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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. SRC kinase regulation in progressively invasive cancer.

    Directory of Open Access Journals (Sweden)

    Weichen Xu

    Full Text Available Metastatic progression is a multistep process that involves tumor growth and survival, motility and invasion, and subsequent proliferation in an inappropriate environment. The Src protein tyrosine kinase has been implicated in many of the biochemical pathways that drive these behaviors. Although Src itself is only rarely mutated in human tumors, its aberrant activity has been noted in various cancers and suggested to serve as a barometer of metastatic potential. With these features in mind, we examined Src kinase regulation at the structural, enzymatic, and expression levels as a function of progressively invasive prostate cancer cell lines. Surprisingly, both total Src content and kinase activity decrease with increasing cell line aggressiveness, an observation that appears to be inconsistent with the well-documented role of Src in the signaling pathways that drive growth and invasion. However, we do observe a direct correlation between Src kinase specific activity (total Src kinase activity/total Src content and metastatic aggressiveness, possibly suggesting that in highly aggressive cell lines, key signaling enzymes are globally recruited to drive the cancerous phenotype. In addition, although the expected enhanced phosphorylation of Src at Tyr-416 (activation site is present in the most aggressive prostate cancer cell lines, unexpectedly high phosphorylation levels at the Tyr-527 inhibitory site are observed as well. The latter, rather than representative of inhibited enzyme, is more indicative of primed Src responsive to local phosphorylated binding partners.

  5. (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.

  6. 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...

  7. 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.

  8. 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...

  9. The Role of pH Regulation in Cancer Progression.

    Science.gov (United States)

    McIntyre, Alan; Harris, Adrian L

    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.

  10. PHD2: from hypoxia regulation to disease progression.

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    Meneses, Ana M; Wielockx, Ben

    2016-01-01

    Oxygen represents one of the major molecules required for the development and maintenance of life. An adequate response to hypoxia is therefore required for the functioning of the majority of living organisms and relies on the activation of the hypoxia-inducible factor (HIF) pathway. HIF prolyl hydroxylase domain-2 (PHD2) has long been recognized as the major regulator of this response, controlling a myriad of outcomes that range from cell death to proliferation. However, this enzyme has been associated with more pathways, making the role of this protein remarkably complex under distinct pathologies. While a protective role seems to exist in physiological conditions such as erythropoiesis; the picture is more complex during pathologies such as cancer. Since the regulation of this enzyme and its closest family members is currently considered as a possible therapy for various diseases, understanding the different particular roles of this protein is essential.

  11. MUC1 Regulates PDGFA Expression During Pancreatic Cancer Progression

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    Sahraei, Mahnaz; Roy, Lopamudra Das; Curry, Jennifer M; Teresa, Tinder L; Nath, Sritama; Besmer, Dahlia; Kidiyoor, Amritha; Dalia, Ritu; Gendler, Sandra J; Mukherjee, Pinku

    2012-01-01

    Pancreatic Ductal Adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility, and metastasis. Its expression is known to be associated with poor prognosis in patients. However, the precise mechanism remains elusive. We report a novel association of MUC1 with Platelet-Derived Growth Factor-A (PDGFA). PDGFA is one of the many drivers of tumor growth, angiogenesis, and metastasis in PDA. Using mouse PDA models as well as human samples, we show clear evidence that MUC1 regulates the expression and secretion of PDGFA. This, in turn, influences proliferation and invasion of pancreatic cancer cells leading to higher tumor burden in vivo. In addition, we reveal that MUC1 over expressing cells are heavily dependent on PDGFA both for proliferation and invasion while MUC1-null cells are not. Moreover, PDGFA and MUC1 are critical for translocation of βcatenin to the nucleus for oncogenesis to ensue. Finally, we elucidate the underlying mechanism by which MUC1 regulates PDGFA expression and secretion in pancreatic cancer cells. We show that MUC1 associates with Hif1-α, a known transcription factor involved in controlling PDGFA expression. Furthermore, MUC1 facilitates Hif1-α translocation to the nucleus. In summary, we have demonstrated that MUC1-induced invasion and proliferation occurs via increased exogenous production of PDGFA. Thus, impeding MUC1 regulation of PDGFA signaling may be therapeutically beneficial for patients with PDA. PMID:22266848

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

    Science.gov (United States)

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

    2016-07-01

    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.

  13. 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.

  14. [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.

  15. 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…

  16. 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.

  17. 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.

  18. Research progress of photoperiod regulated genes on flowering time in rice.

    Science.gov (United States)

    Deyan, Kong; Shoujun, Chen; Liguo, Zhou; Huan, Gao; Lijun, Luo; Zaochang, Liu

    2016-06-20

    Rice flowering regulation is an extremely complex process, which is controlled by genetic factors and external environment. Photoperiodic regulatory pathway is pivotal to control flowering in rice, in which florigen genes Hd3a and RTF1 are at the core and they are regulated by upstream Hd1-dependent, Ehd1-dependent, as well as both Hd1- and Ehd1-independent pathways. The three pathways bring a variety of light signal information together to Hd3a and RTF1 for further integration, and then transmit the signals in the form of florigen to the downstream flowering related genes. In this review, we summarize the research progress of photoperiod regulated genes on flowering time in rice, including the photoreceptors and circadian rhythm genes, the florigens, its upstream, downstream and interacting genes. We hope to provide a reference for in-depth study of rice flowering regulation.

  19. 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

    (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat β-cells, and overexpression...... of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2...... the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower β-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of β-cell function during progression of T1D...

  20. 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.

  1. LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice.

    Science.gov (United States)

    Kim, Jeesun; Singh, Anup Kumar; Takata, Yoko; Lin, Kevin; Shen, Jianjun; Lu, Yue; Kerenyi, Marc A; Orkin, Stuart H; Chen, Taiping

    2015-12-02

    Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by dynamic epigenetic changes. Although the signalling pathways regulating CDK1 activity are well defined, the functional significance of epigenetic changes remains largely unknown. Here we show that LSD1, a lysine demethylase, regulates histone H3 lysine 4 di-methylation (H3K4me2) in mouse oocytes and is essential for meiotic progression. Conditional deletion of Lsd1 in growing oocytes results in precocious resumption of meiosis and spindle and chromosomal abnormalities. Consequently, most Lsd1-null oocytes fail to complete meiosis I and undergo apoptosis. Mechanistically, upregulation of CDC25B, a phosphatase that activates CDK1, is responsible for precocious meiotic resumption and also contributes to subsequent spindle and chromosomal defects. Our findings uncover a functional link between LSD1 and the major signalling pathway governing meiotic progression.

  2. 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.

  3. 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

    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...... glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies.......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...... 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...

  4. MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

    Science.gov (United States)

    Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

    2016-01-01

    The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

  5. Regulation of p53 by ING family members in suppression of tumor initiation and progression.

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    Jafarnejad, Seyed Mehdi; Li, Gang

    2012-06-01

    The INhibitor of Growth (ING) family is an evolutionarily conserved set of proteins, implicated in suppression of initiation and progression of cancers in various tissues. They promote cell cycle arrest, cellular senescence and apoptosis, participate in stress responses, regulate DNA replication and DNA damage responses, and inhibit cancer cell migration, invasion, and angiogenesis of the tumors. At the molecular level, ING proteins are believed to participate in chromatin remodeling and transcriptional regulation of their target genes. However, the best known function of ING proteins is their cooperation with p53 tumor suppressor protein in tumor suppression. All major isoforms of ING family members can promote the transactivition of p53 and the majority of them are shown to directly interact with p53. In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway. It seems that p53 pathway is the main mechanism by which ING proteins exert their functions. Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-β and NF-κB, by ING proteins is also observed. This review summarizes the current understanding of the mutual interactions and cooperation between different members of ING family with p53 pathway and implications of this cooperation in the suppression of cancer initiation and progression.

  6. 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.

  7. Intratesticular signals regulate germ cell progression and production of qualitatively mature spermatozoa in vertebrates

    Directory of Open Access Journals (Sweden)

    Rosaria eMeccariello

    2014-05-01

    Full Text Available Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic-pituitary control, being regulated by the secretion of pituitary gonadotropins, FSH and LH, in response to stimulation exerted by Gonadotropin Releasing Hormone (GnRH from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intragonadal signals sustains the production of high quality mature spermatozoa. In this review we focus on the recent advances in the area of the intragonadal signals supporting sperm development.

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

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    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.

  9. 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.

  10. Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis.

    Science.gov (United States)

    Aaker, Joshua D; Patineau, Andrea L; Yang, Hyun-Jin; Ewart, David T; Gong, Wuming; Li, Tongbin; Nakagawa, Yasushi; McLoon, Steven C; Koyano-Nakagawa, Naoko

    2009-12-01

    The sequential steps of neurogenesis are characterized by highly choreographed changes in transcription factor activity. In contrast to the well-studied mechanisms of transcription factor activation during neurogenesis, much less is understood regarding how such activity is terminated. We previously showed that MTGR1, a member of the MTG family of transcriptional repressors, is strongly induced by a proneural basic helix-loop-helix transcription factor, NEUROG2 in developing nervous system. In this study, we describe a novel feedback regulation of NEUROG2 activity by MTGR1. We show that MTGR1 physically interacts with NEUROG2 and represses transcriptional activity of NEUROG2. MTGR1 also prevents DNA binding of the NEUROG2/E47 complex. In addition, we provide evidence that proper termination of NEUROG2 activity by MTGR1 is necessary for normal progression of neurogenesis in the developing spinal cord. These results highlight the importance of feedback regulation of proneural gene activity in neurodevelopment.

  11. 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.

  12. 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

    by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription......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......-phase boundary in growth-stimulated cells and that the NPAT promoter responds to activation by E2F proteins. We demonstrate that endogenous E2F proteins interact with the promoter of the NPAT gene in vivo and that induced expression of E2F1 stimulates NPAT mRNA expression, supporting the idea that the expression...

  13. HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1 gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.

  14. 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

  15. 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

  16. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

    Science.gov (United States)

    Lee, Eun Ju; Jan, Arif Tasleem; Baig, Mohammad Hassan; Ashraf, Jalaluddin Mohammad; Nahm, Sang-Soep; Kim, Yong-Woon; Park, So-Young; Choi, Inho

    2016-08-01

    Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.-Lee, E. J., Jan, A. T., Baig, M. H., Ashraf, J. M., Nahm, S.-S., Kim, Y.-W., Park, S.-Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

  17. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression.

    Science.gov (United States)

    Paradisi, Andrea; Maisse, Carine; Coissieux, Marie-May; Gadot, Nicolas; Lépinasse, Florian; Delloye-Bourgeois, Céline; Delcros, Jean-Guy; Svrcek, Magali; Neufert, Clemens; Fléjou, Jean-François; Scoazec, Jean-Yves; Mehlen, Patrick

    2009-10-06

    Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-kappaB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-kappaB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.

  18. Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression

    Science.gov (United States)

    Zhang, Mingdi; Qin, Yiyu; Zuo, Bin; Gong, Wei; Zhang, Shenglai; Gong, Yurong; Quan, Zhiwei; Chu, Bingfeng

    2017-01-01

    Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes. Therefore, these results indicate that NRARP is an important clinical biomarker in thyroid carcinoma and it promotes EMT induction as well as the progression of PTCs via NOTCH signaling activation. PMID:28207739

  19. miR-107 regulates tumor progression by targeting NF1 in gastric cancer.

    Science.gov (United States)

    Wang, Shizhi; Ma, Gaoxiang; Zhu, Haixia; Lv, Chunye; Chu, Haiyan; Tong, Na; Wu, Dongmei; Qiang, Fulin; Gong, Weida; Zhao, Qinghong; Tao, Guoquan; Zhou, Jianwei; Zhang, Zhengdong; Wang, Meilin

    2016-11-09

    Our previous genome-wide miRNA microarray study revealed that miR-107 was upregulated in gastric cancer (GC). In this study we aimed to explore its biological role in the pathogenesis of GC. Integrating in silico prediction algorithms with western blotting assays revealed that miR-107 inhibition enhanced NF1 (neurofibromin 1) mRNA and protein levels, suggesting that NF1 is one of miR-107 targets in GC. Luciferase reporter assay revealed that miR-107 suppressed NF1 expression by binding to the first potential binding site within the 3'-UTR of NF1 mRNA. mRNA stable assay indicated this binding could result in NF1 mRNA instability, which might contribute to its abnormal protein expression. Functional analyses such as cell growth, transwell migration and invasion assays were used to investigate the role of interaction between miR-107 and its target on GC development and progression. Moreover, We investigated the association between the clinical phenotype and the status of miR-107 expression in 55 GC tissues, and found the high expression contributed to the tumor size and depth of invasion. The results exhibited that down regulation of miR-107 opposed cell growth, migration, and invasion, whereas NF1 repression promoted these phenotypes. Our findings provide a mechanism by which miR-107 regulates NF1 in GC, as well as highlight the importance of interaction between miR-107 and NF1 in GC development and progression.

  20. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

    Directory of Open Access Journals (Sweden)

    Tamara eMirzapoiazova

    2015-07-01

    Full Text Available Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA, which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2. This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was performed on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, migration, extravasation and urokinase plasminogen activator (uPA activation assays with or without high molecular weight HA (HMW-HA or low molecular weight HA (LMW-HA. In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs.Results: We provide evidence that HABP2 is an important regulator of lung cancer progression. HABP2 expression was increased in several subtypes of patient non-small cell lung cancer samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, migration and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~2 fold and lung metastasis by ~10 fold compared to vector control cells (n=5 per condition.Conclusions: Our data suggests a possible direct effect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.

  1. 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.

  2. Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2010-04-01

    Full Text Available Abstract Background Bax inhibitor-1 (BI-1 is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1 to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2 to determine whether HCV and HBV infections modulate said expression. Methods We examined 62 patients: 39 with chronic hepatitis (CH (31 HCV-related and 8 HBV-related; 7 with cirrhosis (6 HCV-related and 1 HBV-related; 13 with hepatocellular carcinoma (HCC [7 in viral cirrhosis (6 HCV- and 1 HBV-related, 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. Results CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P Conclusions BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.

  3. 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.

  4. Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC.

    Science.gov (United States)

    Qi, Yinliang; Dai, Yuanchang; Gui, Shuyu

    2016-10-01

    Protein tyrosine-phosphatases (PTPs) play important roles in various biological processes. Deregulation in PTP function has been implicated in carcinogenesis and tumour progression in many cancer types. However, the role of protein tyrosine phosphatase receptor type B (PTPRB) in non-small-cell lung cancer (NSCLC) tumorigenesis has not been investigated. Lentiviral vector expressing PTPRB cDNA or shRNA was infected into A549 and H1299 cell lines, followed by cell proliferation, colony formation, soft agar and invasion assays. A549 xenograft mouse model was used to evaluate in vivo function of PTPRB. Quantitative polymerase chain reaction (PCR) was used to measure PTPRB expression in NSCLC patient samples. Kaplan Meier analysis was performed to assess association between PTPRB expression and patient overall survival (OS). Multivariate analysis was performed to evaluate prognostic significance of PTPRB. Overexpression of PTPRB reduced cell proliferation rate, colony formation efficiency, soft agar growth and cell invasion in A549 and H1299 cells, as well as tumour growth rate in A549 xenograft. Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2. Additionally, PTPRB was down-regulated in NSCLC patient and was associated with patient OS. PTPRB regulates Src phosphorylation and tumorigenesis in NSCLC. PTPRB may serve as an independent prognostic biomarker for NSCLC patients.

  5. 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.

  6. 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.

  7. Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.

    Science.gov (United States)

    Feng, Yan-Min; Liang, Gui-Jin; Pan, Bo; Qin, Xun-Si; Zhang, Xi-Feng; Chen, Chun-Lei; Li, Lan; Cheng, Shun-Feng; De Felici, Massimo; Shen, Wei

    2014-01-01

    A critical process of early oogenesis is the entry of mitotic oogonia into meiosis, a cell cycle switch regulated by a complex gene regulatory network. Although Notch pathway is involved in numerous important aspects of oogenesis in invertebrate species, whether it plays roles in early oogenesis events in mammals is unknown. Therefore, the rationale of the present study was to investigate the roles of Notch signaling in crucial processes of early oogenesis, such as meiosis entry and early oocyte growth. Notch receptors and ligands were localized in mouse embryonic female gonads and 2 Notch inhibitors, namely DAPT and L-685,458, were used to attenuate its signaling in an in vitro culture system of ovarian tissues from 12.5 days post coitum (dpc) fetus. The results demonstrated that the expression of Stra8, a master gene for germ cell meiosis, and its stimulation by retinoic acid (RA) were reduced after suppression of Notch signaling, and the other meiotic genes, Dazl, Dmc1, and Rec8, were abolished or markedly decreased. Furthermore, RNAi of Notch1 also markedly inhibited the expression of Stra8 and SCP3 in cultured female germ cells. The increased methylation status of CpG islands within the Stra8 promoter of the oocytes was observed in the presence of DAPT, indicating that Notch signaling is probably necessary for maintaining the epigenetic state of this gene in a way suitable for RA stimulation. Furthermore, in the presence of Notch inhibitors, progression of oocytes through meiosis I was markedly delayed. At later culture periods, the rate of oocyte growth was decreased, which impaired subsequent primordial follicle assembly in cultured ovarian tissues. Taken together, these results suggested new roles of the Notch signaling pathway in female germ cell meiosis progression and early oogenesis events in mammals.

  8. 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.

  9. [Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges].

    Science.gov (United States)

    Feng, Jing-Xian; Wang, Jia-wen; Lin, Jun-sheng; Diao, Yong

    2014-11-01

    Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

  10. VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu Liu

    Full Text Available Valosin containing protein (VCP/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of IκBα and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.

  11. 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.

  12. Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

    Science.gov (United States)

    Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

    2017-02-09

    Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2(+)/ErbB2(+)) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2(+)/ErbB2(+) breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2(+)/ErbB2(+) breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer.

  13. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression.

    Science.gov (United States)

    Maity, Biswanath; Stewart, Adele; O'Malley, Yunxia; Askeland, Ryan W; Sugg, Sonia L; Fisher, Rory A

    2013-08-01

    Breast cancer is a large global health burden and the most frequently diagnosed malignancy in women worldwide. Here, we utilize RGS6(-/-) mice to interrogate the role of regulator of G protein signaling 6 (RGS6), localized to the ductal epithelium in mouse and human breast, as a novel tumor suppressor in vivo. RGS6(-/-) mice exhibit accelerated 7,12-dimethylbenza[α]anthracene (DMBA)-induced tumor initiation and progression, as well as decreased overall survival. Analysis of carcinogenic aberrations in the mammary glands of DMBA-treated mice revealed a failure of the DNA damage response concurrent with augmented oncogenesis in RGS6(-/-) animals. Furthermore, RGS6 suppressed cell growth induced by either human epidermal growth factor receptor 2 or estrogen receptor activation in both MCF-7 breast cancer cells and mammary epithelial cells (MECs). MECs isolated from RGS6(-/-) mice also showed a deficit in DMBA-induced ATM/p53 activation, reactive oxygen species generation and apoptosis confirming that RGS6 is required for effective activation of the DNA damage response in these cells, a critical countermeasure against carcinogen-mediated genotoxic stress. The ability of RGS6 to simultaneously enhance DNA-damage-induced apoptotic signaling and suppress oncogenic cell growth likely underlie the accelerated tumorigenesis and cellular transformation observed in DMBA-treated RGS6(-/-) mice and isolated MECs, respectively. Unsurprisingly, spontaneous tumor formation was also seen in old female RGS6(-/-) but not in wild-type mice. Our finding that RGS6 is downregulated in all human breast cancer subtypes independent of their molecular classification indicates that obtaining a means to restore the growth suppressive and pro-apoptotic actions of RGS6 in breast might be a viable means to treat a large spectrum of breast tumors.

