localized deubiquitinating enzyme (DUB) that displays tumor suppressor properties in the BAP1-null NCI-H226 lung carcinoma cell line. Studies that have altered BAP1 cellular levels or enzymatic activity have reported defects in cell cycle progression, notably at the G1/S transition. Recently BAP1 was shown to associate with the transcriptional regulator host cell factor 1 (HCF-1). The BAP1/HCF-1 interaction is mediated by the HCF-1 K...

  16. 7α-Hydroxypregnenolone, a new key regulator of amphibian locomotion: discovery, progress and prospect.

    Science.gov (United States)

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean-Luc; Vaudry, Hubert

    2012-05-01

    Seasonally-breeding amphibians have served as excellent animal models to investigate the biosynthesis and biological actions of neurosteroids. Previous studies have demonstrated that the brain of amphibians possesses key steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones, and other various neurosteroids. We recently found that the brain of seasonally-breeding newts actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. This novel amphibian neurosteroid acts as a neuronal modulator to stimulate locomotor activity in newts. Subsequently, the mode of action of 7α-hydroxypregnenolone has been demonstrated in the newt brain. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in synthesis of 7α-hydroxypregnenolone have also been demonstrated in the newt brain. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to increase locomotor activity under stress. This review summarizes the discovery, progress and prospect of 7α-hydroxypregnenolone, a new key regulator of amphibian locomotion.

  17. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma.

    Science.gov (United States)

    Wu, Yi-Ju; Jan, Yee-Jee; Ko, Bor-Sheng; Liang, Shu-Man; Liou, Jun-Yang

    2015-01-01

    There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3's regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation. PMID:26083935

  18. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-Ju [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China); Jan, Yee-Jee [Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Ko, Bor-Sheng [Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan (China); Liang, Shu-Man; Liou, Jun-Yang, E-mail: jliou@nhri.org.tw [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China)

    2015-06-15

    There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3’s regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation.

  19. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yi-Ju Wu

    2015-06-01

    Full Text Available There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC. 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK, c-Jun N-terminal kinase (JNK and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK expression, thereby enhancing epithelial-mesenchymal transition (EMT and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70 expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3's regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation.

  20. An emerging model for BAP1's role in regulating cell cycle progression.

    Science.gov (United States)

    Eletr, Ziad M; Wilkinson, Keith D

    2011-06-01

    BRCA1-associated protein-1 (BAP1) is a 729 residue, nuclear-localized deubiquitinating enzyme (DUB) that displays tumor suppressor properties in the BAP1-null NCI-H226 lung carcinoma cell line. Studies that have altered BAP1 cellular levels or enzymatic activity have reported defects in cell cycle progression, notably at the G1/S transition. Recently BAP1 was shown to associate with the transcriptional regulator host cell factor 1 (HCF-1). The BAP1/HCF-1 interaction is mediated by the HCF-1 Kelch domain and an HCF-1 binding motif (HBM) within BAP1. HCF-1 is modified with ubiquitin in vivo, and ectopic studies suggest BAP1 deubiquitinates HCF-1. HCF-1 is a chromatin-associated protein thought to both activate and repress transcription by linking appropriate histone-modifying enzymes to a subset of transcription factors. One known role of HCF-1 is to promote cell cycle progression at the G1/S boundary by recruiting H3K4 histone methyltransferases to the E2F1 transcription factor so that genes required for S-phase can be transcribed. Given the robust associations between BAP1/HCF-1 and HCF-1/E2Fs, it is reasonable to speculate that BAP1 influences cell proliferation at G1/S by co-regulating transcription from HCF-1/E2F-governed promoters. PMID:21484256

  1. Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition

    International Nuclear Information System (INIS)

    Increased collagen deposition provides physical and biochemical signals to support tumor growth and invasion during breast cancer development. Therefore, inhibition of collagen synthesis and deposition has been considered a strategy to suppress breast cancer progression. Collagen prolyl-4-hydroxylase α subunit 2 (P4HA2), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. However, expression and function of P4HA2 in breast cancer progression are not well investigated. Gene co-expression analysis was performed in the published microarray datasets to identify potential regulators of collagen I, III, and IV in human breast cancer tissue. Expression of P4HA2 was silenced by shRNAs, and its activity was inhibited by 1, 4-DPCA, a prolyl-4-hydroxylase inhibitor. Three-dimensional culture assay was used to analyze roles of P4HA2 in regulating malignant phenotypes of breast cancer cells. Reduced deposition of collagen I and IV was detected by Western blotting and immunofluorescence. Control and P4HA2-silenced breast cancer cells were injected into fat pad and tail vein of SCID mice to examine effect of P4HA2 on tumor growth and lung metastasis. Using gene co-expression analysis, we showed that P4HA2 was associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression. P4HA2 mRNA levels were significantly upregulated in breast cancer compared to normal mammary tissue. Increased mRNA levels of P4HA2 correlated with poor clinical outcome in breast cancer patients, which is independent of estrogen receptor status. Silencing P4HA2 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen I and IV. We also found that knockdown of P4HA2 inhibited mammary tumor growth and

  2. miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

    Science.gov (United States)

    Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-01-01

    MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3′-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-β-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression. PMID:27036021

  3. Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies.

    Science.gov (United States)

    Gallagher, William M; Bergin, Orla E; Rafferty, Mairin; Kelly, Zoë D; Nolan, Ilse-Maria; Fox, Edward J P; Culhane, Aedin C; McArdle, Linda; Fraga, Mario F; Hughes, Linda; Currid, Caroline A; O'Mahony, Fiona; Byrne, Aileen; Murphy, Alison A; Moss, Catherine; McDonnell, Susan; Stallings, Raymond L; Plumb, Jane A; Esteller, Manel; Brown, Robert; Dervan, Peter A; Easty, David J

    2005-11-01

    The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling techniques to identify molecular determinants of melanoma progression within a unique panel of isogenic human melanoma cell lines. When a poorly tumorigenic cell line, derived from an early melanoma, was compared with two increasingly aggressive derivative cell lines, the expression of 66 genes was significantly changed. A similar pattern of differential gene expression was found with an independently derived metastatic cell line. We further examined these melanoma progression-associated genes via use of a tailored TaqMan Low Density Array (LDA), representing the majority of genes within our cohort of interest. Considerable concordance was seen between the transcriptomic profiles determined by DNA microarray and TaqMan LDA approaches. A range of novel markers were identified that correlated here with melanoma progression. Most notable was TSPY, a Y chromosome-specific gene that displayed extensive down-regulation in expression between the parental and derivative cell lines. Examination of a putative CpG island within the TSPY gene demonstrated that this region was hypermethylated in the derivative cell lines, as well as metastatic melanomas from male patients. Moreover, treatment of the derivative cell lines with the DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine (DAC), restored expression of the TSPY gene to levels comparable with that found in the parental cells. Additional DNA microarray studies uncovered a subset of 13 genes from the above-mentioned 66 gene cohort that displayed re-activation of expression following DAC treatment, including TSPY, CYBA and MT2A. DAC suppressed tumor cell growth in vitro. Moreover, systemic treatment of mice with DAC attenuated growth of melanoma xenografts, with consequent re-expression of TSPY mRNA. Overall, our data support

  4. The effects of environmental regulation and technical progress on CO2 Kuznets curve: An evidence from China

    International Nuclear Information System (INIS)

    Based on environmental Kuznets curve theory, a panel data model which takes environmental regulation and technical progress as its moderating factors was developed to analyse the institutional and technical factors that affect the path of low-carbon economic development. The results indicated that there was a CO2 emission Kuznets curve seen in China. Environmental regulation had a significant moderating effect on the curve, and the inflection of CO2 emissions could come substantially earlier under stricter environmental regulation. Meanwhile, the impact of technical progress on the low-carbon economic development path had a longer hysteresis effect but restrained CO2 emission during its increasing stage and accelerated its downward trend during the decreasing stage which was conducive to emission reduction. Strict environmental regulation could force the high-carbon emitting industries to transfer from the eastern regions to the central or the western regions of China, which would make the CO2 Kuznets curve higher in its increasing stage and lower in its decreasing stage than that under looser regulation. Furthermore, energy efficiency, energy structure, and industrial structure exerted a significant direct impact on CO2 emissions; we should consider the above factors as essential in the quest for low-carbon economic development. - Highlights: • Estimate moderating effect of environmental regulation and technical progress on EKC. • There was a CO2 emission Kuznets curve in effect in China. • Environmental regulation presents significant moderating effect on EKC. • Technical progress moderates the relationship between income and CO2 emissions

  5. Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression.

    Science.gov (United States)

    Liu, Che-Ming; Hsieh, Chia-Ling; Shen, Chia-Ning; Lin, Cheng-Chieh; Shigemura, Katsumi; Sung, Shian-Ying

    2016-09-01

    Distant organ metastasis of prostate cancer is a puzzle, and various theories have successively arisen to explain the mechanism of lethal cancer progression. While perhaps agreeable to many cancer biologists, the very statement of "seed and soil" proposed by Stephan Paget in 1881 is arguably still the major statement for organ-specific cancer metastasis. Since recent studies showed important correlations of regulation of cancer cells and the microenvironment, exosomes from cancer and stromal cells seem to create another important niche for metastasis. Stromal cells pretreated with exosomes from metastatic cancer cells increase the potential of change stromal cells. The poorly metastatic cancer cells could also enhance malignancy through transfer of proteins, microribonucleic acid and messenger ribonucleic acid to recipient cancer cells. Herein, we reviewed extracellular exosomes as a factor involved in cross-talk between stromal and prostate cancer epithelial cells. PMID:27397852

  6. NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

    Science.gov (United States)

    Teixeira, Leonardo K; Carrossini, Nina; Sécca, Cristiane; Kroll, José E; DaCunha, Déborah C; Faget, Douglas V; Carvalho, Lilian D S; de Souza, Sandro J; Viola, João P B

    2016-09-01

    The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

  7. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Wan Junhu; Chin Y Eugene; Zhang Hongquan; Zhan Jun; Li Shuai; Ma Ji; Xu Weizhi; Liu Chang; Xue Xiaowei; Xie Yuping; Fang Weigang

    2015-01-01

    Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

  8. RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn

    2014-04-18

    Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

  9. Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas.

    Science.gov (United States)

    Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao

    2015-11-10

    The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80, CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs.

  10. Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors

    International Nuclear Information System (INIS)

    Cancer invasion and metastasis develops through a series of steps that involve the loss of cell to cell and cell to matrix adhesion, degradation of extracellular matrix and induction of angiogenesis. Different protease systems (e.g., matrix metalloproteinases, MMPs) are involved in these steps. MMP-10, one of the lesser studied MMPs, is limited to epithelial cells and can facilitate tumor cell invasion by targeting collagen, elastin and laminin. Enhanced MMP-10 expression has been linked to poor clinical prognosis in some cancers, however, mechanisms underlying a role for MMP-10 in tumorigenesis and progression remain largely unknown. Here, we report that MMP-10 expression is positively correlated with the invasiveness of human cervical and bladder cancers. Using commercial tissue microarray (TMA) of cervical and bladder tissues, MMP-10 immunohistochemical staining was performed. Furthermore using a panel of human cells (HeLa and UROtsa), in vitro and in vivo experiments were performed in which MMP-10 was overexpressed or silenced and we noted phenotypic and genotypic changes. Experimentally, we showed that MMP-10 can regulate tumor cell migration and invasion, and endothelial cell tube formation, and that MMP-10 effects are associated with a resistance to apoptosis. Further investigation revealed that increasing MMP-10 expression stimulates the expression of HIF-1α and MMP-2 (pro-angiogenic factors) and PAI-1 and CXCR2 (pro-metastatic factors), and accordingly, targeting MMP-10 with siRNA in vivo resulted in diminution of xenograft tumor growth with a concomitant reduction of angiogenesis and a stimulation of apoptosis. Taken together, our findings show that MMP-10 can play a significant role in tumor growth and progression, and that MMP-10 perturbation may represent a rational strategy for cancer treatment

  11. Processes regulating progressive nitrogen limitation under elevated carbon dioxide: a meta-analysis

    Science.gov (United States)

    Liang, Junyi; Qi, Xuan; Souza, Lara; Luo, Yiqi

    2016-05-01

    The nitrogen (N) cycle has the potential to regulate climate change through its influence on carbon (C) sequestration. Although extensive research has explored whether or not progressive N limitation (PNL) occurs under CO2 enrichment, a comprehensive assessment of the processes that regulate PNL is still lacking. Here, we quantitatively synthesized the responses of all major processes and pools in the terrestrial N cycle with meta-analysis of CO2 experimental data available in the literature. The results showed that CO2 enrichment significantly increased N sequestration in the plant and litter pools but not in the soil pool, partially supporting one of the basic assumptions in the PNL hypothesis that elevated CO2 results in more N sequestered in organic pools. However, CO2 enrichment significantly increased the N influx via biological N fixation and the loss via N2O emission, but decreased the N efflux via leaching. In addition, no general diminished CO2 fertilization effect on plant growth was observed over time up to the longest experiment of 13 years. Overall, our analyses suggest that the extra N supply by the increased biological N fixation and decreased leaching may potentially alleviate PNL under elevated CO2 conditions in spite of the increases in plant N sequestration and N2O emission. Moreover, our syntheses indicate that CO2 enrichment increases soil ammonium (NH4+) to nitrate (NO3-) ratio. The changed NH4+/NO3- ratio and subsequent biological processes may result in changes in soil microenvironments, above-belowground community structures and associated interactions, which could potentially affect the terrestrial biogeochemical cycles. In addition, our data synthesis suggests that more long-term studies, especially in regions other than temperate ones, are needed for comprehensive assessments of the PNL hypothesis.

  12. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes.

    Directory of Open Access Journals (Sweden)

    Dallas R Donohoe

    Full Text Available A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germfree colonocytes. However, (13C-glucose metabolic-flux experiments and biochemical assays demonstrated that they shifted their glucose metabolism away from mitochondrial oxidation/CO(2 production and toward increased glycolysis/lactate production, which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH levels and activity. Consistent with perturbed PDH function, the addition of butyrate, but not glucose, to germfree colonocytes ex vivo stimulated oxidative metabolism. As a result of this energetic defect, germfree colonocytes exhibited a partial block in the G(1-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells.

  13. Safety regulation of geological disposal of radioactive waste: progress since Cordoba and remaining challenges

    International Nuclear Information System (INIS)

    Claudio Pescatore, Deputy Division Head (NEA) presented a paper, the purpose of which was to recall where we stood at the time of the Cordoba Workshop (1997) on the regulation of disposal of long-lived radioactive waste, to review developments since then, to present the key existing issues, and reflect on the remaining challenges and possible responses. The overview study on progress in regulation for geological disposal since the Cordoba workshop [NEA/RWMC/RF(2008)6], provides a good list of references regarding the first two issues. The presentation of the existing issues takes advantage of the synthesis of the responses to a questionnaire completed by the regulatory organisations in preparation for this workshop. It warns regulators and implementers that international work to date seems to have created an expectation in the mind of the public and in some organisations that nothing less than a guarantee by the regulator is needed of maintaining current levels of protection of both individuals and populations practically forever, regardless of the impracticality of this. This expectation needs to be replaced with a carefully and clearly explained understanding of the choices involved in dealing with long-lived radioactive waste against a background of our responsibilities to both current and future generations and our practical capacity to deliver them. Concerning the current major challenges faced in regulation, the paper comes back to the issue of the 'guarantee' by the regulator and it observes that there is no doubt that there is a willingness to do the best to comply with the principle of protection and that we are broadly convinced that current concepts for geological disposal, supported by multiple lines of reasoning and application of best available techniques (BAT) will meet that principle. However, we do not have the capacity to prove or guarantee this, nor do we believe that it is possible in practice. Although we are advised that it is neither

  14. The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+ mouse.

    Directory of Open Access Journals (Sweden)

    James P White

    Full Text Available Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+ mouse is not known. Cachexia progression was studied in Apc(Min/+ mice that were either weight stable (WS or had initial (≤5%, intermediate (6-19%, or extreme (≥20% body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172, AMPK activity, and raptor phosphorylation (Ser 792 were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

  15. MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1.

    Directory of Open Access Journals (Sweden)

    Michelle Lenarduzzi

    Full Text Available Despite improvements in therapeutic approaches for head and neck squamous cell carcinomas (HNSCC, clinical outcome has remained disappointing, with 5-year overall survival rates hovering around 40-50%, underscoring an urgent need to better understand the biological bases of this disease. We chose to address this challenge by studying the role of micro-RNAs (miRNAs in HNSCC. MiR-193b was identified as an over-expressed miRNA from global miRNA profiling studies previously conducted in our lab, and confirmed in HNSCC cell lines. In vitro knockdown of miR-193b in FaDu cancer cells substantially reduced cell proliferation, migration and invasion, along with suppressed tumour formation in vivo. By integrating in silico prediction algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1 was identified to be a target of miR-193b. Concordantly, miR-193b knockdown decreased NF1 transcript and protein levels significantly. Luciferase reporter assays confirmed the direct interaction of miR-193b with NF1. Moreover, p-ERK, a downstream target of NF1 was also suppressed after miR-193b knockdown. FaDu cells treated with a p-ERK inhibitor (U0126 phenocopied the reduced cell proliferation, migration and invasion observed with miR-193b knockdown. Finally, HNSCC patients whose tumours expressed high levels of miR-193b experienced a lower disease-free survival compared to patients with low miR-193b expression. Our findings identified miR-193b as a potentially novel prognostic marker in HNSCC that drives tumour progression via down-regulating NF1, in turn leading to activation of ERK, resulting in proliferation, migration, invasion, and tumour formation.

  16. PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Zhu, Jiang [Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Ozaki, Toshinori [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuohku, Chiba 260-8717 (Japan); Bu, Youquan, E-mail: buyqcn@aliyun.com [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China)

    2015-03-13

    Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

  17. Globalisation, technological progress and changes in regulations and institutions: Which impact on the rise of earnings inequality in OECD countries?

    OpenAIRE

    Chen, Wen-Hao; Förster, Michael; Llena-Nozal, Ana

    2013-01-01

    This paper examines the distributive impact of economic globalisation, technological progress and changes in labour market policies, regulations and institutions in OECD countries over the past quarter century, up to the Great Recession. It identifies the relevant pathways between macro-economic developments and earnings inequality among the whole working-age population by accounting for both changes in wage dispersion among workers and changes in earnings gaps between the employed and non-em...

  18. Inhibitor of DNA binding 1 regulates cell cycle progression of endothelial progenitor cells through induction of Wnt2 expression.

    Science.gov (United States)

    Xia, Xi; Yu, Yang; Zhang, Li; Ma, Yang; Wang, Hong

    2016-09-01

    Endothelial injury is a risk factor for atherosclerosis. Endothelial progenitor cell (EPC) proliferation contributes to vascular injury repair. Overexpression of inhibitor of DNA binding 1 (Id1) significantly promotes EPC proliferation; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated the role of Id1 in cell cycle regulation of EPCs, which is closely associated with proliferation. Overexpression of Id1 increased the proportion of EPCs in the S/G2M phase and significantly increased cyclin D1 expression levels, while knockdown of Id1 arrested the cell cycle progression of EPCs in the G1 phase and inhibited cyclin D1 expression levels. In addition, it was demonstrated that Id1 upregulated wingless‑type mouse mammary tumor virus integration site family member 2 (Wnt2) expression levels and promoted β‑catenin accumulation and nuclear translocation. Furthermore, Wnt2 knockdown counteracted the effects of Id1 on cell cycle progression of EPCs. In conclusion, the results of the present study indicate that Id1 promoted Wnt2 expression, which accelerated cell cycle progression from G1 to S phase. This suggests that Id1 may promote cell cycle progression of EPCs, and that Wnt2 may be important in Id1 regulation of the cell cycle of EPCs. PMID:27432753

  19. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  20. JNK does not regulate meiotic progression in Xenopus oocytes: The strange case of pJNK and pERK.

    Science.gov (United States)

    Yue, Jicheng; López, José M

    2016-08-01

    Xenopus ERK2, also known as Xp42 MAPK, is activated by progesterone and regulates meiotic progression in the oocytes through activation of the phosphatase Cdc25C and inhibition of the protein kinase Myt1, thus promoting dephosphorylation and activation of cyclinB/Cdc2 (MPF). Indeed, it has been reported that stress protein kinases p38 and JNK are activated during meiotic progression and, more specifically, that p38γ regulates meiosis through activation of Cdc25C. However, the role of JNK in meiotic progression is not so clear, and despite a 42kDa protein is detected with pJNK antibodies (XpJNK-p42), the specific isoform activated by progesterone has not been characterized in detail. The serine/threonine kinase MEKK1, an upstream activator of JNK and p38, is activated during stress conditions and regulates apoptosis in different cell types. Here we show that ectopic expression of a constitutively active MEKK1 in Xenopus oocytes induces phosphorylation of p38, JNK and ERK and accelerates meiotic progression induced by progesterone. Inhibition of each individual pathway reduces the acceleration of meiosis induced by MEKK1. However, constitutively active MEKK1 induces phosphorylation of two JNK isoforms (p40 and p49, corresponding to JNK1-1 and JNK1-2 respectively) distinct to the p42 protein detected with pJNK antibodies during meiotic progression (XpJNK-p42). Moreover, a constitutively active MKK7, which specifically activates the JNK signaling pathway and induces phosphorylation of the p40 and p49 isoforms, does not accelerate meiotic progression. Immunoprecipitation of the p42 protein with pJNK antibodies and subsequent analysis by mass spectrometry shows that XpJNK-p42 is, in fact, pERK2. Ectopic expression of ERK2 in oocytes treated with progesterone or hyperosmotic shock indicates that ERK2 is phosphorylated in both conditions but is only detected with pJNK antibodies in progesterone-treated oocytes. In addition, mature oocytes only present a moderate increase

  1. YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of survivin.

    Science.gov (United States)

    Zhang, Wenjing; Gao, Yijun; Li, Fuming; Tong, Xinyuan; Ren, Yan; Han, Xiangkun; Yao, Shun; Long, Fei; Yang, Zhongzhou; Fan, Hengyu; Zhang, Lei; Ji, Hongbin

    2015-11-01

    The serine/threonine kinase LKB1 is a well-characterized tumor suppressor that governs diverse cellular processes, including growth, polarity, and metabolism. Somatic-inactivating mutations in LKB1 are observed in about 15% to 30% of non-small cell lung cancers (NSCLC). LKB1 inactivation confers lung adenocarcinomas (ADC) with malignant features that remain refractory to therapeutic intervention. YAP activation has been linked to LKB1 deficiency, but the role of YAP in lung ADC formation and progression is uncertain. In this study, we showed that ectopic expression of YAP in type II alveolar epithelial cells led to hyperplasia in mouse lungs. YAP overexpression in the Kras(G12D) lung cancer mouse model accelerated lung ADC progression. Conversely, YAP deletion dramatically delayed the progression of lung ADC in LKB1-deficient Kras(G12D) mice. Mechanistic studies identified the antiapoptotic oncoprotein survivin as the downstream mediator of YAP responsible for promoting malignant progression of LKB1-deficient lung ADC. Collectively, our findings identify YAP as an important contributor to lung cancer progression, rationalizing YAP inhibition in the context of LKB1 deficiency as a therapeutic strategy to treat lung ADC.

  2. Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity.

    Directory of Open Access Journals (Sweden)

    Indra Tumurbaatar

    Full Text Available Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

  3. Surfactant Protein A Suppresses Lung Cancer Progression by Regulating the Polarization of Tumor-Associated Macrophages

    OpenAIRE

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Kuramoto, Takuya; Tabata, Sho; Yukishige, Sawaka; Abe, Shinji; Hanibuchi, Masaki; Kakiuchi, Soji; Saijo, Atsuro; Aono, Yoshinori; Uehara, Hisanori; Yano, Seiji; Ledford, Julie G.; Sone, Saburo; Nishioka, Yasuhiko

    2013-01-01

    Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcino...

  4. Overcoming hypoxia-mediated tumor progression: Combinatorial approaches targeting pH regulation, angiogenesis and immune dysfunction

    Directory of Open Access Journals (Sweden)

    Paul C. Mcdonald

    2016-03-01

    Full Text Available Hypoxia is an important contributor to the heterogeneity of the microenvironment of solid tumors and is a significant environmental stressor that drives adaptations which are essential for the survival and metastatic capabilities of tumor cells. Critical adaptive mechanisms include altered metabolism, pH regulation, epithelial-mesenchymal transition, angiogenesis, migration/invasion, diminished response to immune cells and resistance to chemotherapy and radiation therapy. In particular, pH regulation by hypoxic tumor cells, through the modulation of cell surface molecules such as extracellular carbonic anhydrases (CAIX and CAXII and monocarboxylate transporters (MCT-1 and MCT-4 functions to increase cancer cell survival and enhance cell invasion while also contributing to immune evasion. Indeed, CAIX is a vital regulator of hypoxia mediated tumor progression, and targeted inhibition of its function results in reduced tumor growth, metastasis, and cancer stem cell function. However, the integrated contributions of the repertoire of hypoxia-induced effectors of pH regulation for tumor survival and invasion remain to be fully explored and exploited as therapeutic avenues. For example, the clinical use of anti-angiogenic agents has identified a conundrum whereby this treatment increases hypoxia and cancer stem cell components of tumors, and accelerates metastasis. Furthermore, hypoxia results in the infiltration of myeloid-derived suppressor cells (MDSCs, regulatory T cells (Treg and Tumor Associated Macrophages (TAMs, and also stimulates the expression of PD-L1 on tumor cells, which collectively suppress T-cell mediated tumor cell killing. Therefore, combinatorial targeting of angiogenesis, the immune system and pH regulation in the context of hypoxia may lead to more effective strategies for curbing tumor progression and therapeutic resistance, thereby increasing therapeutic efficacy and leading to more effective strategies for the treatment of

  5. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

    DEFF Research Database (Denmark)

    Fløyel, Tina; Brorsson, Caroline; Nielsen, Lotte B;

    2014-01-01

    Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (...

  6. Recent Progress in Understanding Subtype Specific Regulation of NMDA Receptors by G Protein Coupled Receptors (GPCRs

    Directory of Open Access Journals (Sweden)

    Kai Yang

    2014-02-01

    Full Text Available G Protein Coupled Receptors (GPCRs are the largest family of receptors whose ligands constitute nearly a third of prescription drugs in the market. They are widely involved in diverse physiological functions including learning and memory. NMDA receptors (NMDARs, which belong to the ionotropic glutamate receptor family, are likewise ubiquitously expressed in the central nervous system (CNS and play a pivotal role in learning and memory. Despite its critical contribution to physiological and pathophysiological processes, few pharmacological interventions aimed directly at regulating NMDAR function have been developed to date. However, it is well established that NMDAR function is precisely regulated by cellular signalling cascades recruited downstream of G protein coupled receptor (GPCR stimulation. Accordingly, the downstream regulation of NMDARs likely represents an important determinant of outcome following treatment with neuropsychiatric agents that target selected GPCRs. Importantly, the functional consequence of such regulation on NMDAR function varies, based not only on the identity of the GPCR, but also on the cell type in which relevant receptors are expressed. Indeed, the mechanisms responsible for regulating NMDARs by GPCRs involve numerous intracellular signalling molecules and regulatory proteins that vary from one cell type to another. In the present article, we highlight recent findings from studies that have uncovered novel mechanisms by which selected GPCRs regulate NMDAR function and consequently NMDAR-dependent plasticity.

  7. Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression

    Science.gov (United States)

    Abbott, Jonathan J.; Piñeiro, Roberto; Buus, Richard; Iezzi, Manuela; Ricci, Francesca; Bergamaschi, Daniele; Ostano, Paola; Chiorino, Giovanna; Lattanzio, Rossano; Broggini, Massimo; Piantelli, Mauro; Maffucci, Tania; Falasca, Marco

    2016-01-01

    It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2β is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2β regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2β expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2β in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2β-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2β regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2β inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2β is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2β plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2β may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread. PMID:26934321

  8. Profitability - Vector Sustainable Development, Progress and Viable Accounting Normalization Requirements - Going Statutory Audit and Regulations

    OpenAIRE

    Tudose Geanina Gabriela; Petroianu Grazia-Oana; Dãucianu (Avram) Mihaela

    2014-01-01

    In a market economy, profitability is a sine qua non for the very existence of businesses [3] and entrepreneurs professionalism correlation result, the material and technical and financial resources invested, the motivation of employees and social dialogue amid scientific and technical progress and development requirements ensuring sustainable. Managers must obtain return entities considering the requirements of accounting policy, that should take into account the conventions of prudence, ind...

  9. Mechanisms of bioluminescence, chemiluminescence and of their regulation. Progress report, one year period through March 1976

    Energy Technology Data Exchange (ETDEWEB)

    Seliger, H H

    1976-01-01

    Progress is reported on a 10-yr study of the production and role of excited states in biological systems and the mechanisms involved in bioluminescence and chemoluminescence. An hypothesis of the origin of bioluminescence is presented that is based on the mixed function oxygenase reaction. Techniques of absolute measurements of light intensities and spectral composition were applied in studies of bioluminescence of marine dinoflagellates and the chemiluminescence of carcinogenic polycyclic aromatic hydrocarbons as the result of enzymatic hydroxylation. (CH)

  10. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Skerker

    2005-10-01

    Full Text Available Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein-protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK-CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this

  11. TTIP as a Platform for Progress in Pharma and Medtech Regulations

    DEFF Research Database (Denmark)

    Van Vooren, Bart

    2016-01-01

    Opponents of the transatlantic trade and investment partnership treaty (TTIP) fear that, the EU might lose the capacity to protect public health as it deems appropriate. The freedom to regulate would be jeopardized because TTIP would bind the EU to the United States’ regulatory interests, which...... are expressly or implicitly assumed to live up to a ‘lower’ standard than those in the EU. The ‘TTIP-leaks’ provide a good opportunity to examine the potential impact of the agreement on EU public health regulation. We conclude that TTIP negotiation documents on pharmaceuticals and medical devices do...... not suggest that EU public health is threatened. In both areas, negotiations focus on relatively technical-procedural issues where benefits are clearly mutual. On pharmaceuticals, the benefits of mutual recognition of good manufacturing practices (GMP) exist for consumers, regulators and business alike...

  12. Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus.

    Science.gov (United States)

    Gora, Kasia G; Cantin, Amber; Wohlever, Matthew; Joshi, Kamal K; Perchuk, Barrett S; Chien, Peter; Laub, Michael T

    2013-03-01

    Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division.

  13. Talking with the Public about Regulating High-level Waste Disposal: Recent Progress

    Energy Technology Data Exchange (ETDEWEB)

    Kotra, J. P.; Leslie, B. W.

    2003-02-26

    Increasing public confidence in the U.S. Nuclear Regulatory Commission (NRC) as an effective and independent regulator is an explicit goal of the Agency (1). Consistent with long-established mechanisms and procedures, NRC provides the public access to its decision-making process. Recently, during the course of a rulemaking required by statute, NRC examined its means for inviting public access as well as the NRC staff's effectiveness in furthering public confidence in it's actions as a regulator. When developing new, site-specific regulations for the proposed geologic repository at Yucca Mountain, Nevada, NRC's Division of Waste Management found it necessary to adapt and improve its efforts to inform and involve the public in NRC's decision making process. Major changes were made to the way in which technical staff prepare for speaking to general audiences. The format used for public meetings was modified to encourage dialogue with participants. Handout and presentation materials that explain NRC's role and technical topics of concern in plain language were developed and are regularly updated. NRC successfully applied these and other institutional changes as it completed final regulations for Yucca Mountain and while developing and introducing a draft license review plan for public comment.

  14. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

    Science.gov (United States)

    de Oliveira, Joana T; Ribeiro, Cláudia; Barros, Rita; Gomes, Catarina; de Matos, Augusto J; Reis, Celso A; Rutteman, Gerard R; Gärtner, Fátima

    2015-01-01

    The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness. PMID:26222311

  15. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT, in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.

  16. Regulation of polyamine synthesis in plants. Final progress report, July 1, 1991--December 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Malmberg, R.L.

    1995-07-01

    This research focused on unusual post-translational modifications occuring in a arginine decarboxylase cDNA clone in oats. A novel regulatory mechanism for polyamines was explored and an attempt was made to characterize it. A plant ornithine decarboxylase cDNA was identified in Arabidopsis. Further work remains on the mechanisms of polyamine regulation and function in plants.

  17. NPAT expression is regulated by E2F and is essential for cell cycle progression

    DEFF Research Database (Denmark)

    Gao, Guang; Bracken, Adrian P; Burkard, Karina;

    2003-01-01

    NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G(1)/S-pha...

  18. A genetic analysis of Adh1 regulation. Progress report, June 1991--February 1992

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-03-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  19. 14-3-3 family members act coordinately to regulate mitotic progression.

    Science.gov (United States)

    Dalal, Sorab N; Yaffe, Michael B; DeCaprio, James A

    2004-05-01

    The mitosis promoting phosphatase, cdc25C, is a target of both the DNA replication and DNA damage checkpoint pathways. These pathways regulate cdc25C function, in part, by promoting the association of cdc25C with 14-3-3 proteins, which results in the retention of cdc25C in the cytoplasm. To determine which 14-3-3 proteins were required to regulate cdc25C function, we tested the ability of various 14-3-3 family members to form a complex with and negatively regulate cdc25C in human cells. Two 14-3-3 family members, 14-3-3epsilon and 14-3-3gamma specifically formed a complex with cdc25C but not with the 14-3-3 binding defective cdc25C mutant, S216A. In addition, 14-3-3epsilon and 14-3-3gamma inhibited the ability of cdc25C, but not the S216A mutant, to induce premature chromatin condensation (PCC) in U-2OS cells. These results suggested that the reduction in PCC by 14-3-3epsilon and 14-3-3gamma was due to inhibition of cdc25C function. In contrast, 14-3-3sigma was unable to form a complex with cdc25C, but was able to inhibit the ability of both wild type cdc25C and S216A to induce PCC. This suggests that 14-3-3sigma regulates entry into mitosis independently of cdc25C and 14-3-3epsilon and 14-3-3gamma. Thus, specific members of the 14-3-3 family of proteins may act coordinately to maintain the DNA replication checkpoint by regulating the activity of different cell cycle proteins. PMID:15107609

  20. miR-200c Inhibits Melanoma Progression and Drug Resistance through Down-Regulation of Bmi-1

    Science.gov (United States)

    Liu, Shujing; Tetzlaff, Michael T.; Cui, Rutao; Xu, Xiaowei

    2013-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. Melanoma is the most aggressive skin cancer that is resistant or rapidly develops resistance to a variety of chemotherapeutic agents. The role of miRNAs in melanoma progression and drug resistance has not been well studied. Herein, we demonstrate that miR-200c is down-regulated in melanomas (primary and metastatic) compared with melanocytic nevi. Overexpression of miR-200c in melanoma cells resulted in significantly decreased cell proliferation and migratory capacity as well as drug resistance. miR-200c overexpression resulted in significant down-regulation of BMI-1, ABCG2, ABCG5, and MDR1 expression and in a concomitant increase in E-cadherin levels. Knockdown of BMI-1 showed similar effects as miR-200c overexpression in melanoma cells. In addition, miR-200c overexpression significantly inhibited melanoma xenograft growth and metastasis in vivo, and this correlated with diminished expression of BMI-1 and reduced levels of E-cadherin in these tumors. The effects of miR-200c on melanoma cell proliferation and migratory capacity and on self-renewal were rescued by overexpression of Bmi-1, and the reversal of these phenotypes correlated with a reduction in E-cadherin expression and increased levels of ABCG2, ABCG5, and MDR1. Taken together, these findings demonstrate a key role for miR-200c in melanoma progression and drug resistance. These results suggest that miR-200c may represent a critical target for increasing melanoma sensitivity to clinical therapies. PMID:22982443

  1. Role of the tumor microenvironment in regulating apoptosis and cancer progression.

    Science.gov (United States)

    Yaacoub, Katherine; Pedeux, Remy; Tarte, Karin; Guillaudeux, Thierry

    2016-08-10

    Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented. PMID:27224890

  2. [Progress in calcium regulation in myocardial and vascular ischemia-reperfusion injury].

    Science.gov (United States)

    He, Xi; Bi, Xue-Yuan; Wang, Hao; Yu, Xiao-Jiang; Zang, Wei-Jin

    2012-06-25

    Ischemia-reperfusion injury (IRI) has been recognized as a serious problem for therapy of cardiovascular diseases. Calcium regulation appears to be an important issue in the study of IRI. This article reviews calcium regulation in myocardial and vascular IRI, including the calcium overload and calcium sensitivity in IRI. This review is focused on the key players in Ca(2+) handling in IRI, including membrane damage resulting in increase in Ca(2+) influx, reverse-mode of Na(+)-Ca(2+) exchangers leading to increased Ca(2+) entry, the decreased activity of sarcoplasmic reticulum (SR) Ca(2+)-ATPase causing SR Ca(2+) uptake dysfunction, and increased activity of Rho kinase. These key players in Ca(2+) homeostasis will provide promising strategies and potential targets for therapy of cardiovascular IRI. PMID:22717637

  3. The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the Size of Developmental Fields.

    Directory of Open Access Journals (Sweden)

    Natalia Barrios

    2015-08-01

    Full Text Available During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a key, evolutionarily conserved, role in territorial specification. Here we show that in the imaginal discs, reduced function of Iroquois genes promotes cell proliferation by accelerating the G1 to S transition. Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex. We demonstrate that physical interaction of the Iroquois protein Caupolican with Cyclin E-containing protein complexes, through its IRO box and Cyclin-binding domains, underlies its activity in cell-cycle control. Thus, Drosophila Iroquois proteins are able to regulate cell-autonomously the growth of the territories they specify. Moreover, our results provide a molecular mechanism for a role of Iroquois/Irx genes as tumour suppressors.

  4. [Iron regulation of gene expression in the Bradyrhizobium japonicum/soybean symbiosis]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Guerinot, M.L.

    1992-06-01

    We wish to address the question of whether iron plays a regulatory role in the Bradyrhizobium japonicum/soybeam symbiosis. Iron may be an important regulatory signal in planta as the bacteria must acquire iron from their plant hosts and iron-containing proteins figure prominently in all nitrogen-fixing symbioses. For example, the bacterial partner is believed to synthesize the heme moiety of leghemoglobin, which may represent as much as 25--30% of the total soluble protein in an infected plant cell. For this reason, we have focused our attention on the regulation by iron of the first step in the bacterial heme biosynthetic pathway. The enzyme which catalyzes this step, 5-aminolevulinic acid synthase, is encoded by the hemA gene which we had previously cloned and sequenced. Specific objectives include: to define the cis-acting sequences which confer iron regulation on the B. japonicum hemA gene; to identify trans-acting factors which regulate the expression of hemA by iron; to identify new loci which are transcriptionally responsive to changes in iron availability; and to examine the effects of mutations in various known regulatory genes for their effect on the expression of hemA.

  5. Talking with the public about regulating high-level waste disposal: recent progress in risk communication

    International Nuclear Information System (INIS)

    Building and maintaining public trust that the U.S. Nuclear Regulatory Commission (NRC) is an effective and independent regulator, is explicitly stated as a performance goal for the agency. To be fully effective in carrying out our mission to protect public health and safety and the environment, the public must view the NRC as a reliable, objective, open an efficient regulator. The NRC has always sought to afford the public access to our decision making process. More recently, however, we have come to better appreciate the value of dialogue with stake-holders and the importance of expanding the opportunities for public interaction and participation in our regulatory process. In particular, in developing new, site-specific regulations for a proposed geologic repository at Yucca Mountain, Nevada, we have found the need to adapt and expand our efforts to inform and to involve the public in our decision-making process. The institutional changes made to carry out this new approach, and the positive, albeit preliminary, responses to these changes are discussed in this paper. (authors)

  6. Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.

    Directory of Open Access Journals (Sweden)

    Stéphane Brunet

    Full Text Available Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.

  7. The role of miRNA regulation in cancer progression and drug resistance

    DEFF Research Database (Denmark)

    Joshi, Tejal

    RNAs in the context of cancer biology, drug resistance and disease progression. The first project described in Chapter 6 addresses the problem of tamoxifen resistance, an anti-estrogen drug that is generally highly effective in the treatment of ER-positive breast cancers. The underlying molecular mechanisms......This PhD thesis presents the work carried out at Center for Biological Sequence Analysis, Technical University of Denmark. The projects presented in this thesis are a purely bioinformatic in nature. Included in this thesis are the two projects that focus on the gene regulatory events mediated by mi...... for the acquired resistance to tamoxifen are not very well understood. Therefore, with the aid of miRNA and gene expression profiles for MCF7/S0.5 (tamoxifen sensitive) and three MCF7/S0.5 derived tamoxifen resistant cell lines, we obtained several miRNA-mediated regulatory events in the tamoxifen resistant cell...

  8. [Regulation of terpene metabolism]. Annual progress report, March 15, 1991--March 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1992-12-31

    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  9. Coordination of Recombination with Meiotic Progression in the Caenorhabditis elegans Germline by KIN-18, a TAO Kinase That Regulates the Timing of MPK-1 Signaling.

    Science.gov (United States)

    Yin, Yizhi; Donlevy, Sean; Smolikove, Sarit

    2016-01-01

    Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome. In addition, ectopic germ-cell differentiation and enhanced levels of apoptosis were observed in kin-18 mutants. These defects correlate with ectopic activation of MPK-1 that includes premature, missing, and reoccurring MPK-1 activation. Late progression defects in kin-18 mutants are suppressed by inhibiting an upstream activator of MPK-1 signaling, KSR-2. However, the acceleration of recombination events observed in kin-18 mutants is largely MPK-1-independent. Our data suggest that KIN-18 coordinates meiotic progression by modulating the timing of MPK-1 activation and the progression of recombination events. The regulation of the timing of MPK-1 activation ensures the proper timing of apoptosis and is required for the formation of functional oocytes. Meiosis is a conserved process; thus, revealing that KIN-18 is a novel regulator of meiotic progression in C. elegans would help to elucidate TAO kinase's role in germline development in higher eukaryotes.

  10. [Regulation of terpene metabolism]. Annual progress report, March 15, 1990--March 14, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-12-31

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target ``regulatory`` enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C{sub 15}-C{sub 30}) produced by oil glands.

  11. Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells.

    Science.gov (United States)

    Po'uha, Sela T; Kavallaris, Maria

    2015-01-01

    Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for γ-actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that γ-actin plays a role in mitosis. Herein, we investigated the effect of γ-actin in mitosis and demonstrated that γ-actin is important in the distribution of β-actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of γ-actin depletion was replicated with a range of mitotic inhibitors, suggesting that γ-actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of γ-actin enhanced centrosome amplification in cancer cells and caused a significant delay in prometaphase/metaphase. This prolonged prometaphase/metaphase arrest was due to mitotic defects such as uncongressed and missegregated chromosomes, and correlated with an increased presence of mitotic spindle abnormalities in the γ-actin depleted cells. Collectively, these results demonstrate a previously unknown role for γ-actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity.

  12. Progress in Regulation of Anthocyanins%花青素苷调控研究进展

    Institute of Scientific and Technical Information of China (English)

    樊荣辉; 黄敏玲

    2013-01-01

    Anthocyanins are main determinants of plant flower colors.In recent years,with rapid development of molecular bio-technology and research,the regulation mechanism of anthocyanins has become increasingly clear.In order to provide theoretical reference for flower color improving,this review describes regulation mechanism about biosynthesis of anthocyanins,modification of anthocyanidins,co-pigments,vacuole pH value,metal ions and transcription factors.%花青素苷是决定植物花色的主要色素.近年来,随着分子生物学技术的发展及研究的深入,花青素苷调控机理越来越清晰.该文主要论述了花青素苷生物合成、分子修饰、助色素、液泡pH值、金属离子、转录因子等调控机制,以期为花色改良提供理论参考.

  13. ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression

    Directory of Open Access Journals (Sweden)

    David S. Rickman

    2010-12-01

    Full Text Available To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC, we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3 emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

  14. ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression.

    Science.gov (United States)

    Rickman, David S; Chen, Ying-Bei; Banerjee, Samprit; Pan, Yihang; Yu, Jindan; Vuong, Terry; Perner, Sven; Lafargue, Christopher J; Mertz, Kirsten D; Setlur, Sunita R; Sircar, Kanishka; Chinnaiyan, Arul M; Bismar, Tarek A; Rubin, Mark A; Demichelis, Francesca

    2010-12-01

    To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

  15. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  16. Heme oxygenase-1 regulates the progression of K/BxN serum transfer arthritis.