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

    Directory of Open Access Journals (Sweden)

    Craig S Nowell

    2011-11-01

    Full Text Available 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 multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find no evidence for a role for Foxn1 in TEC fate-choice. Rather, we show it is required for stable entry into both the cortical and medullary TEC differentiation programmes and subsequently is needed at increasing dosage for progression through successive differentiation states in both cortical and medullary TEC. We further demonstrate regulation by Foxn1 of a suite of genes with diverse roles in thymus development and/or function, suggesting it acts as a master regulator of the core thymic epithelial programme rather than regulating a particular aspect of TEC biology. Overall, our data establish a genetics-based model of cellular hierarchies in the TE lineage and provide mechanistic insight relating titration of a single transcription factor to control of lineage progression. Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development.

  15. 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...... interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found...... regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.Oncogene advance online publication, 12 May 2008; doi:10.1038/onc.2008.146....

  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. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    Science.gov (United States)

    2011-09-01

    the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression PRINCIPAL INVESTIGATOR: Paula J. McKeown-Longo, Ph.D...2011 4. TITLE AND SUBTITLE Fibronectin Matrix Remodeling in the Regulation of the 5a. CONTRACT NUMBER W81XWH-10-1-0755 Inflammatory Response within...hypothesis that force dependent unfolding of fibronectin in the tumor stroma drives an inflammatory response within the lung tumor microenvironment

  18. 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.

  19. 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.

  20. SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma.

    Science.gov (United States)

    Liao, Anyan; Shi, Ranran; Jiang, Yuliang; Tian, Suqing; Li, Panpan; Song, Fuxi; Qu, Yalan; Li, Jinna; Yun, Haiqin; Yang, Xiangshan

    2016-01-01

    Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.

  1. 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.

  2. 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)

  3. 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

  4. Targeting pH regulating proteins for cancer therapy-Progress and limitations.

    Science.gov (United States)

    Parks, Scott K; Pouysségur, Jacques

    2017-01-27

    Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pHi) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pHi regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pHi in the continued presence of external acidification (pHe). Considerable experimentation has revealed targets that successfully disrupt tumour pHi regulation in efforts to develop novel means to weaken or kill tumour cells. However, redundancy in these pH-regulating proteins, which include Na(+)/H(+) exchangers (NHEs), carbonic anhydrases (CAs), Na(+)/HCO3(-) co-transporters (NBCs) and monocarboxylate transporters (MCTs) has prevented effective disruption of tumour pHi when individual protein targeting is performed. Here we synthesise recent advances in understanding both normoxic and hypoxic pH regulating mechanisms in tumour cells with an ultimate focus on the disruption of tumour growth, survival and metastasis. Interactions between tumour acidity and other cell types are also proving to be important in understanding therapeutic applications such as immune therapy. Promising therapeutic developments regarding pH manipulation along with current limitations are highlighted to provide a framework for future research directives.

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

    DEFF Research Database (Denmark)

    Van Vooren, Bart; Ryckmann, Charlotte

    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...

  6. Allelic deletions of cell growth regulators during progression of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, H; von der Maase, H; Christensen, M

    2000-01-01

    Cell growth regulators include proteins of the p53 pathway encoded by the genes CDKN2A (p16, p14arf), MDM2, TP53, and CDKN1A (p21) as well as proteins encoded by genes like RB1, E2F, and MYCL. In the present study we investigated allelic deletions of all these genes in each recurrent bladder tumor...

  7. Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

    DEFF Research Database (Denmark)

    Aszodi, Attila; Hunziker, Ernst B; Brakebusch, Cord;

    2003-01-01

    -actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21...

  8. 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.

  9. 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.

  10. 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.

  11. The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment

    OpenAIRE

    2012-01-01

    We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are ...

  12. Influence of Tumor Microenvironment on the Molecular Regulation of Prostate Cancer Progression

    Science.gov (United States)

    2011-08-01

    well plates. Lysates were prepared from cultured cells in a solution containing 50 mM Tris, pH 7.5; 120 mM NaCl; 0.5% Nonidet p - 40 ; 40 M...metastatic progression. Adv Cancer Res, 2007. 97: p . 225-46. 40 . Mimori, K., et al., Coexpression of matrix metalloproteinase-7 (MMP-7) and epidermal...day period. Results are means ± SE of three independent experiments. * P , 0.05 (students t-test) compared to cell number at day 1 ±SEM (B

  13. 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.

  14. RNA metabolism in the regulation of protein synthesis in plants. Progress report, 1975-1979

    Energy Technology Data Exchange (ETDEWEB)

    Key, J L

    1979-01-01

    The major objectives of the research for the contract period covered by this report were (1) to gain an insight into the sequence organization of the DNA of soybean, emphasizing the arrangement of single copy or unique sequences and repetitive sequences of DNA throughout the genome, (2) to characterize soybean RNAs relative to nucleotide sequence complexity and kinetics of synthesis and turnover of poly A/sup +/ mRNA, and (3) to study ribosomal proteins directed to an analysis of possible changes in proteins which relate to the activation of 80S ribosomes and thus mRNA utilization and protein synthesis in response to environmental stimuli. Even with greatly reduced funding compared to that requested, objectives 1 and 2 were substantially accomplished. Because of reduced funding and the 20-month no cost extension, relatively little progress was made on objective 3. Accordingly objectives 1 and 2 will be summarized in some detail; a brief account of progress is presented on objective 3.

  15. AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.

    Directory of Open Access Journals (Sweden)

    Itay Israel Shemesh

    Full Text Available Diabetic nephropathy (DN is characterized by proliferation of mesangial cells, mesangial expansion, hypertrophy and extracellular matrix accumulation. Previous data have cross-linked PKB (AKT to TGFβ induced matrix modulation. The non-toxic compound AS101 has been previously shown to favorably affect renal pathology in various animal models and inhibits AKT activity in leukemic cells. Here, we studied the pharmacological properties of AS101 against the progression of rat DN and high glucose-induced mesangial dysfunction. In-vivo administration of AS101 to Streptozotocin injected rats didn't decreased blood glucose levels but ameliorated kidney hypotrophy, proteinuria and albuminuria and downregulated cortical kidney phosphorylation of AKT, GSK3β and SMAD3. AS101 treatment of primary rat glomerular mesangial cells treated with high glucose significantly reduced their elevated proliferative ability, as assessed by XTT assay and cell cycle analysis. This reduction was associated with decreased levels of p-AKT, increased levels of PTEN and decreased p-GSK3β and p-FoxO3a expression. Pharmacological inhibition of PI3K, mTORC1 and SMAD3 decreased HG-induced collagen accumulation, while inhibition of GSK3β did not affect its elevated levels. AS101 also prevented HG-induced cell growth correlated to mTOR and (rpS6 de-phosphorylation. Thus, pharmacological inhibition of the AKT downstream pathway by AS101 has clinical potential in alleviating the progression of diabetic nephropathy.

  16. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression

    Directory of Open Access Journals (Sweden)

    Giuliana Rossi

    2016-03-01

    Full Text Available Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway.

  17. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression

    Science.gov (United States)

    Rossi, Giuliana; Antonini, Stefania; Bonfanti, Chiara; Monteverde, Stefania; Vezzali, Chiara; Tajbakhsh, Shahragim; Cossu, Giulio; Messina, Graziella

    2016-01-01

    Summary Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway. PMID:26923583

  18. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

    OpenAIRE

    Tamara eMirzapoiazova; Nurbek eMambetsariev; Frances E Lennon; Bolot eMambetsariev; Joshua E. Berlind; Ravi eSalgia; Singleton, Patrick A.

    2015-01-01

    Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was...

  19. HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression

    OpenAIRE

    Mirzapoiazova, Tamara; Mambetsariev, Nurbek; Frances E Lennon; Mambetsariev, Bolot; Joshua E. Berlind; Salgia, Ravi; Singleton, Patrick A.

    2015-01-01

    Background Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, hyaluronan binding protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics. Methods Immunohistochemical an...

  20. Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.

    Science.gov (United States)

    Sumantran, Venil N; Mishra, Pratik; Sudhakar, N

    2015-04-01

    A new hallmark of cancer involves acquisition of a lipogenic phenotype which promotes tumorigenesis. Little is known about lipid metabolism in melanomas. Therefore, we used BRB (Biometrics Research Branch) class comparison tool with multivariate analysis to identify differentially expressed genes in human cutaneous melanomas, compared with benign nevi and normal skin derived from the microarray dataset (GDS1375). The methods were validated by identifying known melanoma biomarkers (CITED1, FGFR2, PTPRF, LICAM, SPP1 and PHACTR1) in our results. Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. Out of the 18 genes, 13 were confirmed by KEGG pathway analysis and 10 were also significantly upregulated in human melanoma cell lines of NCI-60 Cell Miner database. Results showed that melanomas upregulated PPARGC1A transcription factor and its target genes regulating synthesis of fatty acids (SCD) and complex lipids (FABP3 and ACSL3). Melanoma also upregulated genes which prevented lipotoxicity (CPT2 and ACOT7) and regulated lipid second messengers, such as phosphatidic acid (AGPAT-4, PLD3) and inositol triphosphate (ITPKB, ITPR3). Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma. Overall, the microarray analysis of GDS-1375 dataset indicated that melanomas can become lipogenic by upregulating genes, leading to increase in fatty acid metabolism, metabolism of specific lipid second messengers, and ganglioside synthesis.

  1. [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.

  2. The impact of regulations, safety considerations and physical limitations on research progress at maximum biocontainment.

    Science.gov (United States)

    Shurtleff, Amy C; Garza, Nicole; Lackemeyer, Matthew; Carrion, Ricardo; Griffiths, Anthony; Patterson, Jean; Edwin, Samuel S; Bavari, Sina

    2012-12-01

    We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP) conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.

  3. The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment

    Directory of Open Access Journals (Sweden)

    Jean Patterson

    2012-12-01

    Full Text Available We describe herein, limitations on research at biosafety level 4 (BSL-4 containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.

  4. 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...... lines. Following a systems biology approach of integrating evidences of functional interactions such as transcription factor (TF)-miRNA interactions, we have identified a number of biologically relevant pathways involved in the development of tamoxifen resistance. Chapter 7 presents a study highlighting...

  5. [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.

  6. 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.

  7. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

    Science.gov (United States)

    Yang, Lei; Zhu, Jia; Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Zhu, Junya; Shao, Mengting; Xiao, Jinzhang; Cao, Jie; Gu, Xiaodan; Zhang, Shusen; Wang, Yingying

    2015-01-01

    PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.

  8. 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.

  9. [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.

  10. 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.

  11. 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.

  12. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Science.gov (United States)

    Contreras, R. A.; Djouad, F.

    2016-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression. PMID:27847522

  13. 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.

  14. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression.

    Science.gov (United States)

    Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R; Dal, Fulya; Kim, Sangwon F; Menter, David G; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A

    2016-05-01

    COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy.

  15. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Directory of Open Access Journals (Sweden)

    R. A. Contreras

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

  16. [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.

  17. 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.

  18. Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity

    Science.gov (United States)

    Zhao, Hong-Yi; Zhang, Shu-Di; Zhang, Kai; Wang, Xi; Zhao, Qing-Yan; Zhang, Shu-Juan; Dai, Zi-Xuan; Qian, Yong-Sheng; Zhang, You-Jing; Wei, Hao-Tian; Tang, Yan-Hong; Huang, Cong-Xin

    2017-01-01

    Background: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. Methods: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. Results: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms2, P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. Conclusions: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway. PMID:28091409

  19. 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.

  20. Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-09-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.

  1. 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.

  2. 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.

  3. 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)

  4. Structure and regulation of an archaebacterial promoter: An in vivo study. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, C.J.

    1993-12-31

    In the initial grant period the authors have devised an in vivo assay system for the analysis of gene expression in the halophilic archaea. This system has been used to analyzed the H. volcanii tRNALys promoter where it was found that the a 40 bp fragment carrying BoxA and BoxB sequences in sufficient for in vivo expression. Detailed analysis of the BoxA element indicates that the BoxA TA sequence is essential for efficient expression. Support for the hypothesis that all archaea share common transcriptional signals was obtained when a methanogen tRNAGln gene, with its associated BoxA sequence, was found to direct its own transcription in H. volcanii. In related experiments a eukaryotic RNA polymerase 3 terminator was found to act as a strong termination signal in H. volcanii. Sequence comparisons between this element and mapped RNA 3{prime} ends indicates that T-rich sequences may be important role in directing termination in vivo. Finally, in an attempt to establish a model system to study regulated gene expression, the authors have isolated a DNA fragment that encodes a heat shock inaudible transcript. This gene will not serve as a model for detailed studies of the mechanisms of gene expression in the archaea.

  5. 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

  6. 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:

  7. 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.

  8. 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.

  9. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

    Science.gov (United States)

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

  10. 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

  11. EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

    Directory of Open Access Journals (Sweden)

    Lescaille Géraldine

    2012-03-01

    Full Text Available Abstract Backgrounds An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC progression. Methods Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. Results OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Conclusions Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

  12. Soluble common gamma chain exacerbates COPD progress through the regulation of inflammatory T cell response in mice

    Directory of Open Access Journals (Sweden)

    Lee B

    2017-03-01

    Full Text Available Byunghyuk Lee,1 Eunhee Ko,1 Jiyeon Lee,2 Yuna Jo,1 Hyunju Hwang,1 Tae Sik Goh,1,3 Myungsoo Joo,2 Changwan Hong1 1Department of Anatomy and Cell Biology, Pusan National University School of Medicine, 2Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, 3Department of Orthopedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan, South Korea Abstract: Cigarette smoking (CS is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN is systemically reduced in the CSE group. Overexpression of sγc enhances the cellularity and IFNγ production of CD8 T cells in LN and also enhances Th1 and Th17 differentiation of CD4 T cells in the respiratory tract. Mechanistically, the downregulation of sγc expression mediated by CSE is required to prevent excessive inflammatory T cell responses. Therefore, our data suggest that sγc may be one of the target molecules for the control of immunopathogenic progresses in COPD. Keywords: COPD, T cell, soluble common gamma chain, cytokine

  13. Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.

    Science.gov (United States)

    Kuramitsu, Yasuhiro; Wang, Yufeng; Okada, Futoshi; Baron, Byron; Tokuda, Kazuhiro; Kitagawa, Takao; Akada, Junko; Nakamura, Kazuyuki

    2013-09-01

    QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone derived from QR-32 which shows strong tumorigenicity. A recent study showed there to be differentially expressed up-regulated and down-regulated proteins in these cells, which were identified by proteomic differential display analyses by using two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small proteins of less than 20 kDa. Their function is the regulation of actin assembly. Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of binding to actin filaments. Cofilin-1 plays roles in cell migration, proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is mainly expressed in skeletal and cardiac muscles. There are many reports showing the positive correlation between the level of cofilin-1 and cancer progression. We have also reported an increased expression of cofilin-1 in pancreatic cancer tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2 was significantly less expressed in pancreatic cancer tissues. Therefore, the present study investigated the comparison of the levels of cofilin-1 and cofilin-2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2 was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On the other hand, the difference of the intensities of the bands of cofilin-1 (18 kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a quite different intensity between QR-32 and QRsP-11, with much higher intensities in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa protein recognized by the antibody against cofilin-1 is a possible biomarker for progressive tumor cells.

  14. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

    Science.gov (United States)

    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

    2016-08-02

    ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

  15. Down-regulation of neogenin accelerated glioma progression through promoter Methylation and its overexpression in SHG-44 Induced Apoptosis.

    Directory of Open Access Journals (Sweden)

    Xinmin Wu

    Full Text Available BACKGROUND: Dependence receptors have been proved to act as tumor suppressors in tumorigenesis. Neogenin, a DCC homologue, well known for its fundamental role in axon guidance and cellular differentiation, is also a dependence receptor functioning to control apoptosis. However, loss of neogenin has been reported in several kinds of cancers, but its role in glioma remains to be further investigated. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analysis showed that neogenin level was lower in glioma tissues than in their matching surrounding non-neoplastic tissues (n = 13, p<0.01. By immunohistochemical analysis of 69 primary and 16 paired initial and recurrent glioma sections, we found that the loss of neogenin did not only correlate negatively with glioma malignancy (n = 69, p<0.01, but also glioma recurrence (n = 16, p<0.05. Kaplan-Meier plot and Cox proportional hazards modelling showed that over-expressive neogenin could prolong the tumor latency (n = 69, p<0.001, 1187.6 ± 162.6 days versus 687.4 ± 254.2 days and restrain high-grade glioma development (n = 69, p<0.01, HR: 0.264, 95% CI: 0.102 to 0.687. By Methylation specific polymerase chain reaction (MSP, we reported that neogenin promoter was methylated in 31.0% (9/29 gliomas, but absent in 3 kinds of glioma cell lines. Interestingly, the prevalence of methylation in high-grade gliomas was higher than low-grade gliomas and non-neoplastic brain tissues (n = 33, p<0.05 and overall methylation rate increased as glioma malignancy advanced. Furthermore, when cells were over-expressed by neogenin, the apoptotic rate in SHG-44 was increased to 39.7% compared with 8.1% in the blank control (p<0.01 and 9.3% in the negative control (p<0.01. CONCLUSIONS/SIGNIFICANCE: These observations recapitulated the proposed role of neogenin as a tumor suppressor in gliomas and we suggest its down-regulation owing to promoter methylation is a selective advantage for glioma genesis, progression and recurrence

  16. 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.

  17. 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.

  18. 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.

  19. Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation to induce apoptosis during initial stages of experimental colorectal cancer.

    Science.gov (United States)

    Vaish, Vivek; Rana, Chandan; Piplani, Honit; Vaiphei, Kim; Sanyal, Sankar Nath

    2014-03-01

    In the present study we have elaborated the putative mechanisms could be followed by the non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and Celecoxib in the regulation of cell cycle checkpoints along with tumor suppressor proteins to achieve their chemopreventive effects in the initial stages of experimental colorectal cancer. Male Sprague-Dawley rats were administered with 1,2-dimethylhydrazine dihydrochloride (DMH) to produce early stages of colorectal carcinogenesis. The mRNA expression profiles of various target genes were analyzed by RT-PCR and validated by quantitative real-time PCR, whereas protein expression was analyzed by Western blotting. Nuclear localization of transcription factors or other nuclear proteins was analyzed by electrophoretic mobility shift assay and immunofluorescence. Flowcytometry was performed to analyze the differential apoptotic events and cell cycle regulation. Molecular docking studies with different target proteins were also performed to deduce the various putative mechanisms of action followed by Sulindac and Celecoxib. We observed that DMH administration has abruptly increased the proliferation of colonic cells which is macroscopically visible in the form of multiple plaque lesions and co-relates with the disturbed molecular mechanisms of cell cycle regulation. However, co-administration of NSAIDs has shown regulatory effects on cell cycle checkpoints via induction of various tumor suppressor proteins. We may conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated regulation of cell proliferation, where down regulation of NF-κB signaling and activation of PPARγ might serve as important additional events in vivo.

  20. 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.

  1. 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)

  2. The collagen triple helix repeat containing 1 facilitates hepatitis B virus-associated hepatocellular carcinoma progression by regulating multiple cellular factors and signal cascades.

    Science.gov (United States)

    Zhang, Rui; Cao, Yanhua; Bai, Lan; Zhu, Chengliang; Li, Rui; He, Hui; Liu, Yingle; Wu, Kailang; Liu, Fang; Wu, Jianguo

    2015-12-01

    Hepatitis B virus (HBV) infection is one of the major causes of acute and chronic liver diseases, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCC accounts for more than 85% of primary liver cancers and is the seventh most common cancer and the third leading cause of cancer-related deaths. However, the mechanism by which HBV induces HCC is largely unknown. Collagen triple helixes repeat containing 1 (CTHRC1) is a secreted protein and has characteristics of a circulating hormone with potentially broad implications for cell metabolism and physiology. CTHRC1 is associated with human cancers, but its effect on HCC is unknown. Here, we revealed that CTHRC1 expression is highly correlated with HCC progression in HBV-infected patients, and demonstrated that HBV stimulates CTHRC1 expression by activating nuclear factor-kappa B (NF-κB) and cAMP response element binding protein (CREB), through extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/c-JNK) pathway. In addition, CTHRC1 activates hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) through regulating phosphoinosmde-3-kinase/protein kinase B/mammalian target of rapamycin (PI-3K/AKT/mTOR) pathway. More interestingly, CTHRC1 enhances colony formation, migration, and invasion of hepatoma cells by regulating p53 and stimulating matrix metalloproteinase-9 (MMP-9) expression. In addition, knock-down of CTHRC1 results in the repression of HBV-associated carcinogenesis in nude mice. Thus, we revealed a novel mechanism by which HBV facilitates HCC development through activating the oncoprotein CTHRC1, which in turn enhances HBV-related HCC progression by stimulates colony formation, migration, and invasion of hepatoma cells through regulating multiple cellular factors and signal cascades.

  3. CIP2A modulates cell-cycle progression in human cancer cells by regulating the stability and activity of Plk1.

    Science.gov (United States)

    Kim, Jae-Sung; Kim, Eun Ju; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu

    2013-11-15

    Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1-dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development.

  4. Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines:Colo-320 and SW1116

    Institute of Scientific and Technical Information of China (English)

    Jing Yuan FANG; Ying Xuan CHEN; Juan LU; Rong LU; Li YANG; Hong Yin ZHU; Wei Qi GU; Lun Gen LU

    2004-01-01

    The aim of this study is to assess the effects of DNA methylation and histone acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methylation-specific PCR, and the acetylated status of the histones associated with the p21wAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry.We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21 WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73,c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.

  5. 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.

  6. Recent progress of appetite regulation in central nervous system%中枢食欲调节研究进展

    Institute of Scientific and Technical Information of China (English)

    程笑冰; 宁光

    2009-01-01

    Concordant ingestion of appetite regulation internet is the basic physiological activity of human. Appetite regulation relates to complicate mechanisms and involves many systems and factors. Their impacting and controlling formed the appetite regulation internet. The hypothalamus plays a crucial role in re-cepting,integrating and releasing signals of energy status in central nervous system. The consummated con-struction of hypothalamus about appetite regulation and the finding of new regulation factors are very impor-tant for the learning of mechanism of obesity and diabetes and the development of drugs.%食欲调节网络的协调性摄食活动是维持人类生命的基本生理活动,食欲调节具有复杂而精细的调节机制,而下丘脑正是接受、整合与发放食欲调节信号、维持体重稳定的重要中枢.中枢神经系统或外周组织产生的具有促/抑食欲作用的神经内分泌因子在下丘脑形成复杂的食欲调节网络和相互投射的神经环路,对食欲进行精确的调控.不断完善下丘脑食欲调节区域,不断发现新的调控因子及其作用机制,对深入了解肥胖及糖尿病的病理生理机制及设计开发各种有效控制体重和血糖的药物有重大意义.

  7. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer

    Science.gov (United States)

    Heger, Zbynek; Merlos Rodrigo, Miguel Angel; Michalek, Petr; Polanska, Hana; Masarik, Michal; Vit, Vitezslav; Plevova, Mariana; Pacik, Dalibor; Eckschlager, Tomas; Stiborova, Marie

    2016-01-01

    The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential. PMID:27824899

  8. 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.

  9. Sirtuin1功能及调控研究进展%PROGRESS IN FUNCTIONS AND REGULATION OF SIRTUIN 1

    Institute of Scientific and Technical Information of China (English)

    赵雯; 李方晖; 肖冰

    2012-01-01

    Sirtuin 1 (SIR.T1) is the largest among the seven members of the sirtuin family of class HI nicoiinamide ade-nine dinucleoude (NAD ( + ))-dependent protein deacetylases, which is the most widely studied longevity factor in recent studies. In addition to achieve the epigenelic regulation by the acetylation of lysine residues in histories, SIRT1 can also regulate the activity of several other key cellular proteins, which have emerged as critical regulators of cell growth, differentiation, and apoptolic programs. Recent studies have found that SIRT1 regulation on cell functions is not only through the level of its activity, but also through subcellular localization. SIRT1 shuttles between nucleus and cytoplasm and the level of SIRT1 activity and its physiological function regulation still need to be further studied.%Sirtuin 1(SIRTl)是依赖于烟酰胺腺(嘿)呤二核苷酸辅酶(nicotinamide adenine dinucleotide,NAD+)的去乙酰化酶(Sirtuins,SIRTs)家族7个成员中最大的一个,是近年来研究最为广泛的长寿因子.SIRT1除了对组蛋里赖氨酸残基去乙酰化修饰调节表现遗传外,SIRT1还可以调节细胞其他关键蛋白活性,控制细胞增殖、分化和细胞凋亡等生理功能.量近研究发现,SIRT1调控细胞功能除了与其酶活性水平有关,也可能风其在细胞中的定位有关.SIRT1在细胞核质之间穿梭和SIRT1活性水平及其相对应的生理功能仍需深入研究.

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

    Energy Technology Data Exchange (ETDEWEB)

    Matsunaga, Toshiyuki, E-mail: matsunagat@gifu-pu.ac.jp [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Soda, Midori; Yamamura, Keiko [Laboratory of Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); El-Kabbani, Ossama [Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052 (Australia); Tajima, Kazuo [Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181 (Japan); Ikari, Akira [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Hara, Akira [Faculty of Engineering, Gifu University, Gifu 501-1193 (Japan)

    2014-07-15

    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

  11. Beta-endorphin neuron regulates stress response and innate immunity to prevent breast cancer growth and progression.

    Science.gov (United States)

    Sarkar, Dipak K; Zhang, Changqing

    2013-01-01

    Body and mind interact extensively with each other to control health. Emerging evidence suggests that chronic neurobehavioral stress can promote various tumor growth and progression. The biological reaction to stress involves a chemical cascade initiated within the central nervous system and extends to the periphery, encompassing the immune, endocrine, and autonomic systems. Activation of sympathetic nervous system, such as what happens in the "fight or flight" response, downregulates tumor-suppressive genes, inhibits immune function, and promotes tumor growth. On the other hand, an optimistic attitude or psychological intervention helps cancer patients to survive longer via increase in β-endorphin neuronal suppression of stress hormone levels and sympathetic outflows and activation of parasympathetic control of tumor suppressor gene and innate immune cells to destroy and clear tumor cells.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Molecular mechanisms and clinical applications of miR-22 in regulating malignant progression in human cancer (Review)

    Science.gov (United States)

    Wang, Jingyu; Li, Yuan; Ding, Meiman; Zhang, Honghe; Xu, Xiaoming; Tang, Jinlong

    2017-01-01

    miRNAs (microRNAs) have been validated to play fateful roles in the occurrence and development of cancers by post-transcriptionally targeting 3′-untranslated regions of the downstream gene mRNAs to repress mRNA expression. Mounting investigations forcefully document that not only does miR-22 biologically impinge on the processes of senescence, energy supply, angiogenesis, EMT (epithelial-mesenchymal transition), proliferation, migration, invasion, metastasis and apoptosis, but also it genetically or epigenetically exerts dual (inhibitory/promoting cancer) effects in various cancers via CNAs (copy number alterations), SNPs (single nucleotide polymorphisms), methylation, acetylation and even more momentously hydroxymethylation. Additionally, miR-22 expression may fluctuate with cancer progression in the body fluids of cancer patients and miR-22 could amplify its inhibitory or promoting effects through partaking in positive or negative feedback loops and interplaying with many other related miRNAs in the cascade of events, making it possible for miR-22 to be a promising and complementary or even independent cancer biomarker in some cancers and engendering profound influences on the early diagnosis, therapeutics, supervising curative effects and prognosis. PMID:28000852

  18. 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.

  19. Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.

    Directory of Open Access Journals (Sweden)

    Nathaniel G Jones

    2014-01-01

    Full Text Available The African trypanosome, Trypanosoma brucei, maintains an integral link between cell cycle regulation and differentiation during its intricate life cycle. Whilst extensive changes in phosphorylation have been documented between the mammalian bloodstream form and the insect procyclic form, relatively little is known about the parasite's protein kinases (PKs involved in the control of cellular proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi cell line library was generated, allowing independent inducible knockdown of each of the parasite's 190 predicted protein kinases. Screening of this library using a cell viability assay identified ≥42 PKs that are required for normal bloodstream form proliferation in culture. A secondary screen identified 24 PKs whose RNAi-mediated depletion resulted in a variety of cell cycle defects including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis, 15 of which are novel cell cycle regulators. A further screen identified for the first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2, depletion of which promoted bloodstream to procyclic form differentiation. RDK1 is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39 phosphatase cascade to block uncontrolled bloodstream to procyclic form differentiation, whilst RDK2 is a PK whose depletion efficiently induces differentiation in the absence of known triggers. Thus, the RNAi kinome library provides a valuable asset for functional analysis of cell signalling pathways in African trypanosomes as well as drug target identification and validation.

  20. Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

    Science.gov (United States)

    Azevedo, Hátylas; Fujita, André; Bando, Silvia Yumi; Iamashita, Priscila; Moreira-Filho, Carlos Alberto

    2014-01-01

    Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE) genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative behavior of

  1. Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

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    Hátylas Azevedo

    Full Text Available Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative

  2. 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.

  3. 氧化应激对成骨细胞功能的影响%Research progress of oxidation stress in regulating of osteoblast function

    Institute of Scientific and Technical Information of China (English)

    王小菊; 冯正平

    2015-01-01

    Osteoporosis (OP) is an metabolic bone disease that affects human health, and its initiation and progress are closely related with the osteoblast function, such as proliferation, differentiation, apoptosis, and autophagy.ROS, the main source of oxidation stress, affects osteoblast function.To date, the research in mecha-nisms of oxidation stress on osteoblast function and relationship between autophagy and apoptosis, proliferation and differentiation have made great progress, and this paper makes a review about research of oxidation stress in regula-tion of osteoblast function.%骨质疏松的发生、发展与成骨细胞增殖、分化、凋亡和自噬等功能密切相关。活性氧( ROS)所致的氧化应激影响成骨细胞功能。本文对氧化应激影响成骨细胞功能的分子机制及与自噬与凋亡、增殖、分化间的相互联系作一综述。

  4. Estrogen Receptor (ER)α-regulated Lipocalin 2 Expression in Adipose Tissue Links Obesity with Breast Cancer Progression*

    Science.gov (United States)

    Drew, Brian G.; Hamidi, Habib; Zhou, Zhenqi; Villanueva, Claudio J.; Krum, Susan A.; Calkin, Anna C.; Parks, Brian W.; Ribas, Vicent; Kalajian, Nareg Y.; Phun, Jennifer; Daraei, Pedram; Christofk, Heather R.; Hewitt, Sylvia C.; Korach, Kenneth S.; Tontonoz, Peter; Lusis, Aldons J.; Slamon, Dennis J.; Hurvitz, Sara A.; Hevener, Andrea L.

    2015-01-01

    Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity. PMID:25468909

  5. Up-regulation of fibroblast growth factor 19 and its receptor associates with progression from fatty liver to hepatocellular carcinoma

    Science.gov (United States)

    Doughtie, Anne; Cui, Guozhen; Li, Xuanyi; Pandit, Harshul; Yang, Yingbin; Li, Suping; Martin, Robert

    2016-01-01

    Background Human fibroblast growth factor 19 (FGF19), its receptor (FGFR4) and EpCAM play an important role in cell proliferation, differentiation, motility, and overexpression have been linked to hepatocellular carcinoma (HCC). The aim of this study was to evaluate the FGF19 signals responsible for the progression of HCC arising from fatty liver. Results FGF19 level was significantly increased in the HCC patients' serum compared to non-HCC controls. The IHC results demonstrated significant increases of protein expressions of FGF19, FGFR4 and EpCAM in specimens with fatty liver, NASH, cirrhosis, and HCC compared to healthy liver tissue. There was a significant positive correlation between the protein expressions (FGF19, FGFR4, and EpCAM) and histopathologic changes from FL to HCC. Furthermore, FGF19 was positively correlated with FGFR4 and with EpCAM. Materials and Methods FGF19 protein levels in serum and tissues were determined by ELISA assay. The FGFR4, and EpCAM expression and tissue distribution were further evaluated by immunohistochemical staining in tissue array samples. FGF19, FGFR4 and EpCAM expressions between the different histologic stages of fatty liver steatohepatitis-cirrhosis-HCC carcinogenesis sequence were compared to healthy hepatic tissue. Conclusions Overexpression of FGF19/FGFR4 significantly correlated with EpCAM as a marker of hepatic cancer stem cells within the fatty liver-steatosis-cirrhosis-HCC sequence. Impact This is the first study to elucidate FGF19/FGFR4 signaling in favor of HCC cells developing as indicated by increased EpCAM within the carcinogenesis sequence from fatty liver to hepatocellular carcinoma. Our study has the potential to yield novel and cost effective screening strategies for HCC patients. PMID:27447573

  6. Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.

    Science.gov (United States)

    Nagashima, Katsuyuki; Fukushima, Hidefumi; Shimizu, Kouhei; Yamada, Aya; Hidaka, Masumi; Hasumi, Hisashi; Ikebe, Tetsuro; Fukumoto, Satoshi; Okabe, Koji; Inuzuka, Hiroyuki

    2017-02-07

    Folliculin-interacting protein 1 and 2 (FNIP1 and FNIP2) play critical roles in preventing renal malignancy through their association with the tumor suppressor FLCN. Mutations in FLCN are associated with Birt-Hogg-Dubé (BHD) syndrome, a rare disorder with increased risk of renal cancer. Recent studies indicated that FNIP1/FNIP2 double knockout mice display enlarged polycystic kidneys and renal carcinoma, which phenocopies FLCN knockout mice, suggesting that these two proteins function together to suppress renal cancer. However, the molecular mechanism functionally linking FNIP1/FNIP2 and FLCN remains largely elusive. Here, we demonstrated that FNIP2 protein is unstable and subjected to proteasome-dependent degradation via β-TRCP and Casein Kinase 1 (CK1)-directed ubiquitination in a nutrition-dependent manner. Degradation of FNIP2 leads to lysosomal dissociation of FLCN and subsequent lysosomal association of mTOR, which in turn promotes the proliferation of renal cancer cells. These results indicate that SCFβ-TRCP negatively regulates the FLCN complex by promoting FNIP degradation and provide molecular insight into the pathogenesis of BHD-associated renal cancer.

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

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    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. Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression.

    Science.gov (United States)

    Gong, Yixuan; Wang, Li; Chippada-Venkata, Uma; Dai, Xudong; Oh, William K; Zhu, Jun

    2016-10-18

    To understand the heterogeneity of prostate cancer (PCa) and identify novel underlying drivers, we constructed integrative molecular Bayesian networks (IMBNs) for PCa by integrating gene expression and copy number alteration data from published datasets. After demonstrating such IMBNs with superior network accuracy, we identified multiple sub-networks within IMBNs related to biochemical recurrence (BCR) of PCa and inferred the corresponding key drivers. The key drivers regulated a set of common effectors including genes preferentially expressed in neuronal cells. NLGN4Y-a protein involved in synaptic adhesion in neurons-was ranked as the top gene closely linked to key drivers of myogenesis subnetworks. Lower expression of NLGN4Y was associated with higher grade PCa and an increased risk of BCR. We show that restoration of the protein expression of NLGN4Y in PC-3 cells leads to decreased cell proliferation, migration and inflammatory cytokine expression. Our results suggest that NLGN4Y is an important negative regulator in prostate cancer progression. More importantly, it highlights the value of IMBNs in generating biologically and clinically relevant hypotheses about prostate cancer that can be validated by independent studies.

  9. [Studies of the genetic regulation of the Thermomonospora cellulase complex]. Progress report, June 1, 1990--January 10, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.B.

    1992-08-01

    The goals of this project are to determine the molecular mechanisms regulating cellulose synthesis in the soil bacterium Thermomonosporafusca and to determine the molecular mechanism by which T.fusca cellulases degrade crystalline cellulose. We have determined a structure for the T.fusca E{sub 2} catalytic subunit (E{sub 2}-30) by x-ray crystallography. This structure is quite similar to that of T.reesei CBHU but there are a number of differences. One is that the E{sub 2} active site is in a cleft while that of CBHII is in a tunnel. This is an expected result since E{sub 2} is an endocellulase. Large amounts of homogenous E{sub 5} catalytic subunit have been prepared and attempts to crystallize it are underway. Crystals of E{sub 2}-30 were soaked in cellobiose and modified crystals detracted well, however difference Fourier analysis showed many changes, so that we could not localize cellobiose in the 3-D structure of E{sub 2}-30. This implies that binding of cellobiose causes a significant change in the structure of E{sub 2}-30. The stereochemistry of the cleavage catalyzed by E{sub l}, E{sub 2} and E{sub 5} was determined in collaboration with Dr. Stephen Withers and E{sub 1} and 2 inverted the glycoside linkage while E{sub 5} does not. The entire E{sub l} and E{sub 4} genes have been induced into Streptomyces lividans where they are expressed at a high level and the E{sub l} and E{sub 4} are completely secreted into the medium. Studies on the synergism between the exocellulase E{sub 3} and the endocellulases E{sub 2} or E{sub 5} show that both exo and endocellulase activities are stimulated when they are assayed together.

  10. 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.

  11. 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.

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    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.

  12. 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.

  13. A parameter for IL-10 and TGF-ß mediated regulation of HIV-1 specific T cell activation provides novel information and relates to progression markers.

    Science.gov (United States)

    Lind, Andreas; Brekke, Kristin; Pettersen, Frank Olav; Mollnes, Tom Eirik; Trøseid, Marius; Kvale, Dag

    2014-01-01

    HIV replication is only partially controlled by HIV-specific activated effector T cells in chronic HIV infection and strategies are warranted to improve their efficacy. Chronic T cell activation is generally accompanied by regulation of antigen-specific T cell responses which may impair an effective control of chronic infections. The impact of HIV-induced T cell regulation on individual patients' disease progression is largely unknown, since classical T cell activation assays reflect net activation with regulation as unknown contributing factor. We here explore a quantitative parameter for antigen-induced cytokine-mediated regulation (R(AC) of HIV-specific effector T cell activation by functional antibody-blockade of IL-10 and transforming growth factor-β. HIV Env- and Gag-specific T cell activation and R(AC) were estimated in peripheral blood mononuclear cells from 30 treatment-naïve asymptomatic HIV-infected progressors (CD4 count 472/µl, HIV RNA 37500 copies/ml) stimulated with overlapping peptide panels for 6 days. R(AC) was estimated from differences in T cell activation between normal and blocked cultures, and related to annual CD4 loss, immune activation (CD38) and microbial translocation (plasma lipopolysaccharides). R(AC) was heterogeneously distributed between individual patients and the two HIV antigens. Notably, RAC did not correlate to corresponding classical activation. Env R(AC) correlated with CD38 and CD4 loss rates (r> = 0.37, p = <0.046) whereas classical Gag activation tended to correlate with HIV RNA (r = -0.35, p = 0.06). 14 patients (47%) with low R(AC)'s to both Env and Gag had higher CD8 counts (p = 0.014) and trends towards lower annual CD4 loss (p = 0.056) and later start with antiretroviral treatment (p = 0.07) than the others. In contrast, patients with high RAC to both Env and Gag (n = 8) had higher annual CD4 loss (p = 0.034) and lower CD8 counts (p = 0.014). R(AC) to Env and Gag was not

  14. A parameter for IL-10 and TGF-ß mediated regulation of HIV-1 specific T cell activation provides novel information and relates to progression markers.