    Directory of Open Access Journals (Sweden)

    Rita Brines

    Full Text Available BACKGROUND: Heme oxygenase-1 (HO-1 is induced in many cell types as a defense mechanism against stress. We have investigated the possible role of endogenous HO-1 in the effector phase of arthritis using the K/BxN serum transfer model of arthritis in HO-1 heterozygous and homozygous knock-out mice. METHODOLOGY/PRINCIPAL FINDINGS: Arthritis was induced in C57/Black-6 xFVB (HO-1(+/+, HO-1(+/- and HO-1(-/- mice by intraperitoneal injection of 150 µl serum from arthritic K/BxN mice at days 0 and 2. Blood was collected and animals were sacrificed at day 10. Histological analysis was performed in ankle sections. The levels of inflammatory mediators were measured in serum and paw homogenates by enzyme-linked immunosorbent assay or Multiplex technology. The incidence of arthritis was higher in HO-1(+/- and HO-1(-/- groups compared with HO-1(+/+. The inflammatory response was aggravated in HO-1(+/- mice as shown by arthritic score and the migration of inflammatory cells that could be related to the enhancement of CXCL-1 production. In addition, the HO-1(+/- group showed proteoglycan depletion significantly higher than HO-1(+/+ mice. Serum levels of matrix metalloproteinase-3, monocyte chemotactic protein-1, plasminogen activator inhibitor-1, E-selectin and intercellular adhesion molecule-1 were increased in arthritic HO-1(-/- mice, whereas vascular endothelial growth factor and some cytokines such as interferon-γ showed a reduction compared to HO-1(+/+ or HO-1(+/- mice. In addition, down-regulated gene expression of ferritin, glutathione S-reductase A1 and superoxide dismutase-2 was observed in the livers of arthritic HO-1(+/- animals. CONCLUSION/SIGNIFICANCE: Endogenous HO-1 regulates the production of systemic and local inflammatory mediators and plays a protective role in K/BxN serum transfer arthritis.

  17. [Regulation of terpene metabolism]. Annual progress report, March 15, 1989--March 14, 1990

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C{sub 10}) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C{sub 15} C{sub 20}, C{sub 30}, C{sub 40}) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C{sub 15}) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  18. SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression.

    Directory of Open Access Journals (Sweden)

    Chuntao Gao

    Full Text Available Stem cell factor (SCF and hypoxia-inducible factor-1α (HIF-1α both have important functions in pancreatic ductal adenocarcinoma (PDAC. This study aims to analyze the expression and clinicopathological significance of SCF and HIF-1α in PDAC specimens and explore the molecular mechanism at PDAC cells in vitro and in vivo. We showed that the expression of SCF was significantly correlated with HIF-1α expression via Western blot, PCR, chromatin immunoprecipitation (ChIP assay, and luciferase assay analysis. The SCF level was also correlated with lymph node metastasis and the pathological tumor node metastasis (pTNM stage in PDAC samples. The SCF higher-expression group had significantly lower survival rates than the SCF lower-expression group (p<0.05. Hypoxia up-regulated the expression of SCF through the hypoxia-inducible factor (HIF-1α in PDAC cells at the protein and RNA levels. When HIF-1α was knocked down by RNA interference, the SCF level decreased significantly. Additionally, ChIP and luciferase results demonstrated that HIF-1α can directly bind to the hypoxia response element (HRE region of the SCF promoter and activate the SCF transcription under hypoxia. The results of colony formation, cell scratch, and transwell migration assay showed that SCF promoted the proliferation and invasion of PANC-1 cells under hypoxia. Furthermore, the down-regulated ability of cell proliferation and invasion following HIF-1α knockdown was rescued by adding exogenous SCF under hypoxia in vitro. Finally, when the HIF-1α expression was inhibited by digoxin, the tumor volume and the SCF level decreased, thereby proving the relationship between HIF-1α and SCF in vivo. In conclusion, SCF is an important factor for the growth of PDAC. In our experiments, we proved that SCF, a downstream gene of HIF-1α, can promote the development of PDAC under hypoxia. Thus, SCF might be a potential therapeutic target for PDAC.

  19. SCF, Regulated by HIF-1α, Promotes Pancreatic Ductal Adenocarcinoma Cell Progression

    Science.gov (United States)

    Chen, Jing; Ren, He; Zhang, Huan; Wang, Xiuchao; Lang, Mingxiao; Liu, Jingcheng; Gao, Song; Zhao, Xiao; Sheng, Jun; Yuan, Zhanna; Hao, Jihui

    2015-01-01

    Stem cell factor (SCF) and hypoxia-inducible factor-1α (HIF-1α) both have important functions in pancreatic ductal adenocarcinoma (PDAC). This study aims to analyze the expression and clinicopathological significance of SCF and HIF-1α in PDAC specimens and explore the molecular mechanism at PDAC cells in vitro and in vivo. We showed that the expression of SCF was significantly correlated with HIF-1α expression via Western blot, PCR, chromatin immunoprecipitation (ChIP) assay, and luciferase assay analysis. The SCF level was also correlated with lymph node metastasis and the pathological tumor node metastasis (pTNM) stage in PDAC samples. The SCF higher-expression group had significantly lower survival rates than the SCF lower-expression group (p<0.05). Hypoxia up-regulated the expression of SCF through the hypoxia-inducible factor (HIF)-1α in PDAC cells at the protein and RNA levels. When HIF-1α was knocked down by RNA interference, the SCF level decreased significantly. Additionally, ChIP and luciferase results demonstrated that HIF-1α can directly bind to the hypoxia response element (HRE) region of the SCF promoter and activate the SCF transcription under hypoxia. The results of colony formation, cell scratch, and transwell migration assay showed that SCF promoted the proliferation and invasion of PANC-1 cells under hypoxia. Furthermore, the down-regulated ability of cell proliferation and invasion following HIF-1α knockdown was rescued by adding exogenous SCF under hypoxia in vitro. Finally, when the HIF-1α expression was inhibited by digoxin, the tumor volume and the SCF level decreased, thereby proving the relationship between HIF-1α and SCF in vivo. In conclusion, SCF is an important factor for the growth of PDAC. In our experiments, we proved that SCF, a downstream gene of HIF-1α, can promote the development of PDAC under hypoxia. Thus, SCF might be a potential therapeutic target for PDAC. PMID:25799412

  20. Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway.

    Science.gov (United States)

    Zhang, Xiaotian; Ma, Sai; Zhang, Ran; Li, Shuang; Zhu, Di; Han, Dong; Li, Xiujuan; Li, Congye; Yan, Wei; Sun, Dongdong; Xu, Bin; Wang, Yabin; Cao, Feng

    2016-03-01

    It has been reported that oncostatin M (OSM) could initiate cardiomyocyte dedifferentiation both in vivo and in vitro. OSM-induced cardiomyocyte dedifferentiation might be a new target for the treatment of diabetic cardiomyopathy (DCM). This study was designed to determine the role of OSM in cardiomyocyte dedifferentiation and the progression of DCM. A mouse DCM model was established to evaluate the effects of OSM in vivo. Echocardiography was applied to determine cardiac function. Sirius red staining was used to detect fibrosis area. Transmission electron microscopy was used to evaluate mitochondria impairment. Real-time polymerase chain reaction and western blot analysis were performed to detect relative mRNA expressions and cardiomyocyte dedifferentiation-related protein expressions, respectively. OSM treatment induced similar impaired cardiac function and cardiac ultrastructure impairment to those detected in DCM mice. The expressions of dedifferentiation markers of cardiomyocyte (Runx1, and α-SM-actin) were up-regulated in the OSM-treated mice compared with those in the control group. To further demonstrate the important role of OSM, OSM receptor knockout (Oβ(ko)) mice were used. In Oβ(ko) mice, cardiomyocytes dedifferentiation markers of c-kit, Runx1, and atrial natriuretic peptide were down-regulated, with attenuated DCM injury and abrogated OSM/B-Raf/Mek/Erk signaling pathway. In conclusion, OSM-induced cardiomyocyte dedifferentiation plays a crucial role in the progression of DCM. The mechanism of OSM-induced cardiomyocyte dedifferentiation is associated with B-Raf/Mek/Erk signaling pathway through the OSM receptor Oβ. PMID:26837420

  1. Specific changes in the expression of imprinted genes in prostate cancer-implications for cancer progression and epigenetic regulation

    Institute of Scientific and Technical Information of China (English)

    Teodora Ribarska; Klaus-Marius Bastian; Annemarie Koch; Wolfgang A Schulz

    2012-01-01

    Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation,enhancer of zeste homologue 2 (EZH2)overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer.DNA methylation,EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes.Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes,expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2).A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms.Instead,selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes,which might function in the prostate to limit cell growth induced viathe PI3K/Akt pathway,modulate androgen responses and regulate differentiation.Whereas dysregulation of IG F2 may constitute an early change in prostate carcinogenesis,inactivation of this imprinted gene network is rather associated with cancer progression.

  2. Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.

    Science.gov (United States)

    Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M; Nomura, Daniel; Luo, Kunxin

    2015-02-10

    Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells.

  3. Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression.

    Science.gov (United States)

    Boekhout, Michiel; Yuan, Ruixue; Wondergem, Annelotte P; Segeren, Hendrika A; van Liere, Elsbeth A; Awol, Nesibu; Jansen, Imke; Wolthuis, Rob M F; de Bruin, Alain; Westendorp, Bart

    2016-03-01

    E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression.

  4. Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qi-lin; Yang, Tian-lun [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yin, Ji-ye [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Peng, Zhen-yu [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yu, Min [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Chen, Fang-ping, E-mail: xychenfp@public.cs.hn.Cn [Department of Haematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China)

    2009-11-06

    Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 {mu}g/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT{sub 1}) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 {mu}mol/L) induced HUVECs arrested at G{sub 0}/G{sub 1}, enhanced the expression level of AT{sub 1} mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT{sub 1} mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G{sub 0}/G{sub 1} and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

  5. 转录终止及其调控%The progress of transcription termination and regulation

    Institute of Scientific and Technical Information of China (English)

    夏珺; 李建军; 王梁华

    2012-01-01

    Regulation of gene expression often occurs at the level of transcription. More recently, the transition from initiation to elongation has been better defined. While much less is known about the mechanism of the transcription termination, particularly in eukaryotes. It's well known that in prokaryotes, there are two pathways: Rho-dependent termination and Rho-independent termination. In eukaryotes, there are also two transcription termination pathways: poly(A)-dependent and Sen 1-dependent termination. The selection of the two PolII termination pathways is regulated by the degree of CTD phosphorylation. Large numbers of genes still exist the phenomenon of premature termination (i.e., attenuation). In prokaryotes, trp operons perform this function well. In eukaryotes, Sen 1-dependent termination pathway in fact functions as a mechanism of attenuation. A new study reveals that Mpkl can block Sen 1-mediated premature transcription termination, which is independent of its catalytic activity. This function is mediated by an interaction between Mpkl and the Pafl subunit of the Pafl elongation complex. In conclusion, it's meaningful for transcription termination in the regulation of gene expression.%转录是基因表达调控的重要环节,对转录起始和延长水平已了解甚多,但对转录终止,尤其是真核生物转录终止还知之甚少.已知原核生物转录终止有两种模式:依赖Rho因子和不依赖于Rho因子的内在型转录终止子.近来在真核生物中也提出了两种转录终止模式:依赖poly(A)加工信号和依赖Sen1的转录终止.基因转录时,随着RNA聚合酶C末端结构域(carboxy-terminal domain,CTD)末端磷酸化的变化,可选择不同的转录终止模式.大部分基因在转录时还存在提前终止的现象:如原核生物的色氨酸操纵子;而在真核生物中,依赖Sen1的转录终止模式事实上就是一种衰减模式.最新研究发现,Mpk1可以阻断依赖Sen1的转录而提前终止,这

  6. Regulation of alcohol fermentation by Escherichia coli. Progress report, July 1988--June 1989

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.P.

    1989-12-31

    The purpose of this project is to elucidate the way in which the fermentative synthesis of ethanol is regulated in the facultative anaerobe Escherichia coli. We are also investigating the control of other genes required for fermentation and anaerobic growth. We have isolated both structural and regulatory mutations affecting the expression of alcohol dehydrogenase, the enzyme responsible for the final step in alcohol synthesis. Some of these regulatory mutations also affect other anaerobically induced genes. The adh gene has been cloned and sequenced. The ADH protein is one of the largest highly expressed proteins in E. coli and requires approximately 2700bp of DNA for its cloning sequence. We have also isolated mutations affecting the fermentative lactate dehydrogenase. In consequence it is now possible to construct E. coli strains defective in the production of any one or more of their normal fermentation products (i.e. formate, acetate, lactate, ethanol and succinate). The factors affecting the ratio of fermentation products are being investigated by in vivo NMR spectroscopy.

  7. Regulation and market power in the Spanish liquefied petroleum gas industry: Progress or failure?

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Alejandro; Huerta, Emilio [Departamento de Gestion de Empresas, Universidad Publica de Navarra, Campus de Arrosadia, 31006 Pamplona, Navarra (Spain)

    2007-07-15

    This paper presents a detailed study of the structure, market power and competition in the distribution sector for liquefied petroleum gas (LPG), within Spain. It is a segment of energy consumption and supply that is not often given serious attention, despite the fact that LPG is a crucial source of energy to many households, in many countries in Europe and in the rest of the world. Despite formally being an open and liberalized sector, the Spanish LPG market is characterized by high concentration within the industry; Repsol Butano, the dominant operator, practically controls the entire value chain. These structural characteristics probably justify state intervention in the form of price fixing, in order to guarantee accessible prices for final consumers. Nevertheless, applying this tool has had negative effects on the opening and liberalization process. On the one hand, it fails to encourage entry or an increase in the participation of new operators; on the other, it has considerably deteriorated the economic and financial performance of the distribution agents that are subjected to two strong forces. First, the dominant operator looks after its own interests and its income; and second, the Government tries to defend the interests of final consumers by fixing prices that inadequately remunerate the activity. This shows the contradictory regulatory actions that try to promote competition, and then establish mechanisms to regulate activity by fixing prices that act as price limits. These government set prices discourage new competitors from entering. (author)

  8. Regulation and market power in the Spanish liquefied petroleum gas industry: Progress or failure?

    International Nuclear Information System (INIS)

    This paper presents a detailed study of the structure, market power and competition in the distribution sector for liquefied petroleum gas (LPG), within Spain. It is a segment of energy consumption and supply that is not often given serious attention, despite the fact that LPG is a crucial source of energy to many households, in many countries in Europe and in the rest of the world. Despite formally being an open and liberalized sector, the Spanish LPG market is characterized by high concentration within the industry; Repsol Butano, the dominant operator, practically controls the entire value chain. These structural characteristics probably justify state intervention in the form of price fixing, in order to guarantee accessible prices for final consumers. Nevertheless, applying this tool has had negative effects on the opening and liberalization process. On the one hand, it fails to encourage entry or an increase in the participation of new operators; on the other, it has considerably deteriorated the economic and financial performance of the distribution agents that are subjected to two strong forces. First, the dominant operator looks after its own interests and its income; and second, the Government tries to defend the interests of final consumers by fixing prices that inadequately remunerate the activity. This shows the contradictory regulatory actions that try to promote competition, and then establish mechanisms to regulate activity by fixing prices that act as price limits. These government set prices discourage new competitors from entering. (author)

  9. Regulation and market power in the Spanish liquefied petroleum gas industry: Progress or failure?

    International Nuclear Information System (INIS)

    This paper presents a detailed study of the structure, market power and competition in the distribution sector for liquefied petroleum gas (LPG), within Spain. It is a segment of energy consumption and supply that is not often given serious attention, despite the fact that LPG is a crucial source of energy to many households, in many countries in Europe and in the rest of the world. Despite formally being an open and liberalized sector, the Spanish LPG market is characterized by high concentration within the industry; Repsol Butano, the dominant operator, practically controls the entire value chain. These structural characteristics probably justify state intervention in the form of price fixing, in order to guarantee accessible prices for final consumers. Nevertheless, applying this tool has had negative effects on the opening and liberalization process. On the one hand, it fails to encourage entry or an increase in the participation of new operators; on the other, it has considerably deteriorated the economic and financial performance of the distribution agents that are subjected to two strong forces. First, the dominant operator looks after its own interests and its income; and second, the Government tries to defend the interests of final consumers by fixing prices that inadequately remunerate the activity. This shows the contradictory regulatory actions that try to promote competition, and then establish mechanisms to regulate activity by fixing prices that act as price limits. These government set prices discourage new competitors from entering

  10. Properties and regulation of biosynthesis of cottonseed storage proteins. Comprehensive progress report, December 1, 1976 to September 1, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Dure, III, L S

    1979-01-01

    The regulation of gene expression in cotton seed embryogenesis was studied by attempting to define what gene products are likely to be highly regulated during this developmental progression. The flow of nitrogen into the free amino acids pools of the developing cotyledons, and into the principal nitrogen nutritional reserve of the seed, the storage proteins was measured. This was continued by following the flow of nitrogen from the storage proteins to the principal exported amino acid asparagine that occurs during the first several days of germination. In this fashion the rise and fall of certain enzymes of amino acid intermediary metabolism could be postulated, and in some cases, verified. The subsets of abundant mRNAs whose appearance and disappearance coincided with developmental events in cotyledon embryogenesis/germination with the short range goal of identifying proteins/enzyme activities were delineated as well as their mRNAs that represent specific developmental stages and the long range goal of using these representatives as probes for studying the mechanisms controlling the rise and fall of these mRNAs and their protein products.

  11. Progress in the Study of Acupuncture in Regulating Post-Cerebral Ischemia/Reperfusion Cell-Apoptosis Related Gene Expression

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 曾因明

    2003-01-01

    @@ Cerebralvascular disease has already become one of the serious illnesses that threatens human health. Along with the development of medicine, although the therapeutic method harvested huge progress, currently ideal therapeutic methods are lacking. The conventional acupuncture has definite therapeutic effect on cerebropathy. Clinical practice and various animal experiments confirmed that acupuncture could alleviate the pathologic damage after cerebral ischemic injury and promote the nerve function recovery. Past studies showed that the role of acupuncture in treating cerebral ischemia is realized through alleviating post-ischemic neuron necrosis, while recent study discovered that acupuncture has inhibitory effect on post-ischemia induced neuronal necrosis(1), which brought the mechanism of acupuncture in treating cerebral ischemia from the biochemical and metabolical level to the molecular biologic level. The studies revealed that after cerebral ischemia, many genes were induced to express themselves, protein product they coded directly or indirectly participated in the regulation of post-cerebral ischemia apoptosis of neuron, some promoting the apoptosis, while others inhibiting apoptosis with some of the function still unclear. The anti-apoptotic effect of acupuncture is accomplished through regulating the relevant apoptotic gene expression(2), and now it is reviewed as follows:

  12. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.

    Science.gov (United States)

    Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V

    2015-04-15

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.

  13. Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3

    Science.gov (United States)

    Tao, Ting; Shi, Hui; Lo, Li Jan; Wang, Yingchun; Chen, Jun; Peng, Jinrong

    2016-01-01

    Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis. PMID:27657329

  14. ANGPTL4 Correlates with NSCLC Progression and Regulates Epithelial-Mesenchymal Transition via ERK Pathway.

    Science.gov (United States)

    Zhu, Xiaoming; Guo, Xiaobin; Wu, Sen; Wei, Li

    2016-08-01

    Purpose Lung cancer remains the leading cause of cancer deaths with intricate mechanisms. In the present study, we evaluated the clinical significance and biological role of ANGPTL4 in non-small cell lung cancer (NSCLC), the most common lung cancer subtype. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for examining the mRNA level of ANGPTL4 in NSCLC tissues and adjacent non-tumor tissues, NSCLC cell lines, and the immortalized human bronchial epithelial cell line HBE, respectively. A tissue microarray was used for analyzing the relationship between ANGPTL4 expression and the clinicopathological parameters of NSCLC patients. Commercial lentivirus expressing shRNAs was used for silencing ANGPTL4. Cell Counting Kit-8 (CCK-8) was employed for evaluating the cell proliferation ability and transwell with or without matrigel was used for cell migration and invasion assay. Results As the result, ANGPTL4 was over-expressed in NSCLC tissues compared with benign lung tissues. Silencing ANGPTL4 expression strongly inhibited the proliferation, migration, and invasion of A549 and H520 cells, which was in accordance with the increase of epithelial marker E-cadherin and decrease of mesenchymal marker vimentin. By screening the ERK, AKT, EGFR, and STAT3 pathways, we found that cell growth, migration, and invasion arrest induced by loss of ANGPTL4 expression was partially attributable to down-regulation of ERK signaling. Conclusion These results suggested that ANGPTL4 was essential for proliferation and metastasis of lung cancer cells and might serve as a novel target for the treatment of lung cancer. PMID:27166634

  15. Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

    International Nuclear Information System (INIS)

    Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation

  16. Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Si-Jian [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China); Wu, Yue-Bing [Department of Internal Medicine Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Cai, Shang [Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 21500 (China); Pan, Yi-Xin; Liu, Wei [Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Bian, Liu-Guan [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China); Sun, Bomin [Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Sun, Qing-Fang, E-mail: sunqingfang11@163.com [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China)

    2015-03-13

    Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation.

  17. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN.

    Science.gov (United States)

    Chen, W-T; Zhu, G; Pfaffenbach, K; Kanel, G; Stiles, B; Lee, A S

    2014-10-16

    Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. PTEN (phosphatase and tenson homolog deleted on chromosome 10), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cP(f/f)78(f/f)). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months, cP(f/f)78(f/f) livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis and liver injury, implying that GRP78 protects the liver against PTEN-null-mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cP(f/f)78(f/f) livers. Strikingly, bile duct cells in cP(f/f)78(f/f) livers maintained wild-type (WT) GRP78 level, whereas adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective JNK activation, β-catenin downregulation, along with PDGFRα upregulation, which was unique to cP(f/f)78(f/f) livers at 6 months. Development of both HCC and CC was accelerated and was evident in cP(f/f)78(f/f) livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, c78(f/f) livers

  18. MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Correia, Nádia C; Fragoso, Rita; Carvalho, Tânia; Enguita, Francisco J; Barata, João T

    2016-01-01

    Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1-positive cell line extends mouse survival in a xenotransplant model of human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness. PMID:27550837

  19. Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Li; John M Wo; Mukunda B Ray; Whitney Jones; Ruifeng R Su; Susan Ellis; Robert C G Martin

    2006-01-01

    AIM: To investigate the expression of cyclooxygenase-2(COX-2) and epithelial growth factor receptor (EGFR)throughout the progression of Barrett's esophagus (BE).METHODS: COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined.Areas of COX-2 and EGFR expression were quantified by using computer Imaging System.RESULTS: The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma (EAC). A positive correlation was found between COX-2 expression and EGFR expression.CONCLUSION: COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

  20. MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer (NSCLC) through down-regulation of CYP1B1.

    Science.gov (United States)

    Mao, Ming; Wu, Zhouqing; Chen, Jiakuan

    2016-09-16

    Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Herein, we demonstrated that miR-187-5p is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-187-5p was decreased obviously in NSCLC tissues. Down-regulation of miR-187-5p was associated with TNM stage and postoperative survival. Overexpression of miR-187-5p inhibited the growth and metastasis of NSCLC cells. The CYP1B1 was a direct target of miR-187-5p and promoted the growth and metastasis of NSCLC cells. Further study showed that CYP1B1 could reverse the inhibitory effect of miR-187-5p on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-187-5p in the progression of NSCLC. Thus, miR-187-5p may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention. PMID:27495872

  1. 生长素调节植物花发育的研究进展%Research Progress on Auxin Regulation in Flower DeveloPment

    Institute of Scientific and Technical Information of China (English)

    严希; 彭剑涛

    2015-01-01

    花是被子植物的繁殖器官,花的发育是植物繁衍后代的关键环节。大量研究表明,花发育受到基因、植物激素、温度等多种内外因素的调控,生长素在此过程中扮演着不可或缺的角色。本文介绍了国内外生长素调控花发育研究的进展,尤其是生长素极性运输、生长素含量变化以及生长素信号转导在花器官发育过程中的作用。%Flower is the reproductive organ of angiosperm,and flower development is the key step in the progress of reproduction. Numerous researches have indicated that flower development is regulated by genes,plant hor-mones,temperature,and so on. Plant hormones,especially auxin,play indispensable roles in regulation of flow-er development. In this review we introduced the research progress on auxin regulation in flower development. Effects of polar auxin transport,changes in auxin contents and auxin signal transduction on the development of flower were reviewed in particular.

  2. DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21{sup Cip1}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Woong; Kim, Hyeng-Soo; Kim, Seonggon; Hwang, Junmo; Kim, Young Hun; Lim, Ga Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Sohn, Wern-Joo [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Yoon, Suk-Ran [Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kim, Jae-Young [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Park, Tae Sung [Department of Laboratory Medicine, Kyung Hee University School of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702 (Korea, Republic of); Park, Kwon Moo [Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422 (Korea, Republic of); Ryoo, Zae Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Sanggyu, E-mail: slee@knu.ac.kr [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer DACH1 increases cyclin D, F and Cdk 1, 4, 6 in mouse myeloid progenitor cells. Black-Right-Pointing-Pointer The knockdown of DACH1 blocked the cell cycle progression of HL-60 cells. Black-Right-Pointing-Pointer The novel effect of DACH1 related with cell cycle regulation and leukemogenesis. -- Abstract: The cell-fate determination factor Dachshund, a component of the Retinal Determination Gene Network (RDGN), has a role in breast tumor proliferation through the repression of cyclin D1 and several key regulators of embryonic stem cell function, such as Nanog and Sox2. However, little is known about the role of DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the differential expression levels of extensive cell cycle regulators controlled by DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced p27{sup Kip1} and repressed p21{sup Cip1}, which is a pivotal characteristic of the myeloid progenitor. Furthermore, DACH1 significantly increased the expression of cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21{sup Cip1}, which in turn decreased the phosphorylation of the Rb protein. The expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced expression of DACH1 in mouse myeloid progenitor cells.

  3. Recent Progress on Liver Kinase B1 (LKB1: Expression, Regulation, Downstream Signaling and Cancer Suppressive Function

    Directory of Open Access Journals (Sweden)

    Ren-You Gan

    2014-09-01

    Full Text Available Liver kinase B1 (LKB1, known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK, salt-inducible kinase (SIK, sucrose non-fermenting protein-related kinase (SNRK and brain selective kinase (BRSK signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers.

  4. Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

    OpenAIRE

    Detjen, K.; Yang, J; Logsdon, C D

    1995-01-01

    Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in t...

  5. Regulations of enzymes in animals: effects of developmental processes, cancer and radiation. Progress report XI, 1 May 1976--30 April 1977

    Energy Technology Data Exchange (ETDEWEB)

    Knox, W.E.

    1977-06-01

    Two outstandingly successful studies were among those outlined in the proposal last year. They are the first and last topics summarized in this progress report: the first evidence that the chemical composition of human tumors can probably be predicted on the basis of our previous studies in the rat, and the elucidation of the function of the arginine-proline pathway, its importance in fetal and tumor tissues, and its regulation. The variety of other studies are summarized under headings somewhat different from those used in the original proposal, in order to denote more clearly what was actually found, but all proposed topics have been studied to some extent.

  6. Thermal regulation of functional groups in running water ecosystems. Progress report, October 1, 1975--June 30, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Cummins, K.W.; Klug, M.J.

    1976-07-01

    Progress is reported on the following research projects: characterization of functional groups of running water organisms, particularly macroconsumers; studies on relationship of functional groups to qualitative and quantitative characteristics of organic inputs to stream ecosystems; studies on relationship of functional groups to thermal regimes; and dimensioning the control of feeding and growth by temperature and food quality and quantity and determining the extent of compensatory action of each. (HLW)

  7. The job-search grind: perceived progress, self-reactions, and self-regulation of search effort

    NARCIS (Netherlands)

    C. Wanberg; J. Zhu; E.A.J. van Hooft

    2010-01-01

    Guided by theory and research on self-regulation and goal pursuit, we offer a framework for studying the dynamics of unemployed individuals’ job search. A daily survey over three weeks demonstrated vacillation in job seeker affect and, to a lesser extent, "reemployment efficacy." Daily perceived job

  8. Human Transcription Factor hTAFII150 (CIF150) Is Involved in Transcriptional Regulation of Cell Cycle Progression

    OpenAIRE

    Martin, Jay; Halenbeck, Robert; Kaufmann, Jörg

    1999-01-01

    Here we present evidence that CIF150 (hTAFII150), the human homolog of Drosophila TAFII150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAFII150) seems to be less tightly associated with human transcription factor IID than hTAFII130 is associated with hTAFII250. The transient functional knockout of CIF150 (hTAFII150) protein led to cell cycle arrest at the ...

  9. N-glycosylation at Asn residues 554 and 566 of E-cadherin affects cell cycle progression through extracellular signal-regulated protein kinase signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Hongbo Zhao; Xiliang Zha; Lidong Sun; Liying Wang; Zhibin Xu; Feng Zhou; Jianmin Su; Jiawei Jin; Yong Yang; Yali Hu

    2008-01-01

    E-cadherin, which has a widely acknowledged role in mediating calcium-dependent cell-cell adhesion between epithelial cells, also functions as a tumor suppressor. The ectodomain of human E-cadherin contains four potential N-glycosylation sites at Asn residues 554, 566, 618, and 633.We investigated the role of E-cadherin N-glycosylation in cell cycle progression by site-directed mutagenesis. We showed previously that all four potential N-glycosylation sites of E-cadherin were N-glycosylated in human breast carcinoma MDA-MB-435 cells. Removal of N-glycan at Asn633 dramatically affected E-cadherin stability. In this study we showed that E-cadherin mutant missing N-glycans at Asn554, Asn566 and Asn618 failed to induce cell cycle arrest in G1 phase and to suppress cell proliferation in comparison with wild-type E-cadherin. Moreover, N-glycans at Asn554 and Asn566, but not at Asn618, seemed to be indispensable for E-cadherin-mediated suppression of cell cycle progression.Removal of N-glycans at either Asn554 or Asn566 of E-cadherin was accompanied with the activation of the extracellular signal-regulated protein kinase signaling pathway. After treatment with PD98059, an inhibitor of the extraceilular signal-regulated protein kinase signaling pathway, wild-type E-cadherin transfected MDA-MB-435 and E-cadherin N-glycosylation-deficient mutant transfected MDA-MB-435 cells had equivalent numbers of cells in G1 phase. These findings implied that N-glycosylation might be crucial for E-cadherin-mediated suppression of cell cycle progression.

  10. Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

    International Nuclear Information System (INIS)

    Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21Cip1, p27Kip1, p15INK4B, and p16INK4A) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors

  11. Human Transcription Factor hTAFII150 (CIF150) Is Involved in Transcriptional Regulation of Cell Cycle Progression

    Science.gov (United States)

    Martin, Jay; Halenbeck, Robert; Kaufmann, Jörg

    1999-01-01

    Here we present evidence that CIF150 (hTAFII150), the human homolog of Drosophila TAFII150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAFII150) seems to be less tightly associated with human transcription factor IID than hTAFII130 is associated with hTAFII250. The transient functional knockout of CIF150 (hTAFII150) protein led to cell cycle arrest at the G2/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAFII150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAFII150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAFII150) function. We defined a CIF150 (hTAFII150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAFII150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression. PMID:10409744

  12. Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence

    OpenAIRE

    Nowell, Craig S; Nicholas Bredenkamp; Stéphanie Tetélin; Xin Jin; Christin Tischner; Harsh Vaidya; Sheridan, Julie M.; Frances Hogg Stenhouse; Raphaela Heussen; Andrew J H Smith; C Clare Blackburn

    2011-01-01

    The forkhead transcription factor Foxn1 is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC) development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of Foxn1. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at ...

  13. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

    OpenAIRE

    Jiang, Yindi; Hsieh, Jenny

    2014-01-01

    Cell cycle regulation is one of the most fundamental mechanisms to control various biological processes, including the proliferation of neural stem/progenitor cells (NSPCs) in adult mouse brain. This study shows that histone deacetylase 3 (HDAC3), a well-studied epigenetic factor, is required for the proliferation of neural stem cells. We also demonstrate that HDAC3 controls gap 2 and mitosis phase of cell cycle through stabilization of cell cycle protein cyclin-dependent kinase 1. These find...

  14. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    Science.gov (United States)

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology. PMID:26145291

  15. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    Science.gov (United States)

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

  16. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

    International Nuclear Information System (INIS)

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-L-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. - Highlights: • 9,10-PQ promotes invasion, metastasis and tumorigenicity in lung cancer cells. • The 9,10-PQ-elicited promotion is possibly due to AKR1B10 up-regulation

  17. Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guo-Liang Huang

    Full Text Available OBJECTIVES: The role of heparanase (HPSE gene in cancers including hepatocellular carcinoma (HCC is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in three different aspects: (1 loss of heterozygosity (LOH by a custom SNP microarray and DNA copy number by real-time PCR; (2 mRNA level by qRT-PCR; and (3 protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed. RESULTS: Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111 of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112 of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80 of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients. CONCLUSIONS: The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

  18. Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling.

    Science.gov (United States)

    Guo, Huabei; Nagy, Tamas; Pierce, Michael

    2014-11-01

    Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression.

  19. Research Progress in Regulation of Pokemon and MicroRNA on Carcinogensis and Progress for Colon Cancer%Pokemon及microRNA调控结肠癌发生发展的研究进展

    Institute of Scientific and Technical Information of China (English)

    别延红

    2013-01-01

    Pokemon蛋白(也被称为LRF、ZBTB7、OCZF、FBI-1),即POK红系髓性致癌因子(erythroid ontogenic factor),是转录抑制因子POK家族的一员,现已被确认为原癌基因.微小核糖核酸microRNA (miRNA)是近年来研究最活跃的细胞调控因子,miRNA是一种22~25个核苷酸之间的非编码RNA,能在转录和翻译水平上调控基因表达,它们都在结肠癌中发挥作用.文章对Pokemon、miRNA调控结肠癌发生发展的研究进行综述.%POK erythroid myeloid ontogenic factor (Pokemon),also called as LRF,ZBTB7,OCZF or FBI-1,has been identified as an oncogene.MicroRNAs (miRNAs) are 22~25 nucleotides long,non-coding RNAs,which could regulate transcriptional and translational gene expression.Both Pokemon and miRNAs play very important roles in colon cancer.This paper reviews on Pokemon and miRNA regulating carcinogensis and progress for colon cancer.

  20. Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains.

    Science.gov (United States)

    Michael, J V; Wurtzel, J G T; Goldfinger, L E

    2016-05-30

    In this study, we assessed the contributions of plasma membrane (PM) microdomain targeting to the functions of H-Ras and R-Ras. These paralogs have identical effector-binding regions, but variant C-terminal targeting domains (tDs) which are responsible for lateral microdomain distribution: activated H-Ras targets to lipid ordered/disordered (Lo/Ld) domain borders, and R-Ras to Lo domains (rafts). We hypothesized that PM distribution regulates Ras-effector interactions and downstream signaling. We used tD swap mutants, and assessed effects on signal transduction, cell proliferation, transformation and tumorigenesis. R-Ras harboring the H-Ras tD (R-Ras-tH) interacted with Raf, and induced Raf and ERK phosphorylation similar to H-Ras. R-Ras-tH stimulated proliferation and transformation in vitro, and these effects were blocked by both MEK and PI3K inhibition. Conversely, the R-Ras tD suppressed H-Ras-mediated Raf activation and ERK phosphorylation, proliferation and transformation. Thus, Ras access to Raf at the PM is sufficient for MAPK activation and is a principal component of Ras mitogenesis and transformation. Fusion of the R-Ras extended N-terminal domain to H-Ras had no effect on proliferation, but inhibited transformation and tumor progression, indicating that the R-Ras N-terminus also contributes negative regulation to these Ras functions. PI3K activation was tD independent; however, H-Ras was a stronger activator of PI3K than R-Ras, with either tD. PI3K inhibition nearly ablated transformation by R-Ras-tH, H-Ras and H-Ras-tR, whereas MEK inhibition had a modest effect on Ras-tH-driven transformation but no effect on H-Ras-tR transformation. R-Ras-tH supported tumor initiation, but not tumor progression. While H-Ras-tR-induced transformation was reduced relative to H-Ras, tumor progression was robust and similar to H-Ras. H-Ras tumor growth was moderately suppressed by MEK inhibition, which had no effect on H-Ras-tR tumor growth. In contrast, PI3K inhibition

  1. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D;

    2008-01-01

    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC......25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA...

  2. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

    Directory of Open Access Journals (Sweden)

    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  3. Glutathione transferases P1/P2 regulate the timing of signaling pathway activations and cell cycle progression during mouse liver regeneration.

    Science.gov (United States)

    Pajaud, J; Ribault, C; Ben Mosbah, I; Rauch, C; Henderson, C; Bellaud, P; Aninat, C; Loyer, P; Morel, F; Corlu, A

    2015-01-15

    Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification of endogenous noxious compounds and xenobiotics. They also regulate phosphorylation activities of MAPKinases in a catalytic-independent manner. Previous studies have demonstrated the regulation of JNK-dependent pathway by GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte proliferation following partial hepatectomy (PH). Using a conventional double knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first wave of hepatocyte proliferation. The lowered proliferation was associated with the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF expression and delayed and/or altered activation of STAT3, JNK and ERK1/2 signaling pathways. In addition, the expression and/or activation of cell cycle regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating that the absence of GSTP1/2 delayed the entry into and progression through the G1 phase of the cell cycle and impaired the synchrony of proliferation in hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun and ATF2 were activated during the early steps of the liver regeneration in wild-type animals, the constitutively active JNK found in the quiescent liver of Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient induction of antioxidant enzymes and nitric oxide synthase were also delayed or repressed during the regenerative response. Altogether our results demonstrate that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial phases of liver regeneration.

  4. Non-coding RNA LINC00857 is predictive of poor patient survival and promotes tumor progression via cell cycle regulation in lung cancer

    Science.gov (United States)

    Wang, Lihui; He, Yanli; Liu, Weijun; Bai, Shengbin; Xiao, Lei; Zhang, Jie; Dhanasekaran, Saravana M.; Wang, Zhuwen; Kalyana-Sundaram, Shanker; Balbin, O. Alejandro; Shukla, Sudhanshu; Lu, Yi; Lin, Jules; Reddy, Rishindra M.; Carrott, Philip W.; Lynch, William R.; Chang, Andrew C.; Chinnaiyan, Arul M.; Beer, David G.; Zhang, Jian; Chen, Guoan

    2016-01-01

    We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target. PMID:26862852

  5. Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

    Science.gov (United States)

    Yang, S D; Yu, J S; Lee, T T; Ni, M H; Yang, C C; Ho, Y S; Tsen, T Z

    1995-10-01

    Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

  6. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity.

    Science.gov (United States)

    Nabti, Ibtissem; Marangos, Petros; Bormann, Jenny; Kudo, Nobuaki R; Carroll, John

    2014-03-17

    Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes. PMID:24637322

  7. In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Che-Ming Liu

    Full Text Available Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4 expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.

  8. Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm

    Institute of Scientific and Technical Information of China (English)

    Zhen Wang; Fang Wang; Wei-Qi Wang; Qian Gao; Wan-Li Wei; Yun Yang; Guo-Ying Wang

    2004-01-01

    AIM: To study the function of N-myc downstream-regulated gene 1 (NDRG1) in colorectal carcinogenesis and its correlation with tumor lymph node metastasis.METHODS: NDRG1 was detected at its protein level by immunohistochemistry (IHC) and image analysis (IA), and NDRG1 mRNA was detected by in situ hybridization (ISH)in formalin-fixed and paraffin-embedded sections with a total of 190 specimens including 38 normal colorectal mucosae, 31 colorectal adenomas, 45 non-metastatic colorectal carcinomas (CRCs), 38 metastatic primary CRC and subsequently regional lymph nodes respectively. At the same time, the correlations of NDRG1 with sex, age of patients and histological types of colorectal carcinomas were observed.RESULTS: NDRG1 proteins were gradually increased in colorectal carcinogenesis (P<0.05 or P<0.01). There was a significant difference in the expression of NDRG1 between non-metastatic and metastatic CRCs (P<0.05), and the correlation was positive (P<0.01, rs=0.329). However, there was no obvious difference in the expression of NDRG1 between the primary sites of CRCs and that in the metastatic sites of corresponding regional lymph nodes, nor was there an apparent difference in sex, age, and histological types.The expression of NDRG1 mRNA was generally in concordance with that of NDRG1 protein.CONCLUSION: NDRG1 gene may play an important role in colorectal carcinogenesis. In addition, NDRG1 may be a putative tumor metastasis promoter gene and is regarded as one of the molecular biological markers that can forecast early metastasis of CRCs. NDRG1 gene in the metastatic sites of regional lymph nodes may preserve its expression characteristics in the primary sites of CRCs to some extent.The expression of NDRG1 is not affected by sex, age and histological types. The role of NDRG1 in tumor metastatic process can be demonstrated byin vivo and in vitro.

  9. Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.

    Directory of Open Access Journals (Sweden)

    Hideki Mutai

    Full Text Available Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5, and auditory brainstem response (ABR thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (--epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.

  10. Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.

    Science.gov (United States)

    Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

    2015-01-01

    Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.

  11. 诱导型一氧化氮合酶的研究进展%Research progress of inducible nitric oxide synthase regulation

    Institute of Scientific and Technical Information of China (English)

    林碧; 李仕燕; 商庆龙

    2015-01-01

    Inducible nitric oxide synthase (iNOS) generates nitric oxide(NO), and it also plays an important roles in inflammation,infection and cancer.Gene polymorphism of iNOS is related to some diseases, while iNOS is regulated by some factors.As a part of fine regulation in oxidation stress, the mechanism of iNOS regulation is essential to elucidatete process such as infection,tumor and immunity.Here we summarize the research progress about iNOS in the area of its transcription, post-transcription, and molecular inhibitors.%诱导型一氧化氮合酶(iNOS)产生一氧化氮(NO)在炎症、感染、癌症等多种疾病中发挥着重要的作用.iNOS基因多态性与多种疾病有关,而iNOS也受多种因素调节.作为体内氧化应激精细调节的一部分,认识iNOS的调控机制,对于探索感染、肿瘤和免疫等过程非常必要.近年来,有关机体对iNOS的调控作用的研究主要集中在转录水平、转录后翻译水平、抑制剂分子等方面并取得了较大进展.

  12. Regulation of macrophage inhibitory factor (MIF) by epidermal growth factor receptor (EGFR) in the MCF10AT model of breast cancer progression.

    Science.gov (United States)

    Lim, Simin; Choong, Lee-Yee; Kuan, Chong Poh; Yunhao, Chen; Lim, Yoon-Pin

    2009-08-01

    Genetic aberration of EGFR is one of the major molecular characteristics of breast cancer. However, the molecular changes associated with EGFR signaling during different stages of breast cancer development have not been studied. In this study, complementary two-dimensional-DIGE and iTRAQ technologies were used to profile the expression level of proteins in 4 isogenic cell lines in the MCF10AT model of breast cancer progression following a time course of EGF stimulation. A total of 80 proteins (67 from iTRAQ, 15 from DIGE, 2 common in both) were identified to be up- or down-regulated by EGF treatment. Following EGF stimulation, the expression level of MIF, a cytokine that has been implicated in many human cancers, was decreased in MCF10A1 normal breast mammary epithelial cells, increased in MCF10AT1k preneoplastic and MCF10CA1h low grade breast cancer cells, but showed no obvious difference in the MCF10CA1a high grade cancer cells. The increase in MIF expression level following EGF treatment could also be observed in A431 cervical cancer cells. EGF-induced increases of MIF expression levels in CA1h breast cancer cells were abrogated when MEK, but not PIK3CA, was knocked down. In addition, silencing of MIF diminished the proliferation of EGF-stimulated CA1h cells when compared to control cells. Taken together, our data suggested an EGFR --> MEK --> MIF proliferative pathway that has never been reported previously and that this pathway "evolves" during disease progression as modeled by the MCF10AT system. Revelation of the novel relationship between MIF and EGF may contribute to an integrated understanding of the roles of these oncogenic factors during breast cancer development.