    Directory of Open Access Journals (Sweden)

    Andreas Lind

    Full Text Available HIV replication is only partially controlled by HIV-specific activated effector T cells in chronic HIV infection and strategies are warranted to improve their efficacy. Chronic T cell activation is generally accompanied by regulation of antigen-specific T cell responses which may impair an effective control of chronic infections. The impact of HIV-induced T cell regulation on individual patients' disease progression is largely unknown, since classical T cell activation assays reflect net activation with regulation as unknown contributing factor. We here explore a quantitative parameter for antigen-induced cytokine-mediated regulation (R(AC of HIV-specific effector T cell activation by functional antibody-blockade of IL-10 and transforming growth factor-β. HIV Env- and Gag-specific T cell activation and R(AC were estimated in peripheral blood mononuclear cells from 30 treatment-naïve asymptomatic HIV-infected progressors (CD4 count 472/µl, HIV RNA 37500 copies/ml stimulated with overlapping peptide panels for 6 days. R(AC was estimated from differences in T cell activation between normal and blocked cultures, and related to annual CD4 loss, immune activation (CD38 and microbial translocation (plasma lipopolysaccharides. R(AC was heterogeneously distributed between individual patients and the two HIV antigens. Notably, RAC did not correlate to corresponding classical activation. Env R(AC correlated with CD38 and CD4 loss rates (r> = 0.37, p = <0.046 whereas classical Gag activation tended to correlate with HIV RNA (r = -0.35, p = 0.06. 14 patients (47% with low R(AC's to both Env and Gag had higher CD8 counts (p = 0.014 and trends towards lower annual CD4 loss (p = 0.056 and later start with antiretroviral treatment (p = 0.07 than the others. In contrast, patients with high RAC to both Env and Gag (n = 8 had higher annual CD4 loss (p = 0.034 and lower CD8 counts (p = 0.014. R(AC to Env and Gag was not

  15. 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.

  16. Pattern-Recognition Receptor Signaling Regulator mRNA Expression in Humans and Mice, and in Transient Inflammation or Progressive Fibrosis

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    Maciej Lech

    2013-09-01

    Full Text Available The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2, CD180, SIGIRR, TANK, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, SHP1, SHP2, TOLLIP, IRF4, SIKE, NLRX1, ERBIN, CENTB1, and Clec4a2 in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. Additionally, we characterized their expression profiles in mononuclear blood cells upon bacterial endotoxin, which showed a consistent induction of A20, SOCS3, IRAK-M, and Clec4a2 in human and murine cells. Furthermore, we studied the expression pattern in transient kidney ischemia-reperfusion injury versus post-ischemic atrophy and fibrosis in mice. A20, CD180, ST2, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, IRF4, CENTB1, and Clec4a2 were all induced, albeit at different times of injury and repair. Progressive fibrosis was associated with a persistent induction of these factors. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to PRR-mediated innate immunity, which seems to be involved in tissue injury, tissue regeneration and in progressive tissue scarring.

  17. 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。

  18. 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

  19. The Involvement of Corin in the Progression of Diabetic Erectile Dysfunction in a Rat Model by Down-Regulating ANP /NO/cGMP Signal Pathway.

    Science.gov (United States)

    Wang, Jian; Mi, Yuanyuan; Yuan, Fenglai; Wu, Sheng; You, Xiaoming; Dai, Feng; Huang, Yi; Cao, Jia; Zhu, Jin; Xue, Boxin; Zhu, Lijie

    2017-01-20

    This study was aimed to analyze the potential role of Corin in the procession of diabetic ED and to explore the underlying mechanism. Diabetic ED rat model was constructed and the characteristics of diabetic ED and control rats were recorded at 4, 8, 12 and 16 weeks. qRT-PCR and Western bloting were used to detected the mRNA and protein levels. Intracellular cGMP detection was accomplished using a commercial radioimmunoassay method. Vascular endothelial cell from rat corpus cavernosum spiral artery was isolated and transfected with si- Corin to analyzed the potential role of Corin. Cell viability was assessed using crystal violet. The results showed that diabetic ED rats showed significantly higher glucose level, and lower body weight, ICP level and ICP/MAP ratio at 12 and 16 weeks in diabetic ED rats compared with control rats. The protein levels of Corin, atrial natriuretic peptide (ANP)and eNOS, and the level of cGMP were significantly down-regulated in corpus cavernosum in diabetic ED rats, revealing the potential role of Corin in NO-associated diabetic ED. Further studies proved that defect of Corin not only inhibited the vascular endothelial cell viability in high-glucose condition, but also suppressed ANP, eNOS and cGMP expression in vascular endothelial cells. To sum up, Corin contributes to the progression of diabetic ED and the underlying mechanism is associated with the down-regulation of ANP /NO/cGMP signal pathway. This article is protected by copyright. All rights reserved.

  20. Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.

    Science.gov (United States)

    Bach, Anne-Sophie; Derocq, Danielle; Laurent-Matha, Valérie; Montcourrier, Philippe; Sebti, Salwa; Orsetti, Béatrice; Theillet, Charles; Gongora, Céline; Pattingre, Sophie; Ibing, Eva; Roger, Pascal; Linares, Laetitia K; Reinheckel, Thomas; Meurice, Guillaume; Kaiser, Frank J; Gespach, Christian; Liaudet-Coopman, Emmanuelle

    2015-09-29

    The lysosomal protease cathepsin D (Cath-D) is overproduced in breast cancer cells (BCC) and supports tumor growth and metastasis formation. Here, we describe the mechanism whereby Cath-D is accumulated in the nucleus of ERα-positive (ER+) BCC. We identified TRPS1 (tricho-rhino-phalangeal-syndrome 1), a repressor of GATA-mediated transcription, and BAT3 (Scythe/BAG6), a nucleo-cytoplasmic shuttling chaperone protein, as new Cath-D-interacting nuclear proteins. Cath-D binds to BAT3 in ER+ BCC and they partially co-localize at the surface of lysosomes and in the nucleus. BAT3 silencing inhibits Cath-D accumulation in the nucleus, indicating that Cath-D nuclear targeting is controlled by BAT3. Fully mature Cath-D also binds to full-length TRPS1 and they co-localize in the nucleus of ER+ BCC where they are associated with chromatin. Using the LexA-VP16 fusion co-activator reporter assay, we then show that Cath-D acts as a transcriptional repressor, independently of its catalytic activity. Moreover, microarray analysis of BCC in which Cath-D and/or TRPS1 expression were silenced indicated that Cath-D enhances TRPS1-mediated repression of several TRPS1-regulated genes implicated in carcinogenesis, including PTHrP, a canonical TRPS1 gene target. In addition, co-silencing of TRPS1 and Cath-D in BCC affects the transcription of cell cycle, proliferation and transformation genes, and impairs cell cycle progression and soft agar colony formation. These findings indicate that Cath-D acts as a nuclear transcriptional cofactor of TRPS1 to regulate ER+ BCC proliferation and transformation in a non-proteolytic manner.

  1. 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.

  2. 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.

  3. 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.

  4. Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.

    Science.gov (United States)

    Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun

    2017-01-01

    Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may

  5. The expression of VEGF-A is down regulated in peripheral blood mononuclear cells of patients with secondary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Ellen Iacobaeus

    Full Text Available BACKGROUND: Most patients with relapsing-remitting multiple sclerosis (RRMS eventually enter a secondary progressive (SPMS phase, characterized by increasing neurological disability. The mechanisms underlying transition to SPMS are unknown and effective treatments and biomarkers are lacking. Vascular endothelial growth factor-A (VEGF-A is an angiogenic factor with neuroprotective effects that has been associated with neurodegenerative diseases. SPMS has a prominent neurodegenerative facet and we investigated a possible role for VEGF-A during transition from RRMS to SPMS. METHODOLOGY/PRINCIPAL FINDINGS: VEGF-A mRNA expression in peripheral blood mononuclear (PBMC and cerebrospinal fluid (CSF cells from RRMS (n = 128, SPMS (n = 55 and controls (n = 116 were analyzed using real time PCR. We demonstrate reduced expression of VEGF-A mRNA in MS CSF cells compared to controls (p<0.001 irrespective of disease course and expression levels are restored by natalizumab treatment(p<0.001. VEGF-A was primarily expressed in monocytes and our CSF findings in part may be explained by effects on relative monocyte proportions. However, VEGF-A mRNA expression was also down regulated in the peripheral compartment of SPMS (p<0.001, despite unchanged monocyte counts, demonstrating a particular phenotype differentiating SPMS from RRMS and controls. A possible association of allelic variability in the VEGF-A gene to risk of MS was also studied by genotyping for six single nucleotide polymorphisms (SNPs in MS (n = 1114 and controls (n = 1234, which, however, did not demonstrate any significant association between VEGF-A alleles and risk of MS. CONCLUSIONS/SIGNIFICANCE: Expression of VEGF-A in CSF cells is reduced in MS patients compared to controls irrespective of disease course. In addition, SPMS patients display reduced VEGF-A mRNA expression in PBMC, which distinguish them from RRMS and controls. This indicates a possible role for VEGF-A in the mechanisms regulating

  6. 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.

  7. 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

  8. Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression.

    Science.gov (United States)

    Zhang, You-Yuan; Liu, Ze-Bing; Ye, Xuan-Guang; Ren, Wei-Min

    2016-10-01

    Treatment with high iodine concentrations can delay oncogenic activation effects, reduce cell growth and return thyroid-specific gene and protein expression levels to normal. During rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) 3 activation, excess iodine can act as a protective agent in thyroid follicular cells. The chemokine receptor CCR7 serves a critical role in lymphocyte trafficking into and within lymph nodes, the preferential metastatic site for PTC. However, the potential associations between chemokine (C‑C motif) ligand 21 (CCL21)/C‑C chemokine receptor type 7 (CCR7) interaction and iodine concentrations in primary cultures of PTC with RET/PTC expression remain unclear. Proliferation assays of primary cultures of PTC cells with RET/PTC1 and RET/PTC3 expression indicated that CCR7 activation by its specific ligand, CCL21, was associated with significantly increased cell proliferation. Flow cytometry data indicated that CCL21/CCR7 interaction significantly increased the fraction of cells in the G2/M phase of the cell cycle. Western blotting indicated that CCL21/CCR7 interaction significantly upregulated cyclin A, cyclin B1 and cyclin‑dependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signal‑regulated kinase (P‑ERK). Co-immunoprecipitation confirmed that there was interaction between P‑ERK and cyclin A, cyclin B1 or CDK1, particularly in the presence of CCL21. Sodium iodide (NaI, 10-5 M) significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 interaction contributes to G2/M progression of RET/PTC‑expressing cells via the ERK pathway in association with 10‑5 M NaI.

  9. Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation.

    Science.gov (United States)

    Souza, Ana Carolina P; Bocharov, Alexander V; Baranova, Irina N; Vishnyakova, Tatyana G; Huang, Yuning G; Wilkins, Kenneth J; Hu, Xuzhen; Street, Jonathan M; Alvarez-Prats, Alejandro; Mullick, Adam E; Patterson, Amy P; Remaley, Alan T; Eggerman, Thomas L; Yuen, Peter S T; Star, Robert A

    2016-04-01

    Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein A-I-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild-type to CD36 knockout mice and wild-type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild-type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild-type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreased renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression.

  10. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    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...... 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...... 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...

  11. SPLUNC1 regulates cell progression and apoptosis through the miR-141-PTEN/p27 pathway, but is hindered by LMP1.

    Directory of Open Access Journals (Sweden)

    Pan Chen

    Full Text Available Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1 in the carcinogenesis of nasopharyngeal carcinoma (NPC. Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.

  12. 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.

  13. Population Based Assessment of MHC Class 1 Antigens Down Regulation as Marker in Increased Risk for Development and Progression of Breast Cancer From Benign Breast Lesions

    Science.gov (United States)

    2006-01-01

    Risk for Development and Progression of Breast Cancer from Benign Breast Lesions” antigen retrieval solution in the microwave . Lastly, tissue... Microwave and citrate buffer antigen-retrieval substitutions yielded comparable results. Lab 2 demonstrated that a negative control is useful as an...the infiltrating lymphocytes in germinal centers and dendritic cells as seen in case 1. Microsatellite Analysis Labs 1, 2, and 4 performed

  14. 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.

  15. Glucose-stimulated DNA synthesis through mammalian target of rapamycin (mTOR) is regulated by KATP channels: effects on cell cycle progression in rodent islets.

    Science.gov (United States)

    Kwon, Guim; Marshall, Connie A; Liu, Hui; Pappan, Kirk L; Remedi, Maria S; McDaniel, Michael L

    2006-02-10

    The aim of this study was to define metabolic signaling pathways that mediate DNA synthesis and cell cycle progression in adult rodent islets to devise strategies to enhance survival, growth, and proliferation. Since previous studies indicated that glucose-stimulated activation of mammalian target of rapamycin (mTOR) leads to [3H]thymidine incorporation and that mTOR activation is mediated, in part, through the K(ATP) channel and changes in cytosolic Ca2+, we determined whether glyburide, an inhibitor of K(ATP) channels that stimulates Ca2+ influx, modulates [3H]thymidine incorporation. Glyburide (10-100 nm) at basal glucose stimulated [3H]thymidine incorporation to the same magnitude as elevated glucose and further enhanced the ability of elevated glucose to increase [3H]thymidine incorporation. Diazoxide (250 microm), an activator of KATP channels, paradoxically potentiated glucose-stimulated [3H]thymidine incorporation 2-4-fold above elevated glucose alone. Cell cycle analysis demonstrated that chronic exposure of islets to basal glucose resulted in a typical cell cycle progression pattern that is consistent with a low level of proliferation. In contrast, chronic exposure to elevated glucose or glyburide resulted in progression from G0/G1 to an accumulation in S phase and a reduction in G2/M phase. Rapamycin (100 nm) resulted in an approximately 62% reduction of S phase accumulation. The enhanced [3H]thymidine incorporation with chronic elevated glucose or glyburide therefore appears to be associated with S phase accumulation. Since diazoxide significantly enhanced [3H]thymidine incorporation without altering S phase accumulation under chronic elevated glucose, this increase in DNA synthesis also appears to be primarily related to an arrest in S phase and not cell proliferation.

  16. 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.

  17. 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.

  18. Involvement of ERK1/2, p38 MAPK, and PI3K/Akt signaling pathways in the regulation of cell cycle progression by PTHrP in colon adenocarcinoma cells.

    Science.gov (United States)

    Calvo, Natalia; Martín, María Julia; de Boland, Ana Russo; Gentili, Claudia

    2014-08-01

    Parathyroid hormone-related peptide (PTHrP) is distributed in most fetal and adult tissues, and its expression correlates with the severity of colon carcinoma. Recently we obtained evidence that in Caco-2 cells, a cell line from human colorectal adenocarcinoma, exogenous PTHrP increases the number of live cells, via ERK1/2, p38 MAPK, and PI3-kinase and induces the expression of cyclin D1, a cell cycle regulatory protein. In this study, we further investigated the role of PTHrP in the regulation of the cell cycle progression in these intestinal cells. Flow cytometry analysis revealed that PTHrP treatment diminishes the number of cells in the G0/G1 phase and increases the number in both S and G2/M phases. The hormone increases the expression of CDK6 and diminishes the amount of negative cell cycle regulators p27Kip1, p15INK4B, and p53. However, PTHrP does not modify the expression of cyclin D3, CDK4, and p16INK4A. In addition, inhibitors of ERK1/2 (PD98059), p38 MAPK (SB203580), and PI3Kinase (LY294002) reversed PTHrP response in Caco-2 cells. Taken together, our results suggest that PTHrP positively modulates cell cycle progression and changes the expression of proteins involved in cell cycle regulation via ERK1/2, p38 MAPK, and PI3K signaling pathways in Caco-2 cells.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Progress on Regulation of Gene Expression in Giardia lamblia%蓝氏贾第鞭毛虫基因表达调控的研究进展

    Institute of Scientific and Technical Information of China (English)

    王乙惠; 李雅杰

    2011-01-01

    蓝氏贾第鞭毛虫是一种重要的致病性寄生虫,人体感染后主要引起腹泻和营养不良等症状.作为一种源真核生物,其基因表达调控机制可能与其他真核生物有较大的区别.本文从蓝氏贾第虫鞭毛虫启动子、转录因子、转录后调节、翻译起始和表观遗传学等方面,对贾第虫基因表达调控的研究进展进行综述.%Giardia lamblia is an important human pathogen that causes diarrhea and malnutrition. As a late-branching eukaryote, G. lamblia may have special mechanisms for regulating gene expression which differ from other eukaryotes. In this paper, the mechanisms that governing regulation of G. lamblia gene expression, such as promoters, transcription factors, transcriptional regulation, translation initiation and epigenetic mechanisms are summarized.

  4. 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.

  5. Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells "in vitro" and correlating with progression "in vivo".

    Science.gov (United States)

    Perico, Maria Elisa; Grasso, Silvia; Brunelli, Matteo; Martignoni, Guido; Munari, Enrico; Moiso, Enrico; Fracasso, Giulio; Cestari, Tiziana; Naim, Hassan Y; Bronte, Vincenzo; Colombatti, Marco; Ramarli, Dunia

    2016-11-08

    The expression of Prostate Specific-Membrane Antigen (PSMA) increases in high-grade prostate carcinoma envisaging a role in growth and progression. We show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and MAPK pathways thus promoting proliferation and survival. PSMA activity was dependent on the assembly of a macromolecular complex including filamin A, beta1 integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and Y1173 EGF-independent residues. Silencing or blocking experiments with drugs demonstrated that all the complex components were required for full PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that p130CAS and EGFR exerted a major role. All PSMA complex components were found assembled in multiple samples of two high-grade prostate carcinomas and associated with EGFR phosphorylation at Y1086. The expression of p130CAS and pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS 5+5. Patients with Gleason Score ≤5 resulted negative whereas those with GS≥5 expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases, respectively.Collectively, our results demonstrate for the first time that PSMA recruits a functionally active complex which is present in high-grade patients. In addition, two components of this complex, p130CAS and the novel pEGFRY1086, correlate with progression in castration-resistant patients and could be therefore useful in therapeutic or surveillance strategies of these patients.

  6. 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.

  7. 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

  8. 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....

  9. Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55 for timely mitotic progression.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Juanes

    Full Text Available Entry into mitosis is triggered by cyclinB/Cdk1, whose activity is abruptly raised by a positive feedback loop. The Greatwall kinase phosphorylates proteins of the endosulfine family and allows them to bind and inhibit the main Cdk1-counteracting PP2A-B55 phosphatase, thereby promoting mitotic entry. In contrast to most eukaryotic systems, Cdc14 is the main Cdk1-antagonizing phosphatase in budding yeast, while the PP2A(Cdc55 phosphatase promotes, instead of preventing, mitotic entry by participating to the positive feedback loop of Cdk1 activation. Here we show that budding yeast endosulfines (Igo1 and Igo2 bind to PP2A(Cdc55 in a cell cycle-regulated manner upon Greatwall (Rim15-dependent phosphorylation. Phosphorylated Igo1 inhibits PP2A(Cdc55 activity in vitro and induces mitotic entry in Xenopus egg extracts, indicating that it bears a conserved PP2A-binding and -inhibitory activity. Surprisingly, deletion of IGO1 and IGO2 in yeast cells leads to a decrease in PP2A phosphatase activity, suggesting that endosulfines act also as positive regulators of PP2A in yeast. Consistently, RIM15 and IGO1/2 promote, like PP2A(Cdc55, timely entry into mitosis under temperature-stress, owing to the accumulation of Tyr-phosphorylated Cdk1. In addition, they contribute to the nuclear export of PP2A(Cdc55, which has recently been proposed to promote mitotic entry. Altogether, our data indicate that Igo proteins participate in the positive feedback loop for Cdk1 activation. We conclude that Greatwall, endosulfines, and PP2A are part of a regulatory module that has been conserved during evolution irrespective of PP2A function in the control of mitosis. However, this conserved module is adapted to account for differences in the regulation of mitotic entry in different organisms.