  13. Progress on General Nitrogen Regulation Protein NtrC%一般氮代谢调控蛋白 NtrC 的研究进展

    Institute of Scientific and Technical Information of China (English)

    李琴; 燕永亮; 苏磊; 战嵛华; 张云华; 王荣富

    2013-01-01

      NtrBC is a two-component system involved in bacteria nitrogen metabolism regulation, and NtrC is a transcription activator protein in response to environmental signal and activates the transcription of target genes. The past studies have indicated that bacterial NtrC plays important roles in regulating diverse processes including nitrogenous compounds utilization, biological nitrogen fixation, the biosynthesis of biopolymer and maintenance on the carbon-nitrogen balance. Studies on NtrC’s overall regulating function are one of the hotspot of microbe metabolic regulatory networks. This paper reviewed the research progress on NtrC in recent years, and described in detail the biological functions of bacterial NtrC, so as to better understand microbian environment adaptation, metabolic diversity, and the molecular mechanism of C-N coupling regulation.%  NtrBC 是细菌氮代谢调控系统中双组分系统,其中 NtrC 是响应环境信号的转录激活蛋白,对靶基因具有转录激活作用。已有的研究表明 NtrC 在细菌氮源利用、生物固氮、高分子胞外聚合物合成、碳氮平衡等方面发挥了重要的调节作用。对 NtrC 的全局调控作用研究,是当前微生物代谢调控网络研究热点之一。综述了细菌 NtrC 近年来的研究进展,详细介绍了细菌 NtrC 的生物学功能及调控机制,以期为更好地了解微生物的环境适应性,代谢多样性和碳氮偶联作用的分子机制奠定理论基础。

  14. ER stress negatively modulates the expression of the miR-199a/214 cluster to regulates tumor survival and progression in human hepatocellular cancer.

    Directory of Open Access Journals (Sweden)

    Quanlu Duan

    Full Text Available BACKGROUND: Recent studies have emphasized causative links between microRNAs (miRNAs deregulation and tumor development. In hepatocellular carcinoma (HCC, more and more miRNAs were identified as diagnostic and prognostic cancer biomarkers, as well as additional therapeutic tools. This study aimed to investigate the functional significance and regulatory mechanism of the miR-199a2/214 cluster in HCC progression. METHODS AND FINDINGS: In this study, we showed that miR-214, as well as miR-199a-3p and miR-199a-5p levels were significantly reduced in the majority of examined 23 HCC tissues and HepG2 and SMMC-7721 cell lines, compared with their nontumor counterparts. To further explore the role of miR-214 in hepatocarcinogenesis, we disclosed that the ER stress-induced pro-survival factor XBP-1 is a target of miR-214 by using western blot assay and luciferase reporter assay. Re-expression of miR-214 in HCC cell lines (HepG2 and SMMC-7721 inhibited proliferation and induced apoptosis. Furthermore, ectopic expression of miR-214 dramatically suppressed the ability of HCC cells to form colonies in vitro and to develop tumors in a subcutaneous xenotransplantation model of the BALB/c athymic nude mice. Moreover, reintroduction of XBP-1s attenuated miR-214-mediated suppression of HCC cells proliferation, colony and tumor formation. To further understand the mechanism of the miR-199a/214 cluster down-expression in HCC, we found that thapsigargin (TG and tunicamycin (TM or hypoxia-induced unfolded protein response (UPR suppresses the expression of the miR-199a/214 cluster in HCC cells. By promoter analysis of the miR-199a2/214 gene, we conjectured NFκB as a potential negative regulator. We further found that UPR and LPS-induced NFκB activation suppressed miR-199a2/214 transcription, and this suppression was reversed by NFκB inhibition in HCC cells. CONCLUSIONS: Our study suggest that modulation of miR-214 levels may provide a new therapeutic approach for

  15. hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression

    Science.gov (United States)

    Pierredon, Sandra; Le Bras, Morgane; Iacovoni, Jason S.; Teulade-Fichou, Marie-Paule; Favre, Gilles; Roché, Henri; Filleron, Thomas; Millevoi, Stefania; Vagner, Stéphan

    2016-01-01

    The expression and role of RNA binding proteins (RBPs) controlling mRNA translation during tumor progression remains largely uncharacterized. Analysis by immunohistochemistry of the expression of hnRNP A1, hnRNPH, RBM9/FOX2, SRSF1/ASF/SF2, SRSF2/SC35, SRSF3/SRp20, SRSF7/9G8 in breast tumors shows that the expression of hnRNP A1, but not the other tested RBPs, is associated with metastatic relapse. Strikingly, hnRNP A1, a nuclear splicing regulator, is also present in the cytoplasm of tumor cells of a subset of patients displaying exceedingly worse prognosis. Expression of a cytoplasmic mutant of hnRNP A1 leads to increased translation of the mRNA encoding the tyrosine kinase receptor RON/MTS1R, known for its function in tumor dissemination, and increases cell migration in vitro. hnRNP A1 directly binds to the 5′ untranslated region of the RON mRNA and activates its translation through G-quadruplex RNA secondary structures. The correlation between hnRNP A1 and RON tumoral expression suggests that these findings hold clinical relevance. PMID:26930004

  16. 国际纳米材料法规及标准进展%Progress of International Regulations and Standards for Nanomaterials

    Institute of Scientific and Technical Information of China (English)

    卢晓静; 李俊芳; 杨海峰; 闫妍; 王超

    2012-01-01

    Due to their special chemical and physical properties, nanomaterials used in consumer products may cause negative impact on the environmental safety and people's health. The current trends of research upon the safety of nanomaterials are introduced, the international laws and regulations about nanomaterials are enumerated, and the progress for related standards-setting is illuminated. The necessity as well as the urgency to establish the standard system for assessing safety of nanomaterials is finally discussed.%纳米材料具有特殊的物理化学性质,在实际应用中可能对环境及健康安全造成负面影响.介绍了国内外纳米材料的安全性研究动态,详述了国际纳米材料法律法规以及相关标准制定工作的进展,论述了建立纳米材料安全评价标准体系的必要性.

  17. 国际纳米材料法规及标准进展%Progress of International Regulations and Standards for Nanomaterials

    Institute of Scientific and Technical Information of China (English)

    卢晓静; 李俊芳; 杨海峰; 闫妍; 王超

    2011-01-01

    Due to their special chemical and physical properties, nanomaterials used in consumer products may cause negative impact on the environmental safety and people's health. The current trends of research upon the safety of nanomaterials are introduced, the international laws and regulations about nanomaterials are enumerated, and the progress for related standards-setting is illuminated. The necessity as well as the urgency to establish the standard system for assessing safety of nanomaterials is finally discussed.%纳米材料具有特殊的物理化学性质,在实际应用中可能对环境及健康安全造成负面影响.介绍了国内外纳米材料的安全性研究动态,详述了国际纳米材料法律法规以及相关标准制定工作的进展,论述了建立纳米材料安全评价标准体系的必要性.

  18. 国际纳米材料法规及标准进展%Progress of International Regulations and Standards for Nanomaterials

    Institute of Scientific and Technical Information of China (English)

    卢晓静; 李俊芳; 杨海峰; 闫妍; 王超

    2011-01-01

    Due to their special chemical and physical properties. Ivmomnurials used in consumer products may cause negative impact on the environmental safely and people s health. The current trends of research upon the safety of manomatirials are introduced, the interimlitinal laws and regulations ahotil nanonutk-rials are enumerated, and the progress for related standards-set lirig is illuminated. The necessity as well as the urgency 10 establish the standard system for assessing safety of nanomaterials is finally discussed.%纳米材料具有特殊的物理化学性质,在实际应用中可能对环境及健康安全造成负面影响.介绍了国内外纳米材料的安全性研究动态,详述了国际纳米材料法律法规以及相关标准制定工作的进展,论述了建立纳米材料安全评价标准体系的必要性.

  19. A Positive Feedback Loop between ATOH7 and a Notch Effector Regulates Cell-Cycle Progression and Neurogenesis in the Retina

    Directory of Open Access Journals (Sweden)

    Florence Chiodini

    2013-03-01

    Full Text Available The HES proteins are known Notch effectors and have long been recognized as important in inhibiting neuronal differentiation. However, the roles that they play in the specification of neuronal fate remain largely unknown. Here, we show that in the differentiating retinal epithelium, the proneural protein ATOH7 (ATH5 is required for the activation of the transcription of the Hes5.3 gene before the penultimate mitosis of progenitor cells. We further show that the HES5.3 protein slows down the cell-cycle progression of Atoh7-expressing cells, thereby establishing conditions for Atoh7 to reach a high level of expression in S phase and induce neuronal differentiation prior to the ultimate mitosis. Our study uncovers how a proneural protein recruits a protein known to be a component of the Notch signaling pathway in order to regulate the transition between an initial phase of selection among uncommitted progenitors and a later phase committing the selected progenitors to neuronal differentiation.

  20. 犬繁殖调控技术研究进展%Current Status and Progress in Canine Reproductive Regulation Technology

    Institute of Scientific and Technical Information of China (English)

    董佳涵; 朱淑文

    2011-01-01

    由于犬具有一些独特的生殖生理特点,使犬的繁殖调控技术的发展一直面临着一些困难.目前犬繁殖调控技术的研究远远落后于其他哺乳动物.本文综述了犬诱导发情、精液保存、人工受精、胚胎移植及克隆等犬的繁殖调控技术国内外研究进展.%Currently, studies on canine reproductive regulation technology are far less developed than that in other mammals.Compared with other mammals, canine reproductive physiology has unique characteristics which make canine reproductive biotechnology faced with some difficulties.This review summaries the following aspects, including induction of estrus in dogs,preservation of semen and artificial insemination (AI) , embryo transfer (ET) and clone, and discusses its current progress and prospect.

  1. 铁调素及其调控机制研究进展%The Progress of the Research on the Hepcidin and Its Regulation Mechanisms

    Institute of Scientific and Technical Information of China (English)

    李笑飞(综述); 李英梅(审校)

    2016-01-01

    铁调素是一种肝脏分泌的小分子肽,其对铁代谢调节起负调控作用。铁的缺乏与过载会导致多种疾病,但机体本身缺乏对铁排泄的调控机制,所以铁调素的负调控作用对维持机体铁代谢平衡尤为重要,对铁调素调控机制的研究也逐渐受到关注。研究发现铁代谢异常、贫血、炎症、缺氧等因素均对铁调素的生成起调控作用,从而间接地影响机体铁代谢平衡。随着分子生物学的发展,在明确铁调素基因表达及分子构成的基础上,对刺激其表达的信号通路也取得了研究进展,如经典的BMP/SMAD信号通路和JAK/STAT信号通路。调节信号通路的调节因子也随之被发现,如铁调素调节蛋白、跨膜丝氨酸蛋白6、Neogenin蛋白、遗传性血色素沉着症候选基因等。它们的发现有助于阐明生理性和病理性铁代谢异常的分子生物学机制,同时使铁调素有望成为新的诊治铁代谢异常疾病的手段。%Hepcidin is a small molecular peptide synthesized and secreted by liver which is responsible for the degenerative regulation of iron metabolism.Iron deficiency and overload will lead to many diseases, because there is no regulation mechanism of iron excretion in human body ,the degenerative regulation of hep-cidin is particularly important to maintain iron metabolism balance.Study on this regulation mechanism has more attention.Study found that abnormal iron metabolism,inflammation,anemia and hypoxia can affect hep-cidin formation and indirectly affect iron metabolism balance .With the development of molecular biology , after clarifying gene expression and molecular signaling pathways of hepcidin ,progress has been made in the pathways of stimulating hepcidin expression,such as the classic BMP/SMAD and JAK/STAT signal path-ways.Regulators have also been found such as HJV,TMPRSS6,Neogenin,HFE,the discovery of which is helpful to elucidate the molecular biological

  2. Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe.

    Directory of Open Access Journals (Sweden)

    Thomas Caspari

    Full Text Available The activity of Cdc2 (CDK1 kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15 by Wee1 kinase in the presence of DNA damage. How Cdc2 can support DNA repair whilst being inactivated by the DNA damage checkpoint remains to be explained. Human CDK1 is phosphorylated by Myt1 kinase at threonine 14 (T14 close to its ATP binding site before being modified at threonine 161 (T167Sp in its T-loop by the CDK-activating kinase (CAK. While modification of T161 promotes association with the cyclin partner, phosphorylation of T14 inhibits the CDK1-cyclin complex. This inhibition is further enforced by the modification of Y15 by Wee1 in the presence of DNA lesions. In S.pombe, the dominant inhibition of Cdc2 is provided by the phosphorylation of Y15 and only a small amount of Cdc2 is modified at T14 when cells are in S phase. Unlike human cells, both inhibitory modifications are executed by Wee1. Using the novel IEFPT technology, which combines isoelectric focusing (IEF with Phos-tag SDS electrophoresis (PT, we report here that S.pombe Cdc2 kinase exists in seven forms. While five forms are phosphorylated, two species are not. Four phospho-forms associate with cyclin B (Cdc13 of which only two are modified at Y15 by Wee1. Interestingly, only one Y15-modified species carries also the T14 modification. The fifth phospho-form has a low affinity for cyclin B and is neither Y15 nor T14 modified. The two unphosphorylated forms may contribute directly to the DNA damage response as only they associate with the DNA damage checkpoint kinase Chk1. Interestingly, cyclin B is also present in the unphosphorylated pool. We also show that the G146D mutation in Cdc2.1w, which renders Cdc2 insensitive to Wee1 inhibition, is aberrantly modified in a Wee1-dependent manner. In conclusion, our work adds support to the idea that two distinct Cdc2 pools regulate cell cycle progression and the response to DNA

  3. Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe.

    Science.gov (United States)

    Caspari, Thomas; Hilditch, Victoria

    2015-01-01

    The activity of Cdc2 (CDK1) kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15) by Wee1 kinase in the presence of DNA damage. How Cdc2 can support DNA repair whilst being inactivated by the DNA damage checkpoint remains to be explained. Human CDK1 is phosphorylated by Myt1 kinase at threonine 14 (T14) close to its ATP binding site before being modified at threonine 161 (T167Sp) in its T-loop by the CDK-activating kinase (CAK). While modification of T161 promotes association with the cyclin partner, phosphorylation of T14 inhibits the CDK1-cyclin complex. This inhibition is further enforced by the modification of Y15 by Wee1 in the presence of DNA lesions. In S.pombe, the dominant inhibition of Cdc2 is provided by the phosphorylation of Y15 and only a small amount of Cdc2 is modified at T14 when cells are in S phase. Unlike human cells, both inhibitory modifications are executed by Wee1. Using the novel IEFPT technology, which combines isoelectric focusing (IEF) with Phos-tag SDS electrophoresis (PT), we report here that S.pombe Cdc2 kinase exists in seven forms. While five forms are phosphorylated, two species are not. Four phospho-forms associate with cyclin B (Cdc13) of which only two are modified at Y15 by Wee1. Interestingly, only one Y15-modified species carries also the T14 modification. The fifth phospho-form has a low affinity for cyclin B and is neither Y15 nor T14 modified. The two unphosphorylated forms may contribute directly to the DNA damage response as only they associate with the DNA damage checkpoint kinase Chk1. Interestingly, cyclin B is also present in the unphosphorylated pool. We also show that the G146D mutation in Cdc2.1w, which renders Cdc2 insensitive to Wee1 inhibition, is aberrantly modified in a Wee1-dependent manner. In conclusion, our work adds support to the idea that two distinct Cdc2 pools regulate cell cycle progression and the response to DNA damage. PMID

  4. Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats.

    Directory of Open Access Journals (Sweden)

    Ashfaq Ahmad

    Full Text Available Hydrogen sulphide (H2S is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C and caffeine in drinking water (62mg/L for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE mRNA was quantified using real time polymerase chain reaction (qPCR.There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05 in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05 in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05 plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II and noradrenaline (NA but attenuates oxidative stress and improves pulse wave velocity which helps to suppress

  5. S100A8/A9 (calprotectin negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Ali Khammanivong

    Full Text Available Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC and other cancers. S100A8/A9 (calprotectin is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like. S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345 phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216 and p-Cdc2 (Thr14/Tyr15 to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14 level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches.

  6. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  7. Early steps in protein synthesis and their regulation: a background study related to the biological effects of radiation. Progress report, July 1, 1975--June 30, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Zamecnik, P.C.

    1976-03-01

    This is a continuing study of protein synthesis, involving a search for the role of Ap/sub 4/A and other unusual nucleotides in growth regulation; studies of the mechanism of action of aminoacyl-tRNA ligases and the effect thereof on protein synthesis; a search for new regulators of the translation step, in cell-free systems; and an effort to improve the sensitivity and quantitation of chemical sequencing at the 3'-end of messenger RNA.

  8. Clinical progress of pressure regulating volume control in mechanical ventilation%呼吸机压力调节容量控制模式在机械通气中的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    韩聪莉; 张睢扬

    2008-01-01

    Pressure regulating volume control is widely used in mechanical ventilation in recent years,especially in noninvasive mechanical ventilation.It reduces endotracheal intubation,incision of tracheal and homologus complication.This article reviews progress,clinical application,mechanism of action and curative effect in mechanical ventilation.%近年来呼吸机压力调节容量控制(pressure regulating volume control,PRVC)模式在机械通气中的临床应用日渐广泛,尤其在无创通气中占有重要地位,可减少患者的气管插管或气管切开以及相应的并发症.本文就呼吸机PRVC模式在机械通气中的发展、临床应用、作用机制及疗效预测作一综述.

  9. Regulation of IGF-1-dependent cyclin D1 and E expression by hEag1 channels in MCF-7 cells: the critical role of hEag1 channels in G1 phase progression.

    Science.gov (United States)

    Borowiec, Anne-Sophie; Hague, Frédéric; Gouilleux-Gruart, Valérie; Lassoued, Kaiss; Ouadid-Ahidouch, Halima

    2011-05-01

    Insulin-like Growth Factor-1 (IGF-1) plays a key role in breast cancer development and cell cycle regulation. It has been demonstrated that IGF-1 stimulates cyclin expression, thus regulating the G1 to S phase transition of the cell cycle. Potassium (K(+)) channels are involved in the G1 phase progression of the cell cycle induced by growth factors. However, mechanisms that allow growth factors to cooperate with K(+) channels in order to modulate the G1 phase progression and cyclin expression remain unknown. Here, we focused on hEag1 K(+) channels which are over-expressed in breast cancer and are involved in the G1 phase progression of breast cancer cells (MCF-7). As expected, IGF-1 increased cyclin D1 and E expression of MCF-7 cells in a cyclic manner, whereas the increase of CDK4 and 2 levels was sustained. IGF-1 stimulated p21(WAF1/Cip1) expression with a kinetic similar to that of cyclin D1, however p27(Kip1) expression was insensitive to IGF-1. Interestingly, astemizole, a blocker of hEag1 channels, but not E4031, a blocker of HERG channels, inhibited the expression of both cyclins after 6-8h of co-stimulation with IGF-1. However, astemizole failed to modulate CDK4, CDK2, p21(WAF1/Cip1) and p27(Kip1) expression. The down-regulation of hEag1 by siRNA provoked a decrease in cyclin expression. This study is the first to demonstrate that K(+) channels such as hEag1 are directly involved in the IGF-1-induced up-regulation of cyclin D1 and E expression in MCF-7 cells. By identifying more specifically the temporal position of the arrest site induced by the inhibition of hEag1 channels, we confirmed that hEag1 activity is predominantly upstream of the arrest site induced by serum-deprivation, prior to the up-regulation of both cyclins D1 and E. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:21315112

  10. Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

    Institute of Scientific and Technical Information of China (English)

    Yuting Lin; Junichi Fukuchi; Richard A Hiipakka; John M Kokontis; Jialing Xiang

    2007-01-01

    Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers.However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-mediated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.

  11. 自我调节学习研究的新进展%The New Progress of the Studies on Self-regulated Learning

    Institute of Scientific and Technical Information of China (English)

    金军伟; 张振新

    2007-01-01

    文章介绍了自我调节学习(self-regulated learning,简称SRL)的含义、研究价值, 以及SRL的维度,最后指出了当前自我调节学习研究中的新进展,展望了未来的研究趋向.

  12. Isoforms of elongation factor eEF1A may be differently regulated at post-transcriptional level in breast cancer progression

    Directory of Open Access Journals (Sweden)

    Vislovukh A. A.

    2013-01-01

    Full Text Available Eukaryotic translation elongation factor 1A exists as two 98 % homologous isoforms: eEF1A1 (A1 and eEF1A2 (A2 which are tissue and development specific. Despite high homology in an open reading frame (ORF region, mRNAs coding for eEF1A1 and eEF1A2 are different in their untranslated regions (UTR, suggesting a possibility of their dissimilar post-transcriptional regulation. Aim. To analyze the existence of cis-acting motifs in the UTRs of EEF1A1/A2 mRNAs, to confirm the possibility of post-transcriptional control of eEF1A1 and eEF1A2 expression. Methods. An ensemble of bioinformatic methods was applied to predict regulatory motifs in the UTRs of EEF1A1/A2 mRNAs. Dual-luciferase reporter assay was employed to detect post-transcriptional regulation of eEF1A1/A2 expression. Results. Numerous regulatory motifs in the UTR of EEF1A1/A2 mRNAs were found bioinformatically. The experimental evidence was obtained for the existence of negative regulation of EEF1A1 and positive regulation of EEF1A2 mRNA in the model of breast cancer development. Conclusions. EEF1A1 and EEF1A2 mRNAs contain distinct motifs in the UTRs and are differently regulated in cancer suggesting the possibility of their control by different cellular signals.

  13. 乳腺泌乳过程中葡萄糖对乳糖合成调控的研究进展%Research progress of glucose regulates the lactose bio-synthesis of the lactation progress in the mammary gland

    Institute of Scientific and Technical Information of China (English)

    孙晓旭; 林叶; 高学军; 李庆章

    2013-01-01

    就乳腺泌乳过程中葡萄糖调控乳糖生物合成做一综述.主要研究了乳腺中葡萄糖参与乳糖的生物合成过程、葡萄糖的跨膜转运机制及葡萄糖对乳糖合成关键酶的调节.%Made an overview of the glucose regulates the lactose bio-synthesis of the lactation progress in the mammary gland.My expermental study is about the procedure ofbio-synthesis between glucose and lactose in the mammary gland,the mechanism of transmembrance transport of glucose,and the regulation of glucose for the lactose synthesizing a key enzyme.

  14. The Essential Role of Phosphoinositide 3-Kinases (PI3Ks) in Regulating Pro-Inflammatory Responses and the Progression of Cancer

    Institute of Scientific and Technical Information of China (English)

    Keqiang Chen; Pablo Iribarren; Wanghua Gong; Ji-Ming Wang

    2005-01-01

    Phosphoinositide 3-Kinases (PI3Ks) are proteins coupled to a variety of cell surface receptors and play a key role in signal transduction cascade regulating fundamental cellular functions such as transcription, proliferation, and survival. PI3Ks also are important in disease processes such as inflammation and cancer. The aim of this review is to outline current understandings of the PI3K family, mechanism of their activation, their role in inflammatory responses and the development of malignant tumors.

  15. TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell-cycle progression: a novel target for BRAF-mutated colorectal tumors.

    Science.gov (United States)

    Condelli, Valentina; Piscazzi, Annamaria; Sisinni, Lorenza; Matassa, Danilo Swann; Maddalena, Francesca; Lettini, Giacomo; Simeon, Vittorio; Palladino, Giuseppe; Amoroso, Maria Rosaria; Trino, Stefania; Esposito, Franca; Landriscina, Matteo

    2014-11-15

    Human BRAF-driven tumors are aggressive malignancies with poor clinical outcome and lack of sensitivity to therapies. TRAP1 is a HSP90 molecular chaperone deregulated in human tumors and responsible for specific features of cancer cells, i.e., protection from apoptosis, drug resistance, metabolic regulation, and protein quality control/ubiquitination. The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. Remarkably, BRAF downstream pathway is modulated by TRAP1 regulatory activity: indeed, TRAP1 silencing induces (i) ERK phosphorylation attenuation, (ii) cell-cycle inhibition with cell accumulation in G0-G1 and G2-M transitions, and (iii) extensive reprogramming of gene expression. Interestingly, a genome-wide profiling of TRAP1-knockdown cells identified cell growth and cell-cycle regulation as the most significant biofunctions controlled by the TRAP1 network. It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. Finally, the dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells. Therefore, this novel TRAP1 function represents an attractive therapeutic window to target dependency of BRAF-driven tumors on TRAP1 translational/quality control machinery.

  16. The budding yeast Cdc48(Shp1 complex promotes cell cycle progression by positive regulation of protein phosphatase 1 (Glc7.

    Directory of Open Access Journals (Sweden)

    Stefanie Böhm

    Full Text Available The conserved, ubiquitin-selective AAA ATPase Cdc48 regulates numerous cellular processes including protein quality control, DNA repair and the cell cycle. Cdc48 function is tightly controlled by a multitude of cofactors mediating substrate specificity and processing. The UBX domain protein Shp1 is a bona fide substrate-recruiting cofactor of Cdc48 in the budding yeast S. cerevisiae. Even though Shp1 has been proposed to be a positive regulator of Glc7, the catalytic subunit of protein phosphatase 1 in S. cerevisiae, its cellular functions in complex with Cdc48 remain largely unknown. Here we show that deletion of the SHP1 gene results in severe growth defects and a cell cycle delay at the metaphase to anaphase transition caused by reduced Glc7 activity. Using an engineered Cdc48 binding-deficient variant of Shp1, we establish the Cdc48(Shp1 complex as a critical regulator of mitotic Glc7 activity. We demonstrate that shp1 mutants possess a perturbed balance of Glc7 phosphatase and Ipl1 (Aurora B kinase activities and show that hyper-phosphorylation of the kinetochore protein Dam1, a key mitotic substrate of Glc7 and Ipl1, is a critical defect in shp1. We also show for the first time a physical interaction between Glc7 and Shp1 in vivo. Whereas loss of Shp1 does not significantly affect Glc7 protein levels or localization, it causes reduced binding of the activator protein Glc8 to Glc7. Our data suggest that the Cdc48(Shp1 complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits.

  17. αB-Crystallin regulates expansion of CD11b⁺Gr-1⁺ immature myeloid cells during tumor progression.

    Science.gov (United States)

    Dieterich, Lothar C; Schiller, Petter; Huang, Hua; Wawrousek, Eric F; Loskog, Angelica; Wanders, Alkwin; Moons, Lieve; Dimberg, Anna

    2013-01-01

    The molecular chaperone αB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. αB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether αB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in αB-crystallin-deficient mice. Notably, αB-crystallin is prominently expressed in CD11b(+) Gr-1(+) immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low αB-crystallin expression. αB-Crystallin deficiency results in a 3-fold higher accumulation of CD11b(+) Gr-1(+) IMCs in tumors and a significant rise in CD11b(+) Gr-1(+) IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b(+) Gr-1(+) IMCs in chronically inflamed livers in αB-crystallin-deficient mice. The effect of αB-crystallin on IMC accumulation is limited to pathological conditions, as CD11b(+) Gr-1(+) IMCs are not elevated in naive mice. Through ex vivo differentiation of CD11b(+) Gr-1(+) cells, we provide evidence that αB-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of αB-crystallin in limiting expansion of CD11b(+) Gr-1(+) IMCs in diverse pathological conditions.

  18. Research Progress on Epigenetic Regulation of Flowering Repressor FLC%抽薹开花抑制因子FLC表观遗传调控研究进展

    Institute of Scientific and Technical Information of China (English)

    肖旭峰; 范淑英

    2013-01-01

    FLOWERING LOCUS C(FLC)是植物抽薹开花调控网络中关键的开花决定因子。随着表观遗传学的发展,人们发现组蛋白修饰等表观调控FLC的表达在植物抽薹开花时间调控中起着非常重要的作用。FLC的抑制因子或促进因子通过改变组蛋白氨基酸的共价修饰(如乙酰化、甲基化等),影响FLC基因所在区域的染色质重塑,调控FLC转录表达水平,从而调节植物抽薹开花。本文就近年来国内外对植物抽薹开花关键调控基因FLC及表观遗传调控其表达研究现状进行了综述,并针对目前研究中存在的问题提出了今后的研究方向和重点。%FLOWERING LOCUS C(FLC)is a key deciding factor in regulating plant bolting and flowering network.Along with the development of epigenetics,scientists found that histone modi-fication and other epigenetic regulation of FLC expression played very important role in regulating plant bolting and flowering.Chromatin covalent modification included acetylation and methylation of lysine and arginine.The recent characterization of FLC repressors and activators has shown that some of these regulatory proteins are involved in the covalent modification of FLC chromatin and controlling the flow-ering time.This paper reviewed the present internal and external status on studying the regulating gene FLC for plant bolting and flowering,and epigenetic regulation and its expression.The paper also pro-vided direction and focus for future studies according the problems existing in present research.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  20. Theoretical and Empirical Research Progress in Evaluating Environmental Regulation Strength%环境规制强度测度理论与实证进展

    Institute of Scientific and Technical Information of China (English)

    李钢; 李颖

    2012-01-01

    With increasing importance of environmental issues in the global economy and politics fields, Envi- ronmental regulation has been a research focus in the field of economics. A great amount of inspiring achievements constantly enrich people's understanding of environmental regulation itself and its impacts in the perspective of Eco- nomics. Although theoretical research has generated a lot of breakthroughs, empirical study in this field is facing obstacles of evaluating indicator, that is how to choose and acquire appropriate indicators to make comparisons among countries or industries. Due to lack of appropriate and consistent evaluating indicator, similar empirical re- searches often reach to contrary conclusions or insignificant regression results, making the conclusions of empirical researches less convincing. By researching and comparing domestic and foreign literatures of Environmental Regula- tion, it's found that foreign indicators follow a clear development route, from qualitative description to simple quan- titative indicator and then to composite index, from input oriented to output-oriented. Input-oriented indicator includes Pollution Abatement Cost (similar indicator such as regulation compliance cost), pollution control invest- ment, number of inspections and government expenditure, while output-oriented indicator includes discharge fee/ tax and major pollutants emissions. After being introduced into empirical study by Walter & Ugelow( 1979), com- posite index has experienced a transformation from mainly input-oriented indicator based to input-oriented indicator based while EPI index has been created and widely used to describe a country's environmental performance. Do- mestic literatures mainly cpncentrate on two kinds of simple quantitative indicators, Pollution Control Investment and Pollutant Emissions, and composite index based on them. In recent years, indicator selection in domestic re- search has been developed to be more complex and various

  1. The dual role of FOXF2 in regulation of DNA replication and the epithelial-mesenchymal transition in breast cancer progression.

    Science.gov (United States)

    Lo, Pang-Kuo; Lee, Ji Shin; Liang, Xiaohui; Sukumar, Saraswati

    2016-10-01

    Dysregulation of Forkhead-box (FOX) transcription factors is linked to cancers of numerous tissue types. Here, we report that FOXF2 is frequently silenced in luminal-type and HER2-positive breast cancers, but is overexpressed in basal-like breast cancers; thus, FOXF2 appears to play distinct roles in different breast cancer subtypes. Inactivation of FOXF2 in luminal-type and HER2-positive breast cancers is attributable to epigenetic silencing. Silencing of FOXF2 is associated with poor prognosis in luminal-type breast cancer. Ectopic expression of FOXF2 in luminal and HER2-positive breast cancer cells suppresses their tumorigenic properties in vitro and in vivo via inhibition of the CDK2-RB-E2F cascade. The in vivo function of FOXF2 is to maintain the stringency of DNA replication, and its loss triggers dysregulation of DNA replication, which in turn activates the p53 checkpoint pathway. Besides its role in cell cycle regulation, FOXF2 is functionally required for mobility and epithelial-to-mesenchymal transition (EMT) of normal breast epithelial cells. In basal-like breast cancer cells, the cell-cycle function of FOXF2 is impaired. However, the EMT function of FOXF2 is still required for mobility, invasiveness and anchorage-independent growth of basal-like breast cancer cells. Our gene expression profiling studies demonstrate that FOXF2 regulates the expression of genes implicated in cell cycle and EMT regulation. Moreover, FOXF2 is highly co-expressed with basal- and metastasis-related genes in breast cancer. These findings suggest that FOXF2 has a dual role in breast tumorigenesis and functions as either a tumor suppressor or an oncogene depending on the breast tumor subtype. PMID:27377963

  2. Luteolin Inhibits Breast Cancer Development and Progression In Vitro and In Vivo by Suppressing Notch Signaling and Regulating MiRNAs

    Directory of Open Access Journals (Sweden)

    Da-Wei Sun

    2015-11-01

    Full Text Available Background/Aims: This study aims to investigate the effect of Luteolin on breast cancer in vitro and in vivo and the interaction between miRNAs and Notch signaling after Luteolin intervention, and illustrates the possible underlying mechanism and regulation loop. Methods: Cell growth/survival assays and cell cycle analyses were performed to evaluate cell survival in vitro. Scratch tests, cell invasion assays and tube formation assays were carried out to analyze cell viability and identify the impact of Luteolin on angiogenesis. Critical components in the Notch pathway including proteins and mRNAs were detected by Western blotting analyses, ELISA assays and real-time reverse transcription-polymerase chain reaction. Matrix metalloproteinases activity was evaluated by gelatin zymography analyses. MiRNAs were analyzed by miRNA expression assays. After MDA-MB-231 cells were separately transfected with Notch-1 siRNA/cDNA and miRNA mimics, the above assays were also carried out to examine potential tumor cell changes. Xenograft models were applied to evaluate the treatment potency of Luteolin in breast cancer. Results: Luteolin significantly inhibited breast cancer cell survival, cell cycle, tube formation and the expression of Notch signaling-related proteins and mRNAs, and regulated miRNAs. After introducing Notch-1 siRNA and miRNA mimics, MDA-MB-231 cells presented with changes in miRNA levels, reduced Notch signaling-related proteins, and decreased tumor survival, invasion and angiogenesis. Conclusion: Luteolin inhibits Notch signaling by regulating miRNAs. However, the effect of miRNAs on the Notch pathway could be either Luteolin-dependent or Luteolin-independent. Furthermore, Notch-1 alteration may inversely change miRNAs levels. Our data demonstrates that Luteolin, miRNAs and the Notch pathway are critical in breast cancer development and prognosis.

  3. Research progress of neuropeptide Y on the regulation of bone metabolism%神经肽Y对骨代谢调节的研究进展

    Institute of Scientific and Technical Information of China (English)

    于小奎; 朱兵

    2013-01-01

    In the study of the relation between nervous system and bone metabolism, neuropeptides, especially neuropeptide Y (NPY), play an important role.NPY can regulate the activity of osteoblasts and osteoclasts through binding with the specific Y receptor, especially Y1 receptor and Y2 receptor, to play an important role in the physiological and pathological process of bone. This article briefly introduces the distribution and function of NPY and its receptors, and analyzes the regulating effect of NPY on bone metabolism from the aspects of bone resorption, bone formation, and bone healing, in order to deepen the understanding of the regulation of NPY on bone metabolism.%在神经系统与骨代谢关系的研究中,神经肽起着重要作用,尤其是神经肽Y(Neuropeptide Y,NPY)。 NPY可通过结合其特异性Y受体,尤其是Y1受体和Y2受体,来调节成骨细胞和破骨细胞的活性,在骨的生理与病理过程中起重要作用。通过简要介绍NPY及其受体的分布特点与作用,从骨形成、骨吸收及骨愈合方面分析了NPY对骨代谢的调节作用,以期进一步加深NPY对骨代谢调节的认识。

  4. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten

    1999-01-01

    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  5. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition

    Science.gov (United States)

    Parikh, Aditya; Lee, Christine; Joseph, Peronne; Marchini, Sergio; Baccarini, Alessia; Kolev, Valentin; Romualdi, Chiara; Fruscio, Robert; Shah, Hardik; Wang, Feng; Mullokandov, Gavriel; Fishman, David; D'Incalci, Maurizio; Rahaman, Jamal; Kalir, Tamara; Redline, Raymond W.; Brown, Brian D.; Narla, Goutham; Difeo, Analisa

    2014-01-01

    Ovarian cancer is a leading cause of cancer deaths among women. Effective targets to treat advanced epithelial ovarian cancer (EOC) and biomarkers to predict treatment response are still lacking because of the complexity of pathways involved in ovarian cancer progression. Here we show that miR-181a promotes TGF-β-mediated epithelial-to-mesenchymal transition via repression of its functional target, Smad7. miR-181a and phosphorylated Smad2 are enriched in recurrent compared with matched-primary ovarian tumours and their expression is associated with shorter time to recurrence and poor outcome in patients with EOC. Furthermore, ectopic expression of miR-181a results in increased cellular survival, migration, invasion, drug resistance and in vivo tumour burden and dissemination. In contrast, miR-181a inhibition via decoy vector suppression and Smad7 re-expression results in significant reversion of these phenotypes. Combined, our findings highlight an unappreciated role for miR-181a, Smad7, and the TGF-β signalling pathway in high-grade serous ovarian cancer.

  6. The cellular distribution of Na+/H+ exchanger regulatory factor 1 is determined by the PDZ-I domain and regulates the malignant progression of breast cancer

    Science.gov (United States)

    Du, Guifang; Gu, Yanan; Hao, Chengcheng; Yuan, Zhu; He, Junqi; Jiang, Wen G.; Cheng, Shan

    2016-01-01

    The oncogenic role of ectopic expression of Na+/H+ exchanger regulatory factor 1 (NHERF1) was recently suggested. Here, we show that NHERF1 was upregulated in high grades compared with low grades. Increased NHERF1 expression was correlated with poor prognosis and poor survival. NHERF1 expression was higher in the nucleus of cancer cells than in contiguous non- mammary epithelial cells. A novel mutation, namely NHERF1 Y24S, was identified in human breast cancer tissues and shown to correspond to a conserved residue in the PDZ-I domain of NHERF1. Truncation and mutation of the PDZ-I domain of NHERF1 increased the nuclear distribution of the NHERF1 protein, and this redistribution was associated with the malignant phenotype of breast cancer cells, including growth, migration, and adhesion. The present results suggest a role for NHERF1 in the progression of breast cancer mediated by the nuclear distribution of the NHERF1 protein, as determined by the truncation or key site mutation of the PDZ-I domain. PMID:27097111

  7. The rotamase Pin1 is up-regulated, hypophosphorylated and required for cell cycle progression in head and neck squamous cell carcinomas.

    Science.gov (United States)

    Wiegand, Susanne; Dakic, Branka; Rath, Ariane F E; Makarova, Galina; Sterz, Carolina; Meissner, Wolfgang; Bette, Michael; Adamkiewicz, Jürgen; Müller-Brüsselbach, Sabine; Müller, Rolf; Werner, Jochen A; Mandic, Robert

    2009-10-01

    The peptidyl-prolyl cis/trans isomerase Pin1 has been implicated in malignant transformation in multiple studies, however, little is known about its potential impact in head and neck cancer. This study evaluates the role of Pin1 in head and neck squamous cell carcinomas (HNSCCs). Pin1 expression and level of phosphorylation was evaluated by Western blot analysis and 2D-gel-electrophoresis. Pin1 was inhibited with juglone (5-hydroxy-1,4-naphthalenedione) or Pin1 specific siRNA and its influence on cell cycle checkpoint distribution was assessed by FACS analysis. Pin1 overexpression was found in HNSCC tissues and cell lines. 2D-gel-electrophoresis data pointed to Pin1 being hypophosphorylated in HNSCC cells which is consistent with overactivation of this rotamase. Inhibition of HNSCC cells with juglone or Pin1 siRNA induced the cell cycle inhibitor p21(WAF1/Cip1) with a concomitant reduction of cells in G2/M and an increased fraction of cells with fragmented DNA. Cell death did not correlate with significant levels of apoptosis in Pin1 depleted HNSCC cells. In summary, the data shows that Pin1 is overexpressed and hypophosphorylated in HNSCC, and that inhibition of Pin1 blocks cell cycle progression and triggers tumor cell death. Pin1 therefore could represent a new target for the development of improved HNSCC targeting drugs.

  8. 内源性大麻素系统调节瘙痒的研究进展%Progress of the regulation of endocannabinoid system on pruritus

    Institute of Scientific and Technical Information of China (English)

    刘秀兰; 上官王宁

    2012-01-01

    Background Pruritus can be caused by numerous drugs and diseases,but the pathogenesis of pruritus is still not clearly elucidated.It has been shown that the endocannabinoid system plays an important role in regulating pruritus and influences the occurrence and development of pruritus.Objective To review home and abroad literatures relating to the regulation of endocannabinoid system on pruritus in recent years. Content Cannabinoid receptor 1 agonist reduces pruritus while its antagonist induces pruritus.Cannabinoid receptor 2 antagonist,endocannabinoids simiar compounds and fatty acid amide hydrolase indirectly inhibit pruritus.Furthermore the antipruritic effect of endocannabinoids may be partly mediated by transient receptor potential vanilloid type. Trend The endocannabinoid system could serve as antipruritic targets for different etiology of itch,but the mechanisms via which the endocannabinoid system regulate pruritus remains unclear,requiring further study and discussion.%背景 很多药物和疾病都能引起瘙痒,但目前有关瘙痒的病理生理学还不完全清楚.研究发现,内源性大麻素系统在调节瘙痒中起着重要的作用,影响着瘙痒的发生与发展.目的 就近年来国内外有关内源性大麻素系统调节瘙痒的文献作一综述. 内容 大麻素受体1 (cannabinoid receptor 1,CB1)激动剂缓解瘙痒,拮抗剂诱发瘙痒.大麻素受体2(cannabinoid receptor 2,CB2)拮抗剂、内源性大麻素类化合物和脂肪酰胺水解酶(fatty acid amide hydrolase,FAAH)间接抑制瘙痒.此外,内源性大麻素的止痒作用可能部分是通过瞬时受体电位香草类受体(transient receptor potential vanilloid type,TRPV)介导的.趋向 内源性大麻素系统可能成为将来各种病因学全身性瘙痒的止痒靶点,但其调节瘙痒的机制还不十分清楚,需要进一步的研究和探讨.

  9. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control

    DEFF Research Database (Denmark)

    Brorsson, Caroline Anna; Nielsen, Lotte Brøndum; Andersen, Marie Louise Max;

    2016-01-01

    1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...

  10. Recent Progress in Jasmonates Regulation of Plant Growth and Development%茉莉素调控植物生长发育的研究进展

    Institute of Scientific and Technical Information of China (English)

    冯孟杰; 徐恒; 张华; 朱英

    2015-01-01

    Jasmonates are the important hormone signals that regulate a wide range of processes in plants. The roles of jasmonates in plant defense responses against herbivory and plant responses to other biotic and abiotic stresses were reviewed by many researchers. In this paper, we are focused on another important role of jasmon-ates in plant development, ranging from growth and photosynthesis to reproductive development, and the mo-lecular mechanisms of jasmonate signaling.%茉莉素(jasmonates, JA)是一类重要的植物内源激素,有着广泛的生物学功能,在植物的生长发育、抵抗逆境胁迫的过程中扮演着重要的角色。本文将对茉莉素调控植物生长发育的功能及相应的分子机制做简要的综述。

  11. The Research Progress of Mitochondria and Cell Regulation%线粒体与细胞调控的研究进展

    Institute of Scientific and Technical Information of China (English)

    汤浩(综述); 林春龙(审校)

    2015-01-01

    线粒体是一种细胞器,广泛存在于除红细胞以外的大多数细胞体内,同时也是细胞进行氧化磷酸化、三羧酸循环及氧化呼吸链的主要场所,产生 ATP,提供细胞活动所需能量,同时线粒体也参与细胞代谢的多个环节,如细胞增殖、凋亡等。近年来,线粒体与细胞调控对疾病的发生、发展成为潜在的研究热点。因此,明确线粒体在细胞调控中的作用机制,以便更好地认识及指导对相关性疾病的治疗具有重要意义。%Mitochondria is a cell organelle,which widely exists in the majority of the cells except red blood cells,at the same time,it is an important place for cell to carry out oxidative phosphorylation ,three tri-carboxylic acid cycle and oxidative respiratory chain , producing ATP for the requirement of cell activity , moreover,mitochondria also participates in multiple processes of cell metabolism ,such as cell proliferation, apoptosis,etc.In recent years,the mitochondria and cell regulation on the occurrence of diseases has become a potential research hotspot.Therefore clarifying the mechanism of cell regulation in mitochondria has a great significance for understanding and guiding the treatment of associated diseases.

  12. Aquaporin 3 is regulated by estrogen in the chicken oviduct and is involved in progression of epithelial cell-derived ovarian carcinomas.

    Science.gov (United States)

    Yang, C; Lim, W; Bae, H; Song, G

    2016-04-01

    Aquaporins (AQPs) are membrane proteins that passively deliver water across the plasma membrane to play an important role in maintaining cell shape. Members of the AQP family are distributed in most of the tissues in the human body and perform a variety of functions based on the water homeostasis suitable for each organ. However, there is little known about the expression and regulation of AQP family members in chickens. Therefore, we determined the expression of AQPs in various tissues of chickens. Among 13 isotypes, AQP3 was highly expressed in the chicken oviduct. Expression of AQP3 messenger RNA (mRNA) increased in the magnum (P glandular and luminal epithelia of the magnum and isthmus of oviducts of diethylstilbestrol-treated chicks. In addition, the pattern of expression of AQP3 changed in an estrogen-dependent manner during the molting period. During the regenerative period of the oviduct after molting, expression of AQP3 mRNA increased coordinately with increasing concentrations of estradiol (P < 0.001), whereas expression of AQP3 mRNA decreased as concentrations of estradiol in plasma decreased in response to induced molting (P < 0.001). Also, expression of the AQP3 increased (P < 0.001) in cancerous ovaries of laying hens. In conclusion, AQP3 does not simply function to transport water into and out of cells but also appears to be closely involved in development of the chicken oviduct, which is regulated by estrogens. Furthermore, our results suggest AQP3 as a new diagnostic for early detection and treatment of epithelial cell-derived ovarian carcinomas. PMID:26808975

  13. Regulation of exosomes in tumor:research progress%外泌体在肿瘤发生中的调节作用研究进展

    Institute of Scientific and Technical Information of China (English)

    吕程程; 朱运峰

    2016-01-01

    外泌体是由多种类型细胞分泌到胞外的纳米级小囊泡,富含蛋白质、mRNA、微RNA(miRNA)、DNA和脂质等生物活性分子,能参与细胞间的物质交换与信息交流,从而影响细胞的生理功能。外泌体中的活性分子能促进肿瘤血管的新生,对肿瘤的发生、侵袭和迁移具有重要的调节作用。此外,外泌体在肿瘤的诊治方面也有重要价值。本文主要综述外泌体的生物学特征及其与肿瘤发生的密切关系,以及外泌体中miRNA在肿瘤诊断和治疗方面应用的研究进展。%Exosomes are extracellular nanoparticles secreted by multiple types of cells,which are enriched for some bioactive molecules,such as proteins,messcge RNA(mRNA),micro RNA(miRNA), DNA and lipid. These molecules are documented to be involved in the process of intercellular material exchange and signal communication,thus affecting the function of cells. Also,exosomes are considered to participate in tumor angiogenesis,cancer progression and metastasis,but the mechanism remains obscure. Exosomes are of great value for the diagnosis and treatment of tumor. The correlations between exosomes and tumorigenesis and tumor metastasis as well as their clinical applications are summarized in this review.

  14. UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression.

    Science.gov (United States)

    Deen, Ashik Jawahar; Arasu, Uma Thanigai; Pasonen-Seppänen, Sanna; Hassinen, Antti; Takabe, Piia; Wojciechowski, Sara; Kärnä, Riikka; Rilla, Kirsi; Kellokumpu, Sakari; Tammi, Raija; Tammi, Markku; Oikari, Sanna

    2016-08-01

    Hyaluronan content is a powerful prognostic factor in many cancer types, but the molecular basis of its synthesis in cancer still remains unclear. Hyaluronan synthesis requires the transport of hyaluronan synthases (HAS1-3) from Golgi to plasma membrane (PM), where the enzymes are activated. For the very first time, the present study demonstrated a rapid recycling of HAS3 between PM and endosomes, controlled by the cytosolic levels of the HAS substrates UDP-GlcUA and UDP-GlcNAc. Depletion of UDP-GlcNAc or UDP-GlcUA shifted the balance towards HAS3 endocytosis, and inhibition of hyaluronan synthesis. In contrast, UDP-GlcNAc surplus suppressed endocytosis and lysosomal decay of HAS3, favoring its retention in PM, stimulating hyaluronan synthesis, and HAS3 shedding in extracellular vesicles. The concentration of UDP-GlcNAc also controlled the level of O-GlcNAc modification of HAS3. Increasing O-GlcNAcylation reproduced the effects of UDP-GlcNAc surplus on HAS3 trafficking, while its suppression showed the opposite effects, indicating that O-GlcNAc signaling is associated to UDP-GlcNAc supply. Importantly, a similar correlation existed between the expression of GFAT1 (the rate limiting enzyme in UDP-GlcNAc synthesis) and hyaluronan content in early and deep human melanomas, suggesting the association of UDP-sugar metabolism in initiation of melanomagenesis. In general, changes in glucose metabolism, realized through UDP-sugar contents and O-GlcNAc signaling, are important in HAS3 trafficking, hyaluronan synthesis, and correlates with melanoma progression. PMID:26883802

  15. 维生素E对动物营养调控的研究进展%Research Progress of Vitamin E on the Regulation of Animal Nutrition

    Institute of Scientific and Technical Information of China (English)

    方福平; 夏先林; 顾明

    2012-01-01

    Vitmnin E is a major nutrition - regulating liposoluble vitamin in nutritions of animals with a biological function of biological antioxidation, better immunization, anti - irritability and stable reproductive function of animals. Therefore, this article collects and arranges some materials of vitamin E such as function principle, method and effect of nutritionregulating only for reference.%维生素E是一种脂溶性维生素,在动物体内具有生物抗氧化、增强免疫、抗应激及维持动物正常生殖机能等生物学功能,是动物营养中的重要营养调控剂。文章就维生素E的作用原理、营养调控方法及效果等方面综述了维生素E对动物营养调控的研究进展。

  16. 细菌纤维素的合成与调控进展%Progress in synthesis and regulation of bacterial cellulose

    Institute of Scientific and Technical Information of China (English)

    李欣; 颜彩玲; 潘凌鸿; 黄建忠

    2011-01-01

    Bacterial cellulose (BC) was a kind of natural high purity biopolymer compared with the lignocellu-lose, the production and processing of BC was more convenient and environment-friendly, thus it made BC be a promising biomaterial. At present, Quconacetobacter was found to be the highest yield BC-producing strain. In this review, the synthesis and the regulation mechanism of Quconacetobacter BC, the genetical engineering methods and culture methods for higher BC production were discussed.%细菌纤维素是1种天然的高纯度生物多聚物,与木质纤维素相比,其生产和加工过程更为方便和环保,因此已成为1种极有潜力的生物材料.葡糖酸醋杆菌是目前已知的产纤维素能力最高的菌株.综述了葡糖酸醋杆菌的细菌纤维素合成和调控机制以及为提高产量所进行的基因工程手段和培养方法.

  17. Progressive Business

    DEFF Research Database (Denmark)

    Christiansen, Christian O.

    2016-01-01

    Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

  18. Progress in the study on mitochondrial regulation of pancreaticβ-cell function%线粒体与胰岛β细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    李莉; 胡纯(综述); 孙林(审校)

    2016-01-01

    All forms of diabetes share the common etiology of impaired pancreatic β-cell insulin release to meet the high demands of peripheral tissues. In pancreatic β-cells, mitochondria serve to integrate the metabolism of exogenous nutrients into energy output, which eventually leads to insulin release. As such, mitochondrial dysfunction underlies β-cell failure and the development of diabetes. Mitochondrial regulation of β-cell function occurs through many diverse pathways, including metabolic coupling, maintenance of mitochondria mass, generation of reactive oxygen species , and through interaction with other cellular organelles. In this chapter, we will examine the factors responsible for mitochondrial biogenesis and degradation and their roles in the balance of mitochondrial mass in β-cells. Furthermore, we will focus on the importance of enzymatic regulators of mitochondrial fuel metabolism and control of mitochondrial mass to pancreatic β-cell function, describing how defects in these pathways ultimately lead to diabetes. Clarifying the causes of β-cell mitochondrial dysfunction may inform new approaches to treat underlying etiologies of diabetes.%胰岛β细胞功能不能满足外周胰岛素的需求是所有类型的糖尿病的共同发病机制。在胰腺β细胞,线粒体将外源性营养物质代谢成能量输出,最终导致胰岛素释放。因此,线粒体功能障碍为β细胞衰竭和糖尿病发生的基础。线粒体调节通过多种途径——包括代谢偶联,线粒体质量的维护和活性氧的产生,以及与其他细胞器之间的相互作用调节β细胞功能。本文将评价线粒体生物起源和退化的主要影响因素和其在β细胞线粒体质量平衡中的作用,并着重阐述线粒体能量物质代谢相关酶调节和线粒体质量对胰岛β细胞功能的重要性,以及这些通路的缺陷如何最终引起糖尿病。明确β细胞线粒体功能障碍的原因可能有助于产生治

  19. The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

    International Nuclear Information System (INIS)

    The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despite this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time. -- Highlights: • Shb is an adaptor protein operating downstream of tyrosine kinase receptors. • Shb deficiency reduces hematopoietic stem cell proliferation. • The proliferative effect of Shb occurs via increased

  20. The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Karin [Department of Medical Cell Biology, Uppsala University, Uppsala 751 23 (Sweden); Heffner, Garrett; Wenzel, Pamela L.; Curran, Matthew [HHMI, Children' s Hospital Boston, Harvard Medical School, Boston, 02115 MA (United States); Grawé, Jan [Department of Genetics and Pathology, Uppsala University, Uppsala 75185 (Sweden); McKinney-Freeman, Shannon L. [Department of Hematology, St. Jude Children' s Research Hospital, Memphis, TN 38105 (United States); Daley, George Q. [HHMI, Children' s Hospital Boston, Harvard Medical School, Boston, 02115 MA (United States); Welsh, Michael, E-mail: michael.welsh@mcb.uu.se [Department of Medical Cell Biology, Uppsala University, Uppsala 751 23 (Sweden)

    2013-07-15

    The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despite this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time. -- Highlights: • Shb is an adaptor protein operating downstream of tyrosine kinase receptors. • Shb deficiency reduces hematopoietic stem cell proliferation. • The proliferative effect of Shb occurs via

  1. Genome-wide screen identified let-7c/miR-99a/miR-125b regulating tumor progression and stem-like properties in cholangiocarcinoma

    Science.gov (United States)

    Lin, K-Y; Ye, H; Han, B-W; Wang, W-T; Wei, P-P; He, B; Li, X-J; Chen, Y-Q

    2016-01-01

    Cholangiocarcinoma (CCA), which is a poor prognosis malignancy that arises from the malignant transformation of cholangiocytes, is associated with chronic inflammation of the biliary epithelium. Thus far, the molecular mechanisms of the origin and neoplastic processes of CCA that are promoted by inflammation are still unclear and need to be fully elucidated. Here using small RNA sequencing to determine the microRNA (miRNA) expression profiles in CCA, we found that let-7c, miR-99a and miR-125b, which are three miRNAs of the same cluster, were downregulated in CCA and targeted interleukin 6 (IL-6), IL-6R and type 1 insulin-like growth factor, which are important cytokines and receptors of the IL-6/signal transducer and activator 3 (STAT3) pathway and have key roles in inflammation and CCA initiation. We also found that enforced expression of let-7c, miR-99a or miR-125b could reduce the activity of STAT3 and further suppress CCA tumorigenicity in vivo and inhibit the migration and invasion of CCA cells in vitro. Surprisingly, let-7c/miR-99a/miR-125b cluster also significantly decreased the ability of CCA cells for cancer stem cell-like mammosphere generation by downregulating CD133 and CD44, which suggests the pivotal roles of let-7c, miR-99a and miR-125b in CCA by regulating both inflammation and stem-like properties. Our findings showed potential links between miRNAs and inflammation, and provide a potential treatment strategy for developing an miRNA-based therapy via IL-6/STAT3 targeting for CCA. PMID:26455324

  2. Progress of 20-HETE on blood pressure and glucose regulation%20-HETE调控血压及血糖的研究进展

    Institute of Scientific and Technical Information of China (English)

    赖光锐; 赵彦艳

    2014-01-01

    The cytochrome P450 4A and 4F family catalyze the metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).20-HETE has two contradictory effects in the development of hypertension.One is prohypertension resulting from constriction of the small arteries.The other is anti-hypertension caused by inhibition of sodium reabsorption.In the animal modes of hypertension,they suggested that 20-HETE is not only closely associated with hypertension,but also accompanies with blood glucose abnormalities.Furthermore,the abnormal 20-HETE level was also found in some diabetic animal models and human affected with diabetes.In this paper,20-HETE on blood pressure and glucose regulation was reviewed.%细胞色素P450 (CYP) 4A和4F酶将花生四烯酸代谢生成二十羟基二十碳四烯酸(20-HETE),20-HETE一方面通过收缩外周血管起升高血压作用,另一方面,通过抑制水钠吸收起抗高血压作用.在高血压动物模型中发现20-HETE不仅仅与高血压密切相关,还发现20-HETE的变化伴随着血糖的异常,而后在糖尿病动物模型及人群中也证实了20-HETE的改变.该文就对20-HETE在血压、血糖调控方面作一综述.

  3. BMPR2-pSMAD1/5 signaling pathway regulates RUNX2 expression and impacts the progression of dedifferentiated chondrosarcoma.

    Science.gov (United States)

    Yang, Kang; Tang, Xiao-Dong; Guo, Wei; Xu, Xiao-Long; Ren, Ting-Ting; Ren, Cong-Min; Wang, Shi-Dong; Bao, Xing; Zhang, Fan; Sun, Kun-Kun

    2016-01-01

    Bone morphogenetic protein receptors (BMPRs) are multifunctional proteins; they have indispensible roles in the process of BMP signaling. However, their function in dedifferentiated chondrosarcoma is uncertain. It has been reported that BMPR2 is associated with chondrosarcoma. Moreover, the detection of BMPR2 is more frequent in dedifferentiated chondrosarcomas (DDCS) than in conventional chondrosarcomas (CCS). BMPR2, phospho-SMAD1/5 (pSMAD1/5), and runt-related transcription factor 2 (RUNX2) expressions were found to be associated with the pathological grades of chondrosarcoma and could be a promising target of treatment outcome. Moreover, BMPR2 was found to induce the RUNX2 expression via pSmad1/5. Knockdown of BMPR2 and pSmad1/5 results in the downregulation of RUNX2 expression in DDCS cells, while the upregulation of BMPR2 and Smad1/5 in CCS cells leads to increased RUNX2 expression. The luciferase reporter gene assay suggested that BMPR2 can induce the RUNX2 expression at the transcriptional level. By chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA), it was found that pSmad1/5 combined directly to RUNX2. The in vivo tumorigenicity assay in mice showed that the inhibition of BMPR2 or Smad1/5 in DDCS cell line reduced tumor growth, while the upregulation of BMPR2 or Smad1/5 in CCS cell line increased tumor growth. Furthermore, a BMPR signaling inhibitor, LDN-193189, was introduced to investigate its role as a potential drug to treat DDCS. Taken together, the present-study results suggest that BMPR2-pSmad1/5 signaling pathway has an important role in regulating not only the RUNX2 expression but also the tumorigenesis of DDCS. PMID:27429845

  4. Wnt和Notch信号通路在肺癌干细胞调控中的研究进展%The Research Progress of Wnt and Notch Pathways in the Regulation of Lung Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    况里杉; 罗虎

    2013-01-01

    Cancer stem cells which have self-renewal and multi-directional differentiation potential are a small number of undifferentiated cell group and they play an important role in the development and progression of human tumors. The lung cancer stem cells were thought to be the root of lung cancer with renewal, differentiation, metastasis and tumorigenesis capacity. Recent researches indicate that lung cancer stem cells are under the co-regulation of the inside genes themselves and the microenvironmental signals around them. Wnt and Notch signal pathways which are two classic development regulation pathways play important roles in them. The profound research on Wnt and Notch signal pathways in the regulation of lung cancer stem cells is beneficial to the discovery of potential targets for the treatment and diagnosis of lung cancer.%肿瘤干细胞是具有自我更新和多向分化潜能的少部分未分化细胞,在多种肿瘤的发生、发展中发挥重要作用.肺癌干细胞被认为是肺癌发生的根源,具有自我更新、分化、转移、致瘤性等特征.已有研究表明,肺癌干细胞受自身内在基因和其所处微环境信号的共同调控,两条经典的发育调控通路Wnt、Notch在其中发挥重要作用.深入研究Wnt和Notch信号通路在肺癌干细胞调控中的作用,有望在肺癌的诊断及治疗中找到新靶点.

  5. Progress on Immune Regulation of Cow Endometritis%奶牛子宫内膜炎免疫调控研究进展

    Institute of Scientific and Technical Information of China (English)

    胡广胜; 王旭荣; 杨峰; 陈炅然; 苗小楼; 王玲; 罗金印; 李新圃; 李宏胜

    2013-01-01

    Cow endometritis is considered to be one of the important factors of infertility w hich blocked the development of dairy industry .The immunoregulation of uterus is affected by many factors at different de-gree during the course of endometritis development .The main immune defense mechanisms of uterus in cows include cell-mediated immunity and humoral immunity which work through specific immunity and non-specific immunity ,respectively .At the present ,it is reported that immunoregulation substances (cy-tokines ,hormone ,natural product and antigen et al ) could stimulate immune response or enhance immuni-ty of cow to regulate inflammation in cow uterus .This paper summarized immunologic mechanisms and immunoregulation involved cow endometritis ,which will be the foundation for further study of this disease and guideline of the new immune preparations and vaccines to prevent and cure cow endometritis .%奶牛子宫内膜炎是造成奶牛不孕的主要原因之一,严重影响奶牛业的发展。奶牛子宫内膜炎炎症发展过程中,多种因素对奶牛子宫的免疫调节均有不同程度的影响。奶牛子宫内的免疫防御机制主要是通过细胞免疫和体液免疫在起作用,其作用过程主要是通过子宫的特异性免疫和非特异性免疫在发挥作用。目前对奶牛子宫炎具有免疫调控作用的物质主要有细胞因子、激素、天然产物及抗原等,这些物质通过刺激奶牛机体的免疫应答,或者提高机体的免疫力而对奶牛子宫的炎症起到调理作用。论文从不同角度、不同层面对奶牛子宫内膜炎免疫机制及免疫调控进行了综述,对于奶牛子宫内膜炎进一步深入研究,研发预防和治疗该病的新型免疫制剂及疫苗提供参考。

  6. 表观遗传调控在肥胖症研究领域中的研究进展%Progress in the studies on epigenetic regulation of obesity

    Institute of Scientific and Technical Information of China (English)

    李森; 吴建新

    2016-01-01

    肥胖症被认为是一种由遗传因素和环境因素共同决定的复杂型疾病,已成为严重影响现代人类健康的公共卫生问题.在肥胖症的发生和发展过程中,表观遗传调控发挥了极其重要的作用.表观遗传主要的调控方式包括DNA的甲基化修饰,非编码RNA和组蛋白翻译后修饰,近年来组蛋白修饰方向的研究获得了较大突破.在此基础上,本文对表观遗传领域的肥胖症相关研究现状和进展进行了简要综述.%Obesity is considered to be a complex disease which is jointly caused by genetic and environmental factors.And it has become one of the most serious public health problems of modern human society.In the occurrence and development of obesity,epigenetic regulation plays an extremely important role.The main way of epigenetic regulation include:the methylation of DNA,non-coding RNA,and histone modifications.Recently,the study of the histone modification became especially thorough and precise.In this paper,we briefly review the status and progress of obesity-related research in the epigenetic

  7. Research Progress on Molecular Mechanism for Regulating Development of Plant Fruit%植物果实发育调控的分子机理研究进展

    Institute of Scientific and Technical Information of China (English)

    蒋励; 张小兰

    2013-01-01

    Fruit development and ripening is a complicated process. Fruit weight, shape, color, quality and flavor will change along with the fruit development and ripening, and be regulated by a series of fruit developmental genes. Studying the molecular mechanism of fruit development is of great importance for improving fruit quality in the future. Therefore, this paper focuses on 2 species: Arabidopsis and tomato, and summarizes the gene excavation and gene interaction involved in fruit development and ripening. Besides, it also overviews the research progress on the molecular mechanisms for regulating fruit development, and provides certain theoretical guidance for future studies on fruit development and plant breeding.%果实的发育与成熟是一个复杂的过程,果实大小、形状、颜色、品质、风味等都随着果实发育和成熟而变化,并受一系列果实发育相关基因的影响和调控.研究植物果实发育调控的分子机理对于今后提高果实品质具有重要的意义.因此,本文主要综述了拟南芥和番茄中果实发育与成熟相关基因的发掘与相互作用,以及果实发育调控的分子机理研究进展,为今后的果实发育研究和育种工作的开展提供一定的理论指导.

  8. Progress of epigenetic regulation in the differentiation of oligodendrocyte%少突胶质细胞发育分化的表观遗传学调控研究进展

    Institute of Scientific and Technical Information of China (English)

    刘驰; 肖岚

    2011-01-01

    少突胶质细胞的发育分化是由遗传的和后生的机制共同参与调控的一系列动态过程,其中,对于后生调控机制的研究称为表观遗传学.既往对少突胶质细胞的研究主要集中在相关基因本身的特性研究.近年来,关于寻址组蛋白修饰的研究使我们对少突胶质细胞发育和衰老过程中基因表达的后生调控有了新的认识.这些理论将有助于我们更好地理解脱髓鞘及衰老后髓鞘修复障碍的原因和防治途径.%The development of oligodendrocyte is a dynamic process that is regulated by genetic and epigenetic program.In the past years, great progresses have been made in the studies of relative gene transcription and expression in oligodendrocyte development.However, epigenetic regulation of gene expression in the differentiation of oligodendrocyte has not been elucidated.Recent studies on addressing histone modifications have increased our knowledge and found new targets regarding the differentiation of oligodendrocyte and aging of brain.These results will provide us with new idea regarding the mechanisms underlying the decreased efficacy of endogenous remyeliation in response to demyelinating injuries with age increasing, and further suggest new strategies for treatment of these problems.

  9. 衣藻性别决定及交配过程中的基因调控%Progress of Gene Regulation Involved in Chlamydomonas Sex Determination and Mating Process

    Institute of Scientific and Technical Information of China (English)

    徐涤; 陈鹏; 邵宏波; 臧晓南; 张学成

    2011-01-01

    阐述了单细胞绿藻衣藻(Chlamydomonas)性别相关基因及其作用机制的研究进展,其中着重介绍了位于mt基因座及少量位于常染色体上的性别相关基因,并分析了它们在营养细胞分化为正负两种交配型的配子细胞、正/负配子的交配以及合子分化的起始这3个关键步骤中的调控作用.%This paper reviewed recent progress of sex-related genes and their mechnisms in unicellular green alga Chlamydomonas.We focused on genes which were gathered on mating-type(mt) locus as well as some additional sex-related genes located in autosomes and their regulations during the following 3 key steps: Plus and minus gamete sexual differentiation from vegetative cells,mating between mt+/mt-gametes,and initiation of zygote differentiation.

  10. Research progress of body fluid neurons in the regulation of innate immunity in Caenorhabditis Elegans%体液调控神经元在调控秀丽线虫固有免疫中的研究进展

    Institute of Scientific and Technical Information of China (English)

    马安然

    2015-01-01

    秀丽隐杆线虫在受到病原菌感染时,会迅速激活固有免疫。神经免疫间的交流可以通过神经系统释放神经递质、神经肽及激素来调控固有免疫反应,包括已知的多巴胺信号通路、TGF-β信号通路和胰岛素信号通路。近年来的研究表明,NPR-1神经环路也参与固有免疫的调控,并且三个体液调控神经元 AQR、PQR 和 URX 是通过 NPR-1神经环路调节固有免疫的。线虫的神经系统只有302个神经元,结构也相对简单,线虫的 npr-1基因可编码与哺乳动物神经肽 Y(neuropeptideY,NPY)具有受体相似的 GPCR,这些优势为研究高等生物神经免疫间交流的分子机制提供了基础。本文就体液调控神经元在调控秀丽线虫固有免疫方面展开讨论,希望可以为高等生物神经免疫间的调节机制提供重要的思路和方法。%Caenorhabditis elegans would rapidly activate innate immunity once being infected with pathogens. Neuro-immune interactions which are through the nervous system to release such as neurotransmitters, neuropeptides and hormones to regulate the innate immune response. Those pathways include known dopamine signaling pathway, TGF-β signaling pathway and insulin signaling pathways. Recent studies show that NPR-1 neural circuits are also involved in the regulation of innate immunity and three neurons AQR, PQR and URX exposed to body fluid are under the regulation of NPR-1 neural circuits. Elegans nervous system has only 302 neurons and the structure is relatively simple and the npr-1 gene of elegans can encode GPCR which is similar to the mammalian neuropeptide Y (neuropeptideY, NPY) receptor, providing an edge for studying higher organisms on neuro-immune interactions. Research progress in relation to the field has been reviewed in present paper.

  11. Regulation of terpene metabolism. Progress report, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1986-01-01

    Studies on the metabolism of terpenes by peppermint (Menta piperita) are described. The studies describe the characterization of enzymes involved in the biosynthesis and catabolism of terpenes and the ultrastructure of the oil glands. 10 refs. (DT)

  12. 48 CFR 32.503-2 - Supervision of progress payments.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Supervision of progress... GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 32.503-2 Supervision of progress payments. (a) The extent of progress payments supervision, by prepayment review...

  13. GnRH依赖型性早熟遗传调控系统研究进展%Research Progress of the Genetic Regulation System in GnRH-dependent Precocious Puberty

    Institute of Scientific and Technical Information of China (English)

    韩威; 李慧芳; 朱云芬; 宋迟; 徐文娟

    2013-01-01

    性早熟在人类上表现为病理状态,而在家禽生产上则是一个具有重要经济价值的性状.人类性早熟调控机理的研究较为透彻,尤其是近年来全基因关联分析方法的应用,使得研究者对于性成熟启动相关新基因发掘及其调控网络的认识更加深入.论文综述了人类GnRH依赖型性早熟(GDPP)的5个基因调控系统,包括kisspeptin系统、γ-GABA系统、NPY和leptin系统、LIN28B系统和NKB系统的研究进展,为禽类早熟性状研究提供依据.%Precocious puberty performs as pathological condition in humans, but it is an important trait in animal production. The research of human precocious puberty regulation mechanism is more thorough, especially in recent years the genome-wide association study method contributes to find more new genes and deeply understand the genetic networks. This paper summarized the progress of genetic systems in human GnRH-dependent precocious puberty, including kisspeptin system, γ-GABA system, NPY and leptin system, LIN28B system and NKB system. These could supply a basis for the relevant study in animals

  14. 大麻素系统与胃肠道内脏痛调控关系的研究进展%Progress in Study on Relationship between Cannabinoids and Regulation of Visceral Pain of Gastrointestinal Tract

    Institute of Scientific and Technical Information of China (English)

    刘宗亮

    2011-01-01

    Abdominal pain is one of the main symptoms of functional gastrointestinal disorders (FGIDs), especially the irritable bowel syndrome (IBS), which severely affects the life quality of patients. However, its pathophysiologic mechanism is complicated and has not been clarified. Cannabinoids has been applied in studies on the mechanism of pain and in clinical treatment, but addiction and other central nervous system side effects have restricted its application.Therefore, the study on peripheral action of cannabinoids is of great significance in raising the efficacy of cannabinoids on curing chronic pain (especially visceral pain). This article reviewed the progress in investigating on the relationship between cannabinoids and regulation of visceral pain of gastrointestinal tract.%腹痛是功能性胃肠病(FGIDs),特别是肠易激综合征(IBS)的主要症状之一,严重影响患者的生活质量.然而,其病理生理学机制复杂且仍未明确.大麻素已被应用于疼痛机制的研究和临床治疗,但成瘾性等中枢系统不良反应限制了其应用.因此,研究大麻素系统的外周作用途径,对提高大麻素治疗慢性疼痛(特别是内脏痛)的效果,具有重要意义.本文就大麻素系统与胃肠道内脏痛调控关系的研究进展作一综述.

  15. Measuring progress

    DEFF Research Database (Denmark)

    Wahlberg, Ayo

    2007-01-01

    . In this paper, I argue that a growing focus on frontier technologies in the life sciences in discussions about bio-power today has come at the cost of empirical investigations into how, for example, 'quality of life' came to be a crucial object of bio-power in the 20th century. Just as Foucault outlined......In recent years, sociological examinations of genetics, therapeutic cloning, neuroscience and tissue engineering have suggested that 'life itself' is currently being transformed through technique with profound implications for the ways in which we understand and govern ourselves and others...... in much the same way that mortality rates, life expectancy or morbidity rates can. By analysing the concrete ways in which human progress has been globally measured and taxonomised in the past two centuries or so, I will show how global stratifications of countries according to their states...

  16. Progress report

    International Nuclear Information System (INIS)

    Progress Report, covering the period up to the end of 1979 year, was sent to the IAEA according to the research agreement No. 1971 /CF. This work covered the following fields: preparation and dummy irradiation experiments with a new experimental capsule of ''CHOUCA-M'' type; measurement of temperature fields and design of specimen holders; measurement of neutron energy spectrum in the irradiation place in our experimental reactor of VVR-S type (Nuclear Research Institute) using a set of activation detectors; unification and calibration of the measurement of neutron fluence with the use of Fe, Cu, Mn-Mg and Co-Al monitors; development and improvement of the measuring apparatus and technique for the dynamic testing of pre-cracked specimens with determination of dynamic parameters of fracture mechanics; preparation and manufacture of testing specimens from the Japanese steels - forging, plate and weld metal; preparation of the irradiation capsule for assembling

  17. Regulating Rho GTPases and their regulators.

    Science.gov (United States)

    Hodge, Richard G; Ridley, Anne J

    2016-08-01

    Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases. PMID:27301673

  18. Impact of resting heart rate on the progression to diabetes in impaired glucose regulation patients%静息心率对糖调节受损人群进展为糖尿病的影响

    Institute of Scientific and Technical Information of China (English)

    宋秋艳; 余玲; 董瑞鸿; 甄月巧; 桑艳红

    2016-01-01

    Objective_ To investigate the effect of resting heart rate on the progression to diabetes in impaired glucose regulation patients. Methods A total of 638 patients with impaired glucose regulation, from January 2011 to December 2012 in our endocrinology clinic, were selected for the study. According to the resting heart rate, patients were divided into four groups:75 beat/min groups. All patients'baseline data were collected. The incidences of diabetes in different resting heart rate groups were compared, and the relationship between resting heart rate and the progression to diabetes was estimated using multiple regression analysis. Results In 704 patients with impaired glucose regulation, 636 patients have been completed 2 years follow-up, or reached the end of follow-up ( diagnosed as diabetes ) , the follow-up rate was 90. 34%. During two years follow-up, the incidence of diabetes of75 beat/min group were 16. 2%, 19. 4%, 25. 0%, and 33. 0%, respectivlely. And the Cochran Armitage trend test showed that χ2 =11. 109, P=0. 001, the difference was statistically significant ( P75次/min组。收集所有患者的基线资料,比较不同静息心率组间糖尿病的发病率,采用多因素回归分析静息心率与糖调节受损患者进展为糖尿病的关系。结果704例糖调节受损患者中,共636例患者完成2年的门诊随访,或达到随访终点(确诊为糖尿病),随访率为90.34%。(1)随访2年期间,75次/min 组糖尿病发生率分别为16.2%、19.4%、25.0%及33.0%,经 Cochran Armitage趋势检验,趋势χ2=11.109,P=0.001。(2)根据入组患者血糖监测结果,将636例糖调节受损患者分为单纯空腹血糖受损组、单纯糖耐量受损组及空腹血糖受损+糖耐量受损组:3组患者均随着静息心率的加快,糖尿病的发生率增高;其中空腹血糖受损+糖耐量受损组患者进展为糖尿病的比例高于单纯空腹血糖受损组及单纯糖耐量受损组。68例进展为糖尿病的糖调节受

  19. Progress on carbohydrate metabolism regulating antioxidant capacity of postharvest Chinese bayberry fruit%糖代谢调控杨梅果实采后抗氧化活性机制研究进展

    Institute of Scientific and Technical Information of China (English)

    施丽愉; 陈伟; 苏新国; 杨震峰

    2013-01-01

    There are accumulated data indicating that the natural antioxidant compounds from Chinese bayberry fruits have biological properties which can enhance human health. Since antioxidant capacity is be-coming an important quality parameter for postharvest fruit, it is focusing on maintaining and improvement of antioxidant activity in fruit during postharvest storage. Carbohydrate metabolism is one of the most important physiological activities of postharvest fruit, and is also closely related to the biosynthesis and metabolism of anthocyanin and phenolic. This paper introduced the antioxidant properties of postharvest Chinese bayberry fruit, and focused on the research progress of carbohydrate metabolism regulating antioxidant capacity in post-harvest Chinese bayberry fruit. Moreover, this paper also indicated the future research highlights to the specific mechanism of carbohydrate metabolism in the biosynthesis and metabolism of anthocyanin and phenolic in bayberry fruit.%杨梅果实中天然抗氧化物质对人类健康的作用日益受到人们的重视,抗氧化活性的大小已成为衡量果实采后品质的一个重要指标,维持和提高果实采后抗氧化能力已成为果实采后贮运保鲜研究中的热点。糖代谢是果实采后主要的生理活动之一,与果实采后花色苷和酚类物质的代谢存在密切的联系。本文简要介绍了杨梅果实的抗氧化特性,重点综述了糖代谢调控果实采后抗氧化活性机制的研究进展,提出了糖代谢调控杨梅果实采后花色苷和酚类物质合成代谢机制的研究展望。

  20. SUMO: regulating the regulator

    Directory of Open Access Journals (Sweden)

    Bossis Guillaume

    2006-06-01

    Full Text Available Abstract Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i the interplay between sumoylation and other post-translational modifications at the level of individual targets and (ii global regulation of SUMO conjugation and deconjugation.

  1. EDITORIAL: Catalysing progress Catalysing progress

    Science.gov (United States)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  2. EDITORIAL: Catalysing progress Catalysing progress

    Science.gov (United States)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  3. Annual progress report 1980

    International Nuclear Information System (INIS)

    The technical support activities of the IPSN to competent administrations in 1980 has been marked: namely by the authorizations of divergence for 9 units EdF-PWR of 900 MW, the authorization project of creation and extension of reprocessing plant of COGEMA at the Hague UP2-800 and the authorization of starting up of the third unit of production of the EURODIF enrichment plant at Tricastin. On the other hand, IPSN has participated at the elaboration of a certain number of legislative and regulation texts relative to the control of nuclear matter, to radioprotection standards and to criteria of safety. For the safety of breeder, the test made at CABRI pile, in the international research program has given confirmation of the validity of theoretical models used in accidents calculations, hypothetical accidents which has allowed to reactualize safety criteria which have to be used for the development of this type of reactor. In worker radioprotection the results obtained in laboratory on the effect of radon, the progress made in personal dosimetry and the action of radioprotection undertaken in uranium mines constitutes a coherent effort. The deep drilling in granit (1000 m) and the experimental associated program which has finished the indispensable scientific data for the future policy in matter of storage of radioactives wastes. IPSN has contributed to progress made in the rules of exploitation of reactors, in the definition of wastes containment -specially at the output of reprocessing plant- in handling machines in hazardeous areas and in the study of environment

  4. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  5. Learning numerical progressions.

    Science.gov (United States)

    Vitz, P C; Hazan, D N

    1974-01-01

    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  6. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  7. Geothermal progress monitor. Progress report No. 1

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

  8. Increased PEA3/E1AF and decreased Net/Elk-3, both ETS proteins, characterize human NSCLC progression and regulate caveolin-1 transcription in Calu-1 and NCI-H23 NSCLC cell lines

    OpenAIRE

    Sloan, Karin A.; Marquez, Hector A.; Li, Jun; Cao, Yuxia; Hinds, Anne; O'Hara, Carl J.; Kathuria, Satinder; Ramirez, Maria I.; Williams, Mary C.; Kathuria, Hasmeena

    2009-01-01

    Caveolin-1 protein has been called a ‘conditional tumor suppressor’ because it can either suppress or enhance tumor progression depending on cellular context. Caveolin-1 levels are dynamic in non-small-cell lung cancer, with increased levels in metastatic tumor cells. We have shown previously that transactivation of an erythroblastosis virus-transforming sequence (ETS) cis-element enhances caveolin-1 expression in a murine lung epithelial cell line. Based on high sequence homology between the...

  9. SSeCKS, a Major Protein Kinase C Substrate with Tumor Suppressor Activity, Regulates G1→S Progression by Controlling the Expression and Cellular Compartmentalization of Cyclin D

    OpenAIRE

    Lin, Xueying; Nelson, Peter; Gelman, Irwin H.

    2000-01-01

    SSeCKS, first isolated as a G1→S inhibitor that is downregulated in src- and ras-transformed cells, is a major cytoskeleton-associated PKC substrate with tumor suppressor and kinase-scaffolding activities. Previous attempts at constitutive expression resulted in cell variants with truncated ectopic SSeCKS products. Here, we show that tetracycline-regulated SSeCKS expression in NIH 3T3 cells induces G1 arrest marked by extracellular signal-regulated kinase 2-dependent decreases in cyclin D1 ex...

  10. Progress against Prostate Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  11. Dysadherin: a new player in cancer progression.

    OpenAIRE

    Nam, Jeong-Seok; Hirohashi, Setsuo; Wakefield, Lalage M.

    2007-01-01

    Dysadherin is a cancer-associated cell membrane glycoprotein that promotes experimental cancer metastasis. Here we review recent work that has provided insights into possible mechanisms of action of this newly recognized player in the cancer progression process. Dysadherin modulates cell phenotype in a number of ways, including down-regulation of E-cadherin-mediated cell adhesion, and up-regulation of chemokine production. In this way, expression of dysadherin in a tumor can influence both th...

  12. Research Progress on Osmotic Balance Regulation Mechanism of Caenorhabditis Elegans%秀丽隐杆线虫调节渗透平衡机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    袁沛; 童杰文; 潘联云; 龚雨顺

    2016-01-01

    It is very important for the growth and development of organism to maintain osmotic pressure bal-ance in vivo .Caenorhabditis elegans is widely used for the research of resistance mechanism under adverse envi-ronmental conditions.In the meantime,the conservation of its evolution provides reference for the study of os-motic pressure regulation in vivo of higher organisms.In this paper,the relative genes and tissues of osmotic pressure regulation in vitro in Caenorhabditis elegans are introduced,the relative pathways of volumn regula-tion in Caenorhabditis elegans are analyzed,and the effects of maintain protein homeostasis on osmotic pressure regulation are reviewed.%维持生物体内渗透压平衡对生物生长发育十分重要。秀丽隐杆线虫(Caenorhabditis elegans )被广泛用于研究生物在不利环境的抗性机制;同时,由于其进化的保守性,可为研究高等生物的体内渗透压调节提供参考。对秀丽隐杆线虫感知体外渗透压的相关基因和组织进行了介绍,分析了秀丽隐杆线虫调节体积的相关通路,综述了维持蛋白质稳态对渗透压的调节作用。

  13. 营养物质调节胰岛素分泌机制的研究进展%Progress on the mechanism of nutrients-regulated insulin secretion

    Institute of Scientific and Technical Information of China (English)

    张碧君; 赵彦艳

    2014-01-01

    胰岛素是人体内唯一起到降低血糖功能的重要激素.它调节机体血糖维持稳定,促进代谢,调节细胞的分裂分化和生长发育.胰岛素分泌不足或分泌功能障碍都将引起机体的糖代谢紊乱,从而引起糖尿病.该文简述营养物质,即糖、脂肪酸和多肽对胰岛素分泌的调节机制,并对可能影响胰岛素分泌的研究进行进一步展望.%Insulin is the only hormone that reduces blood glucose.It also plays a significant role in stabilizing glucose,boosting metabolism and regulating the differentiation of cells.Lack of insulin secretion will cause diabetes mellitus.In this review,we will briefly summarize the regulation of glucose,free fatty acids and polypeptide on insulin secretion.In the end we bring forth the prospect for further study of insulin secretion regulation.

  14. Progress in Research of Yield Formation of Ratooning Rice and Its High-Yielding Key Regulation Technologies%再生稻产量形成特点与关键调控技术研究进展

    Institute of Scientific and Technical Information of China (English)

    徐富贤; 熊洪; 张林; 朱永川; 蒋鹏; 郭晓艺; 刘茂

    2015-01-01

    The development of ratooning rice is a vital way to achieve a full utilization of the solar-thermal resources in autumn, and promote the profit of rice field. On the basis of the reported data and the research results of the author’s study for more than 20 years, the research reviews and the research progress of yield formation mechanism and key control techniques of ratooning rice were summarized. The main results include that: (1) Compared with the lower regeneration buds, the mid-upper regeneration buds of main crop had an earlier heading date, a fewer number of leaves, a faster speed of leaf emergence, shorter growth period, higher bearing panicle rate and grain filing percentage. The mechanism of a large number of regeneration buds’death after full heading of main crop was mainly due to main photosynthate allocation to grains and fewer to regeneration buds during the main crop grain filling period. Regeneration bud growth depends upon not only the improved light condition at the base of main crop plant population, but also the biomass supply. The difference in ratooning ability among cultivars varied with the leaf-grain ratio of main crop. The higher the leaf-grain ratio at heading stage, the more the photosynthetic matter remained in the basic stems for ratooning rice growing at harvesting date of main crop, as a consequence, the better ratooning ability was gained as well. There was a high and significant negative correlation between the ratooning ability and the spikelets per panicle among varieties. (2) The ratooning ability could be divided into 4 stages based on the sink-source characteristics of the main crop and grain yield of ratooning rice. The high-yielding cultivars for main crop and ratooning rice would have the following sink-source traits:160-190 spikelets per panicle, the ratio of leaf area to grain weight 0.0737-0.0827 cm2 per mg, panicles 232.12×104-249.40×104per ha, grain filling percentage 81.54%-85.74%, 1000-grain weight 28

  15. 人端粒酶逆转录酶肿瘤相关反馈调节机制的研究进展%Research progress in the feedback regulation of telomerase reverse transcriptase related in cancer

    Institute of Scientific and Technical Information of China (English)

    刘莹; 董成永; 崔晓楠

    2015-01-01

    人端粒酶逆转录酶( human telomerase reverse transcriptase,hTERT)是端粒酶的催化亚单位,尤其是端粒酶活性的限速因子,大量转录因子参与hTERT的调节。 hTERT在超过90%的肿瘤中表达,对肿瘤细胞的持续增殖发挥着重要作用。此外, hTERT能调节诸如细胞周期调控、细胞信号转导等不同细胞生物学过程中众多基因的表达。因此,hTERT在肿瘤中既是效应因子又是调节因子。然而,hTERT与其靶基因之间的相互作用机制还尚未完全明确。本综述重点关注不同的信号转导通路和基因参与hTERT的反馈调节及其机制,进一步认识端粒酶的非端粒延长功能,从而可能成为肿瘤治疗潜在的新靶点。%Telomerase reverse transcriptase ( TERT) is the catalytic component of telomerase, especially the rate limiting determinant of telomerase activity.A comprehensive network of transcription factors has been shown to be involved in the regulation of TERT.TERT has been reported to be over-expressed in more than 90%of cancers, thereby playing a criti-cal role in sustained proliferation and survival potentials of various cancer cells.Furthermore, accumulating evidence has suggested that TERT could modulate the expression of numerous genes involved in diverse group of cellular processes, in-cluding cell cycle regulation and cellular signaling.Therefore, it indicates that TERT is both an effector and a regulator in carcinoma.However, the mechanisms of the interaction between TERT and its target genes are still not fully understood.In this review, we focus on various signaling pathways and genes that participate in the feedback regulation of TERT and the underlying feedback regulation mechanism of TERT, to further provide new insights into non-telomeric functions of telom-erase and potentially novel therapeutic target for cancer.

  16. Research Progress of the Involvement of Polo-like Kinase-1 in Mitotic Regulation%Polo样蛋白激酶1参与有丝分裂调控的研究进展

    Institute of Scientific and Technical Information of China (English)

    赫玮(综述); 高丰厚(审校)

    2015-01-01

    As a crucial part of the cell cycle,the precise regulation of mitosis is precisely and strictly regulated,and along with the exploration in the regulation of mitosis,the understanding of life has deepened gradually as well.Polo-like kinase 1(PIK1) is involved in different processes of mitosis,and here is to sum-marize the functions,such as the activation of CDK1-Cyclin B complex,formation of spindle,segregation of chromosome and cytokinesis,and depict PLK-1′s significance for mitosis and put forward the possible direc-tions of further studies.%作为细胞周期的关键环节,有丝分裂过程受到严格而精细的调控,随着对有丝分裂调控的探讨与拓展,也逐渐加深了人们对生命本质的理解。研究发现Polo 样蛋白激酶1( PLK1)参与细胞有丝分裂调控的各环节,该文拟归纳总结 Plk1在有丝分裂中诸如 CDK1-Cyclin B 复合物的激活、纺锤体形成、染色体分离和胞质分裂这些过程中的研究进展,并描绘 PLK-1在有丝分裂调控中的作用与意义,为进一步深入探讨PLK-1与有丝分裂调控指出可能的发展方向。

  17. The research progress in the regulation of bone metabolism by Runx2 gene%Runx2基因对骨代谢调控的研究进展

    Institute of Scientific and Technical Information of China (English)

    唐欢; 许海甲; 侯煜东; 方卫军; 李章华

    2014-01-01

    人体骨代谢是一个复杂的过程,是破骨细胞( osteoclast ,OC)吸收旧骨和成骨细胞( osteoblast ,OB)形成新骨的动态平衡的过程。 Runx2(core binding factor alphal 1,核心结合因子a1)是调控成骨细胞和破骨细胞的分化促进骨形成的关键调控因子,通过调控成骨细胞特异性细胞外基质蛋白基因的表达和成骨细胞周期参与成骨细胞的分化过程,促进骨形成和抑制骨吸收。本文就Runx2在骨代谢中的作用作一综述。%Bone metabolism in the human body is a complicate process, which is a dynamic balance that consists of osteoclastic resorption of the old bone and osteoblastic formation of the new bone.Runx2 is the key regulator of bone formation by regulating the differentiation of osteoblasts and osteoclasts.It promotes bone formation and inhibits bone resorption by regulating the expression of specific extracellular matrix protein genes in osteoblasts and the cell cycle of osteoblasts.This paper reviews the effect of Runx2 in bone metabolism.