  10. 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。

  11. MicroRNA与肿瘤糖代谢研究进展%Research progress in microRNA regulation of tumor glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    胡骏; 殷保兵

    2013-01-01

    Aerobic glycolysis,which is also termed as Warburg effect,is one of the most common and profound biochemical phenotypes of tumor ceils.Several oncogenes and tumor suppressors genes have been implicated in aerobic glycolysis.MicroRNAs can control this metabolic switch by regulating oncogenes and tumor suppressors genes in a post-transcriptional way.A deeper understanding of the mechanisms and pathways by which miRNAs regulate the aerobic glycolysis will hopefully lead to a new therapeutic strategy for malignant cancer.%有氧糖酵解(Warburg效应)是肿瘤细胞的重要特征,它是癌基因和抑癌基因共同作用的结果.microRNA (miRNA)能够在转录后水平参与这些癌基因和抑癌基因的表达来调控肿瘤糖代谢方式的转变.对miRNA调控糖代谢机制的深入研究能够提供新的肿瘤治疗策略.

  12. Overexpression of N-terminal kinase like gene promotes tumorigenicity of hepatocellular carcinoma by regulating cell cycle progression and cell motility.

    Science.gov (United States)

    Wang, Jian; Liu, Ming; Chen, Leilei; Chan, Tim Hon Man; Jiang, Lingxi; Yuan, Yun-Fei; Guan, Xin-Yuan

    2015-01-30

    Amplification and overexpression of CHD1L is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC). Here we found that one of CHD1L downstream targets, NTKL, was frequently upregulated in HCC, which was significantly correlated with vascular invasion (P = 0.012) and poor prognosis (P = 0.050) of HCC. ChIP assay demonstrated the binding of CHD1L to the promoter region of NTKL. QRT-PCR study showed that the expression of NTKL positively correlated with CHD1L expression in both clinical samples and cell lines. Functional study found that NTKL had strong oncogenic roles, including increased cell growth, colony formation in soft agar, and tumor formation in nude mice. Further study found that NTKL could promote G1/S transition by decreasing P53 and increasing CyclinD1 expressions. NTKL overexpression could accelerate the mitotic exit and chromosome segregation, which led to the cytokinesis failure and subsequently induced apoptosis. NTKL also regulated cell motility by facilitating philopodia and lamellipodia formation through regulating F-actin reorganization and the phosphorylation of small GTPase Rac1/cdc42. Using co-IP and mass spectrometry approach, we identified the large GTPase dynamin2 as an interacting protein of NTKL, which might be responsible for the phenotype alterations caused by NTKL overexpression, such as cytokinesis failure, increased cell motility and abnormal of cell division.

  13. 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.

  14. Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression.

    Science.gov (United States)

    Coke, Christopher J; Scarlett, Kisha A; Chetram, Mahandranauth A; Jones, Kia J; Sandifer, Brittney J; Davis, Ahriea S; Marcus, Adam I; Hinton, Cimona V

    2016-05-06

    The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells

    Science.gov (United States)

    Wu, Szu-Yuan; Yan, Ming-De; Wu, Alexander T.H.; Yuan, Kevin Sheng-Po; Liu, Shing Hwa

    2016-01-01

    In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively. Moreover, fucoidan reduced the luciferase activity of 3'-untranslated region reporter; treatment of cells with the miR-29c mimic or miR-17-5p inhibitor also produced similar results. These effects of fucoidan inhibited the epithelial-mesenchymal transition in breast cancer cells, as evidenced by an increase in E-cadherin and a drop in N-cadherin, and inhibited breast cancer cell survival, as evidenced by the activation of the phosphoinositide 3-kinase/Akt pathway. Taken together, these findings demonstrate that fucoidan inhibits breast cancer progression by regulating the miR-29c/ADAM12 and miR-17-5p/PTEN axes. Fucoidan is a potential chemopreventive/chemotherapeutic agent for breast cancer. PMID:27994679

  20. MicroRNA library screening identifies growth-suppressive microRNAs that regulate genes involved in cell cycle progression and apoptosis.

    Science.gov (United States)

    Choi, Young-Chul; Yoon, Sena; Byun, Yuree; Lee, Gangtae; Kee, Honghwan; Jeong, Yongsu; Yoon, Jaeseung; Baek, Kwanghee

    2015-12-10

    Micro(mi)RNAs play important and varied roles in tumorigenesis; however, the full repertoire of miRNAs that affect cancer cell growth is not known. In this study, an miRNA library was screened to identify those that affect the growth of A549 tumor cells. Among 300 miRNAs, miR-28-5p, -323-5p, -510-5p, -552-3p, and -608 were the most effective in inhibiting cell growth. More specifically, overexpressing miR-28-5p, -323-5p, and -510-5p induced G1 arrest, as determined by flow cytometry, whereas that of miR-608 induced cell death in a caspase-dependent manner. Moreover, several genes involved in apoptosis and cell cycle progression were downregulated upon overexpression of each of the five miRNAs, with the functional targets of miR-552-3p and miR-608 confirmed by microarray, quantitative real-time PCR, and luciferase reporter assay. In miR-608-transfected cells, B cell lymphoma 2-like 1 (BCL2L1), D-type cyclin 1 (CCND1), CCND3, cytochrome b5 reductase 3 (CYB5R3), phosphoinositide 3-kinase regulatory subunit 2 (PIK3R2), specificity protein 1 (SP1), and phosphorylated Akt were all downregulated, while Bcl-2-interacting killer (BIK) was upregulated. Moreover, miR-608 was determined to have a suppressive function on tumor growth in an NCI-H460 xenograft model. These findings provide insights into the roles of five miRNAs in growth inhibition and their potential function as cancer therapeutics.

  1. Research Progress on Feed-intake Regulation of Pigs%猪采食调控机制研究进展

    Institute of Scientific and Technical Information of China (English)

    陈守云

    2011-01-01

    Feed intake is highly relevant to the growth performance of pig. The improvement of feed intake is considered to be an important contributor to the increase of pig production. The appetite and intake behavior of pig are regulated by various central and peripheral factors,including feeding technique,living circumstance,chemo-factors and metabolic-factors. Hypothala-mus plays a key role in integrating all these signals so as to regulate feed intake. Researches on intake signaling have achieved great improvement,owing to the implication of molecular methods, numerous signaling factors involved in the intake-net have been reported,among which AMPK.mTOR and Leptin have been most attractive to researchers in this area. The present paper summarized the factors influencing feed intake as well as the key role of hypothalamus in regulating feed intake, and probed molecular mechanism of feed intake. Questions involved and research direction were raised and discussed.%猪的采食量与其生长速度、生产性能息息相关.在保证猪健康生长的同时,尽可能地提高其采食量,是提高养猪生产效益的重要途径.猪的食欲和采食行为受到外界环境、饲养技术、自身物理特性、体内化学和代谢因子、中枢和外周信号因子的综合调控.下丘脑在整合各种信号从而发挥采食调控作用的网络中发挥着关键作用.分子生物学手段的应用使得采食信号因子的研究不断取得突破,NPY、CCK、SS、Orexin、Ghrelin等在下丘脑采食调控网络中的作用和信号途径已日渐明朗,而AMPK、mTOR和Leptin更是成为近年来的研究热点.作者从影响猪采食行为的因素、下丘脑的调控作用及影响采食行为的主效因子等方面展开论述,综述了当前国内外在猪采食调控方面的研究进展,针对存在的问题提出讨论,并对接下来的研究方向做出展望.

  2. 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....

  3. 植物花青素苷生物合成及调控的研究进展%Progress on Plant Anthocyanin Biosynthesis and Regulation

    Institute of Scientific and Technical Information of China (English)

    高燕会; 黄春红; 朱玉球; 童再康

    2012-01-01

    花青素苷( anthocyanin)是植物新陈代谢过程中产生的类黄酮物质,决定被子植物花、果实、种皮、茎、叶和根等的颜色,具有重要的营养价值和药理作用.近年来关于花青素生物合成途径的研究已取得突破,综述了植物花青素苷基因研究现状和发展趋势,包括植物花青素生物合成途径、参与生物合成途径中相关的结构基因和调控基因及功能研究以及影响花青素苷生物合成的环境因素等的研究进展.%Anthocyanin with important nutritional and medical usages is flavonoids in plant metabolism, and decides the color of flowers, fruit, testa, stem leaves and roots and so on in angiosperm. Recently studies on the biosynthetic pathway were undertaken continuously. The research status and development tendency of plant anthyocyanin were summarized, including the anthocyanin biosynthetic pathway, structural gene and regulator genes and their functional study participating in the biosynthetic pathway and environment factors affecting the biosynthetic pathway.

  4. 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.

  5. 膳食反式脂肪酸研究进展及安全管理%Progress on the research of trans fatty acids and related regulations

    Institute of Scientific and Technical Information of China (English)

    张坚

    2011-01-01

    研究表明,过量摄入反式脂肪酸可引起血脂代谢紊乱,增加冠心病及其它慢性疾病的发生风险.其对健康的不利影响受到广泛关注.本文就膳食反式脂肪酸的结构特点、食物来源、主要健康危害、不同人群摄入量以及管理现状等问题进行综述.%More evidences implied that over consumption of trans fatty acids can cause dyslipidemia and increase the incidence of coronary heart disease and other chronic diseases.Thus, much more attentions have been attracted by the negative effects of trans fatty acids on health.This review concentrates on the issues of structural characteristics, food source and health risk of trans fatty acids, the intake of trans fatty acids in different population and related regulations.

  6. Research Progress in Transcription and Regulation of Daxx%Daxx的转录抑制及激活调控功能

    Institute of Scientific and Technical Information of China (English)

    易旸; 万艳平

    2011-01-01

    Daxx定位细胞核PODs,可在转录调控中行使转录抑制或转录激活双重功能.Daxx通过转位、化学修饰、染色体调节、直接与转录因子或转录相关蛋白相互作用等多种方式发挥转录调控作用.其中,Daxx通过转位,转录后化学修饰,染色体调节,与转录因子或转录相关蛋白相互作用行使转录抑制功能,但相关研究表明Daxx同样可通过与相关因子相互作用激活转录,但具体作用机制尚不清楚.%Multifunctional protein death domain associate protein ( Daxx ) localizes in promy-leocytic leukaemia protein oncogeneic domains. It plays a dual role ( transcription inhibition or transcription activation ) in transcriptional regulation. Daxx may function by many ways such as translo-cation, chemical modification, chromatin modulation or direct interaction with some transcriptional factors or proteins.

  7. Possibility of the enhanced progression of fetal liver stem/progenitor cells therapy for treating end-stage liver diseases by regulating the notch signaling pathway.

    Science.gov (United States)

    You, Nan; Liu, Weihui; Zhong, Xiao; Dou, Kefeng; Tao, Kaishan

    2012-10-01

    Cell therapy is the most promising therapy for end-stage liver diseases (ESLDs). Fetal liver stem/progenitor cells (FLSPCs) have the advantages of a high survival rate, high proliferation, small volume, and high safety, which make them one of the ideal cells for stem cell therapy for liver diseases. During the early phase of our study, we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency that was similar to the flow cell-sorting method. Additionally, using a fulminant hepatic failure rat model, we demonstrated that FLSPCs can contribute to the recovery of hepatic morphogenesis and function. However, two problems remain to be resolved to explore the therapeutic potential of FLSPCs. First, how can FLSPCs be induced to accurately differentiate into hepatocytes and cholangiocytes? Second, how do FLSPCs maintain self-renewal? The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells. Additionally, our previous findings have shown that the Notch signaling plays an important role in FLSPC differentiation into hepatocytes. Therefore, we hypothesized that the Notch signaling may be involved in the differentiation and self-renewal of FLSPCs. We began a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target, which may become an index for the clinical application of FLSPCs.

  8. Regulation of nuclear envelope dynamics via APC/C is necessary for the progression of semi-open mitosis in Schizosaccharomyces japonicus.

    Science.gov (United States)

    Aoki, Keita; Shiwa, Yuh; Takada, Hiraku; Yoshikawa, Hirofumi; Niki, Hironori

    2013-09-01

    Three types of mitosis, which are open, closed or semi-open mitosis, function in eukaryotic cells, respectively. The open mitosis involves breakage of the nuclear envelope before nuclear division, whereas the closed mitosis proceeds with an intact nuclear envelope. To understand the mechanism and significance of three types of mitotic division in eukaryotes, we investigated the process of semi-open mitosis, in which the nuclear envelope is only partially broken, in the fission yeast Schizosaccharomyces japonicus. In anaphase-promoting complex/cyclosome (APC/C) mutants of Sz. japonicus, the nuclear envelope remained relatively intact during anaphase, resulting in impaired semi-open mitosis. As a suppressor of apc2 mutant, a mutation of Oar2, which was a 3-oxoacyl-[acyl carrier protein] reductase, was obtained. The level of the Oar2, which had two destruction-box motifs recognized by APC/C, was increased in APC/C mutants. Furthermore, the defective semi-open mitosis observed in an apc2 mutant was restored by mutated oar2+. Based on these findings, we propose that APC/C regulates the dynamics of the nuclear envelope through degradation of Oar2 dependent on APC/C during the metaphase-to-anaphase transition of semi-open mitosis in Sz. japonicus.

  9. Progress in Electrical Nerve Stimulation/Regulation Treating Neurogenic Bladder after Spinal Cord Injury%神经电刺激/调节治疗脊髓损伤后神经源性膀胱的研究进展

    Institute of Scientific and Technical Information of China (English)

    王桢; 周仁兰

    2015-01-01

    近年来,脊髓损伤后神经源性膀胱的治疗方式发展迅速,出现了神经电刺激/神经电调节等微创治疗新方法,其临床疗效在国内外已得到广泛认同,其适应症及应用范围亦逐渐扩大。本文将详细综述目前常见的几种神经电刺激/神经电调节技术的使用方法及新进展。%Treatment of neurogenic bladder after spinal cord injury develops rapidly in recent years, minimally invasive treatment of electrical nerve stimulation/regulation emerges, whose clinical efficacy has been widely recognized at home and abroad, the indications and applied range are also gradually expanding. This paper reviews usage and new progress of several common electrical nerve stimulation/regulation technique in detail.

  10. 昆虫滞育相关激素调节的研究进展%Research Progress of the Hormone Regulation of Insect Diapause

    Institute of Scientific and Technical Information of China (English)

    徐晶晶; 陈斌; 郝友进; 司凤玲; 何正波

    2012-01-01

    Insects growth and development are controlled by hormone.Diapause is a special development state.In this state,the significant characteristics are metabolism reducing and arrest of development.In the process of diapause development,a variety of hormone tends to create a network by intercoordination.Diapause plays an important regulatory role in diapause development.Insect neuroendocrine hormone is synthesized by neuroendocrine system and acts as upstream factor to affect insect diapause by regulating the synthesis and release of the downstream hormone.The regulation function of diapause hormone-pher-omone biosynthesis activating neuropeptide and prothoracicotropic hormone in the different type of diapause,insects has been widely studied.Located at the downstream in the network of neuropeptide hormone,the hormones ecdysteroids and juvenile hormone also play important regulatory roles but less studied so far.In addition,the research of hormone receptors will provide an important basis to explain the interaction between hormones; and by adjusting the hormone levels in diapause insect which will provide a new method in the biological control of harmful insects.%昆虫的生长发育离不开激素的调节.滞育作为昆虫特殊的发育状态,其特征是代谢活动显著降低,发育停滞.在滞育发育过程中,各类激素通常相互协调形成网络,发挥着重要的调节作用.在神经内分泌系统中,由神经细胞分泌的神经肽类激素通常作为上游调控激素,通过调节下游激素的合成和分泌从而影响昆虫的滞育发育;蜕皮激素和保幼激素作为下游激素参与到神经肽类激素的调控网络中.目前已克隆得到滞育激素-性信息素合成激活肽和促前胸腺激素的基因,并对二者在不同滞育型昆虫中的调节作用进行了深入研究.此外,激素受体的研究将为解释激素之间的相互作用提供重要依据;而通过滞育昆虫体内激素水平的调节将为有害

  11. 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

  12. Regulations of enzymes in animals: effects of developmental processes, cancer and radiation. Progress report X, 1 May 1975--30 April 1976

    Energy Technology Data Exchange (ETDEWEB)

    Knox, W.E.

    1976-06-01

    The accumulated analysis of tissues shows statistically significant discriminations between normal and neoplastic tissues of a variety of types. The practical identification of cancer by chemical means is thus possible, in principle. The principle itself is of immediate importance: that cancers share a common chemical pattern that can be sought in diagnostic studies, and targeted for therapeutic manipulations. To pursue these studies, additional varieties of transplantable neoplasms were produced and described. The common composition shared by neoplasms bears many resemblances to that of normal immature tissues, and this has reinforced interest in the programmed gene expressions we have studied during development. The development of physiological functions in parallel with the appearance of enzyme components in differentiating tissues has also been a fertile field. Instances of gene mutation associated with absence of an enzyme and consequently with severe functional impairment have been simpler to analyze. A study of phenylketonuria was begun, this time focussing our knowledge of the regulation of gene expression to produce an experimental model of the diesease. A new mutation in the rat causing infantile ichthyosis was identified and isolated. One sign of the disease is hyperkeratosis, analogous to that seen in preneoplastic lesions. The susceptibility of these animals to carcinogenesis in the skin is being studied. The quantitative analysis of numerous enzymes in various tissues has disclosed a variety of new isozymes which have been studied sufficiently to define them as chemically new species and to survey their possible functional importance. The include the several glutaminases, glutamine synthetase and its associated transferase isozyme (glutamine hydroxylamine transferase), and the new arginase of non-hepatic tissues. car

  13. 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.

  14. 微量元素和饲料添加剂调控蛋壳品质的研究进展%Research Progress of Microelement and Feed Additives on Eggshell Quality Regulation

    Institute of Scientific and Technical Information of China (English)

    张亚男; 王晶; 武书庚; 张海军; 齐广海

    2016-01-01

    蛋壳破损是家禽养殖业的重要问题,受日龄、基因、环境、营养和蛋鸡的健康状况等影响。近年来,营养调控蛋壳品质的研究主要集中于微量元素和饲料添加剂。本文简述了微量元素和饲料添加剂影响蛋壳品质的研究进展,以期为生产实践中蛋壳品质的调控提供新措施。饲粮中添加一定水平和形式的锰、微生态制剂、有机酸和中药提取物等均可改善蛋壳品质。%Poor eggshell quality is an important problem in poultry industry, which is affected by many factors such as age, genetic, environmental and nutritional factors, as well as the health status of hens. Many recent studies regarding the effect of nutrition on eggshell quality regulation have focused on dietary microelement and feed additives. This study was summarized the research progress of microelement and feed additives on eggshell quality regulation, in order to provide new measures for regulating eggshell quality in production practice. And the eggshell quality may be positively affected in certain conditions by optimal dietary level and form of manga-nese, as well as by the addition of probiotics, organic acids and herb extracts.

  15. The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast.

    Directory of Open Access Journals (Sweden)

    Richard C Silva

    Full Text Available The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.