  18. The Research Progress on Late Positive Potential of Emotion and Emotion Regulation%情绪、情绪调节的ERPs晚正成分研究进展

    Institute of Scientific and Technical Information of China (English)

    刘艳丽; 许远理

    2012-01-01

    基于神经学方法的运用,情绪、情绪调节研究发现,事件相关电位的晚正成分(LPP)与情绪刺激的自动化加工、有意控制加工之间有着紧密的联系。LPP源于枕叶和后顶叶皮层,由蓝斑——去甲肾上腺素系统对情绪刺激进行反应时产生,反映了注意对情绪刺激的持续偏向和加工。由于个体生活经历、年龄发展及基因的不同,LPP存在个体差异性。情绪调节的ERP研究发现,LPP的时程可作为情绪调节的替代指标。在此基础上,提出ERP在较完整理解情绪加工和调节这一应用领域中的未来发展方向。%Based on the use of neuroscientific methods, researches on emotion and emotion regulation revealed that the late positive potential was closely linked with the automatic and controlled processing of emotional stimuli. The LPP is derived from the occipital and posterior parietal cortex, and generated via the locus coeruleus-norepinepherine system in response to emotional stimuli. The sustained increase in attention toward, and processing of, intrinsically motivating stimuli can be tracked by LPP. Due to different life experience, age, and genes, there are individual differences in the LPP. Event-related potentials studies on emotion regulation have found that the time-course of the LPP can be utilized to index emotion regulation. Based on previous studies, future directions for the application of ERP in achieving a more complete understanding of emotional processing and its regulation are presented.

  19. 可卡因-苯丙胺调节转录肽与脑缺血研究进展%Research progress on cocaine -amphetamine-regulation transcript and cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    周肖英; 孙达; 林莉莉

    2015-01-01

    Cocaine -amphetamine-regulated transcript ( CART ) is an endogenous neuropeptide which participates in various physiological functions.In this paper, the function of cocaine-amphetamine-regula-ted transcript and the relationship between CART and cerebral ischemia are reviewed.%可卡因-苯丙胺调节转录肽( CART)是一种内源性神经肽,参与多方面的生理功能。本文就可卡因-苯丙胺调节转录肽的功能及其与脑缺血的研究进展作一综述。

  20. Research progress about cocaine and amphetamine regulated transcript in diabetes%可卡因-苯丙胺转录调节肽与糖尿病关系研究进展

    Institute of Scientific and Technical Information of China (English)

    隆敏; 周世文

    2012-01-01

    可卡因-苯丙胺转录调节肽(cocaine and amphetamine regulated transcript,CART)是一种丰富表达下丘脑及胰腺组织的神经肽.该文就CART基因表达与糖尿病易感性、CART对进食和胰岛素分泌的调节及其自身表达调控、CART受体及可能的受体后信号通路进行阐述,并提出CART与糖尿病关系,研究亟待解决的问题.%Cocaine and amphetamine regulated transcript (CART) is a recently described neuropeptide widely expressed in the hypothalamus and pancreas. This review describes the re -lationship between CART gene expression and the susceptibility to diabetes, the evidences of CART in food intake and insulinsecretion, and CART expression modulation. Finally, CART receptors and potential post receptor signaling pathways are also described, problems to be solved are put forward as well.

  1. 促性腺激素释放激素(GnRH)结构及调控的研究进展%Research Progress on Structure and Regulation of Gonadotropin-releasing Hormone (GnRH)

    Institute of Scientific and Technical Information of China (English)

    徐元青; 王建林; 邵宝平

    2014-01-01

    促性腺激素释放激素(GnRH)最初被认为是一种下丘脑神经肽,但是越来越多的研究发现该激素具有多重功能,如参与类固醇生成、细胞增殖、受精、粘连细胞外基质和细胞迁移等生理功能的调节,并在动物的生长发育、生殖行为、妊娠、分娩等生命活动中起着至关重要的作用。主要对GnRH的结构特点及其调控进行了综述。%Gonadotropin-releasing hormone (GnRH) is firstly taken as a kind of hypothalamic neuropeptide, but more and more researches show that GnRH has multiple functions, such as participating in the regulation of generation of steroids, cell proliferation, fertilization, adhesion of extracellular matrix, cell migration, etc., and also plays a crucial role in the growth, reproductive behavior, pregnancy and delivery of animals. The structure and regulation of GnRH were summarized.

  2. Regulation of megakaryocytopoiesis.

    Science.gov (United States)

    Caen, J P; Han, Z C; Bellucci, S; Alemany, M

    1999-09-01

    After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various

  3. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Directory of Open Access Journals (Sweden)

    Richa Tripathi

    Full Text Available BACKGROUND: Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. METHODS: This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. RESULTS: 80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively. CONCLUSIONS: These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide

  4. Research Progress of Abscisic Acid Regulation Underlying Water Transport in SPAC System%激素ABA在SPAC水分传输中调节作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    张志亮; 郑彩霞; 康银红; 曾赟; 卢修元

    2016-01-01

    植物激素 ABA是干旱等胁迫条件下大量产生的一种重要的介质,在植物的生长发育、气孔开度、蒸腾抑制等诸多生理过程中起重要的调节作用,受到了很多学科的高度重视。近年来,在植物激素 ABA对植物体各种生理生长和水分的调控机理方面已有大量深入细致的研究。在此基础上综述了植物激素 ABA研究的一些新的理论和发展动态,就植物内源激素 ABA的功能和性质以及 ABA在植物体的生长发育、气孔变化、解剖特性以及水分传导中的调节作用进行了综述。提出了植物激素 ABA研究中存在的问题并对今后 SPAC 水分传输系统中 ABA 研究的重点方向作了进一步展望。%Plant hormone ABA which is important regulatory mediators in drought stress conditions plays an important regulatory in growth and development,stomatal aperture,transpiration suppression and many other physiological processes,so it is highly valued by many subj ects.In recent years,there are many deeply researches in ABA on plant physiological growth processes and water regu-lation mechanism.On the basis of many researches of abscisic acid,this paper reviews recent some new theory and developments. The paper reviewed the endogenous hormone ABA function and nature,regulation of ABA on plant growth and development,ana-tomical characteristics,and hydraulic conductivity of the regulation.We proposed problems desiderate to considerate in ABA re-search and made a further prospect for key research development direction in SPAC system in future work.

  5. 呼吸代谢调控桃果实采后抗氧化活性研究进展%Progress on Antioxidant Capacity of Postharvest Peach Fruit Regulated by Respiratory Metabolism

    Institute of Scientific and Technical Information of China (English)

    梁敏华; 杨震峰; 陈伟; 苏新国

    2013-01-01

    Respiratory metabolism is one of the most important physiological activities of posthavest climacteric fruit, and is also closely related to the biosynthesis of different bioactive compounds. This paper concluded the effect of respiratory metabolism on the biosynthesis and metabolism of antioxidant composition ( such as phenolic acid, flavonol, flavan-3-ol, anthocyanin and carotenoids) and key enzymes expressions in postharvest peach fruit of different varieties ( Red-flesh, Yellow-flesh, and White-flesh) . Based on investigations from the respiration pathway, the paper also discussed the specific mechanism of respiratory metabolism involved in the biosynthesis of such antioxidant compounds, expounded the molecular basis of the biosynthetic pathway and regulation of key enzymes of flavonoids and carotenoids, and clearifed the role and regulation of storage environmental conditions on the antioxdiant properties and antioxidant compounds of harvested fruits during storage. These would provide theoretical basis for regulation of antioxidant compounds metabolism and finally improve the nutritional quality in postharvest fruits.%桃果实为典型的跃变型果实,需要经历呼吸跃变才能成熟可食。呼吸代谢是跃变型果实采后重要的生理活动之一,与果实采后抗氧化物质的形成存在密切的联系。本文从桃果实采后呼吸跃变生理入手,总结了桃果实采后主要酚酸、黄酮醇、黄烷-3-醇、花色苷和类胡萝卜素消长的规律,并进一步从桃果实采后呼吸代谢中间产物及关键酶与上述次生物质代谢关键酶的基因表达水平探讨呼吸代谢对果实采后抗氧化能力的影响作用,明确呼吸代谢在桃果实采后抗氧化活性过程中的可能作用机制。

  6. Research Progress of the Global Regulator IrrE in Deinococcus radiodurans%耐辐射异常球菌全局调控蛋白IrrE的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈震; 周正富; 张维; 陈明; 宋渊; 林敏

    2013-01-01

      全局调控蛋白 IrrE 是异常球菌属中所特有的一种 DNA 损伤修复调节因子,可以显著提高细胞受到损伤时各修复基因的表达。在目前已经完成测序的异常球菌中共发现7种不同来源的 IrrE 蛋白,经序列比对与同源建模,发现其氨基酸序列相似性较高且具有相同的保守结构域,这可能预示了其功能上的相似性。此外,irrE 在大肠杆菌及油菜中表达后,能明显增强宿主的耐盐性,体现了较高应用价值。本综述介绍了异常球菌属及其全局调控蛋白 IrrE 的发现、结构与相关功能,分析与展望了该调控蛋白潜在的应用前景。%  The unique global regulator IrrE, found in Deinococcus, can up-regulate the expression of DNA repair genes in response to DNA damage. Seven types of IrrE protein had been identified in different strains of Deinococcus, the results of sequence alignment and homology modeling suggest that they share a high identity in amino acid sequence and have the same conserved protein regions, which may indicate the similarity in their functions. Besides, when gene irrE expressed in E. coli and B. napus, the salt tolerance of both hosts can be significantly enhanced, which show a very promising future in application. This review introduced the basic traits of Deinococcus and the discovery, structure and related functions of the global regulator IrrE, then we analyzed and prospected its potential application.

  7. Statins and progressive renal disease.

    Science.gov (United States)

    Buemi, Michele; Senatore, Massimino; Corica, Francesco; Aloisi, Carmela; Romeo, Adolfo; Cavallaro, Emanuela; Floccari, Fulvio; Tramontana, Domenico; Frisina, Nicola

    2002-01-01

    Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.

  8. Progressive fractal coding

    OpenAIRE

    Kopilovic, Ivan; Saupe, Dietmar; Hamzaoui, Raouf

    2001-01-01

    Progressive coding is an important feature of compression schemes. Wavelet coders are well suited for this purpose because the wavelet coefficients can be naturally ordered according to decreasing importance. Progressive fractal coding is feasible, but it was proposed only for hybrid fractal-wavelet schemes. We introduce a progressive fractal image coder in the spatial domain. A Lagrange optimization based on rate-distortion performance estimates determines an optimal ordering of the code bit...

  9. IGFBP -1的生理功能及其表达调控的研究进展%Research Progress on Physiological Function and Expression Regulation of Insulin-Like Growth Factor-Binding Protein-1

    Institute of Scientific and Technical Information of China (English)

    赵艳; 卢玲; 刘云章; 周建峰; 谭训刚; 尤锋; 李筠

    2015-01-01

    The insulin -like growth factor -binding proteins ( IGFBPs ) are evolutionarily conserved components of the insulin-like growth factor ( IGF) system.There are six forms of IGFBPs, IGFBP-1~IG-FBP-6 .They have high affinity with IGFs and can regulate the combination of IGFs with their receptors, which provide additional flexibilities in regulating IGF signaling.IGFBP-1, the first identified member of the IGFBP family, is highly inducible under a variety of catabolic conditions.Recent in vivo studies have indica-ted that the IGFBP-1 serves as a molecular switch restricting IGF signaling and diverts the limited energy re-sources from growth and development towards metabolic processes essential for survival under stress condi-tions.This article reviewed the recent understandings of the molecular mechanism of IGFBP-1 regulation and its biological functions.%IGFBPs( Insulin-like growth factor-binding proteins,胰岛素样生长因子结合蛋白)在进化上是高度保守的,在IGF( Insulin-like growth factor,胰岛素样生长因子)系统中共有6种形式的IGFBPs,分别为IG-FBP-1~IGFBP-6,它们与配体IGFs具有高度的亲和性,能够调节IGFs与IGF-R(Insulin-like growth factor receptor,胰岛素样生长因子受体)的结合,这为IGF信号通路的调节提供了灵活的方式。其中,IGFBP-1是IGF结合蛋白家族中第一个被发现和鉴定的成员,一些分解代谢胁迫条件会诱导IGFBP-1 mRNA的高量表达。近年来体内的研究表明IGFBP-1被喻为是限制IGF信号系统功能的“分子开关”。在胁迫条件出现时,IGFBP-1通过限制能量的使用,将生命过程由高耗能的生长发育状态切换到仅能满足生物体生存的基本的低耗能状态。本文就近年来在哺乳类和鱼类模型中IGFBP-1调控的分子机制以及生物学功能的研究进展作一综述。

  10. 氨基酸感应与糖脂代谢调控的研究进展%Research progress on amino acid sensing and its role in the regulation of glucose and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    吕子全; 郭非凡

    2013-01-01

    氨基酸是机体必需的小分子代谢物,其作为信号分子广泛参与了对机体糖脂代谢稳态的维持和调控.研究表明,在糖脂能量代谢的调节过程中,支链氨基酸(尤其是亮氨酸)发挥了重要作用.机体与糖脂代谢相关的多个外周脏器(如肝脏、胰腺、白脂、褐脂、胃肠道等)和代谢调控中枢下丘脑均可以感应外界氨基酸水平的变化,并调节糖脂能量代谢.此外,氨基酸调节糖脂代谢的关键信号通路也已被广泛证实,如mTOR/S6K信号通路、GCN2/ATF4信号通路等.鉴于2型糖尿病等营养相关慢性代谢病的发病率不断攀升,对氨基酸的营养感应和糖脂代谢调控功能进行进一步探索将为代谢性疾病的防控提供重要的指导意义.%Amino acid is a type of micro-molecular metabolite essential for the maintenance of life. As a signal transducing molecule, amino acid extensively participates in the maintenance and regulation of glucose and lipid metabolism homeostasis. Previous research has confirmed the crucial role of amino acid, especially branched chain amino acid (BCAA; e.g., leucine) in the regulation of glucose/lipid and energy homeostasis. The metabolic control center hypothalamus, as well as multiple periphery organs correlated with glucose and lipid metabolism (such as liver, pancreas, white adipose tissue, brown adipose tissue, gastrointestinal tract) can sense the level of amino acid in external environment, and regulate glucose/lipid and energy metabolism. What is more, key signal transduction pathways affected by amino acid in the modulation of glucose and lipid metabolism have been well established, such as mTOR/S6K, GCN2/ATF4 pathway. In the view of constant increase of chronic metabolic diseases such as type 2 diabetes, further exploring on amino acid nutrient sensing and its metabolic control on glucose and lipid metabolism will provide significant guidance for the prevention and control of metabolic diseases.

  11. 磷酸二酯酶参与认知与情绪调节的研究进展%Progress in the role of phosphodiesterases in memory regulation

    Institute of Scientific and Technical Information of China (English)

    陈玲; 徐英; 潘建春

    2012-01-01

    磷酸二酯酶(PDE)催化水解cAMP和cGMP,是细胞内降解cAMP和cGMP的唯一途径.PDE是一个多基因大家族酶,包含11型不同家族,它们的结构,分布以及调节方式对抑制剂的敏感性都不同.PDE选择性抑制剂可通过抑制cAMP或cGMP水解来调节学习记忆障碍等中枢神经系统疾病.因此,PDE被认为在中枢神经系统疾病的治疗上具有重要地位.本综述介绍目前PDE参与学习记忆障碍这一中枢神经系统疾病调节的研究进展,而且PDE作为中枢神经系统疾病的治疗靶点,研究其选择性抑制剂具有重要的意义.%Phosphodiesterases (PDEs) are a super-family of enzymes that are involved in the regulation of the intracellular second messengers cAMP and cGMP by controlling their rates of hydrolysis. There are 11 different PDE families, and each family has typically multiple isof'orms and splice variants. The PDEs differ in their structures , distribution, modes of regulation, and sensitivity to inhibitors. Since PDEs have been demonstrated to play distinct roles in the process of emotion, and related learning and memory, selective PDE inhibitors, by preventing the breakdown of cAMP and/or cGMP, could modulate mood and related cognitive activity. This review discusses the current status and future development in the burgeoning field of PDEs in the central nervous system. It is becoming increasingly clear that PDE inhibitors have therapeutic potential for the treatment of neuropsychiatric disorders involving disturbances of mood, emotion, and cognition.

  12. 维生素D调控儿童肥胖、胰岛素抵抗及其机制的研究进展%Research progress of mechanism of vitamin D in regulating obesity and insulin resistance on children

    Institute of Scientific and Technical Information of China (English)

    王剑清; 刘艳明

    2015-01-01

    维生素 D 有着广泛的生物学效应。维生素 D 不足和缺乏通过影响炎性反应、脂肪细胞因子、氧化应激及线粒体功能等途径增加胰岛素抵抗的风险,引起糖脂代谢紊乱,与儿童肥胖、代谢综合征发生发展密切相关。现就维生素 D 与儿童肥胖、代谢综合征的关系,及其影响糖脂代谢和调控胰岛素抵抗可能的机制进行阐述。%Vitamin D has a wide range of biochemical effects. Insufficiency/ deficiency of vitamin D increases the risk of insulin resistance by ways of inflammation,adipocytokines,oxidative stress and mitochondria function,it could lead to metabolic disorder of glucose and lipid,which closely relates to the incidence and development of obesity and metabolic syndrome on children. This paper presents the relationship between vitamin D with obesity and metabolic syndrome on children,states the possible mechanisms of regulation of glucose/ lipid metabolism and insulin resistance by vitamin D.

  13. Research Progress of Cystic Fibrosis Transmembrane Conductance Regulator Gene and Male Infertility%囊性纤维化跨膜传导因子基因与男性不育

    Institute of Scientific and Technical Information of China (English)

    罗方野

    2010-01-01

    囊性纤维化(cystic fibrosis,CF)是白种人的一种常见致命性常染色体隐性遗传病,由囊性纤维化跨膜传导因子(cystic fibrosis transmembrane conductance regulator,CFTR)基因突变所致.CFTR基因突变在男性不育中多表现为先天性双侧输精管缺如、单侧输精管缺如和精子质量低下.卵胞浆内单精子注射(ICSI)技术使囊性纤维化患者有了生育后代的机会,但同时可能将突变的基因遗传给下一代.因此,胚胎植入前的遗传学诊断与遗传学风险评估非常重要,应该避免将有基因突变的胚胎植入母体子宫,提高生育质量.

  14. MicroRNA对皮肤毛囊发育调控的研究进展%Research Progress on MicroRNA Regulation on Skin and Hair Follicle Development

    Institute of Scientific and Technical Information of China (English)

    张桂山; 徐晶; 姜怀志

    2013-01-01

    MiRNAs are a family of endogenous non-coding single strand small RNAs (19-25 nt),combining target mRNA through basepair complementarity to degrade mRNA or disrupt translation of mRNA,then modulating gene expression.This review summarized the biogenesis and function of miRNAs,profiling miRNAs Expression in the skin and hair follicle and regulation of miRNAs on skin and hair follicle development.%miRNA是一类由19~25个核苷酸组成的内源性非编码单链小分子RNA,通过与靶基因mRNA3,端非编码区配对结合,降解靶mRNA或阻碍其翻译,进而调节靶基因的表达.文章综述了miRNA的生源说及功能、miRNA在皮肤毛囊中的表达检测以及miRNA对皮肤毛囊发育的调控.

  15. Research Progress on Network Regulation of LEAFY(LFY) in Floral Development%LEAFY(LFY)基因在花发育网络调控中的研究进展

    Institute of Scientific and Technical Information of China (English)

    张亚萍; 习珺珺; 于丽霞; 李斌; 高则睿; 鄢波

    2012-01-01

    成花是高等植物生命过程中最重要的阶段,在相当的程度上决定着繁育的成功和失败。综述了花分生组织特性基因LEAFY(LFY)基因,及其花发育(成花诱导途径)网络调控的相关研究进展。LFY基因在植物的营养性生长和生殖生长组织中均表达,从花序分生组织到花器官形成的过程中,LFY都起到重要的作用。%Flowering is a critical event in the life cycle of higher plants which decides the success of breeding to some extent. This article reviewed some correlational researches on floral meristem identity gene LEA FY (LFY), and flower-development-network-regulation. LFY gene expresses widely in both vegetative and reproductive tissues in different higher plants. LFY gene plays an important role from the inflorescence meristem to the forming of floral organs.

  16. Research progress on metabolic mechanism of cembranoid diterpenes and its regulation%类西柏烷二萜代谢机理及调控研究进展

    Institute of Scientific and Technical Information of China (English)

    王冬; 张小全; 杨铁钊; 薛刚; 李丽华

    2014-01-01

    综述了类西柏烷二萜合成的生化途径及其调控因素,并阐述了其在改善作物香味和植物抗虫方面的作用及研究利用前景。类西柏烷二萜主要存在于烟草属植物的腺毛分泌物中,在西柏三烯醇合酶(CBTS)和细胞色素P450加氧酶(CYP450)的催化下经脱氧木酮糖磷酸代谢途径(DXP)合成,这一过程受到基因和多种外界因素的调控。%Biosynthetic and metabolic pathway and regulatory factors of cembranoid diterpenes were introduced, and its application prospective on aroma-improving and insect-resistant were also discussed. Cembranoid diterpenes mainly exists in glandular trichome secretion of Nicotiana plant. It was produced through plastidic deoxyxylulose phosphate (DXP) pathway with cembratrien-ol synthase (CBTS) and cytochrome P450 oxygenase (CYP450) as catalyzer. This process was regulated by gene and various external factors.

  17. Recent progress of orexin in the regulation of the hypothalamic-pituitary-adrenal axis%增食欲素调节下丘脑-垂体-肾上腺轴的研究进展

    Institute of Scientific and Technical Information of China (English)

    王露; 赵玉岩

    2010-01-01

    增食欲素A和增食欲素B是下丘脑神经肽,通过激活两种G蛋白耦联受体发挥作用.增食欲素及其受体表达于下丘脑室旁核和正中隆起,增食欲素受体还表达于脑垂体促皮质激素细胞、肾上腺皮质和髓质.增食欲素能调节摄食、能量代谢平衡、睡醒周期、血压等,还能调节下丘脑-垂体-肾上腺(HPA)轴.现就增食欲素及其受体在HPA轴中枢支和周围支(peripheral branches)的表达及作用机制作一综述.%Orexin A and orexin B are hypothalamic peptides that play roles via two G protein-cou-pled receptors. Orexins and their receptors are expressed in the hypothalamic paraventricular nucleus and me-dian eminence, orexins receptors also expressed in pituitary corticotrophs, adrenal cortex and medulla. Orexins regulate feeding, energy metabolic homeostasis, the sleep/wake cycle, blood pressure and so on, they also modulate the hypothalamic-pituitary-adrenal (HPA) axis. Expression and function of orexins and their recep-tors in the central and peripheral branches of the HPA axis are reviewed in this article.

  18. 旋毛虫对宿主免疫应答调节机制的研究进展%Research Progress on the Mechanism of Host Immune Response Regulated by Trichinella spiralis

    Institute of Scientific and Technical Information of China (English)

    赵葛; 杨文涛; 王春凤; 杨桂连

    2013-01-01

    Trichinosis caused by Trichinella spiralis is a parasitic zoonosis with world-wide distribution, which impacts on the development of animal husbandry and food safety, and thus threatens human health. T. spiralis has the ability to evade the host immune response, which results in forming a long-term infection in the host. The previous studies indicated that a changed host immune state due to T. spiralis was an important reason for the evasion. Among the factors, cytokines, dendritic cells and regulatory T cells played an important role in the regulation of the host immune process.%旋毛虫病是由旋毛虫(Trichinella spiralis)引起的一种呈世界性分布的人兽共患寄生虫病,严重影响畜牧业发展和食品安全,从而威胁人类健康.旋毛虫具有逃避宿主免疫应答进而在宿主体内形成长期感染的能力.研究认为,旋毛虫改变宿主免疫状态是其逃避免疫应答的重要原因,其中细胞因子、树突状细胞和调节性T细胞在其调节宿主免疫过程中发挥着重要作用.

  19. 双底物特异性酪氨酸磷酸化调节激酶A(DYRK1A)的研究进展%The research progress of dual specificity tyrosine-phosphorylation- regulated kinase 1 A

    Institute of Scientific and Technical Information of China (English)

    张照; 夏海滨

    2015-01-01

    双底物特异性酪氨酸磷酸化调节激酶A( dual specificity tyrosime-pjospjorylatiom-regulated ki-mase 1A,DYRK1A)是一种与唐氏综合征发生密切相关并在进化上非常保守的重要蛋白激酶。DYRK1A参与神经发育、细胞增殖与分化及肿瘤发生等生理过程以及神经退行性疾病的病理发生过程。此外,DYRK1A在其他疾病的病理形成及信号通路调控方面也发挥重要作用。本文对DYRK1A的基因结构、分布、功能及其在疾病中的相关作用作一综述,为针对该基因研究领域提供有价值的信息。

  20. Progression i musikundervisningen

    DEFF Research Database (Denmark)

    Dahlbæk, Annelise

    Hvad er progression? ; Musikalitetsbegrebet ; Fælles mål for musik ; Modeller som redskab ; Stemmen : sang ; Sammenspil ; Dans og bevægelse ; Lytning......Hvad er progression? ; Musikalitetsbegrebet ; Fælles mål for musik ; Modeller som redskab ; Stemmen : sang ; Sammenspil ; Dans og bevægelse ; Lytning...

  1. Natalizumab in progressive MS

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Ratzer, Rikke; Börnsen, Lars;

    2014-01-01

    OBJECTIVE: Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis (MS). The objective of the study was to examine the effects of natalizumab in progressive MS. METHODS: In an open-label phase 2A study, 24 patients with progre...

  2. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C;

    2016-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants asso...

  3. Telomerase Regulation

    OpenAIRE

    Cifuentes-Rojas, Catherine; Dorothy E Shippen

    2011-01-01

    The intimate connection between telomerase regulation and human disease is now well established. The molecular basis for telomerase regulation is highly complex and entails multiple layers of control. While the major target of enzyme regulation is the catalytic subunit TERT, the RNA subunit of telomerase is also implicated in telomerase control. In addition, alterations in gene dosage and alternative isoforms of core telomerase components have been described. Finally, telomerase localization,...

  4. The research progress of epigenetic regulation of T helper cell differentiation%表观遗传学调控 Th 细胞分化发育的研究进展

    Institute of Scientific and Technical Information of China (English)

    淮文英; 杨福权; 唐玉琴; 张天娥; 刘伟伟

    2016-01-01

    CD4 +helper T cells (Th cells) differentiate into different cell subsets in order to resist or adapt to the environment chan -ges under the condition of antigen stimulation and body micro-environment , and the process of cells differentiation is controlled by the complex regulatory network of cytokines and transcription factors .Epigenetics is a science that does not involve the change of DNA se-quences and changes gene expression such as DNA methylation and chromatin structure , and passes between the parental and filial gen-eration.Epigenetics have an important influence on the differentiation regulation of immune cells and the heritability of T helper cell lin -eage.%CD4+辅助性T细胞( Th细胞)在抗原刺激与机体微环境调控下分化发育为不同的细胞亚群以对抗或适应外界环境改变,而分化过程受控于由细胞因子和转录因子所组成的复杂调控网络。表观遗传学是研究不涉及DNA序列变化的DNA甲基化谱、染色质结构状态等对基因表达的改变,并在亲代与子代之间传递的一门科学。表观遗传对免疫细胞的分化调控和Th细胞亚群可遗传性等方面具有重要影响。

  5. The Research Progress of EAAT3 in Neural Functional Regulation%谷氨酸转运体3在神经功能调节中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    王沛齐; 刘娜; 周恩禄

    2016-01-01

    Glutamate is a primary excitatory neurotransmitter of the central nervous system ( CNS ) in mammals .When a lot of excitatory amino acid accumulate in synaptic cleft ,it will produce neurotoxic effect or even cell death,which may further cause cognitive dysfunction and other neuropsychiatric disorder .There are many reasons to induce excitatory amino acid accumulation , and the change of excitatory amino acid trans-porters( EAAT) is one of the reasons,and EAAT3 is one of the glutamate transporters ,which plays an impor-tant role in regulating glutamate concentration between synapsis and the synthesis of glutathione( antioxidant of CNS) .Besides,EAAT3 itself is closely associated with nerve protection and cognitive function as well .%谷氨酸是哺乳动物中枢神经系统内一种主要的兴奋性神经递质,当神经元突触间隙出现大量兴奋性氨基酸堆积时,就可造成神经毒性作用甚至细胞死亡,进而出现认知功能改变及其他的精神神经疾病. 引起兴奋性氨基酸堆积的原因很多,其中兴奋性氨基酸转运体( EAAT)的改变与其密切相关,而EAAT3是谷氨酸转运体之一,它对突触间谷氨酸浓度的调控、谷胱甘肽(中枢神经系统的抗氧化剂)的合成具有重要意义. 另外,EAAT3本身与神经保护以及认知功能也密切相关.

  6. 有色光环境调控眼球生长发育的研究进展%Research progress of the regulation of eyeball growth by artificial colored light

    Institute of Scientific and Technical Information of China (English)

    刘鹏飞; 肖林

    2013-01-01

    视觉发育离不开正常的光信号刺激,良好的视觉环境对屈光发育尤为重要.随着人工有色光源在日常生活中的普及,逐渐替代自然光环境,可能干扰正常视觉发育过程.近年来国内外许多学者建立各种研究模型,观察不同人工有色光环境通过光学离焦、作为敏感视锥细胞中介信号、类似形觉剥夺以及调节不同蛋白分子等机制对正常及近视眼球生长和视觉发育产生影响,探讨可能的调控信号及通路,目前仍未完全明确.%Visual development is inseparable from the optical signals.The suitable visual environment is particularly important for the refractive development.However,with the gradual changing from the natural light to the artificial light environment,normal vision developmental processes is affected.The recent data and related clinical researches show that the precise pathogenesis is still unknown.The different color artifinal light affects the vision development through the possible mechanisms,such as optical defocus,being as agent signal of sensitive cone cells,simulating the vision deprived,or regulating the cell protein,etc..

  7. 逆境胁迫下植物表观遗传机制的研究进展%Research Progresses of Stress-induced Epigenetic Regulation Mechanism in Plant

    Institute of Scientific and Technical Information of China (English)

    冉莉萍; 孔月琴; 方婷婷; 王幼平

    2014-01-01

    植物着地固定生长不能主动逃避外界危害,只能依靠自身的一些响应机制来防御外界胁迫,表观遗传调控在这个响应机制中起着重要的作用,主要表现在DNA甲基化、组蛋白修饰、染色质重塑及非编码RNA。植物在遭受低温、高温、干旱、盐、重金属、病毒及激素等因素胁迫后,通过调节抗逆相关基因的表达来响应外界危害。综述表观遗传修饰在各种胁迫下的调控机制,为作物的抗逆研究提供理论依据。%Plant as sedentary organisms, needs to adapt their gene activity to the adverse or stressful environmental challenges. Epigenetic regulation accompanies stressful environments, such as extreme temperature, drought, salinity, heavy metal, pathogen and hormones etc., which lead to the impressive development and phenotype variation of different plant species with adaptability to unfavorable conditions. In this paper, the current research status of epigenetic changes induced by stresses, including DNA methylation, histone post-translational modification, chromatin modification, non-coding RNA, as well as the interaction between these epigenetic incidences were reviewed.

  8. 植物离区发育及调控信号的多样性研究进展%Research Progress on Diversities of Plant Abscission Zone Development and Regulation Signaling

    Institute of Scientific and Technical Information of China (English)

    廖文彬; 杨义伶; 李雅韵; 孙建波; 彭明

    2014-01-01

    A particular area in plant that occurs plant organ shedding called as abscission zone (AZ). Nowadays, the researches of plant AZ development mainly focus on modern plants tomato, rice and Arabidopsis thaliana and other important economic crops. The diversities of plant organ abscission and regulation signaling were reviewed in this paper. The main forms of plants organ shedding including flower organ shedding, leaf abscission, fruits shedding, seeds shedding, craze zone, lateral root abscission, etc. the signaling pathways involved in the process of organ shedding were summarized, including flower growth signaling, ethylene and auxin signaling, programmed cell death signaling, ROS signaling, etc. This paper will supply some references for the research on tropical crops abscission zone.%植物器官脱落发生的特定区域叫做离区。植物离区发育及其研究主要集中在番茄、水稻、拟南芥等模式作用与重要的经济作物上。本文主要从植物离区脱落发生的多样性及其调控信号的多样性上进行综述,植物离区脱落的主要形式有:花器官脱落、叶脱落、果实脱落、种子脱落、开裂区脱落、侧根脱落等;主要的调控信号有花发育信号、乙烯与生长素信号、细胞凋亡信号、 ROS信号等。旨在为今后经济作物离区相关基因研究提供理论依据和基础,并对今后离区相关研究的前景进行展望。

  9. Foxa2调控支气管哮喘气道黏液高分泌研究进展%Research progress of Foxa2 regulates asthmatic airway mucus hypersecretion

    Institute of Scientific and Technical Information of China (English)

    袁波; 梁娅莎; 罗凤鸣

    2015-01-01

    支气管哮喘(简称哮喘)是一种由多种细胞及细胞组分参与的慢性气道炎症性疾病,以 Th2型气道炎性反应、气道高反应性、气道重塑为其主要特征。叉头状转录因子2(the fork head box transcription factor-2,Foxa2)基因定位于染色体20p11.21,长度是2242 bp,高表达于气道上皮细胞和肺泡Ⅱ型上皮细胞中。在肺发育过程中,Foxa2参与 Th2型气道炎症、黏液生成以及杯状细胞化生调控。本文从 Foxa2与哮喘气道黏液分泌、杯状细胞化生研究进展作一综述。%Bronchial asthma (asthma)is a chronic airway inflammatory disease involved by many cells and cellular components,whose main features are Th2-dominated airway inflammatory reaction, airway hyperresponsiveness and airway remodeling.The fork head box transcription factor-2 (Foxa2 )is located on chromosome 20p1 1.21,with the length of 2 242 bp,is highly expressed in respiratory epithelial cells and alveolar type Ⅱ epithelial cells.In the process of lung development,Foxa2 regulates Th2-dominated airway inflammatory reaction,mucus formation and goblet cell metaplasia.This review will summarize the role of Foxa2 in asthmatic airway mucus secretion and goblet cell metaplasia.

  10. 细胞外信号调节激酶及其抑制剂的研究进展%Research progress of extracellular regulated protein kinase and its inhibitors

    Institute of Scientific and Technical Information of China (English)

    艾俊涛; 胡高云; 王靓; 李代洪; 谢欣; 李乾斌

    2013-01-01

    细胞外信号调节激酶(ERK)是一个多功能的丝氨酸/苏氨酸蛋白激酶,是MAPK家族的重要成员,在MAPK信号通路中起着重要的作用.ERK通过磷酸化多种底物蛋白来调节细胞多种生理过程,如细胞生长、分裂、增殖、凋亡等,已成为抗癌药物研发的重要靶点.近年来,基于结构的药物设计策略在ERK抑制剂的研究中已得到广泛的应用.本文对ERK的分子结构、作用机制及直接作用于ERK蛋白的ATP竞争性和非竞争性抑制剂的设计思路、化学结构及构效关系做一综述.%Extracellular regulated protein kinase ( ERK) , an important member of MAPK family, is a kind of multifunctional Ser/Thr kinase, which plays an important role in MAPK signaling cascade. Multiple substrates are phosphorylated by ERK leading to alterations in cell growth, differentiation, proliferation and apoptosis, which makes ERK an attractive target for the design and discovery of anti-cancer agents. Recently, structure-based design strategies are widely used in the development of ERK inhibitors. The molecular structures of ERK, mechanism of action, the design of the ATP or non-ATP competitive inhibitors which directly acts on ERK, chemical structure and structure-activity relationship were reviewed in this article.

  11. Chemokines in tumor development and progression

    Energy Technology Data Exchange (ETDEWEB)

    Mukaida, Naofumi, E-mail: naofumim@kenroku.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Chiyoda-ku, Tokyo 102-0075 (Japan); Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan)

    2012-01-15

    Chemokines were originally identified as mediators of the inflammatory process and regulators of leukocyte trafficking. Subsequent studies revealed their essential roles in leukocyte physiology and pathology. Moreover, chemokines have profound effects on other types of cells associated with the inflammatory response, such as endothelial cells and fibroblasts. Thus, chemokines are crucial for cancer-related inflammation, which can promote tumor development and progression. Increasing evidence points to the vital effects of several chemokines on the proliferative and invasive properties of tumor cells. The wide range of activities of chemokines in tumorigenesis highlights their roles in tumor development and progression.

  12. The Progress of AP-2 Protein Regulating Clathrin Mediated Endocytosis%AP-2蛋白调控网格蛋白介导突触囊泡胞吞的研究进展

    Institute of Scientific and Technical Information of China (English)

    顾翔; 袁伟

    2015-01-01

    神经元间的信息传递依赖于神经递质的释放,这一过程离不开正常有效的囊泡循环机制,突触囊泡循环是调控突触囊泡水平和维持神经递质释放的基础。囊泡回收则是循环过程中保证囊泡从突触前膜回收至胞内,参与新一轮囊泡形成和再生的重要保障。网格蛋白介导的内吞是突触囊泡回收的主要途径,衔接蛋白AP-2(adaptin-2)是参与这一内吞过程不同时期的关键蛋白,其通过绑定不同蛋白分子分别从结构和动力的层面参与了囊泡回收过程, AP-2对网格蛋白介导的突触囊泡胞吞过程具有重要意义。本文结合国内外最新研究报道,简要综述了AP-2的结构特点、分子基础、AP-2蛋白调控网格蛋白介导突触囊泡的胞吞及其与听力的关系。%Neural transmission is dependent on the release of neurotransmitter. Synaptic vesicle recycling is the basis of neurotransmitter release. Clathrin-mediated endocytosis plays a key role in the synaptic vesicle reformation. AP-2 is a key protein in different periods of endocytosis, which can bind other protein molecules to regulate the vesicle recycling from the as⁃pects of structure and dynamics. This review summarizes the molecular structure and characteristic of AP-2 and discusses the relationship between clathrin-mediated endocytosis and hearing.

  13. THE PROGRESSION OF UP- REGULATION OF MICRORNA AND ITS TARGET IN GASTRIC CANCER%胃癌中表达上调microRNA及其作用靶点研究进展

    Institute of Scientific and Technical Information of China (English)

    王诗淇; 毕力夫; 苏秀兰

    2012-01-01

    miRNA是一类长度约为20nt,广泛存在于真核生物中的一组内源性非编码调控RNAs,其功能具有多样性,通过对靶基因的调控而影响肿瘤细胞生物进程.胃癌是国内常见恶性肿瘤之一,在我国发病率占各类肿瘤之首,从分子水平研究胃癌发生机制及治疗是研究的热点.目前发现很多miRNA及其作用靶点在胃癌细胞的增值、侵袭、转移、凋亡及和胃癌的治疗、预后均有密切关系.本文就近5a有关胃癌的上调miRNA及其作用靶点的研究做一综述,为今后胃癌中miRNA的筛选及其靶点的验证提供理论依据.%miRNA is a kind of RNAs whose length is approximate 20nt, widely present in the eu-karyotes' endogenous non -coding regulatory RNAs. Its function is variety and it affects the biological processes of tumor cells through the regulation and control of target genes. Gastric cancer is one of the common malignant tumors in China,the incidence of accounting for various types of tumors in the first, from the molecular level of gastric cancer pathogenesis and therapy study is the current hot spots. All of them suggest that there are close relationship between miRNA and its target and invasion, metastasis, apoptosis of gastric cancer cell, treatment of gastric cancer and its prognosis. This paper reviewed the nearest 5 - year research writes of gastric cancer - related increase miRNA and its target,and provides a theoretical basis for the future of miRNAs in the gastric cancer screening and target validation.

  14. 48 CFR 852.236-84 - Schedule of work progress.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Schedule of work progress. 852.236-84 Section 852.236-84 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS...., “Excavation”, “Floor Tile”, “Finish Carpentry”, etc., should be plotted along the vertical axis and...

  15. Regulating Transplants

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Legislation to determine brain death is viewed as essential in controlling the organ transplant industry Organ transplant represents a very sensitive and complicated issue. Experts say the temporary administrative regulations recently promulgated by the Central Government are an important step, but relevant laws and regulations must follow. Among these, the

  16. Cellulose synthase complexes: structure and regulation

    Directory of Open Access Journals (Sweden)

    Lei eLei

    2012-04-01

    Full Text Available This review is to update the most recent progress on characterization of the composition, regulation, and trafficking of cellulose synthase complexes. We will highlight proteins that interact with cellulose synthases, e.g. cellulose synthase-interactive protein 1 (CSI1. The potential regulation mechanisms by which cellulose synthase interact with cortical microtubules in primary cell walls will be discussed.

  17. Research Progress in Regulation of Energy Metabolism by Polyphenols via Intestinal Flora%多酚通过肠道菌群调节能量代谢研究进展

    Institute of Scientific and Technical Information of China (English)

    肖俊松; 单静敏; 曹雁平; 王成涛; 许楠

    2012-01-01

    Polyphenols,a class of plant secondary metabolites,are widely present in the human diet and can be divided into three categories: phenolic acids,polymer tannin and flavonoids.Polyphenols and their gut flora metabolites can selectively adjust the growth of susceptible microorganisms in the gut,promote the growth of beneficial bacteria(such as lactic acid bacteria),and inhibit the proliferation of harmful bacteria,thus causing intestinal micro-ecological changes.Such changes have an important impact on host energy metabolism,which may be achieved through the following aspects: 1) changes in intestinal microbial number and species alter microbial metabolism and the types and quantities of produced enzymes;2) polyphenol metabolites can also act on bacterial cell surface to inhibit enzyme activities,thereby influencing energy metabolism and reducing fat deposition;3) polyphenols regulate energy metabolism by interfering with the human intestinal flora,which can provide new ideas to prevent and treat obesity and related diseases.In this paper,we review the mechanism by which polyphenols can reduce the incidence of obesity by modulating the intestinal flora.%多酚是一类植物次生代谢产物,广泛存在于人类膳食中,一般可分为3大类:酚酸类、聚合单宁类和黄酮类。多酚以及其被肠道菌群代谢的产物,能选择性调节肠道中易感微生物的生长,选择性的促进有益菌群(如乳酸菌)生长,抑制有害菌的增殖,也即引发肠道微生态的改变。这种改变对宿主产生重要影响,对宿主能量代谢的影响可能通过如下实现:1)肠道内微生物数量和种类的变化,改变微生物代谢及产酶的种类和数量;2)多酚代谢产物还可与细菌细胞表面作用,抑制酶的活性,从而影响能量代谢,减少脂肪沉积;3)多酚通过干预人体肠道菌群调整能量代谢,为预防和治疗肥胖及相关性疾病提供了新的研究思路。本文对多酚

  18. Progressive Supranuclear Palsy

    Science.gov (United States)

    Progressive supranuclear palsy (PSP) is a rare brain disease. It affects brain cells that control the movement of your eyes. This leads to ... speech, vision and swallowing problems. Doctors sometimes confuse PSP with Parkinson's disease or Alzheimer's disease. PSP has ...

  19. Physicians’ Progress Notes

    DEFF Research Database (Denmark)

    Bansler, Jørgen; Havn, Erling C.; Mønsted, Troels;

    2013-01-01

    This paper examines physicians’ progress notes, an artifact that, in spite of its obvious importance in the coordination of cooperative work in clinical settings, has not been subjected to systematic study under CSCW auspices. While several studies have addressed the role of the medical record...... in patient care, they have not dealt specifically with the role, structure, and content of the progress notes. As a consequence, CSCW research has not yet taken fully into account the fact that progress notes are coordinative artifacts of a rather special kind, an open-ended chain of prose texts, written...... sequentially by cooperating physicians for their own use as well as for that of their colleagues. We argue that progress notes are the core of the medical record, in that they marshal and summarize the overwhelming amount of data that is available in the modern hospital environment, and that their narrative...