  16. Research progress in multiple regulation pathways of STAT3 in cancer%STAT3的多重调控方式在肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨毅; 袁杰; 牛瑞芳

    2016-01-01

    The activation of the proto-oncogene STAT3 is strongly controlled under physiological conditions. However, obtained evi-dence revealed that STAT3 is persistently activated in cancer cells and contributes to cancer initiation and progression. Studies demon-strated the various functions of activated STAT3 in promoting cancer development and aggravation, including cancer cell proliferation, invasion and metastasis, drug resistance, epithelial-mesenchymal transition, regulation of the tumor microenvironment, and promo-tion of the self-renewal and differentiation of cancer stem cells. Canonically, STAT3 is regulated by signaling pathways mediated by cy-tokines and growth factors. Many studies determined that STAT3 was also regulated by G protein-coupled receptors, cadherin engage-ment, Toll-like receptors, microRNA, and acetylation. We summarized the recent developments in the research on the regulation of STAT3 activation.%生理情况下原癌基因信号传导及转录激活子3(signal transducer and activator of transcription-3,STAT3)的激活受到严格的调控。然而,大量证据表明,STAT3在许多肿瘤细胞中存在持续激活,并在肿瘤的起始与进展中发挥重要作用。目前的研究发现,活化的STAT3能够通过多种方式促进肿瘤的进展,如促进肿瘤细胞的增殖、侵袭转移、耐药、上皮-间质转化、调节肿瘤微环境、促进肿瘤干细胞的更新与分化等。STAT3的激活除了受传统的细胞因子和生长因子信号通路的调控以外,大量的证据显示G-蛋白偶联受体、钙黏素、Toll样受体、miRNA以及乙酰化修饰等也在STAT3活化过程中发挥了重要作用。本文主要针对肿瘤细胞中调控STAT3活化的途径进行综述。

  17. 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

  18. 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.

  19. Research progress of a XLMR related epigenetic regulator PHF8%参与X染色体连锁智力障碍的表观遗传因子——PHF8研究进展

    Institute of Scientific and Technical Information of China (English)

    王香; 朱子奇; 陈频; 陈德桂

    2011-01-01

    PHF8 is a member of the JmjC domain-containing protein family. It catalyzes histone lysine demethylation and regulates gene transcription. Different mutations of PHF8 gene were found in patients of X-linked mental retardation (XLMR). This review focuses on the research progress of PHF8, particularly the relationship between PHF8 and XLMR genesis, and the biochemical and physiological functions of this protein.%PHF8作为JmjC家族中的成员,通过对组蛋白赖氨酸的去甲基化酶活性来调节靶基因的转录.PHF8基因的一系列突变在X染色体连锁智力障碍(XLMR)患者中被发现.主要针对PHF8与XLMR发生的相关性以及PHF8的生化、生理功能进行阐述.

  20. 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...

  1. Research progress of the key regulation mechanism of quorum sensing on food spoilage%食品腐败的关键调控机制之群体感应的研究进展

    Institute of Scientific and Technical Information of China (English)

    朱素芹; 张彩丽; 孙秀娇; 潘玉荣; 揭金鑫; 曾名湧

    2016-01-01

    群体感应是细菌之间的一种细胞密度依赖型信息交流机制,越来越多的研究证明,细菌群体感应与食品腐败变质过程之间存在复杂而紧密的联系,有望成为食品保鲜技术领域中一个极具应用前景的新靶点。本文概述了微生物群体感应、群体感应对食品腐败变质的影响和群体感应抑制剂3个方面的研究进展,重点介绍了食源细菌的群体感应研究进展和群体感应对食品(水产品、肉及肉制品、乳及乳制品和果蔬)腐败变质的影响,旨在为新型食品保鲜技术的开发提供理论指导。%Quorum sensing (QS) is a cell-to-cell communication mechanism used by bacteria to regulate their collective behaviors in a cell density-dependent manner. In recent years, an increasing number of empirical evidences had demonstrated that there was a complex and close relationship between food spoilage and bacterial QS. QS has received much attention as a novel target for food preservation recently which has great applied prospects. This article reviewed some progresses in QS, the effects of QS on food spoilage and QS inhibitor, and the research progress of QS in bacteria isolated from food and the effects of QS on food (such as aquatic products, meat and meat products, milk and milk products, fruits and vegetables) spoilage were emphatically introduced. The aim of present paper is to provide theoretical guidance for the development of new food preservation technology.

  2. Progress in the roles of adenosine receptors in sleep-wake regulation%腺苷受体调节睡眠觉醒作用机制进展

    Institute of Scientific and Technical Information of China (English)

    余劼; 许奇; 王毅群

    2011-01-01

    腺苷是ATP代谢产物,在脑内广泛存在.腺苷受体分为A1、A2A、A2B和A3四种受体(re-ceptor,R)亚型.研究显示:内源性腺苷可能通过A1R和A2A R发挥睡眠调节作用.A1R在中枢系统分布广泛,兴奋位于觉醒系统组胺能、基底前脑胆碱能神经上的A1R,诱发睡眠;腺苷A2AR相对集中分布于前脑区,兴奋A2AR可引起强大的睡眠效应;A2AR可能介导内源性前列腺素D2的睡眠调节作用,是咖啡因促觉醒作用的主要靶点.A1R和A2AR在睡眠觉醒调节中的贡献,至今仍有很大争议,本文综述腺苷受体睡眠调节作用研究进展.%Adenosine, the product of ATP,widely presented in the brain is proposed to be an endogenous sleep-promoting substance. Among 4 subtypes of adenosine receptor (R),A1R, A2AR, A2BR and A3R, it has been reported that both adenosine A1R and A2A R mediate the somnogenic effects of adenosine. Activation of A1 R in the arousal histaminergic posterior hypothalamus, cholinergic basal forebrain and so on promotes sleep. A2A R is mainly localized in the caudate-putaman, nucleus accumbens, olfactory tubercles. Activation of A2AR significantly promotes sleep. A2AR mediates the somnogenic effects of prostaglandin D2, and acts as the target of caffeine. However, the roles of A1R and A2A R in sleep-wake regulation are in debate.This review summarizes the progress in the roles of adenosine receptors in sleep-wake regulation.

  3. The Epigenetic Regulation of Epithelial-Mesenchymal Transition in Cancer Progression%EMT的表观遗传调控在癌症进程中的研究进展

    Institute of Scientific and Technical Information of China (English)

    张建超; 李红昌

    2015-01-01

    Epithelial-mesenchymal transition (EMT), a morphologic program in which cells convert from the epithelial to the mesenchymal state, plays a pivotal role during malignant tumor invasion-metastasis cascade. During the cancer progression, tumor cells undergo a series of dynamic and reversible cell phenotypic states transitions. Phenotypic plasticity of EMT program implies that epigenetic regulators play crucial roles in this process. Several EMT transcription factors can modulate EMT through regulating expression of the key target genes. These master EMT inducers orchestrate EMT program depending on complex epigenetic regulatory mechanisms. Therefore, understanding of epigenetic mechanisms controlling EMT will provide critical insights into the fundamental mechanisms underlying cancer metastasis, and new therapeutic targets for the treatment of malignant tumor.%上皮-间质转化(Epithelial-Mesenchymal Transition,EMT)是上皮细胞通过特定程序转变为间充质细胞的形态学过程,在癌症侵袭-转移级联过程中发挥着重要的作用。在癌症进程中,肿瘤细胞会经过一系列动态和可逆的细胞表型变化。EMT 程序的这种可塑性提示表观遗传调控在这一过程中发挥着重要的作用。EMT 相关的转录因子能够通过调控关键靶基因的表达,从而调节EMT程序。这些主要的EMT诱导因子依赖于表观遗传调控机制,从而调节EMT过程中基因表达变化。因此理解EMT调控的表观遗传机制有助于我们更好地了解肿瘤转移的分子机制,为恶性肿瘤的治疗提供新的靶点和思路。

  4. Progress of animal organs development regulated by let-7 microRNA%let-7microRNA调控动物器官发育的研究进展

    Institute of Scientific and Technical Information of China (English)

    王虹; 滕鸿琦; 施珏平; 张彦定; 张明凤

    2011-01-01

    微小RNA(microRNA,miRNA)是一类在进化上高度保守、长度约20~24 nt的小分子非编码RNA,能通过与靶基因3'非翻译区相结合从而抑制靶基因的翻译或降解靶基因.let-7 microRNA是发现较早的一类miRNA,最早在线虫中发现能调控细胞分裂的时序.此后大量证据表明,let-7参与动物多个器官发育的调控过程,并与人类疾病发生密切相关.该文综述了近年来let-7调控动物脑、神经及心肺系统等器官发育的研究成果,初步阐述了let-7调控动物器官发育可能的作用机制,以期为深入研究let-7的功能奠定基础.%MieroRNAs (miRNAs) are a class of small non-coding RNAs, about 20~24 nucleotides in length. They can inhibit target genes translation or degrade them directly through combination with the complementary sequences in the 3'-UTRs of target mRNAs. The let-7 miRNAs were originally found in the nematode Caenorhabditis elegans,where they mainly regulated the timing of cell division. Increasing evidences indicate that let-7 miRNAs are associated with animal organs development and human diseases. This review summarized the recent progresses about the function of let-7 miRNAs in the development of brain, neuron, lung and cardiovascular system.Meanwhile, we elucidated the possible mechanism of let-7 miRNAs regulating the developmental processes of animal organs that might provide the basis for further illustrating the function of let-7 miRNAs.

  5. 胆固醇7α-羟化酶调节的研究进展%Research progress of the regulation to cholesterol 7α-hydroxylase related to lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    曹扬; 贝伟剑

    2011-01-01

    胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)是在肝脏合成并促使胆固醇转化成胆酸的限速酶,对维持体内胆固醇代谢平衡起到关键作用.CYP7 A1基因表达受脂代谢相关的多个核因子的精细调控,诸如HNF4a,LXR,FXR,SHP和FGF15/19及相关激素等其他因子,以维持胆固醇代谢平衡;多种中药及饮食成分对CYP7A1的基因表达也有明显调节作用,进而影响血脂代谢.本文就近10年来有关CYP7A1调节的研究进展综述如下.%Cholesterol 7α-hydroxylase ( CYP7A1 ), synthesized in liver, is the rate-limiting enzyme that induces cholesterol converse to bile acid, and it plays a vital role in keeping homeostasis of cholesterol metabolism. The expression of CYP1AX is well controlled by nuclear factors that related to lipid metabolism such as HNF4a,LXR,FXR,SHP,FGF15/19 and other hormones. Some traditional Chinese medicine and food ingredients also show regulation to CYPlAi. This paper will make a summary for references about the related research progress on CYP7A1 in recent decades.

  6. 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

  7. 碳水化合物在生物加工过程中的变化与调控%Biotransformation and Regulation during the Bio-progressing of Carbohydrate

    Institute of Scientific and Technical Information of China (English)

    金征宇; 杨瑞金

    2011-01-01

    Biotransformation is the effective approach for full usage of carbohydrate resources. Transglycosylases and isomerases can transform different monosaccharides, oligosaccharides and cyclodextrins naturally existing to functional rare sugars and oligosaccharides, which are novel materials for food, medicine and material industries. This review introduces recent progress in structure characterization and directed evolution of typical transglycosylases and isomerases, the regulation strategies during enzymatic reactions. Scientific issues and the trends of using transglycosylases and isomerases in carbohydrates biotransformation are summarized for providing helpful references to researchers in carbohydrate research.%生物转化是碳水化合物资源高效利用的有效途径.利用转糖基酶和异构化酶将现有的丰富的单糖、寡糖、环糊精等转化为功能性稀有糖、寡糖,为食品、医药、新材料等行业提供新的原料,对于社会经济发展具有明显的推动作用.本文综述了转糖基酶、异构化酶的结构、定向进化、催化过程调控策略等方面的最新研究进展,并就该领域面临的科学问题和发展趋势进行了总结和展望,以期对相关领域研究者有所启发.

  8. Research progress on molecular regulation of ammonium uptake and trans-port in plant%植物对铵态氮的吸收转运调控机制研究进展

    Institute of Scientific and Technical Information of China (English)

    刘婷; 尚忠林

    2016-01-01

    Ammonium is, besides nitrate, the most important nitrogen form being taken up and assimilated by root cells, while, over ammonium accumulation is toxic to plant cells. Thus, ammonium uptake process must be tightly controlled according to plant nitrogen status and external nitrogen availability. AMT-type ammonium transporters have been demonstrated to mediate high-afifnity ammonium uptake across the plasma membrane in roots, and AMT gene expression and its transport activities are strictly controlled on multilevel including tran-scription and translation levels. Here, research progress on plant ammonium uptake and transport mechanism is discussed, especially translational regulation in the recent ifve years.%铵作为重要的氮源被植物根系吸收并同化,但是过量的铵也会对细胞造成毒害。植物必须依据外界环境和自身氮水平来严格调控根系对铵的吸收过程。铵转运蛋白介导的高亲和力铵跨质膜运输是植物根系吸收铵的主要途径, AMT基因的表达及转运活性在转录和蛋白水平等多层面被严格调控。本文对于植物铵吸收和转运机制,尤其是近5年关于蛋白水平调控的最新研究进展进行了评述。

  9. 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。

  10. 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

  11. 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.

  12. 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).

  13. 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

  14. 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)

  15. Recent Progress of Appetite Regulation Mechanism on Children with Simple Obesity%儿童单纯性肥胖食欲调节机制研究进展

    Institute of Scientific and Technical Information of China (English)

    金铃; 孙远岭

    2012-01-01

    The epidemic of obesity is threatening the health of children, obesity develops when energy intake exceeds energy expenditure over time. The hypothalamus plays a crucial role in regulating appetite signals of energy status in central nervous system. The appetite regulation mechanism is very important for the learning of prevention and treatment of obesity.%肥胖严重影响儿童健康,长期能量摄入大于消耗会导致肥胖.下丘脑是食欲调节因子发挥作用的重要中枢,深入了解食欲调节机制对肥胖的防治有重大意义.

  16. 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。

  17. 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

  18. 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.

  19. Particular activation phenotype of T cells expressing HLA-DR but not CD38 in GALT from HIV-controllers is associated with immune regulation and delayed progression to AIDS.

    Science.gov (United States)

    Gonzalez, Sandra M; Taborda, Natalia A; Correa, Luis A; Castro, Gustavo A; Hernandez, Juan C; Montoya, Carlos J; Rugeles, Maria T

    2016-06-01

    The spontaneous control of HIV replication in HIV-controllers underlines the importance of these subjects for exploring factors related to delayed progression. Several studies have revealed fewer immune alterations and effector mechanisms related to viral control, mainly in peripheral blood, in these individuals compared to normal progressors. However, immune characterization of gut-associated lymphoid tissue (GALT), the major target of infection, has not been thoroughly explored in these subjects. We evaluated the following parameters in GALT samples from 11 HIV-controllers and 15 HIV-progressors: (i) frequency and activation phenotype of T cells; (ii) expression of transcription factors associated with immune response profiles; and (iii) frequency of apoptotic cells. Interestingly, HIV-controllers exhibited a particular activation phenotype, with predominance of T cells expressing HLA-DR but not CD38 in GALT. This phenotype, previously associated with better control of infection, was correlated with low viral load and higher CD4(+) T cell count. Furthermore, a positive correlation of this activation phenotype with higher expression of Foxp3 and RORγT transcription factors suggested a key role for Treg and Th17 cells in the control of the immune activation and in the maintenance of gut mucosal integrity. Although we evaluated apoptosis by measuring expression of cleaved caspase-3 in GALT, we did not find differences between HIV-controllers and HIV-progressors. Taken together, our findings suggest that predominance of HLA-DR(+) T cells, along with lower immune activation and higher expression of transcription factors required for the development of Treg and Th17 cells, is associated with better viral control and delayed progression to AIDS.

  20. 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。

  1. 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.

  2. 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.

  3. 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。

  4. 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.

  5. Research Progress on Functional Food Regulating Cholesterol 7-alpha Hydroxylase%以调节胆固醇7α-羟化酶为靶点的功能性食品研究进展

    Institute of Scientific and Technical Information of China (English)

    郭霄; 张勇; 高鹏飞; 姚国强; 孙天松

    2015-01-01

    胆固醇7α-羟化酶(Cholesterol 7-alpha hydroxylase,CYP7A1)在维持胆固醇代谢动态平衡时起重要的作用。通过概述CYP7A1的调控机制,综述近年来报道的益生菌、膳食纤维、多酚类物质等功能性食品对CYP7A1基因表达的调节和影响,展望以CYP7A1为靶点的降胆固醇功能性食品的开发前景,旨在为筛选以CYP7A1为靶点的功能性食品提供参考。%Cholesterol 7-alpha hydroxylase (CYP7A1) have been shown to play an important role in maintaining cholesterol metabolism homeostasis. This review outlined the mechanisms underlying regulation of CYP7A1, the functional food which includes probiotics, dietary fiber and polyphenols affecting CYP7A1 and the regulation of gene expression were summarized. In addition , the development prospect of the cholesterol-lowering functional food targeting CYP7A1 was analyzed. The aim of this review was to provide clues in screening to CYP7A1 targets of functional food.

  6. 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.

  7. 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.

  8. 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

  9. microRNA在固有免疫调控中作用的研究进展%Progress of the stady on microRNA in regulating innate immunity

    Institute of Scientific and Technical Information of China (English)

    孙义锡; 周俊

    2011-01-01

    microRNA(miRNA)是一类内源性的短链非编码RNA分子,能与特定的信使RNA靶向结合,在转录后水平调控基因表达.miRNA可在多个环节参与调控机体固有免疫反应.微生物感染时,miRNA可通过调控模式识别受体信号通路及产生的细胞因子,负性或正性调控固有免疫应答.在病毒感染时,宿主编码的miRNA能抑制病毒复制,而病毒利用自身编码的miRNA靶向结合宿主或病毒基因,干扰宿主抗病毒反应,甚至可以利用宿主编码的miRNA促进病毒自身复制.miRNA也参与调节银屑病、哮喘、风湿性关节炎等慢性炎性疾病,因此miRNA可能成为炎性疾病的一个侯选治疗靶点.%microRNA(miRNA) are endogenous small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific messenger RNAs. miRNA play negative or positive roles in innate immunity by regulating pattern recognition receptor signaling and ensuring cytokine response. Some miRNA encoded by host can inhibit the invasion and replication of viruses. On the other hand, miRNA encoded by viruses can also interfere with anti-viral defense by targeting viral genes or host genes. Sometimes viruses facilitate self replication using miRNA encoded by host. In addition, miRNAs are involved in the regulation of chronic inflammatory diseases , such as psoriasis, asthma and rheumatoid arthritis. Therefore miRNA might be the potential therapeutic targets of inflammatory diseases.

  10. 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。

  11. 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.

  12. 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......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...