  20. Progress for the Paralyzed

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: NIBIB Robotics Progress for the Paralyzed Past Issues / Spring 2013 ... Paralyzed —The expanding options for paralyzed individuals include: robotic arms spinal cord stimulation improved prosthetic limbs restored ...

  1. Progress report for '89

    International Nuclear Information System (INIS)

    The 1989 Progress Report presents the most important scientific and technical achievements of the Nuclear Research Institute's research work. Some specialized products prepared at or fabricated by the NRI are mentioned as well. (author). 24 figs., 8 tabs., 101 refs

  2. Progress report, Physics Division

    International Nuclear Information System (INIS)

    This report reviews events and progress in the following areas: development of the TASCC facility; experimental and theoretical nuclear physics research; radionuclide standardization; condensed matter research; applied mathematics; and computer facility operation

  3. Progress report 1985

    International Nuclear Information System (INIS)

    This progress report of the nuclear physics institute includes five basic subjects: theoretical physics, high energy and intermediate energy physics, nuclear physics, combined research physics and instrumentation (microelectronics, imaging, multidetectors, scintillators,...)

  4. Comparison of spectacle classical progressive and office progressive lenses.

    Science.gov (United States)

    Kozlík, Marek; Knollová, Libuse Nováková

    2013-04-01

    This paper elaborates on analysis of progressive spectacle lenses, to correct presbyopia, which are nowadays offered at the market. The paper describes different types of progressive lenses, their parameters, length and width of their progressive segments. It also describes degressive spectacles lenses--progressive lenses on middle and near distance. The main part of the paper is a comparison of functional differences among different types of progressive spectacles lenses. The paper also addresses correctness of choice of progressive lenses for different works and professions. Lastly, it elaborates on differences of centration of different types of progressive lenses and parameters for correct choice of glasses frame for progressive spectacles lenses. PMID:23837232

  5. [Progressive visual agnosia].

    Science.gov (United States)

    Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

    2011-10-01

    Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

  6. Progress in biological function of Api6/AIM/Spα in immune regulation and lipid metabolism%Api6/AIM/Spα调节免疫和脂质代谢的生物学功能研究

    Institute of Scientific and Technical Information of China (English)

    方严; 刘丹; 练雪梅

    2011-01-01

    Apoptosis inhibitor 6(Api6), also known as AIM and Spα, belongs to the scavenger receptor cysteine rich-superfamily (SRCR-SF). Api6/AIM/Spα, which is secreted exclusively by macrophages, inhibits apoptosis of CD4/CD8 double-positive (CD4+/CD8+) thymocytes, T cells, natural killer T(NKT) cells and macrophags. As a pattern recognition receptor, Api6/AIM/Spα is involved in the recognition of pathogen-associated molecular patterns(e.g. LPS and LTA), which suggests that it plays an important role in the regulation of the innate and adaptive immune systems. It has been confirmed recently that Api6/AIM/Spα increases early atherosclerotic lesion development by decreasing macrophage apoptosis. Api6/AIM/Spα also associates with cytosolic fatty acid synthase (FAS), decreases FAS activity, thereby inducing the lipolytic response within adipocytes and is physiologically relevanting to obesity progression. This paper introduced emphatically the progress in biological function of Api6/ AIM/Spα in immune regulation and lipid metabolism.%凋亡抑制因子6(apoptosis inhibitor 6,Api6),又称作AIM/Spa,是清道夫受体富含半胱氨酸残基超家族新成员.Api6/AIM/Spa由巨噬细胞特异性表达,具有抑制CD4+/CD8+双阳性胸腺细胞、T淋巴细胞、NKT淋巴细胞和巨噬细胞凋亡的作用.作为模式识别受体,Api6/AIM/Spα直接与病原体相关分子模式LPS/LTA结合,在机体固有免疫和适应性免疫中发挥重要的作用.近年研究发现,Api6/AIM/Spα可以通过抑制动脉粥样硬化斑块部位巨噬细胞凋亡加重动脉粥样硬化早期斑块的进展,也可以通过抑制脂肪酸合成酶(FAS)的生物学活性提高脂肪细胞的脂解作用,在肥胖的进展中发挥重要作用.重点综述了Api6/AIM/Spα调节免疫和脂质代谢等生物学功能的研究进展.

  7. Cell cycle regulation in Trypanosoma brucei

    OpenAIRE

    Tansy C Hammarton

    2007-01-01

    Cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. In Trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go...

  8. Progressive Finland sees progress with nuclear projects

    International Nuclear Information System (INIS)

    The Finnish Hanhikivi-1 reactor project is firmly on track and a licence has been granted for construction of a final disposal facility for spent nuclear fuel - the first final repository in the world to enter the construction phase. Significant progress has been made with plans for Finland to build its sixth nuclear reactor unit at Hanhikivi. Fennovoima's licensing manager Janne Liuko said the company expects to receive the construction licence for the Generation III+ Hanhikivi-1 plant in late 2017. The application was submitted to the Finnish Ministry of Employment and the Economy in June 2015.

  9. Progressive Finland sees progress with nuclear projects

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, David [NucNet, Brussels (Belgium)

    2016-02-15

    The Finnish Hanhikivi-1 reactor project is firmly on track and a licence has been granted for construction of a final disposal facility for spent nuclear fuel - the first final repository in the world to enter the construction phase. Significant progress has been made with plans for Finland to build its sixth nuclear reactor unit at Hanhikivi. Fennovoima's licensing manager Janne Liuko said the company expects to receive the construction licence for the Generation III+ Hanhikivi-1 plant in late 2017. The application was submitted to the Finnish Ministry of Employment and the Economy in June 2015.

  10. NOISE REGULATION

    OpenAIRE

    Cristina Voican; Constantin Stanescu

    2012-01-01

    Noise regulation includes statutes or guidelines relating to sound transmission established by national, state or provincial and municipal levels of government. After the watershed passage of the United States Noise Control Act of 1972, other local and state governments passed further regulations. Although the UK and Japan enacted national laws in 1960 and 1967 respectively, these laws were not at all comprehensive or fully enforceable as to address generally rising ambient noise, enforceable...

  11. An overview of osteocalcin progress.

    Science.gov (United States)

    Li, Jinqiao; Zhang, Hongyu; Yang, Chao; Li, Yinghui; Dai, Zhongquan

    2016-07-01

    An increasing amount of data indicate that osteocalcin is an endocrine hormone which regulates energy metabolism, male fertility and brain development. However, the detailed functions and mechanism of osteocalcin are not well understood and conflicting results have been obtained from researchers worldwide. In the present review, we summarize the progress of osteocalcin studies over the past 40 years, focusing on the structure of carboxylated and undercarboxylated osteocalcin, new functions and putative receptors, the role of osteocalcin in bone remodeling, specific expression and regulation in osteoblasts, and new indices for clinical studies. The complexity of osteocalcin in completely, uncompletely and non-carboxylated forms may account for the discrepancies in its tertiary structure and clinical results. Moreover, the extensive expression of osteocalcin and its putative receptor GPRC6A imply that there are new physiological functions and mechanisms of action of osteocalcin to be explored. New discoveries related to osteocalcin function will assist its potential clinical application and physiological theory, but comprehensive investigations are required. PMID:26747614

  12. Expression of Hyaluronan in human tumor progression

    Directory of Open Access Journals (Sweden)

    Boregowda Rajeev K

    2006-01-01

    Full Text Available Abstract Background The development and progression of human tumors is accompanied by various cellular, biochemical and genetic alterations. These events include tumor cells interaction with extracellular matrix molecules including hyaluronan (HA. Hyaluronan is a large polysaccharide associated with pericellular matrix of proliferating, migrating cells. Its implication in malignant transformation, tumor progression and with the degree of differentiation in various invasive tumors has well accepted. It has been well known the role HA receptors in tumor growth and metastasis in various cancer tissues. Previously we have observed the unified over expression of Hyaluronic Acid Binding Protein (HABP, H11B2C2 antigen by the tumor cells in various types progressing tumor tissues with different grades. However, the poor understanding of relation between HA and HA-binding protein expression on tumor cells during tumor progression as well as the asymmetric observations of the role of HA expression in tumor progression prompted us to examine the degree of HA expression on tumor cells vs. stroma in various types of human tumors with different grades. Methods In the present study clinically diagnosed tumor tissue samples of different grades were used to screen the histopathological expression of hyaluronan by using b-PG (biotinylated proteoglycan as a probe and we compared the relative HA expression on tumor cells vs. stroma in well differentiated and poorly differentiated tumors. Specificity of the reaction was confirmed either by pre-digesting the tissue sections with hyaluronidase enzyme or by staining the sections with pre-absorbed complex of the probe and HA-oligomers. Results We show here the down regulation of HA expression in tumor cells is associated with progression of tumor from well differentiated through poorly differentiated stage, despite the constant HA expression in the tumor associated stroma. Conclusion The present finding enlighten the

  13. Comparison of Spectacle Classical Progressive and Office Progressive Lenses

    OpenAIRE

    Kozlík, Marek; Nováková Knollová, Libuše

    2013-01-01

    This paper elaborates on analysis of progressive spectacle lenses, to correct presbyopia, which are nowadays offered at the market. The paper describes different types of progressive lenses, their parameters, length and width of their progressive segments. It also describes degressive spectacles lenses – progressive lenses on middle and near distance. The main part of the paper is a comparison of functional differences among different types of progressive spectacles lenses. The paper also add...

  14. Chronic progressive multiple sclerosis

    International Nuclear Information System (INIS)

    A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

  15. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  16. Regulation of cell division in higher plants. Progress report, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, T.

    1993-09-01

    Recent work on the project has been focused almost exclusively on obtaining and characterizing CDNA clones encoding cylcin-dependent kinases (CDK), and cycling from pea. All of our work up to this time has relied on small PCR-generated CDNA clones of 2 putative pea CDKs and a putative pea mitotic cyclin, as well as anti-CDK antibodies of poor affinity and questionable specificity. Therefore, it has become a high priority for us to generate clones, probes and immunological tools in our own system. As of this writing, we have four putative CDKs (CdkPsl,2,3,& 4) and five putative cyclins (Cyc-Ps1,2,3,4,& 5), the DNA sequences of which have been determined to varying degrees of completeness.

  17. Progress in physical chemistry

    CERN Document Server

    Hempelmann, Rolf

    2008-01-01

    Progress in Physical Chemistry is a collection of recent ""Review Articles"" published in the ""Zeitschrift für Physikalische Chemie"". The second volume of Progress in Physical Chemistry is a collection of thematically closely related minireview articles written by the members of the Collaborative Research Centre (SFB) 277 of the German Research Foundation (DFG). These articles are based on twelve years of intense coordinated research efforts. Central topics are the synthesis and the characterization of interface-dominated, i.e. nanostructured materials, mainly in the solid state but also as

  18. Annual progress report 1981

    International Nuclear Information System (INIS)

    This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a brief description of the progress made in each section of the Institut. Research activities of the Protection department include, radiation effects on man, radioecology and environment radioprotection techniques. Research activities of the Nuclear Safety department include, reactor safety analysis, fuel cycle facilities safety analysis, safety research programs. The third section deals with nuclear material security including security of facilities, security of nuclear material transport and monitoring of nuclear material management

  19. Progress report 1982

    International Nuclear Information System (INIS)

    The progress report describes the scientific work and research results of the institute for radium research and nuclear physics of the Austrian Academy of Sciences for the period of 1982. The progress report covers the subject areas of nuclear theory, nuclear model calculations, experimental nuclear physics and neutron involved reactions, medium energy physics, instrumentation and detectors, evaluation of nuclear data and numerical data processing, dating, applications in medicine, dosimetry and environmental studies. A list of publications of this institute is given. (A.N.)

  20. Der Progress Test Medizin

    OpenAIRE

    Osterberg, K.; Kölbel, S; Brauns, K

    2006-01-01

    In 1999 a interdiciplinary, formative progress test for medical students has been established at the Charité - Universitätsmedizin Berlin. It contents of 200 MC-questions on a graduate level and is performed at the beginning of each semester since then.The ascertained test data is evaluated and reported back in a detailed written feedback to each participant.After initial problems in recruiting new item authors and an efficient administration of test items the progress test now is a well est...

  1. 1985. Annual progress report

    International Nuclear Information System (INIS)

    This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a description of the progress made in each sections of the Institut Research activities of the different departments include: reactor safety analysis, fuel cycle facilities analysis; and associated safety research programs (criticality, sites, transport ...), radioecology and environmental radioprotection techniques; data acquisition on radioactive waste storage sites; radiation effects on man, studies on radioprotection techniques; nuclear material security including security of facilities, security of nuclear material transport, and monitoring of nuclear material management; nuclear facility decommissioning; and finally the public information

  2. Progressive symmetric erythrokeratoderma

    Directory of Open Access Journals (Sweden)

    Gharpuray Mohan

    1990-01-01

    Full Text Available Four patients had symmetrically distributed hyperkeratotic plaques on the trunk and extremities; The lesions in all of them had appeared during infancy, and after a brief period of progression, had remained static, All of them had no family history of similar skin lesions. They responded well to topical applications of 6% salicylic acid in 50% propylene glycol. Unusual features in these cases of progressive symmetric erythrokeratoderma were the sparing of palms and soles, involvement of the trunk and absence of erythema.

  3. 过氧化物酶体增殖物激活受体α、γ调控长链酰基辅酶A合成酶1对肝纤维化进程的影响%Studies on PPAR αand γparticipating in progression of liver fibrosis by regulating ACSL1

    Institute of Scientific and Technical Information of China (English)

    辛萱; 颜红柱; 李维卿; 余宏宇

    2014-01-01

    在肝纤维化的发生发展进程中,过氧化物酶体增殖物激活受体(PPAR)α、γ具有调控脂代谢、脂肪酸代谢和抗肝纤维化等生物学功能,并与调控脂肪代谢的相关酶类关系密切。长链酰基辅酶A合成酶1(ACSL1)作为脂肪代谢的关键酶之一,在肝脏中参与脂质的合成与分解代谢,可引起肝脏内脂质沉积、炎症反应,并在肝脏中直接或间接促进肝纤维化进程。回顾了PPARα、γ和ACSL1各自的生物学功能与作用;简述了PPARα、γ对ACSL1的转录调控机制;从肝脏脂代谢和肝星状细胞活化等两个方面分析了PPARα、γ对ACSL1的调控作用,进而影响肝纤维化进程。从而指出在肝脏中PPARα、γ通过调控ACSL1直接或间接参与肝纤维化进程。%During the development and procession of liver fibrosis,peroxisome proliferator-activated receptor (PPAR)αand γare in charge of the regulation of lipid metabolism,fatty acid metabolism,anti-liver fibrosis,etc.,and are closely related to fat metabolism-re-lated enzymes.As a key enzyme in fat metabolism,acyl-CoA synthetase long-chain family member 1 (ACSL1 )is involved in lipid syn-thesis and catabolism and then causes lipid deposition and inflammation in the liver,so it directly or indirectly promotes hepatic fibrosis.The biological functions and roles of PPARαandγand ACSL1 are reviewed;the action mechanisms of PPARαandγin the transcriptional reg-ulation of ACSL1 are briefly described;the regulatory effects of PPARαandγon ACSL1 and their effects on the progression of hepatic fibro-sis are analyzed from the aspects of liver lipid metabolism and hepatic stellate cell activation.It is pointed out that in the liver PPARαandγare directly or indirectly involved in the progression of hepatic fibrosis by regulating ACSL1 .

  4. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  5. Epigenetic microRNA Regulation

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman

    2011-01-01

    and confirming transcriptional start sites can be difficult. Epigenetics, gene regulatory and DNA modification mechanisms not involving a change to the primary sequence, have been implied in the regulation of a number of miRNA loci. Both epigenetic and miRNA signatures are broadly altered in cancer......, and are thought to play essential roles in cancer etiology and progression. Here, we aimed to identify epigenetic miRNA deregulation in bladder and oral carcinoma, and to develop a robust approach to epigenetic miRNA prediction and detection. In addition, non-canonical epigenetic functions directed by a nuclear...... miRNA were investigated. In summary, we report that the miR-200 family and miR-205 are coordinately epigenetically regulated in a variety of cell lines, tumors and normal tissues. MiR-200c expression is correlated with bladder cancer disease progression, and miR-375 levels in oral rinse can...

  6. Ensembl regulation resources.

    Science.gov (United States)

    Zerbino, Daniel R; Johnson, Nathan; Juetteman, Thomas; Sheppard, Dan; Wilder, Steven P; Lavidas, Ilias; Nuhn, Michael; Perry, Emily; Raffaillac-Desfosses, Quentin; Sobral, Daniel; Keefe, Damian; Gräf, Stefan; Ahmed, Ikhlak; Kinsella, Rhoda; Pritchard, Bethan; Brent, Simon; Amode, Ridwan; Parker, Anne; Trevanion, Steven; Birney, Ewan; Dunham, Ian; Flicek, Paul

    2016-01-01

    New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org. PMID:26888907

  7. Progress report 1979

    International Nuclear Information System (INIS)

    This progress report deals with service oriented work performed at the AAEC Research Establishment in the twelve month period ending September 30, 1979. Services provided by the Engineering Services Division, the Safety Department, Site Information Services Department and Commercial Applications are described

  8. MCNP Progress & Performance Improvements

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Forrest B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bull, Jeffrey S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rising, Michael Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-04-14

    Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

  9. Progress in inertial fusion

    International Nuclear Information System (INIS)

    The requirements for high gain in inertial confinement are given in terms of target implosion requirements. Results of experimental studies of the laser/target interaction and of the dynamics of laser implosion. A report of the progress of advanced laser development is also presented. 3 refs., 8 figs., 1 tab

  10. Stellarator theory: Progress report

    International Nuclear Information System (INIS)

    This paper discusses progress in the following areas: The propagator method; ripple transport in tokamaks; self-consistent bounce-averaged numerical transport; computations: The bootstrap current; comparisons of stellarator ripple transport calculations; and plasma transport in IMS using a 1D fluid transport code

  11. Learning Progressions & Climate Change

    Science.gov (United States)

    Parker, Joyce M.; de los Santos, Elizabeth X.; Anderson, Charles W.

    2015-01-01

    Our society is currently having serious debates about sources of energy and global climate change. But do students (and the public) have the requisite knowledge to engage these issues as informed citizenry? The learning-progression research summarized here indicates that only 10% of high school students typically have a level of understanding…

  12. Quarterly Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Ayman I. Hawari

    2002-12-30

    This report presents the progress made during the first quarter of phase 2 for the project entitled ''Development and Validation of Thermal Neutron Scattering Laws from Applications and Safety Implications in Generation IV Reactor Designs.'' (B204) THIS IS NOT A FINAL REPORT

  13. Managing Progressive MS

    Science.gov (United States)

    ... area of assistive devices for personal hygiene and bathroom adjustments that make toilet functions more effective and safe. They have extensive practical information on devices and techniques. 27 | Managing Progressive MS If you need help with basic activities, get advice and inform ...

  14. Research progress of RNAi

    Institute of Scientific and Technical Information of China (English)

    邹建

    2014-01-01

    the double stranded RNA into cell could cause homologous gene silencing, a phenomenon called RNA interference (RNA interference, RNAi). Research progress of RNA interference characteristics, in this paper, the mechanism of RNA interference technology, RNA interference and existing problems are summarized.

  15. Progress on Display

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    An exhibition in Beijing highlights achievements in China’s autonomous regions An exhibition on social progress in China’s five autonomous re-gions, including Inner Mongolia,Xinjiang, Guangxi, Ningxia and Tibet, opened at the Cultural Palace of Nationalities in Beijing on August 25. It runs until September 17.

  16. Progress in optics

    CERN Document Server

    Wolf, Emil

    2015-01-01

    The Progress in Optics series contains more than 300 review articles by distinguished research workers, which have become permanent records for many important developments, helping optical scientists and optical engineers stay abreast of their fields. Comprehensive, in-depth reviewsEdited by the leading authority in the field

  17. Recent progress in Biophysics

    International Nuclear Information System (INIS)

    Recent progress in biophysics is reviewed, and three examples of the use of physical techniques and ideas in biological research are given. The first one deals with the oxygen transporting protein-hemoglobin, the second one with photosynthesis, and the third one with image formation, using nuclear magnetic resonance. (Author)

  18. Has Macro Progressed?

    OpenAIRE

    Fair, Ray C.

    2009-01-01

    There have been a number of recent papers arguing that there has been considerable convergence in macro research and to the good. This paper considers the question whether what has been converged to is good. Has progress been made in understanding how the macro economy works?

  19. Progressive Retirement Programme

    CERN Multimedia

    HR Department

    2007-01-01

    Following discussion at the Standing Concertation Committee at its meeting on 30 January 2007, the Director-General has approved the extension of the Progressive Retirement Programme with effect from 1 April 2007 until 31 March 2008. Human Resources Department Tel. 74484/74128

  20. Progress report of CJD

    International Nuclear Information System (INIS)

    This paper is the progress report of the Russian Nuclear Data Center at F.E.I., Obninsk. Evaluations have been made for dosimetry reactions and neutron reactions. Analysis of the spectra and the production cross sections were made. (a.n.)

  1. BARC progress report - 1998

    International Nuclear Information System (INIS)

    This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author)

  2. Progress report 1979

    International Nuclear Information System (INIS)

    This progress report deals with technical and research work done at the AAEC Research Establishment in the twelve month period ending September 30, 1979. Work done in the following research divisions is reported: Applied Maths and Computing, Chemical Technology, Engineering Research, Environmental Science, Instrumentation and Control, Isotope, Materials and Physics

  3. BARC progress report - 1997

    International Nuclear Information System (INIS)

    This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author)

  4. Progression og underviserkompetencer

    Directory of Open Access Journals (Sweden)

    Lene Tortzen Bager

    2014-03-01

    Full Text Available På baggrund af en kvalitativ interviewundersøgelse af undervisere ved Aarhus Universitet lavet i 2012, tematiserer artiklen, hvordan undervisere udvikler deres faglige og pædagogiske kompetencer i forhold til at kunne skabe progression inden for innovation og entreprenørskab forstået enten som didaktik, arbejdsformer i faglige forløb eller som fag på universitetet. I arbejdet med progression er det en udfordring at integrere de nye faglige dimensioner i det kernefaglige felt. Den seneste model for progression inden for innovation og entreprenør-skab siger, at det er den lærendes generelle erfaringsniveau, der er den afgørende progressionsskabende faktor (Progressionsmodellen, Fonden for Entreprenørskab, 2013b. Samtidig skelner international forskning inden for studiekompetenceområdet mellem niveauer, hvor indlejret viden er det mest avancerede kompetenceniveau (Barrie, 2002.Ifølge progressionsmodellen og den nævnte kompetenceforskning er erfaring og dybt integreret læring altså centrale dimensioner i progression. Men hvad er underviserens rolle heri? Underviserens professionelle udviklingsarbejde forekommer at være underbelyst i forhold til, at underviseren er den legitime garant for integrationen af nye faglige dimensioner og for den studerendes kompetenceniveau. Interviewundersøgelsen forholder sig til spørgsmålet om progression gennem de deltagende underviseres beskrivelse af betydningslag i entreprenørskabsbegrebet koblet til de praksisformer i undervisningen, der knytter sig hertil samt et indblik i undervisernes refleksioner over deres kompetenceudviklingsprocesser. Artiklens bidrag til progression er at se underviserens motivation og kompetenceudvikling som forudsætninger herfor.  Based on a qualitative study of five teachers in the Faculty of Arts at Aarhus University that took place during 2012, the article thematizes how teachers develop their professional and educational qualifications in innovation and

  5. Progress of ITER vacuum vessel

    International Nuclear Information System (INIS)

    Highlights: ► This covers the overall status and progress of the ITER vacuum vessel activities. ► It includes design, R and D, manufacturing and approval process of the regulators. ► The baseline design was completed and now manufacturing designs are on-going. ► R and D includes ISI, dynamic test of keys and lip-seal welding/cutting technology. ► The VV suppliers produced full-scale mock-ups and started VV manufacturing. -- Abstract: Design modifications were implemented in the vacuum vessel (VV) baseline design in 2011–2012 for finalization. The modifications are mostly due to interface components, such as support rails and feedthroughs for the in-vessel coils (IVC). Manufacturing designs are being developed at the domestic agencies (DAs) based on the baseline design. The VV support design was also finalized and tests on scale mock-ups are under preparation. Design of the in-wall shielding (IWS) has progressed, considering the assembly methods and the required tolerances. Further modifications are required to be consistent with the DAs’ manufacturing designs. Dynamic tests on the inter-modular and stub keys to support the blanket modules are being performed to measure the dynamic amplification factor (DAF). An in-service inspection (ISI) plan has been developed and R and D was launched for ISI. Conceptual design of the VV instrumentation has been developed. The VV baseline design was approved by the agreed notified body (ANB) in accordance with the French Nuclear Pressure Equipment Order procedure

  6. 1995 technical progress report

    International Nuclear Information System (INIS)

    Summaries of the researches are grouped into programs as follows: research and development which covers all the PNRI research projects in 1994; scientific and technological services; and the nuclear regulations, licensing and safeguards of the institute

  7. 1997 technical progress report

    International Nuclear Information System (INIS)

    This report presents the on-going research and development projects of the Philippine Nuclear Research Institute (PNRI) in the fields of agriculture, environment and industry, scientific and technological services and nuclear regulations, licensing and safeguards

  8. 1999 technical progress report

    International Nuclear Information System (INIS)

    This report presents the on-going research and development projects of the Philippine Nuclear Research Institute (PNRI) in the fields of agriculture, environment and industry, scientific and technological services and nuclear regulations, licensing and safeguards

  9. Auxin–Cytokinin Interaction Regulates Meristem Development

    OpenAIRE

    Su, Ying-Hua; Liu, Yu-Bo; Zhang, Xian-Sheng

    2011-01-01

    Plant hormones regulate many aspects of plant growth and development. Both auxin and cytokinin have been known for a long time to act either synergistically or antagonistically to control several significant developmental processes, such as the formation and maintenance of meristem. Over the past few years, exciting progress has been made to reveal the molecular mechanisms underlying the auxin–cytokinin action and interaction. In this review, we shall briefly discuss the major progress made i...

  10. Three-dimensional context regulation of metastasis

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Weaver, Valerie M

    2009-01-01

    stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia...... is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix...

  11. 大豆microRNA基因GmMIR160A负调控植物叶片衰老进程%GmMIR1 60A,a class of soybean microRNA gene, negatively regulates progress of leaf senescence

    Institute of Scientific and Technical Information of China (English)

    李小平; 曾庆发; 张根生; 赵娟

    2015-01-01

    -type soybean through Agrobacterium-medi-ated method with cotyledon node as the explants.Using the time order screening approaches including the antibiotic screen,the genome PCR identification and the phenotypic analysis,we finally generated four transgenic lines (Line OX-3,5,7 and 8)with stable integrated insertion T-DNA.Compared with wild types control,these transgenic plants, successful expressing the transgene showed normal morphological characteristics in respect to roots,stem,leaves, flowers,fruits and seeds but exhibited the increased chlorophyll content and higher maximum quantum efficiency (Fv/Fm)for the first trifoliage leaves during the mature stage.Moreover,GmARFs and GmCYSP 1 ,in which the former are targets ofGmMIR160 and the latter is thought as a soybean senescence marker,were down-regulated dra-matically in the transgenic trifoliage leaves.Taking together,these data indicated that Gma-miR160 might negatively regulate leaf senescence by repression of its targets in soybean.This report uncovered a novel pathway that the plant hormone auxin could modify the processes of leaf senescence by regulating the transcriptional expression of microR-NA gene Gma-miR160 and then repressing the messenger RNA level of auxin responsive factors GmARFs and also provided the new clues for investigating how the plant hormones control the progress of leaf senescence.%叶片衰老是受内外多种因子影响的遗传发育进程.生长素、细胞分裂素和乙烯等多种植物激素是调控叶片衰老的重要内部因子,它们通过长或短距离运输形成叶片组织内特定的区域分布和浓度梯度,从而直接或间接参与植物叶片衰老过程.分子遗传学表明,细胞分裂素和乙烯分别是叶片衰老的抑制子和正调节子,而生长素如何参与叶片衰老的分子机制目前还不清晰.植物体内成熟小分子 RNA 由小 RNA 基因转录并通过特定酶加工形成的21~23 bp的双链RNA分子.这些小分子通过不完全配对方

  12. Internationalisering og progression

    Directory of Open Access Journals (Sweden)

    Lisanne Wilken

    2014-09-01

    Full Text Available I Danmark har vi traditionelt tænkt universiteternes femårige kandidatuddannelser som sammenhængende forløb, hvor den studerende gradvist opbygger en stadig mere specialiseret viden inden for et givet fagområde. Denne idé om progression er i de senere år blevet udfordret fra flere sider. Især er progressionsidéen blevet diskuteret i forhold til tværfaglige uddannelsesforløb, men også de mange internationale uddannelser, der etableres, udfordrer den måde, hvorpå vi traditionelt har forstået progression i det danske uddannelsessystem. På internationale kandidatuddannelser finder vi nemlig typisk både studerende, for hvem kandidatuddannelsen er en forlængelse af en grunduddannelse, og studerende, der har taget deres grunduddannelse et andet sted og muligvis endda i et andet fag. I denne artikel undersøger vi, hvordan undervisere på kandidatuddannelser som både er tværfaglige og internationale forholder sig til progression. Artiklen er skrevet på baggrund af semistrukturerede interviews med undervisere fra tværfaglige, internationale uddannelser ved Aarhus Universitet.University programs in Denmark have traditionally been perceived as a continuous education consisting of three years of basic education followed by two years of specialization within the same discipline. This idea is now being challenged on several fronts. For instance, it is becoming more common for Danish universities to offer interdisciplinary master programs. Also, the trend for greater internationalization in higher education means that programs can attract students from outside Denmark, and these students often come from different academic backgrounds. To investigate how these changes are affecting the way professors who teach on interdisciplinary international masters programs conceive student progress, we carried out semi-structured interviews with teachers on international programs at Aarhus University, the second largest university in Denmark. The

  13. Lactobacillus decelerates cervical epithelial cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Katarina Vielfort

    Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

  14. MAPK Usage in Periodontal Disease Progression

    Directory of Open Access Journals (Sweden)

    Qiyan Li

    2012-01-01

    Full Text Available In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS, induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2 signaling axis is needed for periodontal disease progression: an orally administered p38α inhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP-1, a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression.

  15. Progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Tomohide Hori; Justin H. Nguyen; Shinji Uemoto

    2010-01-01

    BACKGROUND: Three types of progressive familial intrahepatic cholestasis (PFIC) have been identiifed, but their etiologies include unknown mechanisms. DATA SOURCES: A PubMed search on "progressive familial intrahepatic cholestasis" and "PFIC" was performed on the topic, and the relevant articles were reviewed. RESULTS: The etiologies of the three PFIC types still include unknown mechanisms. Especially in PFIC type 1, enterohepatic circulation of bile acid should be considered. Ursodeoxycholic acid, partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS: Since the etiologies and disease mechanisms of PFIC are still unclear, detailed studies are urgently required. Strategies for more advanced therapies are also needed. These developments in the future are indispensable, especially for PFIC type 1 patients.

  16. Recent progress in microcalorimetry

    CERN Document Server

    Calvet, E; Skinner, H A

    2013-01-01

    Recent Progress in Microcalorimetry focuses on the methodologies, processes, and approaches involved in microcalorimetry, as well as heat flow, temperature constancy, and chemistry of alumina and cements.The selection first offers information on the different types of calorimeters; measurement of the heat flow between the calorimeter and jacket boundaries by means of a thermoelectric pile; and constructional details of the microcalorimeter. Discussions focus on classification of calorimeters, use of thermoelectric piles as thermometers, correct measurement of heat flow from a calorimeter conta

  17. CNGS Progress Report 2004

    CERN Document Server

    Bruno, L; Elsener, K; Gaillard, H; López-Hernandez, L A; Meddahi, M; Rangod, Stephane; Roesler, S; Spinks, Alan; Wilhelmsson, M; CERN. Geneva. AB Department

    2004-01-01

    The CNGS project is progressing according to schedule, with the aim to be ready for beam in spring 2006. In this paper, the project status and recent changes to the design of systems and components are summarized. The actions taken in response to the recommendations of the 2003 CNGS Review are described. This report has been drafted in view of the third CNGS Review, held in June 2004.

  18. Three year progress report

    International Nuclear Information System (INIS)

    Progress is reported on the following studies: x-ray and uv effects in photosynthetic organisms; effects of alcohols and oxygen concentration on transforming DNA; free radical studies; sensitization by metal ions; role of the solvated electron in radiation damage to cells; effectiveness of organic and inorganic compounds in sensitizing bacterial spores to high energy radiation; oxygen effects; radiosensitivity of enzyme systems in Chlorella; and effects of pre-irradiation of solutions on spores

  19. Progress in optics

    CERN Document Server

    Wolf, Emil

    2009-01-01

    In the fourty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. The volumes in this series which have appeared up to now contain more than 300 review articles by distinguished research workers, which have become permanent records for many important developments.- Backscattering and Anderson localization of light- Advances in oliton manipulation in optical lattices- Fundamental quantum noise in optical amplification- Invisibility cloaks

  20. Clean Energy Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    For the past several years, the IEA and others have been calling for a clean energy revolution to achieve global energy security, economic growth and climate change goals. This report analyses for the first time progress in global clean energy technology deployment against the pathways that are needed to achieve these goals. It provides an overview of technology deployment status, key policy developments and public spending on RDD&D of clean energy technologies.

  1. Progress in optics

    CERN Document Server

    Wolf, Emil

    2008-01-01

    In the fourty-six years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. The volumes in this series which have appeared up to now contain more than 300 review articles by distinguished research workers, which have become permanent records for many important developments.- Metamaterials- Polarization Techniques- Linear Baisotropic Mediums- Ultrafast Optical Pulses- Quantum Imaging- Point-Spread Funcions- Discrete Wigner Functions

  2. Internationalisering og progression

    DEFF Research Database (Denmark)

    Wilken, Lisanne; Tange, Hanne

    2014-01-01

    means that programs can attract students from outside Denmark, and these students often come from different academic backgrounds. To investigate how these changes are affecting the way professors who teach on interdisciplinary international masters programs conceive student progress, we carried out semi......-structured interviews with teachers on international programs at Aarhus University, the second largest university in Denmark. The article summarizes their opinions and distinguishes In this article we explore how Danish university professors teaching at interdisciplinary international master programs at Danish...

  3. Progressive familial intrahepatic cholestasis

    OpenAIRE

    Baussan Christiane; Gonzales Emmanuel; Davit-Spraul Anne; Jacquemin Emmanuel

    2009-01-01

    Abstract Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appea...

  4. Host genetic factors in susceptibility to HIV-1 infection and progression to AIDS

    Indian Academy of Sciences (India)

    Koushik Chatterjee

    2010-04-01

    HIV-1 infection has rapidly spread worldwide and has become the leading cause of mortality in infectious diseases. The duration for development of AIDS (AIDS progression) is highly variable among HIV–1 infected individuals, ranging from 2–3 years to no signs of AIDS development in the entire lifetime. Several factors regulate the rate at which HIV-1 infection progresses to AIDS. Host genetic factors play an important role in the outcome of such complex or multifactor diseases as AIDS and are also known to regulate the rate of disease progression. This review focuses on the major host genes reported to affect the progression to AIDS in HIV-1 infected individuals.

  5. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  6. Nuclear regulation

    International Nuclear Information System (INIS)

    Today, 112 nuclear power plants, 22 facilities that support these plants, 54 reactors used in research, and approximately 23,000 organizations hold licenses from either the Nuclear Regulator Commission or various states to use radioactive material; other facilities are operated by various government agencies. Eventually most of these facilities will be decommissioned, which involves removing the radioactive material and terminating the license. NRC needs to ensure that licensees appropriately decontaminate their facilities because, under current regulations, NRC cannot specifically require additional cleanup once it terminates a license. This paper presents a GAO report on NRC's decommissioning procedures. In two of eight cases GAO reviewed, NRC fully or partially released sites for unrestricted use where radioactive contamination was higher than its guidelines allowed; in the other cases, NRC's information was inadequate or incomplete. Further, NRC lacks information on the types and amounts of radioactive waste buried on-site. At five sites reviewed by GAO, groundwater has been found to be contaminated by radioactive waste

  7. Signaling mechanisms for regulation of chemotaxis

    Institute of Scientific and Technical Information of China (English)

    Dianqing WU

    2005-01-01

    Chemotaxis is a fascinating biological process, through which a cell migrates along a shallow chemoattractant gradient that is less than 5% difference between the anterior and posterior of the cell. Chemotaxis is composed of two independent,but interrelated processes-motility and directionality, both of which are regulated by extracellular stimuli, chemoattractants.In this mini-review, recent progresses in the understanding of the regulation of leukocyte chemotaxis by chemoattractant signaling are reviewed.

  8. Regulation of aleurone development in cereal grains.

    Science.gov (United States)

    Becraft, Philip W; Yi, Gibum

    2011-03-01

    The aleurone layer of cereal grains is important biologically as well as nutritionally and economically. Here, current knowledge on the regulation of aleurone development is reviewed. Recent reports suggest that the control of aleurone development is more complex than earlier models portrayed. Multiple levels of genetic regulation control aleurone cell fate, differentiation, and organization. The hormones auxin and cytokinin can also influence aleurone development. New technical advances promise to facilitate future progress.

  9. Heparan sulfate regulates ADAM12 through a molecular switch mechanism

    DEFF Research Database (Denmark)

    Sørensen, Hans P; Vives, Romain R; Manetopoulos, Christina;

    2008-01-01

    tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a pro/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase...

  10. Progresses in studies of nuclear actin

    Institute of Scientific and Technical Information of China (English)

    ZHU Xiaojuan; ZENG Xianlu; SONG Zhaoxia; HAO Shui

    2004-01-01

    Actin is a protein abundant in cells. Recently, it has been proved to be universally existent in the nuclei of many cell types. Actin and actin-binding proteins, as well as actin-related proteins, are necessary for the mediation of the conformation and function of nuclear actin, including the transformation of actin between unpolymerized and polymerized, chroinatin remodeling, regulation of gene expression and RNA processing as well as RNA transportation. In this paper, we summarized the progresses in the research of nu clear actin.

  11. 1996 technical progress report

    International Nuclear Information System (INIS)

    Summaries of the researches are grouped into programs as follows: research and development in food and agriculture; research and development in health, environment and industry which includes all the PNRI research projects in 1996; scientific and technological services; and the nuclear regulations, licensing and safeguards of the institute

  12. MEIC Design Progress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y; Douglas, D; Hutton, A; Krafft, G A; Li, R; Lin, F; Morozov, V S; Nissen, E W; Pilat, F C; Satogata, T; Tennant, C; Terzic, B; Yunn, C; Barber, D P; Filatov, Y; Hyde, C; Kondratenko, A M; Manikonda, S L; Ostroumov, P N

    2012-07-01

    This paper will report the recent progress in the conceptual design of MEIC, a high luminosity medium energy polarized ring-ring electron-ion collider at Jefferson lab. The topics and achievements that will be covered are design of the ion large booster and the ERL-circulator-ring-based electron cooling facility, optimization of chromatic corrections and dynamic aperture studies, schemes and tracking simulations of lepton and ion polarization in the figure-8 collider ring, and the beam-beam and electron cooling simulations. A proposal of a test facility for the MEIC electron cooler will also be discussed.

  13. Progress in optics

    CERN Document Server

    Wolf, Emil

    1977-01-01

    In the thirty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. At the time of inception of this series, the first lasers were only just becoming operational, holography was in its infancy, subjects such as fiber optics, integrated optics and optoelectronics did not exist and quantum optics was the domain of only a few physicists. The term photonics had not yet been coined. Today these fields are flourishing and have become areas of specialisation for many science and engineering students and n

  14. PROGRESS IN HELIOSPHERIC PHYSICS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This is an overview of progresses in heliospheric physics made in China in the period of June, 2000 to May, 2002. The report is focused on theoretical studies,modelling and observational analysis of interplanetary physical phenomena, and consists of five sections: the acceleration and heating of the solar wind, corona structures, coronal mass ejections, magnetic reconnection phenomena, and in terplanetary transient phenomena. The main achievements made recently by Chinese scientists in related areas are simply listed in corresponding sections without any priority, only certain editorial consideration.

  15. Progress in optics

    CERN Document Server

    Wolf, Emil

    2006-01-01

    In the thirty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. At the time of inception of this series, the first lasers were only just becoming operational, holography was in its infancy, subjects such as fiber optics, integrated optics and optoelectronics did not exist and quantum optics was the domain of only a few physicists. The term photonics had not yet been coined. Today these fields are flourishing and have become areas of specialisation for many science and engineering students and n

  16. Rapidly progressive tabetic neurosyphilis

    Institute of Scientific and Technical Information of China (English)

    赖伟红; 薛华忠; 韩国柱

    2003-01-01

    Since the sexually transmitted diseases were recognized as a public health problem in China during the early 1980's, the incidence of syphilis has gradually increased. Though there have been case reports of clinical variants of neurosyphilis, including syphilitic cerebrospinal meningitis or meningomyelitis and meningovascular syphilis, occurring in different regions of China,1-3 tabes dorsalis or tabetic neurosyphilis has not yet been reported in China. Here, we report a young man with rapidly progressive tabetic neurosyphilis admitted to our hospital in October 1999.

  17. The Progressive Era.

    Science.gov (United States)

    Chambers, David W

    2005-01-01

    The American College of Dentists was founded in 1920 for the purpose of encouraging young dentists to continue study and to apply science to their practices. This ideal emerged in the Progressive Era, which lasted roughly from 1895 to 1920. The animating spirit of this period was that the human condition could be improved and that the way to achieve this was through science and the use of experts working together. The Progressive Era saw inventions, such as automobiles and airplanes, telephone and radio, that required mass production and brought people together. It also spawned many political and legislative innovations that we now take for granted. Among these are the Food and Drug Administration, the Department of Commerce, and the Federal Trade Commission. Workers' compensation and other social protections were introduced, as were city commissions; the income tax; women's suffrage; and initiative, referendum, and recall. Medicine, for the first time, became an effective way to treat disease as it developed a scientific foundation. PMID:16350929

  18. Progress on the role of the signal transducers and activators of transcription family molecules in the regulation of macrophage polarization%信号转导及转录激活因子家族分子在巨噬细胞极化调控中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    蒋兴伟; 黎燕; 韩根成

    2015-01-01

    Macrophages play a key role in the regulation of inflammation and immune responses,and in the maintenance of immune homeostasis.Under different microenvironments,macrophages function heterogeneously.They can alter themselves into two different types of polarization,classically-activated (M1) and alternatively-activated (M2),in order to display pro-inflammatory or anti-inflammatory functions.Many regulatory molecules are involved in this progress of macrophage polarization.Among these regulatory molecules,signal transducers and activators of transcription (Stats) family is of the most important.Stats family has seven members with similar structures and different functions,called Stat1,Star2,Stat3,Stat4,Stat5a,Stat5b,and Star6.It is clear now that Stats family plays an important role in inflammatory responses,and in the process of macrophage polarization.%巨噬细胞在调控炎症及免疫反应,维持免疫稳态中发挥关键的作用.不同微环境条件下,巨噬细胞功能出现异质性.其可以极化为经典活化(M1)或替代活化(M2)两种不同的极化类型,分别发挥促炎或抑炎的功能.众所周知,许多调控分子参与了巨噬细胞的极化调控过程.在众多的极化调控分子中,信号转导及转录激活因子(Stats)家族是一类最主要的调控分子.Stats家族有7个成员,即Stat1、Stat2、Stat3、Stat4、Stat5a、Stat5b和Stat6.它们结构相似,但功能不同.目前已经明确,Stats分子在机体炎症应答中发挥重要的作用,调控着巨噬细胞的极化进程.

  19. 海参多糖抗肺癌活性及对T细胞免疫功能调节研究进展%Research and progression on anti-lung neoplasm activity and the regulation of T cellular immune ;function by polysaccharide from sea cucumber

    Institute of Scientific and Technical Information of China (English)

    李甜甜; 王相海; 林存智; 朱新红

    2014-01-01

    肺癌是预后极差的恶性肿瘤之一,已经上升到肿瘤死亡原因的首位,成为严重威胁人类健康的恶性肿瘤。肺癌的早期治疗除了手术、放疗和化疗外,生物治疗已经成为重要的辅助手段。海参多糖具有多种生物活性,它是从海参体内提取的一种糖胺聚糖,具有良好的抗凝血和抗血栓作用。研究显示其具有抗肿瘤活性及细胞免疫调节功能,通过抑制肿瘤新生血管的形成和抗凝血来实现抗肿瘤作用,通过激活T细胞调节机体细胞免疫功能。本文就海参多糖在抗肺癌活性及T细胞免疫功能调节方面的基础研究进展进行综述。%The lung cancer is one of very poor malignant tumors in prognosis. It has reached the top of cause of death and become to threaten the health of human in malignant tumor. The biotherapy has become the important adjunctive therapy method for pulmonary cancer, apart from surgery, chemotherapy and radiotherapy. The polysaccharide which was selectived from sea cucumber has more important biologic activity substance. It has satisfactory effects in anticoagulated blood and anti-thrombosis as biotherapy, and it has the function of cyto-immunity and anti-neoplastic activity. The activity was carried out by inhibiting the form of neovascular of tumor and anti-coagulated blood. It reinforces the cellular immune function by activating T cells. So, we reviewed the progression of grounding research in anti-lung tumor activity and the regulation of T cellular immune function for polysaccharide from sea cucumber.