  13. 多年生植物的芽休眠及调控机理研究进展%Progress in Research on Bud Dormancy and Its Regulation Mechanisms in Perennial Plants

    Institute of Scientific and Technical Information of China (English)

    王新超; 马春雷; 杨亚军

    2011-01-01

    芽休眠是一种有益的生物学特性,能够使多年生植物避开不利的环境条件,使种群在不利环境条件下得以生存.综述了多年生植物芽休眠的机制及其调控的研究进展.芽休眠是一个受多个因素和多种基因综合调控的复杂生命现象,其形成和解除受到光照、温度、水分等外界环境因素的影响和调控.在这个过程中,植物体内的激素、糖类、多胺和Ca2+等信号分子以及抗氧化酶类和能量代谢酶类等发生一系列的变化与之相适应.这些变化是在相应的基因表达调控下实现的,这些基因涉及到光、温响应基因,水分响应基因,能量代谢基因,胁迫响应基因,激素相关基因,以及MADS-box转录因子等,它们构成一个复杂的凋控网络,共同控制着芽休眠的形成与解除.结合研究课题提出今后芽休眠机制的研究方向以及在农业上的应用前景.%Bud dormancy can help perennial plants in avoiding or resisting environmental stresses. With this adaptation stratedgy, the species survive and the population persists through the harsh seasons. Recent research on bud dormancy and its regulation mechanism was summarized and reviewed. It was concluded that bud dormancy as a complex biological phenomenon, was controlled by many factors and genes. The changes of environment factors such as light, temperature and water would affect and regulate the formation and release of bud dormancy. During this procedure, the inside physiological changes happened, including changes of signal substances, e. G. Hormone, carbohydrate, polyamine, Ca2+, and some antioxidase and energy metabolism-related enzymes. These changes were regulated by the corresponding genes, such as light- and temperature-corresponding genes, water corresponding genes, energy metabolism-related genes, stress-related genes, hormone-related genes, and MADS-box transcription factors, which constituted complex gene regulatory network and regulate the

  14. Research progress on mechanisms and regulations of bone resorption in orthodontic tooth movement%正畸牙移动中骨吸收机制及其调控的研究进展

    Institute of Scientific and Technical Information of China (English)

    包幸福

    2012-01-01

    破骨细胞在正畸牙移动压力侧骨吸收过程中发挥着重要的作用,针对破骨细胞分化成熟及其发挥功能的调控研究,能为正畸治疗中控制牙齿移动提供新的思路,同时有助于防治正畸治疗中出现的牙根外吸收等.%Osteoclast is responsible for bone resorption in the compression side of orthodontic tooth movement. Regulations to differentiation and mature of osteoclast may provide new horizons of tooth movement control in orthodontic treatment. At the same time, it is helpful to know the similar mechanisms of root resorption.

  15. Physicians’ Progress Notes

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  16. 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...

  17. White matter lesion progression

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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. 中药调控脂质代谢作用机制的研究进展%Research Progress on the Mechanism of Traditional Chinese Medicine in Regulating Lipid Metabo-lism

    Institute of Scientific and Technical Information of China (English)

    孙苏圆(综述); 杨柏灿(审校)

    2015-01-01

    Diseases induced by lipid metabolic disorder have been a serious threat to human health .Tra-ditional Chinese medicine can be used to treat lipid metabolic disorder ,the mechanism has the characteristics of multi-target,multi-link and multi-distribution.It has been reported that traditional Chinese medicine can intervene some lipid metabolism related factors ,and regulate lipid metabolism in multiple ways .Further study on the mechanism of traditional Chinese medicine in treating lipid metabolic diseases using modern molecular biology methods can better develop and utilize traditional Chinese medicine and provide basis for the clinical treatment for lipid metabolic disorder .%脂质代谢紊乱诱发的各类疾病已严重威胁人类健康。中药治疗脂质代谢紊乱性疾病的特点是多靶点、多环节、多分布。研究表明,中药能干预多个重要的脂质代谢相关因子,多途径地调控脂质代谢。运用现代分子生物学手段,进一步深入研究中药多靶点治疗脂质代谢紊乱性疾病的机制,使中药得到更好的开发和利用,可为临床研究治疗脂质代谢紊乱提供依据。

  6. 黄芪调节糖尿病患者血糖稳态作用的研究进展%The research progress of astragalus in regulating blood glucose steady state of diabetes patients

    Institute of Scientific and Technical Information of China (English)

    沙雯君; 陆灏

    2015-01-01

    糖尿病因其日益增高的患病率、较高的致残率和致死率引起社会及医学界的广泛重视,控制血糖可提高糖尿病患者的生存质量。而强化的降糖治疗往往引发低血糖,反复低血糖可致血糖逆向调节障碍,表现为血糖波动较大,阻碍患者血糖趋于正常。黄芪具有控制血糖、减少低血糖、改善胰岛素抵抗的作用,现就黄芪在血糖调节机制中的研究进展进行综述。%In recent decades, the mortality and morbidity of diabetes have increased such that it is becoming a major worldwide public health problem. Intensive blood glucose control could significantly raise the patients life and their survival quality nevertheless it develops hypoglycaemia. Repeated hypoglycemia leads to glucose conterregulate deficiencyand hamper reaching glucose target goals. Astragalus, a traditional Chinese herb used in diabetic therapy for thousands years, has also proven its glucose counterregulationeffect on preventing hypoglycemia. Here, we summarize its glycemic regulation mechanism in different extracts. It is projected that the efficacy and safety of astragalus extracts will be proven in clinical trials and animal experiments in future, and this herb extract might be known as a new class of anti-diabetic drug without hypolycemia danger.

  7. 胆汁酸对糖脂及能量代谢调节作用的研究进展%Recent Progress of the Role of Bile Acids in Regulating Glucose, Lipid and Energy Metabolism

    Institute of Scientific and Technical Information of China (English)

    陈淑芹; 张菁(综述); 方启晨(审校)

    2016-01-01

    Synthesized from cholesterol in the liver,bile acids are the main organic compounds in bile. Previously,bile acids were considered to facilitate the absorption and digestion of lipid-soluble nutrients. Recent studies have shown that bile acids can also function as endocrine signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways,playing important roles in regulating bile acids,glucose and lipid hemostasis as well as energy balance.These bile acid-activated signaling path-ways have pointed toward a new direction for developing therapies of obesity , diabetes and other metabolic diseases.%胆汁酸由胆固醇在肝内合成,是胆汁的主要有机成分。以往对胆汁酸功能的认识主要是其在促进脂类营养物质的消化和吸收方面的作用。近年来研究发现,胆汁酸还是一种有效的内分泌代谢调节因子,能够激活多种核受体和膜受体介导的信号通路,在调节其自身代谢、糖脂代谢的稳态以及能量代谢方面发挥着重要作用。深入研究胆汁酸及其代谢调节通路可为肥胖、糖尿病等代谢性疾病的治疗提供新的方向。

  8. 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.

  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. 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...

  12. Regulation of Terpene Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rodney Croteau

    2004-03-14

    OAK-B135 Research over the last four years has progressed fairly closely along the lines initially proposed, with progress-driven expansion of Objectives 1, 2 and 3. Recent advances have developed from three research thrusts: 1. Random sequencing of an enriched peppermint oil gland cDNA library has given access to a large number of potential pathway and regulatory genes for test of function; 2. The availability of new DNA probes and antibodies has permitted investigation of developmental regulation and organization of terpenoid metabolism; and 3. The development of a transformation system for peppermint by colleagues at Purdue University has allowed direct transgenic testing of gene function and added a biotechnological component to the project. The current status of each of the original research objectives is outlined below.

  13. Rapidly progressive Alzheimer disease.

    Science.gov (United States)

    Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga

    2011-09-01

    Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

  14. 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.

  15. 大电导钙激活钾通道对平滑肌的调控作用研究进展%Progress in regulation of large-conductance calcium-activated potassium channels on smooth muscle

    Institute of Scientific and Technical Information of China (English)

    李汉高; 李芳萍; 张雪梅

    2011-01-01

    Potassium channels are important to distribute in almost each tissue and implicated with many functions of cells, such as the formation of action potential and signal transduction. Large-conductance calcium-activated potassium channel ( BKca/Maxi K) is one of the potassium channels and expressed in many types of cells. The activation of BKca/Maxi K is able to induce the hyperpolarization of plasma membrane and the inhibition of voltagedependent calcium channel activity. So BKca/Maxi K plays an important role in the relaxation of smooth muscle.The pathogenesis of many diseases is also involved in activation and inactivation, expression, or mutation of this potassium channel. BKca/Maxi K participates in the regulation of cardiovascular smooth muscle, myometrial smooth muscle, smooth muscle in the airway and penile erection. Especially, the gene therapy of BKca/Maxi K to erectile dysfunction enjoys some advantages over medication.%钾通道是组织器官中的一种重要通道,几乎所有的组织中都有该通道的分布,并且它在调节细胞功能方面起着极其重要的作用,例如动作电位的形成和信号传导等.大电导钙激活钾通道(BKca/Maxi K)以其广泛的分布,以及参与调节多种细胞功能吸引了更多研究者的关注.BKca/Maxi K的激活可导致细胞膜的超极化,从而抑制电压依赖性钙通道的激活,抑制钙离子内流,引起平滑肌舒张.近年来研究发现,BKca/Maxi K的激活、失活和变异与多种疾病的发病有关,BKca/Maxi K对心血管平滑肌、子宫平滑肌、呼吸道平滑肌和阴茎勃起等具有调控作用,尤其是其基因疗法对阴茎勃起障碍的治疗逐渐显现出较大的优势.

  16. 益生菌兼或益生元对牛肠道菌群调节作用研究进展%Progress on Effect of Probiotics/Prebiotics on Regulation of Gastrointestinal Bacteria Flora of Cows

    Institute of Scientific and Technical Information of China (English)

    朱鹏; 龙淼

    2016-01-01

    Probiotics/prebiotics have the ability to regulate gastrointestinal (GI)microflora balance and ac-tivity.They can significantly affect the structure and activities within the intestinal flora of livestock.The beneficial bacteria (mainly lactic acid bacteria)can occupy the niche,become the dominant bacteria,and can inhibit the growth of molds and their production of mycotoxin.After feeding probiotic bacteria,bovine in-testinal flora diversity are increased,the community of the bacteria in the gastrointestinal become more complexity,and the stability of bovine intestinal flora was enhanced.As the bacteria growth promoting a-gents,maltose oligosaccharides,galactooligosaccharides and other prebiotics are able to be used at different levels by the beneficial bacteria.Currently probiotics/prebiotics have been widely used in various fields such as food,medical care and feed.With its in-depth understanding and mature market or industrial develop-ment,the era of the probiotics/prebiotics will come.%益生菌/益生元具有调节胃肠(GI)菌群平衡及活动的能力,能够显著地影响家畜肠道内菌群的结构和活动,使有益菌(主要是乳酸菌)占有生态位,成为优势菌群,抑制霉菌生长和霉菌毒素的产生。饲喂益生菌后,牛肠道中的菌群呈现多样性,群落的复杂程度增高,牛肠道菌群的微生态稳定性增强。低聚麦芽糖、低聚半乳糖等益生元则能不同程度的被有益菌分解利用,作为有益菌的生长促进剂,发挥其益生作用。目前,益生菌/益生元已被广泛应用于食品、医药保健和饲料等各个领域。随着对其深入的了解和成熟的市场或产业化发展,益生菌/益生元的应用前景很好。

  17. Progress on nitrogen regulation gene expression of plant pathogenic fungi under nitrogen starvation%氮源受限条件下植物病原真菌氮调控基因表达特性

    Institute of Scientific and Technical Information of China (English)

    周晓罡; 姚春馨; 丁玉梅; 陶南; 孙茂林; 张绍松

    2012-01-01

    研究证实植物病害的发生往往是由于植物病原真菌分泌的效应子诱导引起的,在此过程中,调控效应基因表达能够了解病原菌的侵染过程.细胞的营养状况据推测对于效应基因的表达起着重要的作用.已有研究表明在氮胁迫条件下相同效应基因的诱导作用在植株体内和体外是一致的,表明氮源缺乏的环境在植物体进化的早期就已经存在了.文章阐述了在氮受限条件下真菌致病系统中效应基因调控机制及其已经发现的氮调节基因特异性表达研究结果,通过对比几个病原菌中氮调控基因的功能,比较寄主植物体内和体外在氮限制条件下基因的诱导效应,从而揭示出氮的有效性在寄主植物病害发展过程中起到重要作用.%It has been confirmed that the occurrence of plant disease is caused by the effector molecules secreted by plant pathogens. The regulation effector gene expression is an important aspect in understanding of the infection process. The nutritional status of cells has been postulated to be a vital role for effector gene expression. Studies have indicated that the induction of the same effecter genes during growth in vitro as those during growth in planta under nitiogen-starved conditions. This showed that the nitrogen poor environment existed in the early time of plant evolution. This paper describes the system in the pathogenesis of several fungal pathogens and nitrogen in the process of gene expression effects from the results of several species by comparing and contrasting the function of nitrogen regulatory genes, as well as by studying plants in vivo and in vitro gene under nitrogen limitation inductive effect in order to reveal the effectiveness of nitrogen in the development process of host plant disease is an important factor.

  18. 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.

  19. 微小RNA调控肿瘤细胞耐药机制形成的研究进展%Research progress of microRNA regulating the formation of tumor cell resistance mechanism

    Institute of Scientific and Technical Information of China (English)

    孙财

    2015-01-01

    At present,the poor prognosis of conventional chemotherapy for most malignant tumors is an important problem for clinical work,but the tumor cell resistance is one of the important reasons for the failure of chemotherapy.The existence of tumor stem cell resistance ean cause tumor cells to reduce the sensitivity of most chemical drugs after a positive chemotherapy,the recurrence and metastasis of tumor can ultimately endanger the patient's life.The formation mechanism of drug resistance of tumor cells is complex.And there are many signal molecules and signal transduction pathways related with the formation mechanism of drug resistance,but the concrete mechanism is not yet fully clarified.MicroRNA (miRNA) and the formation of tumor drug resistance are highly correlated according to relevant researches.MiRNA can targetedly regulate drug resistance mechanism and plays a very important role in reducing drug resistance of tumor cells.This article intends to review the research advances of the formation mechanism of miRNA resistant tumor cells.%目前,多数恶性肿瘤常规化疗效果差、预后不良,是困扰临床工作的重要难题,而肿瘤细胞耐药性的产生是导致化疗失败的重要原因之一.经过积极化疗后,残存肿瘤干细胞耐药性的存在,可导致肿瘤细胞对多数化学药物敏感性降低,引起肿瘤复发、转移,最终危及患者生命.肿瘤细胞耐药性的形成机制较为复杂,涉及的信号分子及信号通路相对较多,其具体机制尚未完全阐明.根据目前相关研究,微小RNA(miRNA)与肿瘤耐药性的形成高度相关.miRNA通过对耐药机制进行靶向调节,对减少肿瘤细胞耐药性形成起着非常重要的作用.笔者拟就目前miRNA调控肿瘤细胞耐药机制形成的研究进展进行综述.

  20. Progress in Seawater Desalination

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Scientists from the CAS Changchun Institute of Applied Chemistry have made significant progress in developing advanced expertise of seawater desalination. Their work was recently appraised and confirmed by a panel of experts in northeast China's Jilin Province.

  1. 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

  2. Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed

    Institute of Scientific and Technical Information of China (English)

    Chueh-Chuan Yen; Liang-Shun Wang; Min-Hsiung Huang; Biing-Shiung Huang; Cheng-Po Hu; Po-Min Chen; Chi-Hung Lin; Yann-Jang Chen; Chin-Chen Pan; Kai-Hsi Lu; Paul Chih-Hsueh Chen; Jiun-Yi Hsia; Jung-Ta Chen; Yu-Chung Wu; Wen-Hu Hsu

    2005-01-01

    identified. TP63is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.

  3. [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.

  4. IDEOLOGY AND PROGRESS

    Directory of Open Access Journals (Sweden)

    Bogdan Constantin Mihăilescu

    2013-02-01

    Full Text Available The progress theme is very important for the ideologies of the Enlightenment political modernity. Moreover, it had received, with the help of the Enlightenment historicism and rationalism, a mythological dimension. Having in view the historical experience that we have today, it is necessary to give up on progress in thismillenarist meaning. But we are observing – as it also results from the political programs presented in the article – that some of the parties affiliated to the forementioned ideologies are approaching in an inconsistent manner the entire theme of the progress. The recession of this theme is part of a larger cultural context, specific for late modernity, when the ideologies seem to be exhausted. But ideologies survive and this fact certifies their power. They continue to impose different reference criteria on politics, and one of the most significant must remainthe progress. But there is also a more modest way to understand progress. Exactly this kind of approach is presented in this article, an approach which is best understood and commented by the help of Richard Rorty's works. Without having the progress as a desideratum, the negative use of power becomes easier. At the same time, the comparative evaluation of the economic, social or political initiatives,and also the social imperatives as solidarity, social cohesion, or the diminishing of the sufferings become more difficult to realize and pursue.

  5. Parent-Child Attachment and Emotion Regulation

    Science.gov (United States)

    Brumariu, Laura E.

    2015-01-01

    Given the centrality of both parent-child attachment and emotion regulation in children's development and adjustment, it is important to evaluate the relations between these constructs. This article discusses conceptual and empirical links between attachment and emotion regulation in middle childhood, highlights progress and challenges in the…

  6. 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

  7. 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.

  8. Regulated Gene Therapy.

    Science.gov (United States)

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  9. 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

  10. 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.

  11. B淋巴细胞诱导成熟蛋白-1对多发性骨髓瘤中浆细胞分化和存活调控作用的研究进展%Research progress of B lymphocyte induced maturation protein-1 on regulation of differentiation and survival of plasma cells in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张倩男; 姚瑶; 李振宇

    2016-01-01

    多发性骨髓瘤(MM)是一类浆细胞恶性克隆性疾病.近年其发病率呈逐年上升趋势,且迄今尚无治愈方法.从浆细胞分化和存活的调控机制入手,探索MM治疗的新靶点和新策略是一可行的治疗手段.B淋巴细胞诱导成熟蛋白(Blimp)-1是调控浆细胞分化和存活的关键转录因子,但对其在MM中作用的研究迄今尚少.相关研究结果显示,骨髓瘤细胞高表达Blimp-1,RNA干扰沉默Blimp-1表达,可使浆细胞分化消失并伴各型免疫球蛋白(Ig)合成障碍,从而抑制骨髓瘤细胞增殖并诱导其凋亡.笔者拟就Blimp-1调控浆细胞分化和存活在MM中的作用的研究进展进行综述.%Multiple myeloma (MM) is an incurable plasma malignancy and currently the incidence goes up annually.There is one of feasible methods to explore new targets and strategies for the treatment of MM from the regulation of differentiation and survival of plasma cells.B lymphocyte induced maturation protein(Blimp)-1 is a key transcription factor to regulate differentiation and survival of plasma cells,but up to now,items of research articles on Blimp--1 mechanism in MM are very liffle.Related research has shown that myeloma cells highly expressed Blimp-1 and RNA interference silencing Blimp-1 expression eradicated plasma cell differentiation and made each kind of immunoglobulin (Ig) synthesis disorder,thus inhibiting myeloma cells proliferation and inducing its apoptosis.This review focused on the research progress of Blimp-1 on regulation of differentiation and survival of plasma cells in MM.

  12. 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 .

  13. 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

    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...

  14. Regulation of Tumor Progression by Mgat5-Dependent Glycosylation

    Science.gov (United States)

    2002-07-01

    characterized by an earlier onset, greater motor weak-reactive T-cell populations inthe spleen and thymus wereasoin the ness and more days with disease...cells in spleen, thymus ofigosaccharide (numbers in brackets represent linkages of the ’antennae’, left to right). OT, oigosac, and lymph nodes were...domain is also distinct from the other N-acetylglucosaminyltransferases Ile.138. gly-2 complemented the Phaseolus vulgaris leu- in that it has a specific

  15. Involvement and Regulation of Heparanase in Prostate Cancer Progression

    Science.gov (United States)

    2007-02-01

    human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol, 157: 1167-1175, 2000. 19. Nadav, L., Eldor , A...1995). Cell 80: 293–299. Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ et al. (1999). Genes Dev 13: 2490–2501. Nadav L, Eldor A, Yacoby...1991;16: 268-271. 16. Vlodavsky I, Eldor A, Haimovitz-Friedman A, et al. Expression of heparanase by platelets and circu- lating cells of the immune

  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. Progressive Web applications

    CERN Document Server

    CERN. Geneva

    2017-01-01

    Progressive Web Applications are native-like applications running inside of a browser context. In my presentation I would like describe their characteristics, benchmarks and building process using a quick and simple case study example with focus on Service Workers api.

  18. 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.

  19. 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.

  20. Pure progressive aphemia.

    OpenAIRE

    Cohen, L; Benoit, N.; Van Eeckhout, P; Ducarne, B; Brunet, P.