  20. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  1. Embryo culture in teratological surveillance and serum proteins in development. Progress report, 1979-1980

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N.W.

    1980-07-01

    Research progress for the period 1979-1980 is reported. The feasibility of using rat embryo cultures to test the teratogenic activity of serum was studied. The mechanisms regulating the synthesis of serum proteins were investigated. (ACR)

  2. Research progress of plant PP2C-type protein phosphatase in ABA signal transduction and adversity stress regulation mechanism%植物 PP2C 蛋白磷酸酶 ABA 信号转导及逆境胁迫调控机制研究进展

    Institute of Scientific and Technical Information of China (English)

    张继红; 陶能国

    2015-01-01

    Protein phosphatase is the most important and pivotal enzymes in reversible protein phosphorylation regula-ting mechanisms.While the PP2C phosphatase is a kind of serine/threonine residues of protein phosphatase,is the largest protein phosphatase family in higher plants,there are 76 family members,widely exists in living organisms. So far,four kinds of PP2C protein phosphatases have been found in plants.Protein kinase and protein phosphatase catalyzed reversible protein phosphorylation,play an important role in plant signal transduction and physiological me-tabolism,protein phosphorylation exist in almost the signal transduction pathway.Numerous academic studies have shown that plant PP2Cs are involved in multiple signal transduction pathways including PP 2C involved in ABA sig-naling pathway,the response to drought,low temperature,salt stress,participated in the plant wound and seed dor-mancy or germination signal pathway,and exist the different regulation mechanism and the enzyme catalytic activity were dependent on the concentrations of Mg2+ or Mn2+ .In plant PP2Cs protein C-terminal,there are a highly con-served catalytic domains,as well as in their N-terminal,their function are different.The review would provide a brief overview of classification,structure of PP 2Cs ,the interaction between ABA receptor and PP2Cs protein,the recent progresses about their roles in ABA and other stress signal transduction pathway in higher plant.%蛋白磷酸酶(protein phosphatase,PP)是蛋白质可逆磷酸化调节机制中的关键酶,而 PP2C 磷酸酶是一类丝氨酸/苏氨酸残基蛋白磷酸酶,是高等植物中最大的蛋白磷酸酶家族,包含76个家族成员,广泛存在于生物体中。迄今为止,在植物体内已经发现了4种 PP2C 蛋白磷酸酶。蛋白激酶和蛋白磷酸酶协同催化蛋白质可逆磷酸化,在植物体内信号转导和生理代谢中起着重要的调节作用,蛋白质的磷酸化几乎存在于所有的信号转导途

  3. Progress in nanophotonics 3

    CERN Document Server

    Yatsui, Takashi

    2015-01-01

    This book focuses on the recent progress in nanophotonics technology to be used to develop novel nano-optical devices, fabrication technology and advanced systems. It reviews light-emitting diodes and lasers made of silicon bulk crystals in which the light emission principle is based on dressed-photon-phonons. Further topics include: theoretical studies of optoelectronic properties of molecular condensates for organic solar cells and light-emitting devices, the basics of topological light beams together with their important properties for laser spectroscopy, spatially localized modes emerging in nonlinear discrete dynamic systems and theoretical methods to explore the dynamics of nanoparticles by the light-induced force of tailored light fields under thermal fluctuations. These topics are reviewed by leading scientists. This overview is a variable resource for engineers and scientists working in the field of nanophotonics.

  4. BRIF and CARIF progress

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    China Institute of Atomic Energy (CIAE) is currently constructing Beijing rare ion beam facility (BRIF) and is proposing China advanced rare ion beam facility (CARIF). This paper is aiming at introducing the progress of BRIF project and the con ceptual design CARIF. The ISOL type facility BRIF under construction is composed of a 100 MeV 300 ?A proton cyclotron, an ISOL with mass resolution of 20000, and a super-conducting LINAC of 2 MeV/q, and will be commissioned in 2013. CARIF facility proposed is planned to use both ISOL and PF techniques. It is based on a China advanced research reactor CARR that was critical, with ISOL separation of fission fragment, post acceleration to 150 MeV/u, and fragmentation of neu tron-rich fission fragment beam like 132Sn. Such unique combination will allow CARIF to deliver beam intensity better than the best world facilities by more than one order of magnitude.

  5. Vivitron - Progress report 1990

    International Nuclear Information System (INIS)

    The 1990 activity report of the Strasbourg Nuclear Research, concerning the Vivitron project, is presented. After having mounted all the Van de Graaff elements of the Vivitron needed for the generator tests, the tank was closed in July 1990. It was then put under vacuum, leaks were searched for and repaired. Voltage tests started in December and a voltage of 17.6 MV was reached in February. Modifications on the charging system and to improvement of the column protection against sparks are necessary before the voltage tests can be carried on. Great progress has been made in the setting up of the new Vivitron injector and analysing magnet. In this report are included the description of project different development steps, the Vivitron budget and the list of publications, congress contributions and internal reports. 18 figs

  6. Progress report 1981 - 1983

    International Nuclear Information System (INIS)

    This progress report describes the research activities of the Atom-institute of the Austrian Universities of the period 1981-1983. The chapter headings are: (1) Electron- and X-ray physics, thermoluminescence and archeometry. (2) Nuclear physics. (3) Nuclear techniques, electronics and EDP. (4) Neutron- and solid state physics with neutron scattering, low temperature physics, theoretical solid state physics and preparation technique. (5) Radiation chemistry. (6) Radiation protection and dosimetry. Each chapter gives a comprimated overview about the research work done in the described period, illustrated by diagrams and tables, a comprehensive list of publications, each citation provided with an (mostly English) Abstract and a comprehensive list of thesis, which are completed or under preparation in the corresponding working group. Additional chapters give lists of educational work, verbal presentation, cooperations with other institutions and personnel. An annex of photos gives an additional impression of the institute. (A.N.)

  7. Progress in nanophotonics 2

    CERN Document Server

    2013-01-01

    This book focuses the recent progress in nanophotonics technology to be used to develop novel nano-optical devices, fabrication technology, and advanced systems. It begins with a review of near-field excitation dynamics in molecules. Further topics include: wavelength up-converting a phonon-assisted excitation process with degenerate beams and non-degenerate beams in dye grains, a fabrication method of semiconductor quantum dots including self-assembly of InAs quantum dots based on the Stranski-Krastanov growth mode, single-nanotube spectroscopy and time-resolved spectroscopy for studying novel excitonic properties of single-walled carbon nanotubes. The striking features of ecxitons in the carbon nanotube, multiple-exciton states, and microfluidic and extended-nano fluidic techniques. These topics are reviewed by nine leading scientists. This overview is a variable resource for engineers and scientists working in the field of nanophotonics.

  8. Suppression of glioma progression by Egln3.

    Directory of Open Access Journals (Sweden)

    Vicki A Sciorra

    Full Text Available Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3, a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

  9. 29 CFR 1604.3 - Separate lines of progression and seniority systems.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Separate lines of progression and seniority systems. 1604.3 Section 1604.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems....

  10. Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

    NARCIS (Netherlands)

    B. Saltman; B. Singh; C.V. Hedvat; V.B. Wreesmann; R. Ghossein

    2006-01-01

    Background. Genetic screening studies suggest that genetic changes underlie progression from well differentiated, to anoplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. Methods. Tissue microarrarys (TMAs)

  11. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin;

    2010-01-01

    more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...... score. We applied the proposed algorithm on 27 patients with severe emphysema with CT scans acquired five time points, at baseline, after 3, after 12, after 21 and after 24 or 30 months. The results showed consistent emphysema progression with time and the overall progression score correlates...

  12. Project Progress Monitoring and Reporting

    OpenAIRE

    Heikkinen, Elina

    2016-01-01

    Progress monitoring and reporting is a useful tool to project management and control for tracking project performance, producing forecasts and supporting to plan corrective actions during project execution. Additionally progress report is an effective tool for communicating with different project stakeholders. Comprehensive progress monitoring practice is difficult to observe since practices are usually industry and task specific. However literature expresses different methods that are suitab...

  13. Thematic Progression and Textual Coherence in Speech

    Institute of Scientific and Technical Information of China (English)

    周云鹤

    2014-01-01

    Thematic progression can affect the flow of information and directly affect the discourse coherence. This paper analyzes thematic progression patterns of a speech about“people and nature” in the “CCTV Cup”English Speaking Contest and finds that there are three progression patterns in this text, which are parallel progression, continuous progression, and crossing progression.

  14. CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression

    OpenAIRE

    Park, Su Hyung; Yu, Seung Eun; Chai, Young Gyu; Jang, Yeun Kyu

    2014-01-01

    Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained d...

  15. Using Learning Progressions to Monitor Progress across Grades

    Science.gov (United States)

    Hess, Karin K.

    2010-01-01

    Learning progressions (LPs)--descriptive continuums of how students develop and demonstrate more sophisticated understanding over time--have become an increasingly important tool in today's science classrooms. Here the author discusses some of the research behind learning progressions and presents The Science Inquiry Profile for PreK-4. This is a…

  16. Dynamically prioritized progressive transmission

    Science.gov (United States)

    Blanford, Ronald

    1992-04-01

    Retrieval of image data from a centralized database may be subject to bandwidth limitations, whether due to a low-bandwidth communications link or to contention from simultaneous accesses over a high-bandwidth link. Progressive transmission can alleviate this problem by encoding image data so that any prefix of the data stream approximates the complete image at a coarse level of resolution. The longer the prefix, the finer the resolution. In many cases, as little at 1 percent of the image data may be sufficient to decide whether to discard the image, to permit the retrieval to continue, or to restrict retrieval to a subsection of the image. Our approach treats resolution not as a fixed attribute of the image, but rather as a resource which may be allocated to portions of the image at the direction of a user-specified priority function. The default priority function minimizes error by allocating more resolution to regions of high variance. The user may also point to regions of interest requesting priority transmission. More advanced target recognition strategies may be incorporated at the user's discretion. Multispectral imagery is supported. The user engineering implications are profounded. There is immediate response to a query that might otherwise take minutes to complete. The data is transmitted in small increments so that no single user dominates the communications bandwidth. The user-directed improvement means that bandwidth is focused on interesting information. The user may continue working with the first coarse approximations while further image data is still arriving. The algorithm has been implemented in C on Sun, Silicon Graphics, and NeXT workstations, and in Lisp on a Symbolics. Transmission speeds reach as high as 60,000 baud using a Sparc or 68040 processor when storing data to memory; somewhat less if also updating a graphical display. The memory requirements are roughly five bytes per image pixel. Both computational and memory costs may be reduced

  17. Progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Baussan Christiane

    2009-01-01

    Full Text Available Abstract Progressive familial intrahepatic cholestasis (PFIC refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP. Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3, impair biliary phospholipid secretion resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation

  18. Resistance to technological progress

    International Nuclear Information System (INIS)

    This article deals with the tolerance test the constitutional system (Basic Law) of the Federal Republic of Germany is currently put to as a consequence of the resistance to the power structure of this country, which is expressed in the name of protection and defense for the environment and world peace. This biopacifistic resistance movment, the author says, has nothing to do with the legal right to resist, as laid down in art. 20 (4) of the Basic Law. According to the author, this attitude is an offspring of fear of the hazards of technological progress, primarily of nuclear hazards. Practical resistance, the author states, is preceded by theoretical resistance in speech: De-legitimation of the democratic legality, of the parliamentary functions, of the supreme power of the government, and denial of the citizens duty of obedience. The author raises the question as to whether this attitude of disobedience on ecological grounds marks the onset of a fourth stage of development of the modern state, after we have passed through stages characterised by fear of civil war, of tyranny, and of social privation and suffering. There are no new ideas brought forward by the ecologically minded movement, the author says, for re-shaping our institutions or constitutional system. (HP)

  19. PVUSA progress report, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Ellyn, W. [ed.] [Nesbit (William) and Associates, Santa Rosa, CA (United States); Jennings, C. [ed.] [Pacific Gas and Electric Co., San Ramon, CA (United States)

    1991-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. PVUSA participants include Pacific Gas & Electric (PG&E), the US Department of Energy (DOE), the Electric Power Research Institute (EPRI), the California Energy Commission (CEC), and eight utilities and other agencies. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1991, and summarizes key findings and conclusions from work to date. PVUSA offers utilities hands-on experience needed to evaluate and utilize maturing PV technology. The project also provides manufacturers a test bed for their products, encourages technology improvement and cost reductions in PV modules and other system components, and establishes communication channels between utilities and the PV industry. The project consists of two types of demonstrations: Emerging Module Technology (EMT) arrays, which are unproven but promising state-of-the-art PV technologies in 20-kW (nominal) arrays; and Utility Scale (US) systems, which represent more mature PV technologies in 200- to 500-kW turnkey systems.

  20. Quarterly Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    David Gray; Glen Tomlinson

    1998-11-12

    The Federal Energy Technology Center (FETC) at Pittsburgh contracted with the MJTRE Corporation to perform Research Guidance Studies that will assist the Center and other relevant offices in the Department of Energy in evaluating and prioritizing research in the areas of coal and natural gas conversion. MITRE was reorganized in December 1995, which resulted in the formation of Mitretek Systems Inc. Mitretek has been performing this work on MITRE's behalf awaiting completion of contract novation to Mitretek. The contract was novated in February 1998 to Mitretek Systems. The overall objectives of this contract are to provide support to DOE in the following areas: (1) technical and economic analyses of current and future coal-based energy conversion technologies and other similar emerging technologies such as coal-waste coprocessing, natural gas conversion, and biomass conversion technologies for the production of fuels, chemicals and electric power,(2) monitor progress in these technologies with respect to technical, economic, and environmental impact (including climate change), (3) conduct specific and generic project economic and technical feasibility studies based on these technologies, (4) identify long-range R&D areas that have the greatest potential for process improvements, and (5) investigate optimum configurations and associated costs for production of high quality energy products via refining and their performance in end-use applications.

  1. Technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-10-01

    This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation.

  2. Technical progress report

    International Nuclear Information System (INIS)

    This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation

  3. 1993 PVUSA progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generation systems and recent developments in module technology. This report updates the progress of the PVUSA project, review the status and performance of all PV installations during 1993, and summarizes key accomplishments and conclusions for the year. The PVUSA project has five objectives designed to narrow the gap between a large utility industry that is unfamiliar with PV, and a small PV industry that is aware of a potentially large utility market but unfamiliar with how to meet its requirements. The objectives are: to evaluate the performance, reliability, and cost of promising PV modules and balance-of-system (BOS) components side-by-side at a single location; to assess PV system operation and maintenance (O and M) in a utility setting; to compare PV technologies in diverse geographic areas; to provide US utilities with hands-on experience in designing, procuring, and operating PV systems; and to document and disseminate knowledge gained from the project.

  4. Progress of AMOLED technology

    Science.gov (United States)

    Park, Joon Young

    2005-01-01

    We report the technical progress of AMOLED at Samsung SDI, comparing with other technologies. We introduce the voltage-compensational TFT circuit structure to improve the brightness uniformity of AMOLED, which is based on the low temperature poly-silicon. We have developed not only small molecule emitters (phosphorescence and fluorescence) but also polymeric emitters. From red and green phosphors, we achieved longer lifetime and higher efficiency than fluorophors. With the shadow mask patterning and the bottom-emission structure, 20,000-hour lifetime of QCIF device and the power consumption less than 150 mW at 100 cd/m2 (30% on condition) were obtained. In the case of the top-emission structure, we could get high efficiency also by maximizing the light out-coupling efficiency and enhance the color purity to the level of the NTSC. We have developed another patterning technology, "LITI: Laser Induced Thermal Imaging" and fabricated 17-inch full color AMOLED, which is the largest AMOLED based on the low temperature poly-Silicon.

  5. Annual progress report 1980

    International Nuclear Information System (INIS)

    Through the years, the research and development efforts of PAEC have been geared to promoting the peaceful utilization of atomic energy and ensuring public health and safety in the use of atomic energy facilities. Comprehensively discussed are the research projects, activities, supportive services and other areas of accomplishments of PAEC. These are generally divided into categories under I. Research and Development: (a) Food, Agriculture (b) Nuclear Fuels and Power Systems Technology (c) Public Health and Nutrition Research (d) Supportive basic research and (e) Environmental Surveillance; II. Nuclear Safety: (a) Radiological Protection and safety (b) Nuclear Licensing and Safeguards; III. Supportive Technology such as: (a) Radioisotope Production and Development (b) Nuclear Manpower Development (c) Nuclear Information and Public acceptance (d) Program Management (e) Nuclear Regulation. A listing of projects and annotations are included under each category. (RTD)

  6. [Progress in glucaric acid].

    Science.gov (United States)

    Qiu, Yuying; Fang, Fang; Du, Guocheng; Chen, Jian

    2015-04-01

    Glucaric acid (GA) is derived from glucose and commonly used in chemical industry. It is also considered as one of the "Top value-added chemicals from biomass" as carbohydrate monomers to produce various synthetic polymers and bioenergy. The demand for GA in food manufacture is increasing. GA has also attracted public attentions due to its therapeutic uses such as regulating hormones, increasing the immune function and reducing the risks of cancers. Currently GA is produced by chemical oxidation. Research on production of GA via microbial synthesis is still at preliminary stage. We reviewed the advances of glucaric acid applications, preparation and quantification methods. The prospects on production of GA by microbial fermentation were also discussed. PMID:26380405

  7. Periodic progress report, 6 months

    DEFF Research Database (Denmark)

    Juhl, Thomas Winther; Nielsen, Jakob Skov

    This is the first progress report of the BriteEuram project named "High Power Laser Cutting for Heavy Industry" ("Powercut"). The report contains a summary of the objectives of the first period, an overview of the technical progress, a comparison between the planed and the accomplished work...

  8. Construction Progress of CYCIAE-100

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Significant progress has been achieved in 2011 with respect to CYCIAE-100, a key task for the BRIF project. All the work has been fully accomplished in line with the schedule and goals set for the year. 1 General progress for CYCIAE-100

  9. Liver proteomics in progressive alcoholic steatosis

    International Nuclear Information System (INIS)

    Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3

  10. Liver proteomics in progressive alcoholic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Harshica [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Wiktorowicz, John E.; Soman, Kizhake V. [Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Kaphalia, Bhupendra S.; Khan, M. Firoze [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Shakeel Ansari, G.A., E-mail: sansari@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-02-01

    Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3

  11. Scientific Progress in Strategic Management

    DEFF Research Database (Denmark)

    Foss, Nicolai

    Does the RBV represent a case of scientific progress? And has it emerged as the dominant approach to the analysis of competitive advantage for this reason? Conventional criteria for scientific progress, notably those of the growth of knowledge literature, are not particularly helpful...... for understanding this. Instead, it is argued that in order to understand why the RBV is an instance of scientific progress, we should begin from the notion that reduction is at the heart of progress in science, and that many scientists implicitly or explicitly hold this view. The RBV is a case of scientific...... progress because it identified theoretical mechanisms at levels lower than those that were usually investigated in strategy research prior to the RBV. Unfortunately, the micro-emphasis of the RBV gave way during the 1990s to more aggregative modes of theorizing (i.e., the capabilities approach). Thus...

  12. Targeting clotting proteins in cancer therapy - progress and challenges.

    Science.gov (United States)

    Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine

    2016-04-01

    Cancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients. PMID:27067961

  13. Alternation of Macrophage Cytokines in the Progress of Mice Depression and the Regulation of Acupuncture%慢性抑郁症小鼠巨噬细胞相关因子的变化及针刺调节作用

    Institute of Scientific and Technical Information of China (English)

    洪敏; 胡燕; 郑劼; 丁兆云; 牛艳; 邵建华; 王玲玲

    2013-01-01

    OBJECTIVE To study the changes of macrophage-related cytokines in the development of depression, and to explore the immunological mechanism of acupuncture on treating depression. METHODS Chronic unpredictable mild stress (CUMS) was employed to induce depression in mice and open-field test and sucrose preference test were operated during the progress of depression. Simultaneously, the peritoneal macrophages were isolated from mice and were cultured under the stimulation with LPS, ELISA method were used to measure the contents of TNF-α, IL-1β and IL-6 in the supernatant of peritoneal macrophages. Depression mice were given treatment of acupuncture, and the effect of behavior change was observed and the content of macrophage cytokine production was measured respectively. RESULTS 21 days after making model, the model of chronic unpredictable mild depression was generally developing, the secretion ability of IL-lβ and IL-6 in the middle or late stage increased significantly, while the ability of TNF-α did increase but not that obvious. After treatment of acupuncture, behavior indicator was improved and meanwhile the ability of secreting TNF-α, IL-lβ, IL-6 decreased significantly. CONCLUSION The ability of modeling mice secreting inflammatory cytokines by peritoneal macrophages increased in the formation of CUMS depression, which acupuncture can significantly regulate might be one of the mechanisms in improving behavior change.%目的 探讨巨噬细胞相关细胞因子在小鼠抑郁症发生发展过程中的变化,并研究针刺治疗抑郁症的免疫学机制.方法 采用慢性不可预见性中等强度应激(CUMS)造成小鼠抑郁症模型,以开场试验、糖水偏好试验作为行为学评价指标;同时在造模过程中不同时间点,取小鼠腹腔巨噬细胞,培养并以LPS刺激,用ELISA法测定上清液中TNF-α、IL-1β、IL-6的含量;从造模成功开始对模型小鼠进行针刺治疗,观察治疗不同时间后模型小鼠行为

  14. Mechanistic insights into aging, cell cycle progression, and stress response

    Directory of Open Access Journals (Sweden)

    Troy Anthony Alan Harkness

    2012-06-01

    Full Text Available The longevity of an organism depends on the health of its cells. Throughout life cells are exposed to numerous intrinsic and extrinsic stresses, such as free radicals, generated through mitochondrial electron transport, and ultraviolet irradiation. The cell has evolved numerous mechanisms to scavenge free radicals and repair damage induced by these insults. One mechanism employed by the yeast Saccharomyces cerevisiae to combat stress utilizes the Anaphase Promoting Complex (APC, an essential multi-subunit ubiquitin-protein ligase structurally and functionally conserved from yeast to humans that controls progression through mitosis and G1. We have observed that yeast cells expressing compromised APC subunits are sensitive to multiple stresses and have shorter replicative and chronological lifespans. In a pathway that runs parallel to that regulated by the APC, members of the Forkhead box (Fox transcription factor family also regulate stress responses. The yeast Fox orthologues Fkh1 and Fkh2 appear to drive the transcription of stress response factors and slow early G1 progression, while the APC seems to regulate chromatin structure, chromosome segregation, and resetting of the transcriptome in early G1. In contrast, under non-stress conditions, the Fkhs play a complex role in cell cycle progression, partially through activation of the APC. Direct and indirect interactions between the APC and the yeast Fkhs appear to be pivotal for lifespan determination. Here we explore the potential for these interactions to be evolutionarily conserved as a mechanism to balance cell cycle regulation with stress responses.

  15. 1997 Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Cecchini, M.; Crescentini, L.; Ghezzi, L. [ENEA, Centro Ricerche Frascati, Rome (Italy). Nuclear fusion division

    1997-12-31

    1997 was another year of intense activity for the ENEA Nuclear Fusion Division in the evolving scenario of fusion research. With respect to the International Thermonuclear Experimental Reactor (ITER), a major review process has started, originate by the wide perception that the difficult financial situation affecting some of the parties would make it very difficult, practically impossible, to secure funding for the project as it stands. To scale down the size and cost of the machine by reducing the technical objectives, while keeping to the programmatic goal of constructing a demonstration reactor (DEMO) as the following step, appears achievable. Progress in physics was substantial during 1997. Analysis of the huge existing database, complemented by the latest results, had led to a better, more accurate scaling for the confinement time on which to base extrapolation to ITER. Studies of the very promising advanced regimes have been pursued on many tokamaks. The Frascati Tokamak Upgrade (FTU) is well placed in this respect since it is equipped with the right tools, lower hybrid and electron cyclotron radiofrequency heating and current drive systems, to explore the new promised land of low transport from the plasma core. The main highlights of FTU operation in 1997 were related to providing information relevant to these future developments. Transient production of low transport regimes with electron temperatures of 8-9 keV at the plasma center was obtained by taking advantage of the plasma skin effect and precise electron cyclotron power deposition. High-efficiency current drive at high density using lower hybrid waves was demonstrated. High-confinement pellet-enhanced modes of operation and good ion Bernstein wave coupling through the waveguide-type coupler were also achieved. Concerning the IGNITOR experiment, funds were made available only for continuation of the engineering design activities, and nothing has been released so far for manufacturing the additional

  16. HYLIFE-2 progress report

    Energy Technology Data Exchange (ETDEWEB)

    Moir, R.W.; Adamson, M.G.; Bangerter, R.O.; Bieri, R.L.; Condit, R.H.; Hartman, C.W.; House, P.A.; Langdon, A.B.; Logan, B.G.; Orth, C.D.; Petzoldt, R.W.; Pitts, J.H.; Post, R.F.; Sacks, R.A.; Tobin, M.T.; Williams, W.H. (Lawrence Livermore National Lab., CA (United States)); Dolan, T.J.; Longhurst, G.R. (EG and G Idaho, Inc., Idaho Falls, ID (United States)); Hoffman, M.A. (California Univ., Davis, CA (United S

    1991-12-01

    LIFE-II inertial confinement fusion power plant design study uses a liquid fall, in the form of jets to protect the first structural wall from neutron damage, x rays, and blast to provide a 30-y lifetime. This is a progress report of an incomplete and ongoing study. HYLIFE-I used liquid lithium. HYLIFE-11 avoids the fire hazard of lithium by using a molten salt composed of fluorine, lithium, and beryllium (Li{sub 2}Be{sub 4}) called Flibe. Access for heavy-ion beams is provided. Calculations for assumed heavy-ion beam performance show a nominal gain of 70 at 5 MJ producing 350 MJ, about 5.2 times less yield than the 1.8 GJ from a driver energy of 4.5 MJ with gain of 400 for HYLIFE-I. The nominal 1 GWe of power can be maintained by increasing the repetition rate by a factor of about 5.2, from 1.5 to 8 Hz. A higher repetition rate requires faster re-establishment of the jets after a shot, which can be accomplished in part by decreasing the jet fall height and increasing the jet flow velocity. Multiple chambers may be required.In addition, although not considered for HYLIFE-I there is undoubtedly liquid splash that must be forcibly cleared because gravity is too slow, especially at high repetition rates. Splash removal can be accomplished by either pulsed or oscillating jet flows. The cost of electricity is estimated to be 0.10 $/kW{center dot} in constant 1990 dollars, about twice that of future coal and light water reactor nuclear power. The driver beam cost is about one-half the total cost.

  17. HYLIFE-2 progress report

    Energy Technology Data Exchange (ETDEWEB)

    Moir, R.W.; Adamson, M.G.; Bangerter, R.O.; Bieri, R.L.; Condit, R.H.; Hartman, C.W.; House, P.A.; Langdon, A.B.; Logan, B.G.; Orth, C.D.; Petzoldt, R.W.; Pitts, J.H.; Post, R.F.; Sacks, R.A.; Tobin, M.T.; Williams, W.H. [Lawrence Livermore National Lab., CA (United States); Dolan, T.J.; Longhurst, G.R. [EG and G Idaho, Inc., Idaho Falls, ID (United States); Hoffman, M.A. [California Univ., Davis, CA (United States). Dept. of Mechanical Engineering; Schrock, V.E.; Peterson, P.E.; Bai, R.Y.; Chen, X.M.; Liu, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nuclear Engineering; Sze, D.K. [Argonne National Lab., IL (United States); Meier, W.R. [Schafer (W.J.) Associates, Inc., Pleasanton, CA (United States)

    1991-12-01

    LIFE-II inertial confinement fusion power plant design study uses a liquid fall, in the form of jets to protect the first structural wall from neutron damage, x rays, and blast to provide a 30-y lifetime. This is a progress report of an incomplete and ongoing study. HYLIFE-I used liquid lithium. HYLIFE-11 avoids the fire hazard of lithium by using a molten salt composed of fluorine, lithium, and beryllium (Li{sub 2}Be{sub 4}) called Flibe. Access for heavy-ion beams is provided. Calculations for assumed heavy-ion beam performance show a nominal gain of 70 at 5 MJ producing 350 MJ, about 5.2 times less yield than the 1.8 GJ from a driver energy of 4.5 MJ with gain of 400 for HYLIFE-I. The nominal 1 GWe of power can be maintained by increasing the repetition rate by a factor of about 5.2, from 1.5 to 8 Hz. A higher repetition rate requires faster re-establishment of the jets after a shot, which can be accomplished in part by decreasing the jet fall height and increasing the jet flow velocity. Multiple chambers may be required.In addition, although not considered for HYLIFE-I there is undoubtedly liquid splash that must be forcibly cleared because gravity is too slow, especially at high repetition rates. Splash removal can be accomplished by either pulsed or oscillating jet flows. The cost of electricity is estimated to be 0.10 $/kW{center_dot} in constant 1990 dollars, about twice that of future coal and light water reactor nuclear power. The driver beam cost is about one-half the total cost.

  18. 1997 Progress report

    International Nuclear Information System (INIS)

    1997 was another year of intense activity for the ENEA Nuclear Fusion Division in the evolving scenario of fusion research. With respect to the International Thermonuclear Experimental Reactor (ITER), a major review process has started, originate by the wide perception that the difficult financial situation affecting some of the parties would make it very difficult, practically impossible, to secure funding for the project as it stands. To scale down the size and cost of the machine by reducing the technical objectives, while keeping to the programmatic goal of constructing a demonstration reactor (DEMO) as the following step, appears achievable. Progress in physics was substantial during 1997. Analysis of the huge existing database, complemented by the latest results, had led to a better, more accurate scaling for the confinement time on which to base extrapolation to ITER. Studies of the very promising advanced regimes have been pursued on many tokamaks. The Frascati Tokamak Upgrade (FTU) is well placed in this respect since it is equipped with the right tools, lower hybrid and electron cyclotron radiofrequency heating and current drive systems, to explore the new promised land of low transport from the plasma core. The main highlights of FTU operation in 1997 were related to providing information relevant to these future developments. Transient production of low transport regimes with electron temperatures of 8-9 keV at the plasma center was obtained by taking advantage of the plasma skin effect and precise electron cyclotron power deposition. High-efficiency current drive at high density using lower hybrid waves was demonstrated. High-confinement pellet-enhanced modes of operation and good ion Bernstein wave coupling through the waveguide-type coupler were also achieved. Concerning the IGNITOR experiment, funds were made available only for continuation of the engineering design activities, and nothing has been released so far for manufacturing the additional

  19. HYLIFE-2 progress report

    International Nuclear Information System (INIS)

    LIFE-II inertial confinement fusion power plant design study uses a liquid fall, in the form of jets to protect the first structural wall from neutron damage, x rays, and blast to provide a 30-y lifetime. This is a progress report of an incomplete and ongoing study. HYLIFE-I used liquid lithium. HYLIFE-11 avoids the fire hazard of lithium by using a molten salt composed of fluorine, lithium, and beryllium (Li2Be4) called Flibe. Access for heavy-ion beams is provided. Calculations for assumed heavy-ion beam performance show a nominal gain of 70 at 5 MJ producing 350 MJ, about 5.2 times less yield than the 1.8 GJ from a driver energy of 4.5 MJ with gain of 400 for HYLIFE-I. The nominal 1 GWe of power can be maintained by increasing the repetition rate by a factor of about 5.2, from 1.5 to 8 Hz. A higher repetition rate requires faster re-establishment of the jets after a shot, which can be accomplished in part by decreasing the jet fall height and increasing the jet flow velocity. Multiple chambers may be required.In addition, although not considered for HYLIFE-I there is undoubtedly liquid splash that must be forcibly cleared because gravity is too slow, especially at high repetition rates. Splash removal can be accomplished by either pulsed or oscillating jet flows. The cost of electricity is estimated to be 0.10 $/kW· in constant 1990 dollars, about twice that of future coal and light water reactor nuclear power. The driver beam cost is about one-half the total cost

  20. 2004 Progress Report

    International Nuclear Information System (INIS)

    Fusion research is undertaken all over the world with the objective of realising an environmentally responsible source of energy with essentially unlimited and widely distributed fuel reserves. The results of the worldwide efforts made in recent years are now embodied in ITER, the International Thermonuclear Experimental Reactor, designed to produce at least 500 MW of fusion power with a power gain of ten. ITER will test for the first time the interaction of fusion plasma physics with power station technology. In this international framework, during 2004 Fusion Technical and Scientific Unit of ENEA obtained important results in several keys areas. At the Frascati Tokamak Upgrade the lower hybrid microwave system was fully exploited to study the generation and control of the plasma current, and the electron cyclotron heating system reached full power (1.5 MW). With the simultaneous injection of the two waves, good energy confinement regimes with internal transport barriers were obtained at the highest plasma densities ever achieved. Advanced scenario regimes were also addressed in the activities of ENEA at JET. The engineering design of the IGNITOR machine was finalised, and significant progress was made in understanding the plasma physics regimes. Among the technology activities, the qualification of the deposition process of a copper liner on carbon fibre composite (CFC) hollow tiles may be mentioned as the most important achievement. This innovative pre brazed casting process is a competitive candidate for the fabrication of the CFCbased ITER divertor components. ENEA participated in the European activity for the definition and production on an industrial scale of an advanced Nb3Sn strand for the ITER superconducting central solenoid and toroidal field coils. Contributions were also made to the design of the final conductor layout and the characterisation tests. Inertial fusion studies continued along the previous lines, namely, the study of the implosion

  1. 2004 Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Batistoni, Paola; De Marco, Francesco; Pieroni, Leonardo (ed.)

    2005-07-01

    Fusion research is undertaken all over the world with the objective of realising an environmentally responsible source of energy with essentially unlimited and widely distributed fuel reserves. The results of the worldwide efforts made in recent years are now embodied in ITER, the International Thermonuclear Experimental Reactor, designed to produce at least 500 MW of fusion power with a power gain of ten. ITER will test for the first time the interaction of fusion plasma physics with power station technology. In this international framework, during 2004 Fusion Technical and Scientific Unit of ENEA obtained important results in several keys areas. At the Frascati Tokamak Upgrade the lower hybrid microwave system was fully exploited to study the generation and control of the plasma current, and the electron cyclotron heating system reached full power (1.5 MW). With the simultaneous injection of the two waves, good energy confinement regimes with internal transport barriers were obtained at the highest plasma densities ever achieved. Advanced scenario regimes were also addressed in the activities of ENEA at JET. The engineering design of the IGNITOR machine was finalised, and significant progress was made in understanding the plasma physics regimes. Among the technology activities, the qualification of the deposition process of a copper liner on carbon fibre composite (CFC) hollow tiles may be mentioned as the most important achievement. This innovative pre brazed casting process is a competitive candidate for the fabrication of the CFCbased ITER divertor components. ENEA participated in the European activity for the definition and production on an industrial scale of an advanced Nb3Sn strand for the ITER superconducting central solenoid and toroidal field coils. Contributions were also made to the design of the final conductor layout and the characterisation tests. Inertial fusion studies continued along the previous lines, namely, the study of the implosion

  2. Effect of PKC pathway on G1/S progression control in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The effect of PKC activity on G1/S progression in HeLa cells has been studied.The result shows that (ⅰ) PKC activity alteration in G1 phase affects G1/S progression in HeLa cells.It has been observed that G1/S progression is stimulated by PKC agonist TPA and inhibited by PKC inhibitor GF-109203X.(ⅱ) The expression of c-myc and c-jun is stimulated by TPA and inhibited by GF-109203X treatment in early G1 phase.(ⅲ) During G1/S progression,the expression of CyclinD1 is stimulated by TPA treatment and inhibited by GF-109203X treatment.There is no effect on the expression of CDK4.It is likely that PKC pathway regulates G1/S progression through regulating the expression of some early response genes and engine molecules in HeLa cells.

  3. Progress of biodegradable metals

    Institute of Scientific and Technical Information of China (English)

    Huafang Li; Yufeng Zheng; Ling Qin

    2014-01-01

    Biodegradable metals (BMs) are metals and alloys expected to corrode gradually in vivo, with an appropriate host response elicited by released corrosion products, then dissolve completely upon fulfilling the mission to assist with tissue healing with no implant residues. In the present review article, three classes of BMs have been systematically reviewed, including Mg-based, Fe-based and Zn-based BMs. Among the three BM systems, Mg-based BMs, which now have several systems reported the successful of clinical trial results, are considered the vanguards and main force. Fe-based BMs, with pure iron and Fe–Mn based alloys as the most promising, are still on the animal test stage. Zn-based BMs, supposed to have the degradation rate between the fast Mg-based BMs and the slow Fe-based BMs, are a rising star with only several reports and need much further research. The future research and development direction for the BMs are proposed, based on the clinical requirements on controllable degradation rate, prolonged mechanical stability and excellent biocompat-ibility, by optimization of alloy composition design, regulation on microstructure and mechanical properties, and following surface modification.

  4. Progress of biodegradable metals

    Directory of Open Access Journals (Sweden)

    Huafang Li

    2014-10-01

    Full Text Available Biodegradable metals (BMs are metals and alloys expected to corrode gradually in vivo, with an appropriate host response elicited by released corrosion products, then dissolve completely upon fulfilling the mission to assist with tissue healing with no implant residues. In the present review article, three classes of BMs have been systematically reviewed, including Mg-based, Fe-based and Zn-based BMs. Among the three BM systems, Mg-based BMs, which now have several systems reported the successful of clinical trial results, are considered the vanguards and main force. Fe-based BMs, with pure iron and Fe–Mn based alloys as the most promising, are still on the animal test stage. Zn-based BMs, supposed to have the degradation rate between the fast Mg-based BMs and the slow Fe-based BMs, are a rising star with only several reports and need much further research. The future research and development direction for the BMs are proposed, based on the clinical requirements on controllable degradation rate, prolonged mechanical stability and excellent biocompatibility, by optimization of alloy composition design, regulation on microstructure and mechanical properties, and following surface modification.

  5. Progress report. P6

    International Nuclear Information System (INIS)

    In CJD the current work continued concerning EXFOR compilation and fulfillment of NRDC-2000 Recommendations and Actions. Much efforts were applied for restoring CJD Web page. Evaluation works were also in process. Compilation into EXFOR continues on steadily. Since March 2000 up to April 2001 four TRANS tapes containing 69 Entries were prepared and sent to other centers. 25 new EXFOR Entries were compiled. An analysis and an evaluation are made for the threshold reactions cross sections leading to production of the long-lived radioactive nuclides on the irradiation of steel by thermonuclear neutron spectrum. Fifty excitation functions were evaluated. Many of them are considerably different from available evaluations of other libraries. During two years, together with JAERI, comparative analysis was performed of (n,2n) and (n,3n) reactions for 150 fission products from available evaluated data libraries. The result of analysis will be published this year. The joint work on consistent evaluation of some (n,2n) and (n,np) excitation functions for even-even isotopes was made on the basis of empirical systematics. The work was completed on evaluation of the spectra and production cross sections of gamma-rays in inelastic interactions of 14-Mev neutrons with the number of nuclei: Li-6, Li-7, Al, Ti, Cr, Fe, Cu, Pb, Bi, U-235. CJD continues the work on evaluation of neutron data for minor actinides. This year Am-242m will be evaluated, and Np-237, Am-241, Am-243, Cm-243, Cm-244 will be tested and improved. Full file of Bi was prepared. Full files for Pb isotopes are in process of preparation. There exist a plan to analyze full files for isotopes of Cr, Fe, Ni from existing evaluated data libraries, to select more reliable cross sections, and to create improved files for these isotopes. Together with the Theoretical Department the work is in progress on the determination of uncertainties of existing evaluated data and development of covariance matrices for some important

  6. Progress in ITER Construction

    International Nuclear Information System (INIS)

    Full text: Since the entry into force of the ITER Agreement in October 2007, the ITER Organization and the Domestic Agencies have made significant progress in the finalization of the ITER design and the establishment of the baseline. This paper will describe the main advances and achievements since the last IAEA conference. The Integrated Project Schedule has gone through a number of iterations following interactions with Domestic Agencies and their industries. With operating a First Plasma at the end of 2019 construction will be finished and the functionality of all major components will be demonstrated. Through a series of operation and installation campaigns in the following seven years full DT operation should be reached by 2026. The associated resource estimate for the cost of the ITER Organization has been reviewed by an independent panel and has been developed using common project management practices. Attention has been paid to the development of risk based assessments of the schedule giving confidence that this schedule can be achieved if no major unforeseen events happen. The ITER platform has been prepared by Agence ITER France and was finalized by the summer of 2009. The next stage will be the start of the excavation and construction of the anti-seismic support structure for the tokamak building. The road between the harbor of Marseille and the Cadarache site is ready to receive the first test convoys. Just under 90% of the components for ITER will provided in-kind by the Members through so-called Procurement Arrangements, which are bi-lateral agreements between the ITER Organization and the Domestic Agencies. Until now 34 Procurement Arrangements have been signed, representing almost half of the value of the total in-kind contributions. The first Procurement Arrangements concentrated on the long-lead items, such as the Magnet systems, Buildings and the Vacuum Vessel. Most of the Procurement Arrangements for these long-lead items have now been

  7. Der Progress Test Medizin [The Progress Test Medizin

    OpenAIRE

    Osterberg, Katrin; Kölbel, Sebastian; Brauns, Katrin

    2006-01-01

    [english] In 1999 a interdiciplinary, formative progress test for medical students has been established at the Charité - Universitätsmedizin Berlin. It contents of 200 MC-questions on a graduate level and is performed at the beginning of each semester since then. The ascertained test data is evaluated and reported back in a detailed written feedback to each participant. After initial problems in recruiting new item authors and an efficient administration of test items the progress test now is...

  8. Federal Facility Agreement progress report

    Energy Technology Data Exchange (ETDEWEB)

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  9. Federal Facility Agreement progress report

    International Nuclear Information System (INIS)

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas

  10. Progressive Care of Obese Patients.

    Science.gov (United States)

    Dambaugh, Lori A; Ecklund, Margaret M

    2016-08-01

    Obese patients have complex needs that complicate their care during hospitalization. These patients often have comorbid conditions, including hypertension, heart failure, obstructive sleep apnea, pressure ulcers, and difficulty with mobility. Obese patients may be well served in the progressive care setting because they may require more intensive nursing care than can be delivered in a general care unit. Progressive care nurses have core competencies that enable them to safely and effectively care for obese patients. A plan of care with interdisciplinary collaboration illustrates the integrative care for obese progressive care patients. (Critical Care Nurse 2016; 36[4]:58-63). PMID:27481802

  11. Cancer initiation and progression: an unsimplifiable complexity

    Directory of Open Access Journals (Sweden)

    Frezza Eldo E

    2006-10-01

    Full Text Available Abstract Background Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. Conclusion There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours.

  12. Phytoalexins: Current Progress and Future Prospects

    Directory of Open Access Journals (Sweden)

    Philippe Jeandet

    2015-02-01

    Full Text Available Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins started with progress in their biochemistry and bio-organic chemistry, resulting in the determination of their structure, their biological activity, as well as mechanisms of their synthesis and catabolism by microorganisms. Elucidation of the biosynthesis of numerous phytoalexins also permitted the use of molecular biology tools for the exploration of the genes encoding enzymes of their synthesis pathways and their regulators. This has led to potential applications for increasing plant resistance to diseases. Phytoalexins display an enormous diversity belonging to various chemical families such as for instance, phenolics, terpenoids, furanoacetylenes, steroid glycoalkaloids, sulfur-containing compounds and indoles.[...

  13. Does monitoring goal progress promote goal attainment? A meta-analysis of the experimental evidence.

    Science.gov (United States)

    Harkin, Benjamin; Webb, Thomas L; Chang, Betty P I; Prestwich, Andrew; Conner, Mark; Kellar, Ian; Benn, Yael; Sheeran, Paschal

    2016-02-01

    Control theory and other frameworks for understanding self-regulation suggest that monitoring goal progress is a crucial process that intervenes between setting and attaining a goal, and helps to ensure that goals are translated into action. However, the impact of progress monitoring interventions on rates of behavioral performance and goal attainment has yet to be quantified. A systematic literature search identified 138 studies (N = 19,951) that randomly allocated participants to an intervention designed to promote monitoring of goal progress versus a control condition. All studies reported the effects of the treatment on (a) the frequency of progress monitoring and (b) subsequent goal attainment. A random effects model revealed that, on average, interventions were successful at increasing the frequency of monitoring goal progress (d+ = 1.98, 95% CI [1.71, 2.24]) and promoted goal attainment (d+ = 0.40, 95% CI [0.32, 0.48]). Furthermore, changes in the frequency of progress monitoring mediated the effect of the interventions on goal attainment. Moderation tests revealed that progress monitoring had larger effects on goal attainment when the outcomes were reported or made public, and when the information was physically recorded. Taken together, the findings suggest that monitoring goal progress is an effective self-regulation strategy, and that interventions that increase the frequency of progress monitoring are likely to promote behavior change.

  14. Der Progress Test Medizin [The Progress Test Medizin

    Directory of Open Access Journals (Sweden)

    Osterberg, Katrin

    2006-08-01

    Full Text Available [english] In 1999 a interdiciplinary, formative progress test for medical students has been established at the Charité - Universitätsmedizin Berlin. It contents of 200 MC-questions on a graduate level and is performed at the beginning of each semester since then. The ascertained test data is evaluated and reported back in a detailed written feedback to each participant. After initial problems in recruiting new item authors and an efficient administration of test items the progress test now is a well established and accepted feedback instrument and the results of the last years confirmed that knowledge increase of different semesters and different curricula can be shown through a progress test. Since 2000 the workgroup “Progress Test Medizin” cooperates with the university in Witten /Herdecke, and since 2003 the progress test is also performed at four additional medical faculties. This minimizes the effort per participant and therefore allows further development and research. [german] Seit 1999 wird an der Charité - Universitätsmedizin Berlin ein fächerübergreifender, formativer Progress Test für Medizinstudierende durchgeführt. Er beinhaltet 200 MC-Fragen auf Absolventenniveau und wird zu Anfang jedes Semesters durchgeführt. Die erhobenen Daten werden detailliert in bezug auf die Vergleichsgruppe ausgewertet und als Rückmeldung an die Teilnehmer ausgegeben. Nach anfänglichen Schwierigkeiten vor allem bei der Gewinnung neuer Fragenautoren und der effizienten Verwaltung der Testfragen ist der Progress Test Medizin an der Charité mittlerweile ein etabliertes und anerkanntes Feedbackinstrument. Die Ergebnisse der letzten Jahre haben gezeigt, dass mit dem Progress Test der Wissenszuwachs über mehrere Semester und verschiedene Curricula dargestellt werden kann. Seit 2000 kooperiert die Arbeitsgruppe Progress Test Medizin mit der Universität Witten/Herdecke und seit Herbst 2003 wird der Progress Test an vier weiteren deutschen Fakult

  15. CBM progress report 2007

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, N.; Rami, F.; Roehrich, D.; Stroth, J.; Wessels, J.; Zaitsev, Yu

    2008-02-15

    This report documents the activities within the CBM project in 2007. Significant progress has been made in the optimization of the simulation software, the layout and development of detectors, the design of front-end electronics, and the concepts for data acquisition. The simulation and analysis routines have been completely integrated into the software framework (FAIRoot and CBMroot), and can be used now easily by users outside GSI. A breakthrough has been achieved in the development of fast algorithms for track and vertex reconstruction which have been improved in speed by a factor of 10{sup 5}. These fast routines permit to perform high-statistics simulations for detailed detector layout optimization. Full event reconstruction based on realistic detector properties and particle multiplicities as given by microscopic transport models are routinely used in the feasibility studies. A version of the Silicon Tracking System is now implemented in the simulation software comprising 8 detector layers based on microstrip technology only, including the readout cables, and the mechanical detector structure. The studies of open charm detection have been extended to D{sub s}{sup +} and {lambda}{sub c}, taking into account a realistic layout of the Silicon Pixel Microvertex detector. The identification of electrons has been optimized by improved ring recognition algorithms and transition radiation simulations. The Ring Imaging Cherenkov (RICH) detector has been redesigned, resulting in a reduction by a factor of two in mirror size and number of readout channels without reducing the pion rejection capability. The muon detection system has been optimized with respect to the number of detector layers. The muon simulations take into account detector inefficiencies and a segmentation of the muon chambers into pads according to a nominal occupancy of 5% for central Au+Au collisions. Studies for a dimuon trigger show promising results. Radiation dose simulations using the FLUKA

  16. [Domestic violence: any progress?].

    Science.gov (United States)

    Henrion, Roger

    2014-01-01

    Since the publication of the French national survey of violence against women in 2000, the fight against domestic violence has made steady progress. Knowledge of the phenomenon has significantly improved. A nationwide study of murders and manslaughters perpetrated by one partner of a couple against the other has been published annually since 2006. In 2012, domestic violence resulted in the deaths of 314 persons: 166 women, 31 men, 25 children, 9 collateral victims, 14 rivals, and two former spouses killed by their ex-fathers in law. In addition, 67 perpetrators committed suicide (51 men and3 women). The number of victims fluctuates from year to year but has remained fairly stable since 2006 (n=168). Legislation has improved significantly: eight new laws have been passed since 2004, all designed to protect women and to ensure that violent men are restrained and treated. New measures to inform and protect women have been implemented and others have been improved, such as the anonymous helpline (phone no 3919, "domestic violence information"). An inter-ministerial committee on the protection of women from violence and the prevention of human trafficking (MIPROF) was created on 3 January 2013. A website entitled "Stop violence against women " (Stop violences faites aux femmes) is now available. The "Imminent Danger" mobile phone system, designed to alert police if a suspected or known perpetrator breaches restraint conditions, will be extended to the entire country from January 2014. Referees charged with coordinating comprehensive long-tern care of women victims have been deployed at the county level. Information centers on the rights of women and families (CIDFF) now form a local nationwide network. Routine interviews with a midwife during the fourth month of pregnancy, focusing on the woman's emotional, economic and social conditions, have been implemented in 21 % of maternity units and should gradually be generalized. The authorities who have enforced the law have

  17. [Domestic violence: any progress?].

    Science.gov (United States)

    Henrion, Roger

    2014-01-01

    Since the publication of the French national survey of violence against women in 2000, the fight against domestic violence has made steady progress. Knowledge of the phenomenon has significantly improved. A nationwide study of murders and manslaughters perpetrated by one partner of a couple against the other has been published annually since 2006. In 2012, domestic violence resulted in the deaths of 314 persons: 166 women, 31 men, 25 children, 9 collateral victims, 14 rivals, and two former spouses killed by their ex-fathers in law. In addition, 67 perpetrators committed suicide (51 men and3 women). The number of victims fluctuates from year to year but has remained fairly stable since 2006 (n=168). Legislation has improved significantly: eight new laws have been passed since 2004, all designed to protect women and to ensure that violent men are restrained and treated. New measures to inform and protect women have been implemented and others have been improved, such as the anonymous helpline (phone no 3919, "domestic violence information"). An inter-ministerial committee on the protection of women from violence and the prevention of human trafficking (MIPROF) was created on 3 January 2013. A website entitled "Stop violence against women " (Stop violences faites aux femmes) is now available. The "Imminent Danger" mobile phone system, designed to alert police if a suspected or known perpetrator breaches restraint conditions, will be extended to the entire country from January 2014. Referees charged with coordinating comprehensive long-tern care of women victims have been deployed at the county level. Information centers on the rights of women and families (CIDFF) now form a local nationwide network. Routine interviews with a midwife during the fourth month of pregnancy, focusing on the woman's emotional, economic and social conditions, have been implemented in 21 % of maternity units and should gradually be generalized. The authorities who have enforced the law have

  18. Progresses in proton radioactivity studies

    Science.gov (United States)

    Ferreira, L. S.; Maglione, E.

    2016-07-01

    In the present talk, we will discuss recent progresses in the theoretical study of proton radioactivity and their impact on the present understanding of nuclear structure at the extremes of proton stability.

  19. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... inhibitor, can do an even better job of preventing breast cancer than the SERMs. Aromatase inhibitors stop an enzyme ...

  20. Targeting ECM Disrupts Cancer Progression

    DEFF Research Database (Denmark)

    Venning, Freja A; Wullkopf, Lena; Erler, Janine T

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the ex...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.......Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings......, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...

  1. Zolpidem in Progressive Supranuclear Palsy

    Directory of Open Access Journals (Sweden)

    Sandip K. Dash

    2013-01-01

    Full Text Available Progressive supranuclear palsy (PSP is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

  2. Regulation of ROCK Activity in Cancer

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-01-01

    , these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

  3. Epithelial to mesenchymal transition in the progression of tubulointerstitial fibrosis

    Institute of Scientific and Technical Information of China (English)

    LI Min-xia; LIU Bi-cheng

    2007-01-01

    Objective To review the mechanisms of epithelial to mesenchymal transition (EMT) and its role in the progression of tubulointerstitial fibrosis.Data sources The data used in this review were obtained mainly from the studies of EMT reported from 2000-2006.Study selection Relevant articles on studies of EMT in tubulointerstitial fibrosis were selected. Data were mainly extracted from the 45 articles listed in the reference section of this review.Results The process of EMT has gained wide recognition as candidate mechanism in progression of chronic fibrotic disorders. New markers were identified and facilitate the observation of EMT. EMT is regulated by many factors through activation of kinase-dependent signaling cascades. Recent findings suggest that EMT is a reversible process, which can be controlled by factors for their epithelial inducing activities.Conclusion Remarkable progresses of EMT research have been made recently. Preventing or reversing EMT is a promising strategy against renal fibrosis.

  4. Targeting the extracellular matrix to disrupt cancer progression

    Directory of Open Access Journals (Sweden)

    Freja Albjerg Venning

    2015-10-01

    Full Text Available Metastatic complications are responsible for more than 90% of cancer related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multi-step process, with each step involving intricate cross-talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM. Many ECM proteins are significantly de-regulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

  5. Annual Progress report - General Task

    Energy Technology Data Exchange (ETDEWEB)

    Wesnousky, S.G.

    1993-09-30

    This report provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).{close_quotes} A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing tasks.

  6. TTP: Tool for Tumor Progression

    OpenAIRE

    Reiter, Johannes G.; Bozic, Ivana; Chatterjee, Krishnendu; Nowak, Martin A.

    2013-01-01

    In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics an...

  7. Integrin Trafficking and Tumor Progression

    Directory of Open Access Journals (Sweden)

    Sejeong Shin

    2012-01-01

    Full Text Available Integrins are major mediators of cancer cell adhesion to extracellular matrix. Through this interaction, integrins play critical roles in cell migration, invasion, metastasis, and resistance to apoptosis during tumor progression. Recent studies highlight the importance of integrin trafficking, endocytosis and recycling, for the functions of integrins in cancer cells. Understanding the molecular mechanisms of integrin trafficking is pivotal for understanding tumor progression and for the development of anticancer drugs.

  8. Progress Examinations in Pharmacy Education

    OpenAIRE

    Plaza, Cecilia M.

    2007-01-01

    Interest in the use of the progress examination has grown in the current culture of accountability in higher education. The Accreditation Council for Pharmacy Education's (ACPE's) Standards 2007 calls for comprehensive, knowledge- and performance-based examinations as part of a school or college of pharmacy's evaluation and assessment of student learning. Progress examinations have been used primarily in medical education. The purpose of this paper is to provide a brief overview of the litera...

  9. Genetics Home Reference: Lafora progressive myoclonus epilepsy

    Science.gov (United States)

    ... Conditions Lafora progressive myoclonus epilepsy Lafora progressive myoclonus epilepsy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures ( ...

  10. Astrocytes conspire with neurons during progression of neurological disease

    OpenAIRE

    McGann, James C.; Lioy, Daniel T.; Mandel, Gail

    2012-01-01

    As astrocytes are becoming recognized as important mediators of normal brain function, studies into their roles in neurological disease have gained significance. Across mouse models for neurodevelopmental and neurodegenerative diseases, astrocytes are considered key regulators of disease progression. In Rett syndrome and Parkinson’s disease, astrocytes can even initiate certain disease phenotypes. Numerous potential mechanisms have been offered to explain these results, but research into the ...

  11. Defining secondary progressive multiple sclerosis.

    Science.gov (United States)

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  12. Alternative Regulation for North American Electric Utilities

    International Nuclear Information System (INIS)

    After a decade of favorable operating conditions, utilities find themselves faced with accelerating prices for key inputs and a growing need for new capacity. These pressures are likely to prompt increasingly frequent, and perhaps more contentious, rate cases. Steady progress in the development of alternative regulation provides hope that the utility industry will respond to these challenges much better than in 1975-85. (author)

  13. High Hopes on NewRegulators

    Institute of Scientific and Technical Information of China (English)

    LAN XINZHEN

    2011-01-01

    On October 29,China changed the top positions at its three financial regulatory bodies-the China Banking Regulatory Commission (CBRC),China Securities Regulatory Commission (CSRC) and China Insurance Regulatory Commission (CIRC).The mix up will help strengthen financial regulation.Industrial insiders say this indicates maintaining financial stability will become the focus of the Chinese financial industry,instead of the market-oriented and intemational progress in the past few years.

  14. Early Neoplastic Progression Is Complement Independent

    Directory of Open Access Journals (Sweden)

    Karin E. de Visser

    2004-11-01

    Full Text Available Infiltration of leukocytes into premalignant tissue is a common feature of many epithelial neoplasms and is thought to contribute to cancer development. However, the molecular and cellular regulatory mechanisms underlying activation of innate host responses to enhanced neoplastic cell proliferation are largely unknown. Considering the importance of the complement system in regulating inflammation during acute pathologic tissue remodeling, we examined the functional significance of complement component 3 (C3 as a regulator of inflammatory cell infiltration and activation during malignant progression by using a transgenic mouse model of multistage epithelial carcinogenesis, e.g., HPV16 mice. Whereas abundant deposition of C3 is a characteristic feature of premalignant hyperplasias and dysplasias coincident with leukocyte infiltration in neoplastic tissue, genetic elimination of C3 neither affects inflammatory cell recruitment toward neoplastic skin nor impacts responding pathways downstream of inflammatory cell activation, e.g., keratinocyte hyperproliferation or angiogenesis. Taken together, these data suggest that complementindependent pathways are critical for leukocyte recruitment into neoplastic tissue and leukocytemediated potentiation of tumorigenesis.

  15. Regulation of chromosomal replication in Caulobacter crescentus.

    Science.gov (United States)

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle.

  16. PII, the key regulator of nitrogen metabolism in the cyanobacteria

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; ZHAO JinDong

    2008-01-01

    PII proteins are a protein family important to signal transduction in bacteria and plants. PII plays a critical role in regulation of carbon and nitrogen metabolism in cyanobacteria. Through conformation change and covalent modification, which are regulated by 2-oxoglutarate, PII interacts with different target proteins in response to changes of cellular energy status and carbon and nitrogen sources in cyanobacteria and regulates cellular metabolism. This article reports recent progress in PII research in cyanobacteria and discusses the mechanism of PII regulation of cellular metabolism.

  17. Tracking Clean Energy Progress 2013

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-01

    Tracking Clean Energy Progress 2013 (TCEP 2013) examines progress in the development and deployment of key clean energy technologies. Each technology and sector is tracked against interim 2020 targets in the IEA Energy Technology Perspectives 2012 2°C scenario, which lays out pathways to a sustainable energy system in 2050. Stark message emerge: progress has not been fast enough; large market failures are preventing clean energy solutions from being taken up; considerable energy efficiency remains untapped; policies need to better address the energy system as a whole; and energy-related research, development and demonstration need to accelerate. Alongside these grim conclusions there is positive news. In 2012, hybrid-electric vehicle sales passed the 1 million mark. Solar photovoltaic systems were being installed at a record pace. The costs of most clean energy technologies fell more rapidly than anticipated.

  18. Clinical management of progressive myopia.

    Science.gov (United States)

    Aller, T A

    2014-02-01

    Myopia has been increasing in prevalence throughout the world, reaching over 90% in some East Asian populations. There is increasing evidence that whereas genetics clearly have an important role, the type of visual environment to which one is exposed to likely influences the onset, progression, and cessation of myopia. Consequently, attempts to either modify the environment or to reduce the exposure of the eye to various environmental stimuli to eye growth through the use of various optical devices are well under way at research centers around the globe. The most promising of current treatments include low-percentage atropine, bifocal soft contact lenses, orthokeratology, and multifocal spectacles. These methods are discussed briefly and are then categorized in terms of their expected degree of myopia progression control. A clinical strategy is presented for selecting the most effective treatment for the appropriate type of patient at the optimal stage of refractive development to achieve the maximum control of myopia progression. PMID:24357844

  19. Molecular Regulation of Fruit Ripening

    Directory of Open Access Journals (Sweden)

    Sonia eOsorio

    2013-06-01

    Full Text Available Fruit ripening is a highly coordinated developmental process that coincides with seed maturation. The ripening process is regulated by thousands of genes that control progressive softening and/or lignification of pericarp layers, accumulation of sugars, acids, pigments, and release of volatiles. Key to crop improvement is a deeper understanding of the processes underlying fruit ripening. In tomato, mutations blocking the transition to ripe fruits have provided insights into the role of ethylene and its associated molecular networks involved in the control of ripening. However, the role of other plant hormones is still poorly understood. In this review, we describe how plant hormones, transcription factors and epigenetic changes are intimately related to provide a tight control of the ripening process. Recent findings from comparative genomics and system biology approaches are discussed.

  20. Progress, Wealth, and Mathematics Achievement

    DEFF Research Database (Denmark)

    Valero, Paola

    2013-01-01

    light on the grid of intelligibility that makes it possible to fabricate children’s differential achievement in mathematics as a social fact connected to the wealth and development of nations. The emergence of the connection between people’s mathematical qualifications and social progress can be traced......, professional associations argue that the low numbers of people in STEM fields can severely damage the competitiveness of developed nations in international, globalized markets. The narrative that connects progress, economic superiority, and development to citizen’s mathematical competence is made intelligible...

  1. Recent progress in ion sources

    International Nuclear Information System (INIS)

    This paper is intended to survey recent developments in ion sources, particularly work reported at the ''Symposium on Ion Sources and the Formation of Ion Beams'' held in Berkeley in October 1974. The approach here will be to subdivide this topic into three main areas; briefly list and discuss notable progress in each; and finally add some additional detail through a few specific, selected examples. The major items of progress discussed include development of large-area plasma surfaces for multiple- aperture ion sources, a significant increase in available negative-ion current densities, and improved general agreement between extraction electrode design and performance. (U.S.)

  2. Shuttle Risk Progression by Flight

    Science.gov (United States)

    Hamlin, Teri; Kahn, Joe; Thigpen, Eric; Zhu, Tony; Lo, Yohon

    2011-01-01

    Understanding the early mission risk and progression of risk as a vehicle gains insights through flight is important: . a) To the Shuttle Program to understand the impact of re-designs and operational changes on risk. . b) To new programs to understand reliability growth and first flight risk. . Estimation of Shuttle Risk Progression by flight: . a) Uses Shuttle Probabilistic Risk Assessment (SPRA) and current knowledge to calculate early vehicle risk. . b) Shows impact of major Shuttle upgrades. . c) Can be used to understand first flight risk for new programs.

  3. Biogas Opportunities Roadmap Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-12-01

    In support of the Obama Administration's Climate Action Plan, the U.S. Department of Energy, the U.S. Environmental Protection Agency, and U.S. Department of Agriculture jointly released the Biogas Opportunities Roadmap Progress Report, updating the federal government's progress to reduce methane emissions through biogas systems since the Biogas Opportunities Roadmap was completed by the three agencies in July 2014. The report highlights actions taken, outlines challenges and opportunities, and identifies next steps to the growth of a robust biogas industry.

  4. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin;

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

  5. Early Detection of Emphysema Progression

    DEFF Research Database (Denmark)

    Gorbunova, V.; Jacobs, S.S.A.M.; Lo, Pechin Chien Pau;

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

  6. BANKRUPTCY RULES AND PROGRESSIVE TAXATION

    OpenAIRE

    Juan de Dios Moreno Ternero; Antonio Villar Notario

    2002-01-01

    This paper explores the relative progressivity of the main bankruptcy rules in taxation problems. A rule F is more progressive than a rule G when the after-tax income vector generated by F Lorenz dominates that generated by G. We focus our analysis on four classical rules (proportional, equal-awards, equal-losses and Talmud) and on the TAL-family, introduced in Moreno-Ternero & Villar (2002). This family depends on a parameter Theta belongs to [0,1] and encompasses the constrained equal award...

  7. Implementing Program Integrity from an HBCU Perspective: Progress, Problems, and Prospects. An Analysis of Part H, Program Integrity - TRIAD of the Higher Education Act and the Final Rules and Related Interim Final Regulations Published in the "Federal Register" on April 29, 1994.

    Science.gov (United States)

    Blakely, William A.

    This paper examines the impact and implications for the nation's 104 historically black colleges and universities (HBCUs) of the final regulations published in the April 29, 1994 "Federal Register" and traces both the legislative and regulatory history of Part H of the Higher Education Act provisions. The analysis addresses specific issues,…

  8. GENE EXPRESSION PROFILING OF GANGLIOGLIOMA MALIGNANT PROGRESSION BY cDNA ARRAY

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quan-bin; HUANG Qiang; DONG Jun; WANG Ai-dong; SUN Ji-yong; LAN Qing; HU Geng-xi

    2005-01-01

    Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.

  9. Measuring research progress in photovoltaics

    Science.gov (United States)

    Jackson, B.; Mcguire, P.

    1986-01-01

    The role and some results of the project analysis and integration function in the Flat-plate Solar Array (FSA) Project are presented. Activities included supporting the decision-making process, preparation of plans for project direction, setting goals for project activities, measuring progress within the project, and the development and maintenance of analytical models.

  10. Nuclear Physics Division progress report

    International Nuclear Information System (INIS)

    The 1983 progress report of the Nuclear Physics Division, UKAEA Harwell, is divided into four main topics. These are a) nuclear data and technology for nuclear power; b) nuclear studies; c) applications of nuclear and associated techniques, including ion beam techniques and moessbauer spectroscopy; and d) accelerator operation, maintenance and development. (U.K.)

  11. [Eugenics: progress or backward movement?].

    Science.gov (United States)

    González de Cancino, Emilssen

    2007-01-01

    Throughout this article there is a critical analysis of how genetics presents a dilemma for "human progress". So much so, that the legal world aims to create unequivocal norms and guarantees in relation with eugenics in order to avoid attempting against human dignity. The document makes the reader reflect on the ethical problems that eugenics can entail.

  12. Progress in color night vision

    NARCIS (Netherlands)

    Toet, A.; Hogervorst, M.A.

    2012-01-01

    We present an overview of our recent progress and the current state-of-the-art techniques of color image fusion for night vision applications. Inspired by previously developed color opponent fusing schemes, we initially developed a simple pixel-based false color-mapping scheme that yielded fused fal

  13. Recent Progress in Nuclear Astrophysics

    OpenAIRE

    Langanke, K

    1999-01-01

    The manuscript reviews progress achieved in recent years in various aspects of nuclear astrophysics, including stellar nucleosynthesis, nuclear aspects of supernova collapse and explosion, neutrino-induced reactions and their possible role in the supernova mechanism and nucleosynthesis, explosive hydrogen burning in binary systems, and finally the observation of $\\gamma$-rays from supernova remnants.

  14. New progress in Organic FET

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Co-funded by NSFC,MOST and CAS,researchers from the Key laboratory of Organic Solids,Institute of Chemistry,CAS,made new progress in organic field-effect transistors (FET).The results of the study were published recently in the journal of Advanced Materials (2008,20,1286-1290).

  15. [Progressive extrinsic ophthalmoplegia; case report].

    Science.gov (United States)

    Nóbrega, J A; Erwenne, C M; Vilanova, L C; Lima, J G

    1979-12-01

    A case of progressive ophtalmoplegia and ptosis affecting a 12 year old boy is reported. A miopatic pattern was detected by the electromyography, the cerebrospinal fluid showed an increase of the protein content and retinal pigmentary degeneration was detected. This findings call the attention for a more widespread degenerative disorders affecting not only the muscular sistem but other organs as well. PMID:533389

  16. Technological Progress, Exit and Trade

    DEFF Research Database (Denmark)

    Schröder, Philipp; Sørensen, Allan

    productivity exporters are more likely to continue to export, and market exit is typically preceded by periods of contracting market shares. We show that the simple inclusion of exogenous economy wide technological progress into the standard Melitz (2003) model generates a tractable dynamic framework...

  17. Joint energy program makes progress

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ "Clean Energies Facing the Future," a cooperative research program jointly organized by CAS and the BP Group, has made encouraging progress, say experts at an annual sum-up workshop held on 31 July and I August at Tsinghua University in Beijing. The CAS Dalian Institute of Chemical Physics(DICP) has been entrusted as coordinator of the cooperative program between the two sides.

  18. Progress of peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    陈峥嵘

    2002-01-01

    Study on repair of peripheral nerve injury has been proceeding over a long period of time. With the use of microsurgery technique since 1960s,the quality of nerve repair has been greatly improved. In the past 40 years, with the continuous increase of surgical repair methods, more progress has been made on the basic research of peripheral nerve repair.

  19. Progress Report 1985-1986

    International Nuclear Information System (INIS)

    The research directions in the Physics Institute of Universidade Federal do Rio Grande do Sul are presented. The progress reports cavied out in the follow areas are presented: perturbed angular correlation; Moessbauer spectroscopy; ion implantation; magnetism and electronic transport; microelectronics; condensed matter theory; quantum field theory; plasma physics; nuclear physics; astronomy and astrophysics; and instrumentation. (M.C.K.)

  20. Progress in Diffraction Enhanced Imaging

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ In cooperation with the Topography Station of Beijing Synchrotron Radiation under CAS Institute of High Energy Physics, a research group from the CAS Shanghai Institute of Optics and Fine Mechanics (SIOM) has made encouraging progress in the diffraction enhanced imaging technology through phase-contrast microscope by hard X-rays.

  1. Temozolomide suppresses MYC via activation of TAp63 to inhibit progression of human glioblastoma

    OpenAIRE

    Yamaki, Tomohiro; Suenaga, Yusuke; Iuchi, Toshihiko; Alagu, Jennifer; Takatori, Atsushi; Itami, Makiko; Araki, Akinobu; Ohira, Miki; Inoue, Masahiro; Kageyama, Hajime; Yokoi, Sana; Saeki, Naokatsu; Nakagawara, Akira

    2013-01-01

    Glioblastoma multiforme (GBM) is a highly invasive and chemoradioresistant brain malignancy. Temozolomide (TMZ), a DNA-alkylating agent, is effective against GBM and has become the standard first-line drug. However, the mechanism by which TMZ regulates the progression of GBM remains elusive. Here, we demonstrate that TMZ targets TAp63, a p53 family member, inducing its expression to suppress the progression of human GBM. High levels of TAp63 expression in GBM tissues after TMZ treatment was a...

  2. Advancements and progressions in greyhound racing: a professional and personal trajectory

    OpenAIRE

    Payne, Richard Michael

    2016-01-01

    The context of these works is in relation to my work within the world of regulated greyhound racing within the United Kingdom, and represents a progression from my earliest interests in biomechanics and statistical analysis, through the development of this knowledge and the acquisition of new skills as the research progressed. It details my roles within disease control, research into exercise-associated sudden death, and the links with other research threads that stemmed from the first projec...

  3. CRL4Cdt2: Master coordinator of cell cycle progression and genome stability

    OpenAIRE

    Abbas, Tarek; Dutta, Anindya

    2011-01-01

    Polyubiquitin-mediated degradation of proteins plays an essential role in various physiological processes including cell cycle progression, transcription and DNA replication and repair. Increasing evidence supports a vital role for the E3 ubiquitin ligase cullin-4, in conjunction with the substrate recognition factor Cdt2 (CRL4Cdt2), for the degradation of multiple cell cycle-regulated proteins to prevent genomic instability. In addition, it is critical for normal cell cycle progression by en...

  4. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  5. Regulation of Genetic Tests

    Science.gov (United States)

    ... advertised. The Commission has the authority to regulate advertising that delivers health-related information to consumers to ensure that it is not false or misleading. Top of page FDA Regulation and ...

  6. General Theories of Regulation

    NARCIS (Netherlands)

    Hertog, J.A. den

    1999-01-01

    This chapter makes a distinction between three types of theories of regulation: public interest theories, the Chicago theory of regulation and the public choice theories. The Chicago theory is mainly directed at the explanation of economic regulation; public interest theories and public choice theor

  7. Hepcidin: regulation of the master iron regulator

    OpenAIRE

    2015-01-01

    Iron, an essential nutrient, is required for many diverse biological processes. The absence of a defined pathway to excrete excess iron makes it essential for the body to regulate the amount of iron absorbed; a deficiency could lead to iron deficiency and an excess to iron overload and associated disorders such as anaemia and haemochromatosis respectively. This regulation is mediated by the iron-regulatory hormone hepcidin. Hepcidin binds to the only known iron export protein, ferroportin (FP...

  8. Serotonin and the regulation of mammalian energy balance.

    OpenAIRE

    MichaelHDonovan

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms ...

  9. Serotonin and the regulation of mammalian energy balance

    OpenAIRE

    Donovan, Michael H.; Tecott, Laurence H.

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mecha...

  10. Geothermal Progress Monitor report No. 5. Progress report, June 1981

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    Updated information is presented on activities and progress in the areas of electric power plants, direct heat applications, deep well drilling, leasing of federal lands, legislative and regulatory actions, research and development, and others. Special attention is given in this report to 1980 highlights, particularly in the areas of electric and direct heat uses, drilling, and the Federal lands leasing program. This report also includes a summary of the DOE FY 1982 geothermal budget request to Congress.

  11. Alteration of cell cycle progression by Sindbis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  12. Dual role of GRK5 in cancer development and progression.

    Science.gov (United States)

    Gambardella, J; Franco, A; Giudice, C Del; Fiordelisi, A; Cipolletta, E; Ciccarelli, M; Trimarco, B; Iaccarino, G; Sorriento, D

    2016-05-01

    GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechanisms by which GRK5 exerts its effects, and the potential therapeutic strategies to modulate them.

  13. Molecular Network Associated with MITF in Skin Melanoma Development and Progression

    Directory of Open Access Journals (Sweden)

    Ichiro Yajima

    2011-01-01

    Full Text Available Various environmental and genetic factors affect the development and progression of skin cancers including melanoma. Melanoma development is initially triggered by environmental factors including ultraviolet (UV light, and then genetic/epigenetic alterations occur in skin melanocytes. These first triggers alter the conditions of numerous genes and proteins, and they induce and/or reduce gene expression and activate and/or repress protein stability and activity, resulting in melanoma progression. Microphthalmia-associated transcription factor (MITF is a master regulator gene of melanocyte development and differentiation and is also associated with melanoma development and progression. To find better approaches to molecular-based therapies for patients, understanding MITF function in skin melanoma development and progression is important. Here, we review the molecular networks associated with MITF in skin melanoma development and progression.

  14. Views of the regulators

    International Nuclear Information System (INIS)

    In dealing with a challenging problem in occupational exposure the nuclear regulator in South Africa concluded that the involvement of stake holders was critical. Valuable lessons were learnt in the process. These related to co-operation amongst regulators, the involvement of regulators in addressing occupational exposure problems, the training of workers by the regulator and the need for technical training of the workers. In general, it was also learnt that regulators should establish mechanisms to measure and continuously improve the satisfaction of their stake holders. (author)

  15. Creatine kinase in cell cycle regulation and cancer.

    Science.gov (United States)

    Yan, Yong-Bin

    2016-08-01

    The phosphocreatine-creatine kinase (CK) shuttle system is increasingly recognized as a fundamental mechanism for ATP homeostasis in both excitable and non-excitable cells. Many intracellular processes are ATP dependent. Cell division is a process requiring a rapid rate of energy turnover. Cell cycle regulation is also a key point to understanding the mechanisms underlying cancer progression. It has been known for about 40 years that aberrant CK levels are associated with various cancers and for over 30 years that CK is involved in mitosis regulation. However, the underlying molecular mechanisms have not been investigated sufficiently until recently. By maintaining ATP at sites of high-energy demand, CK can regulate cell cycle progression by affecting the intracellular energy status as well as by influencing signaling pathways that are essential to activate cell division and cytoskeleton reorganization. Aberrant CK levels may impair cell viability under normal or stressed conditions and induce cell death. The involvement of CK in cell cycle regulation and cellular energy metabolism makes it a potential diagnostic biomarker and therapeutic target in cancer. To understand the multiple physiological/pathological functions of CK, it is necessary to identify CK-binding partners and regulators including proteins, non-coding RNAs and participating endogenous small molecular weight chemical compounds. This review will focus on molecular mechanisms of CK in cell cycle regulation and cancer progression. It will also discuss the implications of recent mechanistic studies, the emerging problems and future challenges of the multifunctional enzyme CK. PMID:27020776

  16. Seismic Progressive Collapse: Qualitative Point of View

    Directory of Open Access Journals (Sweden)

    H. Wibowo

    2009-01-01

    Full Text Available Progressive collapse is a catastrophic structural phenomenon that can occur because of human-made and natural hazards. In progressive collapse mechanism, a single local failure may cause a significant deformation which then may lead to collapse of a structure. The current practices in progressive collapse analysis and design method generally focus on preventing progressive collapse due to abnormal gravity and blast loads. Progressive collapse behaviour of structures due to earthquake loads has not received as much attention. This paper presents a brief overview of the current state-of-knowledge, insights, and issues related to progressive collapse behaviour of structures caused by earthquake loading.

  17. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The Nuclear Safety Regulations for Nuclear Installations and Nuclear Safety Codes for Nuclear Pressure Retaining Components were issued by the NNSA in 1995. The Atomic Act and Regulations on the Safety Regulation for Transportation of Radioactive Materials have been finished and submitted to the State Council in 1995. At the same time the NNSA organized a revised collection of regulations on nuclear safety in both Chinese and English, titled 'The Collection of Regulations on Nuclear Safety of the People's Republic of China'. To enhance the implementation of newly issued nuclear safety regulations, the NNSA conducted seven times of propagating activities in relation to the regulations for nuclear pressure retaining components and research reactors design and operating in 1995

  18. Sector report for Ofsted : SDC – review of public service regulators

    OpenAIRE

    Sustainable Development Commission

    2009-01-01

    This report sets out the findings so far of the Sustainable Development Commission's review of public service regulators for Ofsted. The report includes the relevant policy context, an assessment of progress against the review goals set out by the SDC at the outset of this review, other progress, future developments and opportunities. Publisher PDF

  19. Molecular profiling of dilated cardiomyopathy that progresses to heart failure

    Science.gov (United States)

    Burke, Michael A.; Chang, Stephen; Wakimoto, Hiroko; Gorham, Joshua M.; Conner, David A.; Christodoulou, Danos C.; Parfenov, Michael G.; DePalma, Steve R.; Eminaga, Seda; Konno, Tetsuo; Seidman, Jonathan G.; Seidman, Christine E.

    2016-01-01

    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10–4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10–33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM. PMID:27239561

  20. Progress of MICE RFCC Module

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A. B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

    2012-05-20

    Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

  1. Progress in front propagation research

    Science.gov (United States)

    Fort, Joaquim; Pujol, Toni

    2008-08-01

    We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined.

  2. Progress in front propagation research

    International Nuclear Information System (INIS)

    We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined

  3. Monochromatic Progressions in Random Colorings

    OpenAIRE

    Vijay, Sujith

    2011-01-01

    Let N^{+}(k)= 2^{k/2} k^{3/2} f(k) and N^{-}(k)= 2^{k/2} k^{1/2} g(k) where 1=o(f(k)) and g(k)=o(1). We show that the probability of a random 2-coloring of {1,2,...,N^{+}(k)} containing a monochromatic k-term arithmetic progression approaches 1, and the probability of a random 2-coloring of {1,2,...,N^{-}(k)} containing a monochromatic k-term arithmetic progression approaches 0, for large k. This improves an upper bound due to Brown, who had established an analogous result for N^{+}(k)= 2^k l...

  4. Progress in front propagation research

    Energy Technology Data Exchange (ETDEWEB)

    Fort, Joaquim [Departament de Fisica, Campus de Montilivi, Universitat de Girona, 17071 Girona, Catalonia (Spain); Pujol, Toni [Departament de Mecanica, Campus de Montilivi, Universitat de Girona, 17071 Girona, Catalonia (Spain)

    2008-08-15

    We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined.

  5. Significance and Progress of Bionics

    Institute of Scientific and Technical Information of China (English)

    Yongxiang Lu

    2004-01-01

    The four topics are described including the driving force and source of the scientific and technological creation, the definition and history of the bionics, the important significance of bionics in the development of the human beings, and the leading edge and progress of bionics. The appetency of human for the creation is the essential motivity of the innovation in science and technology. Nature and society are the objects for us to cognize and serve, meanwhile, the best teachers for us to learn from them. It is only 5 million years for human's development, but evolution of life has over 3.5 billion years history. Although, copying the creation from the human being is important, however, it has much more potential and opportunity in imitating the nature, and more possibility to promote the ability of original innovation. The significance and progress of bionics are summarized, in this paper, and the leading edges of bionics, in the near future, are forecasted.

  6. Progressive multifocal leukoencephalopathy: rheumatological aspects

    Directory of Open Access Journals (Sweden)

    Boris Sergeevich Belov

    2015-01-01

    Full Text Available Progressive multifocal leukoencephalopathy (PML is a severe progressive viral disease that affects the central nervous system in patients with immunodeficiency. It may develop as a complication in patients with systemic inflammatory rheumatic diseases (primarily in those with systemic lupus erythematosus, including that during active antirheumatic therapy. The paper presents data on the etiology, epidemiology, and pathogenesis of the disease, characterizes its clinical presentation, highlights main approaches to its diagnosis, and gives current diagnostic criteria. A questionnaire used to monitor neurological status is shown. The paper emphasizes the importance of this monitoring, for early diagnosis and timely cessation of PML treatment with a drug, a potential trigger, are factors that influence prognosis to the utmost degree.

  7. Recent progress in wormhole dynamics

    OpenAIRE

    Hayward, Sean A.

    2003-01-01

    Space-time wormholes were introduced in Wheeler's idea of space-time foam. Traversible wormholes as defined by Morris & Thorne became popular as potential short cuts across the universe and even time machines. More recently, the author proposed a general theory of wormhole dynamics, unified with black-hole dynamics. This article gives a brief review of the above ideas and summarizes progress on wormhole dynamics in the last year. Firstly, a numerical study of dynamical perturbations of the fi...

  8. Progress in NTHMP Hazard Assessment

    Science.gov (United States)

    Gonzalez, F.I.; Titov, V.V.; Mofjeld, H.O.; Venturato, A.J.; Simmons, R.S.; Hansen, R.; Combellick, R.; Eisner, R.K.; Hoirup, D.F.; Yanagi, B.S.; Yong, S.; Darienzo, M.; Priest, G.R.; Crawford, G.L.; Walsh, T.J.

    2005-01-01

    The Hazard Assessment component of the U.S. National Tsunami Hazard Mitigation Program has completed 22 modeling efforts covering 113 coastal communities with an estimated population of 1.2 million residents that are at risk. Twenty-three evacuation maps have also been completed. Important improvements in organizational structure have been made with the addition of two State geotechnical agency representatives to Steering Group membership, and progress has been made on other improvements suggested by program reviewers. ?? Springer 2005.

  9. Progress in Space Solar Telescope

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper we will summarize the progress in the development of the Chinese Space Solar Telescope (SST) during the past few years. The main scientific objective of SST is to observe the fundamental structure of solar magnetic field with its 1-m optical telescope. The success of 1-m Swedish Solar Telescope and Hinode underscores the importance of this 1-m space telescope. In addition, some key technical problems have been solved.

  10. Gene therapy: progress and predictions

    OpenAIRE

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of ...

  11. The 1989 progress report: Mathematics

    International Nuclear Information System (INIS)

    The 1989 progress report of the laboratory of Mathematics of the Polytechnic School (France) is presented. The investigations reported were performed in the following fields: analysis of nonlinear partial differential equations, quantum mechanics, scattering, fluid dynamics and homogenization, equations, varieties with negative curvature, elliptical problems on surfaces, Dirac operator, geometry of algorithms and formal calculus, singularities, Lie groups, dynamics systems. The published papers, the conferences and the Laboratory staff are listed

  12. Gammasphere software development. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Piercey, R.B.

    1994-01-01

    This report describes the activities of the nuclear physics group at Mississippi State University which were performed during 1993. Significant progress has been made in the focus areas: chairing the Gammasphere Software Working Group (SWG); assisting with the porting and enhancement of the ORNL UPAK histogramming software package; and developing standard formats for Gammasphere data products. In addition, they have established a new public ftp archive to distribute software and software development tools and information.

  13. Hereditary progressive chorea without dementia.

    OpenAIRE

    Schady, W; Meara, R J

    1988-01-01

    A family with hereditary non-Huntington's chorea is presented. Transmission was autosomal dominant with variable penetrance. Chorea commenced in childhood and affected predominantly the head, face and upper limbs. Dysarthria appeared later, followed in two family members by elements of an axial dystonia. There was no intellectual impairment. Unlike previously described families, symptoms progressed steadily up to the eighth decade, causing considerable physical disability.

  14. Progressive hemifacial atrophy: a review

    OpenAIRE

    Tolkachjov, Stanislav N; Patel, Nirav G; Tollefson, Megha M.

    2015-01-01

    Background Progressive Hemifacial Atrophy (PHA) is an acquired, typically unilateral, facial distortion with unknown etiology. The true incidence of this disorder has not been reported, but it is often regarded as a subtype of localized scleroderma. Historically, a debate existed whether PHA is a form of linear scleroderma, called morphea en coup de sabre (ECDS), or whether these conditions are inherently different processes or appear on a spectrum (; Adv Exp Med Biol 455:101–4, 1999; J Eur A...

  15. Progress of nanoscience in China

    Science.gov (United States)

    Zhao, Yu-Liang; Song, Yan-Lin; Song, Wei-Guo; Liang, Wei; Jiang, Xing-Yu; Tang, Zhi-Yong; Xu, Hong-Xing; Wei, Zhi-Xiang; Liu, Yun-Qi; Liu, Ming-Hua; Jiang, Lei; Bao, Xin-He; Wan, Li-Jun; Bai, Chun-Li

    2014-06-01

    Fast evolving nanosciences and nanotechnology in China has made it one o f the front countries of nanotechnology development. In this review, we summarize some most recent progresses in nanoscience research and nanotechnology development in China. The topics we selected in this article include nano-fabrication, nanocatalysis, bioinspired nanotechnology, green printing nanotechnology, nanoplasmonics, nanomedicine, nanomaterials and their applications, energy and environmental nanotechnology, nano EHS (nanosafety), etc. Most of them have great potentials in applications or application-related key issues in future.

  16. Emergent Gravity Paradigm: Recent Progress

    CERN Document Server

    Padmanabhan, T

    2014-01-01

    Research during the last one decade or so suggests that the gravitational field equations in a large class of theories (including, but not limited to, general relativity) have the same status as the equations of, say, gas dynamics or elasticity. This paradigm provides a refreshingly different way of interpreting spacetime dynamics and highlights the fact that several features of classical gravitational theories have direct thermodynamic interpretation. I review the recent progress in this approach, achieved during the last few years.

  17. Progress, Wealth, and Mathematics Achievement

    OpenAIRE

    Valero, Paola

    2013-01-01

    I am interested in discussing the historical conditions that make it possible to formulate the idea that the mathematical qualifications of citizens in modern states is connected to the progress and economic development of nations. I interconnect apparently unrelated areas in an attempt to shed light on the grid of intelligibility that makes it possible to fabricate children’s differential achievement in mathematics as a social fact connected to the wealth and development of nations.The emerg...

  18. Gammasphere software development. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Piercey, R.B.

    1993-05-01

    Activities of the nuclear physics group are described. Progress was made in organizing the Gammasphere Software Working Group, establishing a nuclear computing facility, participating in software development at Lawrence Berkeley, developing a common data file format, and adapting the ORNL UPAK software to run at Gammasphere. A universal histogram object was developed that defines a file format and provides for an objective-oriented programming model. An automated liquid nitrogen fill system was developed for Gammasphere (110 Ge detectors comprise the sphere).

  19. Information Loss from Technological Progress

    International Nuclear Information System (INIS)

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies

  20. Information Loss from Technological Progress

    Science.gov (United States)

    Townsend, P. D.

    2014-12-01

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.