    1993-01-01

    Aphemia, also called anarthria or severe apraxia of speech, is a rare disorder of speech production usually resulting from vascular lesions affecting the inferior premotor cortex of the left hemisphere. A patient presenting with aphemia as the sole manifestation of primary progressive aphasia (PPA) is reported.

  1. Progressive Retirement Programme

    CERN Multimedia

    HR Department

    2009-01-01

    Following the Standing Concertation Committee meeting of 2 December 2008, please note that the Progressive Retirement Programme has been extended by one year, i.e. until 31 March 2010. Further information is available on : https://hr-services.web.cern.ch/hr-services/services-Ben/prp/prp.asp HR Department, tel. 73903

  2. [Progress on transgenic mosquitoes].

    Science.gov (United States)

    Yang, Pin

    2011-04-30

    The genetically modified mosquitoes have been developed aiming to control mosquito-borne diseases by either reducing population sizes or replacing existing populations with vectors unable to transmit the disease. introduces some progress on the generation of transgenic mosquitoes and their fitness in wild population. This paper

  3. 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

  4. 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…

  5. 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

  6. Lymphangiogenesis:A new player in cancer progression

    Institute of Scientific and Technical Information of China (English)

    Masayuki; Nagahashi; Subramaniam; Ramachandran; Omar; M; Rashid; Kazuaki; Takabe

    2010-01-01

    Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new lymphatic vessels) plays an important role in this process.Here,we review the latest f indings of the role of lymphangiogenesis in colorectal cancer progression,and discuss its clinical application as a biomarker and target for new therapy.Understanding the molecular pathways that regulate lymph...

  7. Targeting the extracellular matrix to disrupt cancer progression

    OpenAIRE

    Freja Albjerg Venning; Lena eWullkopf; Janine T. Erler

    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 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 ca...

  8. 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.

  9. 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.

  10. 绿色器官衰老进程中叶绿素降解代谢及其调控的研究进展%Recent Progresses in the Elucidation of Chlorophyll Catabolism and Its Regu-lation during Green Organ Senescence

    Institute of Scientific and Technical Information of China (English)

    陈俊毅; 朱晓宇; 蒯本科

    2014-01-01

    褪绿(degreening)现象是绿色器官衰老的显著标志,其中涉及的叶绿素急速降解是植物衰老的特征性生理生化过程。近十余年来,叶绿素降解的主要生化途径(PAO途径)已基本被阐明。游离的叶绿素及其代谢中间产物具有潜在的光毒性,因此精准调控的叶绿素降解被认为是一个高效有序的解毒过程。目前关于叶绿素降解的全局性调控机制依然知之甚少;多个物种中叶绿素降解关键调控因子SGRs/NYEs的鉴别及其相关作用机理的初步揭示是该领域近年来的最显要进展。上述研究基础预示着近期在叶绿素降解调控的多个方向上可能会取得实质性乃至突破性进展。%Degreening is the most obvious phenotypic change during green organ senescence, and the causal process of rapid chlorophyll degradation is one of the characteristic senescence-associated processes. The major biochemical pathway of senescence-associated chlorophyll degradation, i.e. PAO pathway, has been largely elu-cidated over the past decade or so. Free chlorophyll and its catabolites possess a potential phototoxicity, and therefore the delicately regulated degradation of chlorophyll during senescence is regarded as a detoxiifcation process. So far, the global regulatory mechanism of chlorophyll degradation remains largely unknown. Identiif-cation and functional characterization of the key regulatory factor of chlorophyll degradation STAY-GREEN 1 (SGR1)/NON-YELLOWING 1 (NYE1) in diversiifed species marked a milestone progress of this area in recent years. The areas where signiifcant progresses and/or breakthroughs could be made in the near future are dis-cussed.

  11. 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

  12. Monitoring Radiographic Brain Tumor Progression

    Directory of Open Access Journals (Sweden)

    John H. Sampson

    2011-03-01

    Full Text Available Determining radiographic progression in primary malignant brain tumors has posed a significant challenge to the neuroncology community. Glioblastoma multiforme (GBM, WHO Grade IV through its inherent heterogeneous enhancement, growth patterns, and irregular nature has been difficult to assess for progression. Our ability to detect tumor progression radiographically remains inadequate. Despite the advanced imaging techniques, detecting tumor progression continues to be a clinical challenge. Here we review the different criteria used to detect tumor progression, and highlight the inherent challenges with detection of progression.

  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. 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

  15. 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

  16. Progress in nanophotonics 1

    CERN Document Server

    Ohtsu, Motoichi

    2011-01-01

    This book focuses on the recent progress in nanophotonics technology to be used to develop novel nano-optical devices, fabrication technology, and security systems. It begins with a review of the concept of dressed photons and applications to devices, fabrication, and systems; principles and applications. Further topics include: DNA process for quantum dot chain, photon enhanced emission microscopy, near field spectroscopy of metallic nanostructure, self-organized fabrication of composite semiconductor quantum dots, formation of metallic nanostructure, and nanophotonic information systems with

  17. Recent Progress in PYTHIA

    CERN Document Server

    Sjöstrand, Torbjörn

    2000-01-01

    PYTHIA is a general-purpose event generator for multiparticle production in high-energy physics. After a general introduction and program news survey, some areas of recent physics progress are considered: the matching to matrix elements, especially for W/Z production; charm and bottom hadronization; multiple interactions; and interconnection effects. The report concludes with some words on the future, specifically the ongoing transition to C++.

  18. 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.

  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. 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...

  1. 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

  2. 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.

  3. 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...

  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. Three-dimensional context regulation of metastasis.

    Science.gov (United States)

    Erler, Janine T; Weaver, Valerie M

    2009-01-01

    Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue 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 remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets.

  6. RNA interference of silent mating type information regulation 2 homolog 1 SIRT1 arrests cell cycle progress of prostate cancer PC3 cells%RNA干扰沉默信息调节因子2同源蛋白1阻滞前列腺癌PC3细胞周期

    Institute of Scientific and Technical Information of China (English)

    李驰; 王忠利

    2014-01-01

    Objective:To observe the effects of double-stranded small interfering RNA (siRNA) of the silent mating-type infor-mation regulation 2 homolog 1 (SIRT1) on the cell proliferation, cell cycle progression, and expression levels of the cell cycle negative regulators. These regulators include P21, P27, and phosphorylated retinoblastoma (PRb) proteins present in prostate cancer PC3 cells. This work further aims to explore the possible underlying mechanism for such effects. Methods:PC3 cells were cultured in vitro and then randomly divided into the mock group, scramble siRNA transfected group, and SIRT1 siRNA-transfected group. SIRT1 siRNA ef-ficiency was examined through reverse transcription polymerase chain reaction and Western blot analysis. The inhibitory rate of PC3 cell growth was determined through a methyl thiazolyl tetrazolium assay, and the cell cycle was investigated with the use of flow cytom-etry. The P21 and P27 protein expression levels and PRb status were determined by Western blot assay. Results:Compared with those of the mock and scramble siRNA groups, the expression levels of SIRT1 mRNA and protein significantly decreased in SIRT1 siR-NA-transfected cells. In addition, the inhibitory rate of PC3 cell growth was markedly increased, and the cell cycle of the PC3 cells was arrested at the G1 stage. The expression levels of negative cell cycle regulators, including P21 and P27 protein levels increased, whereas Rb protein phosphorylation was inhibited in SIRT1 siRNA-transfected PC3 cells. Conclusion: SIRT1 RNA interference inhibits PC3 cell growth and arrests cell cycle progression through the upregulation of the P21 and P27 proteins and the inhibition of Rb protein phosphorylation.%目的:观察沉默信息调节因子2同源蛋白1(SIRT1)小干扰RNA(siRNA)对前列腺癌PC3细胞生长增殖、细胞周期和P21、P27细胞周期调节蛋白及视网膜母细胞瘤(retinoblastoma,Rb)蛋白表达变化影响,探讨SIRT1在前列腺癌

  7. 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.

  8. Mathieu Progressive Waves

    Institute of Scientific and Technical Information of China (English)

    Andrei B. Utkin

    2011-01-01

    A new family of exact solutions to the wave equation representing relatively undistorted progressive waves is constructed using separation of variables in the elliptic cylindrical coordinates and one of the Bateman transforms. The general form of this Bateman transform in an orthogonal eurvilinear cylindrical coordinate system is discussed and a specific problem of physical feasibility of the obtained solutions, connected with their dependence on the cyclic coordinate, is addressed. The limiting case of zero eccentricity, in which the elliptic cylindrical coordinates turn into their circular cylindrical counterparts, is shown to correspond to the focused wave modes of the Bessel-Gauss type.

  9. 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.

  10. 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

  11. 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

  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 eyeglass optics].

    Science.gov (United States)

    Köppen, W

    1995-08-01

    In this article product developments for ophthalmic lenses are discussed: new materials, designs and coatings. High-index plastic substrates allow to offer corrections which are simultaneously light and thin and for the first time there are high performant plastic photochromic lenses. Head and eye movements with latest generation's progressives are very similar to natural vision behaviour. Special aspheric designs have been developed for comfortable vision for near and intermediate distances. Finally there are new coatings which protect the high quality surfaces of plastic lenses distinctly longer than before.

  14. 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.

  15. 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...

  16. Identification of novel targets in prostate cancer progression

    NARCIS (Netherlands)

    Ghotra, Veerander Paul Singh

    2013-01-01

    We have developed novel fluorescence bio-imaging based automated models to screen for novel candidate targets involved in prostate cancer metastasis. Utilizing these models and adopting a functional genomics based approach; we identified SYK as a novel regulator of prostate cancer progression. We al

  17. 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.

  18. 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.

  19. 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)

  20. 18 CFR 367.1070 - Account 107, Construction work in progress.

    Science.gov (United States)

    2010-04-01

    ... NATURAL GAS ACT Balance Sheet Chart of Accounts § 367.1070 Account 107, Construction work in progress. (a... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY HOLDING...

  1. Progress in nanophotonics 4

    CERN Document Server

    Yatsui, Takashi

    2017-01-01

    This book presents the recent progress in the field of nanophotonics. It contains review-like chapters focusing on various but mutually related topics in nanophotonics written by the world’s leading scientists. Following the elaboration of the idea of nanophotonics, much theoretical and experimental work has been carried out, and several novel photonic devices, high-resolution fabrication, highly efficient energy conversion, and novel information processing have been developed in these years. Novel theoretical models describing the nanometric light-matter interaction, nonequilibrium statistical mechanical models for photon breeding processes and near-field‐assisted chemical reactions as well as light‐matter interaction are also explained in this book. It describes dressed photon technology and its applications, including implementation of nanophotonic devices and systems, fabrication methods and performance characteristics of ultrathin, ultraflexible organic light‐emitting diodes, organic solar cells ...

  2. Progressive Band Selection

    Science.gov (United States)

    Fisher, Kevin; Chang, Chein-I

    2009-01-01

    Progressive band selection (PBS) reduces spectral redundancy without significant loss of information, thereby reducing hyperspectral image data volume and processing time. Used onboard a spacecraft, it can also reduce image downlink time. PBS prioritizes an image's spectral bands according to priority scores that measure their significance to a specific application. Then it uses one of three methods to select an appropriate number of the most useful bands. Key challenges for PBS include selecting an appropriate criterion to generate band priority scores, and determining how many bands should be retained in the reduced image. The image's Virtual Dimensionality (VD), once computed, is a reasonable estimate of the latter. We describe the major design details of PBS and test PBS in a land classification experiment.

  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. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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)

  10. 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

  11. 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.

  12. 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…

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. IPY Progress and Prospects

    Science.gov (United States)

    Carlson, D.

    2008-12-01

    We can summarize the IPY goals as: (a) make major advances in polar knowledge and understanding; (b) leave a legacy of new or enhanced observational systems, facilities and infrastructure; (c) excite a new generation of polar scientists and engineers, and (d) elicit exceptional interest and participation from polar residents, schoolchildren, the general public, and decision-makers, worldwide. This talk reports on the progress and prospects in each of those areas from an overall international view; separate talks will describe details of future researcher and the IPY outreach efforts. To achieve major advances in knowledge, IPY has entrained the intellectual resources of thousands of scientists, many more than expected, often from 'non- polar' nations, and representing an unprecedented breadth of scientific specialties; integration of those efforts across disciplines to achieve integrated system-level understanding remains a substantial challenge. Many national and international organizations prepare plans to sustain new and improved observational systems, but clear outcomes and the necessary resources remain elusive. International outreach networks gradually build breadth and strength, largely through IPY Polar Science Days and other internationally- coordinated IPY events. A new Association of Polar Early Career Scientists (APECS) devotes talent and energy to shaping the future of polar research. These activities and networks may, with time and with continued international coordination, achieve an exceptional level of interest and participation. In all areas, much work remains.

  19. Nuclear chemistry progress report

    Energy Technology Data Exchange (ETDEWEB)

    Viola, V.E.; Kwiatkowski, K.

    1993-08-01

    This is the annual progress report for the Indiana University nuclear chemistry program for the 1992/1993 year. Accomplishments include the construction, testing, and initial experimental runs of the Indiana Silicon Sphere (ISiS) 4{pi} charged particle detector. ISiS is designed to study energy dissipation and multifragmentation phenomena in light-ion-induced nuclear reactions at medium-to-high energies. Its second test run was to examine 3.6 GeV {sup 3}He beam reactions at Laboratoire National Saturne (LNS) in Saclay. The development and deployment of this system has occupied a great deal of the groups effort this reporting period. Additional work includes: calculations of isotopic IMF yields in the {sup 4}He + {sup 116,124}Sn reaction; cross sections for A = 6 - 30 fragments from the {sup 4}He + {sup 28}Si reaction at 117 and 198 MeV; charging effects of passivated silicon detectors; neck emission of intermediate-mass fragments in the fission of hot heavy nuclei.

  20. Cartilage stem cells: regulation of differentiation.

    Science.gov (United States)

    Solursh, M

    1989-01-01

    The developing limb bud is a useful source of cartilage stem cells for studies on the regulation of chondrogenesis. In high density cultures these cells can progress through all stages of chondrogenesis to produce mineralized hypertrophic cartilage. If the cells are maintained in a spherical shape, single stem cells can progress through a similar sequence. The actin cytoskeleton is implicated in the regulation of chondrogenesis since conditions that favor its disruption promote chondrogenesis and conditions that favor actin assembly inhibit chondrogenesis. Since a number of extracellular matrix receptors mediate effects of the extracellular matrix on cytoskeletal organization and some of these receptors are developmentally regulated, it is proposed that matrix receptor expression plays a central role in the divergence of connective tissue cells during development.

  1. 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

  2. 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...

  3. 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

  4. Scientific progress: Knowledge versus understanding.

    Science.gov (United States)

    Dellsén, Finnur

    2016-04-01

    What is scientific progress? On Alexander Bird's epistemic account of scientific progress, an episode in science is progressive precisely when there is more scientific knowledge at the end of the episode than at the beginning. Using Bird's epistemic account as a foil, this paper develops an alternative understanding-based account on which an episode in science is progressive precisely when scientists grasp how to correctly explain or predict more aspects of the world at the end of the episode than at the beginning. This account is shown to be superior to the epistemic account by examining cases in which knowledge and understanding come apart. In these cases, it is argued that scientific progress matches increases in scientific understanding rather than accumulations of knowledge. In addition, considerations having to do with minimalist idealizations, pragmatic virtues, and epistemic value all favor this understanding-based account over its epistemic counterpart.

  5. Progressive Climate Change on Titan: Implications for Habitability

    Science.gov (United States)

    Moore, J. M.; A. D. Howard

    2014-01-01

    Titan's landscape is profoundly shaped by its atmosphere and comparable in magnitude perhaps with only the Earth and Mars amongst the worlds of the Solar System. Like the Earth, climate dictates the intensity and relative roles of fluvial and aeolian activity from place to place and over geologic time. Thus Titan's landscape is the record of climate change. We have investigated three broad classes of Titan climate evolution hypotheses (Steady State, Progressive, and Cyclic), regulated by the role, sources, and availability of methane. We favor the Progressive hypotheses, which we will outline here, then discuss their implication for habitability.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Progress in mitochondrial epigenetics.

    Science.gov (United States)

    Manev, Hari; Dzitoyeva, Svetlana

    2013-08-01

    Mitochondria, intracellular organelles with their own genome, have been shown capable of interacting with epigenetic mechanisms in at least four different ways. First, epigenetic mechanisms that regulate the expression of nuclear genome influence mitochondria by modulating the expression of nuclear-encoded mitochondrial genes. Second, a cell-specific mitochondrial DNA content (copy number) and mitochondrial activity determine the methylation pattern of nuclear genes. Third, mitochondrial DNA variants influence the nuclear gene expression patterns and the nuclear DNA (ncDNA) methylation levels. Fourth and most recent line of evidence indicates that mitochondrial DNA similar to ncDNA also is subject to epigenetic modifications, particularly by the 5-methylcytosine and 5-hydroxymethylcytosine marks. The latter interaction of mitochondria with epigenetics has been termed 'mitochondrial epigenetics'. Here we summarize recent developments in this particular area of epigenetic research. Furthermore, we propose the term 'mitoepigenetics' to include all four above-noted types of interactions between mitochondria and epigenetics, and we suggest a more restricted usage of the term 'mitochondrial epigenetics' for molecular events dealing solely with the intra-mitochondrial epigenetics and the modifications of mitochondrial genome.

  14. Prime mover progress

    Energy Technology Data Exchange (ETDEWEB)

    Hennagir, T.

    1995-05-01

    Manufacturers continue to upgrade fluidized bed and steam technologies to meet more stringent emission, efficiency and service challenges from global power market customers. Offshore, suppliers are being pushed to provide quality, low-cost production and significant local competitive presence in nearly all international markets. The ability to meet customer and regulatory demands for emissions across different global market segments remains a priority for prime mover suppliers as they develop environmental technical improvements. Products initially developed for the more stringent European regulations are now finding a market in the US. In developing countries, demand continues for utility-size boiler products, but pollution control equipment costs remain a parallel consideration. Industry improvements to steam cycle equipment, namely turbines, continue to reap benefits in terms of efficiency and operational flexibility. Boiler and steam manufacturers` response to global markets remains right on target as product development strategies are constantly adjusted and analyzed to reach an optimum marketing mix. Innovation and advances in prime mover power equipment technology remain a mainstay of suppliers` ability to meet the needs of a changing, competitive clientele.

  15. 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.

  16. Psychological functioning in primary progressive versus secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Vleugels, L; Pfennings, L E; Pouwer, F

    1998-01-01

    (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP......Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary...... progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years...

  17. Targeting ECM Disrupts Cancer Progression.

    Science.gov (United States)

    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 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 is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

  18. Targeting ECM Disrupts Cancer Progression

    Science.gov (United States)

    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 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 is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID:26539408

  19. Molecular phenotypes distinguish patients with relatively stable from progressive idiopathic pulmonary fibrosis (IPF.

    Directory of Open Access Journals (Sweden)

    Kathy Boon

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is a progressive, chronic interstitial lung disease that is unresponsive to current therapy and often leads to death. However, the rate of disease progression differs among patients. We hypothesized that comparing the gene expression profiles between patients with stable disease and those in which the disease progressed rapidly will lead to biomarker discovery and contribute to the understanding of disease pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: To begin to address this hypothesis, we applied Serial Analysis of Gene Expression (SAGE to generate lung expression profiles from diagnostic surgical lung biopsies in 6 individuals with relatively stable (or slowly progressive IPF and 6 individuals with progressive IPF (based on changes in DLCO and FVC over 12 months. Our results indicate that this comprehensive lung IPF SAGE transcriptome is distinct from normal lung tissue and other chronic lung diseases. To identify candidate markers of disease progression, we compared the IPF SAGE profiles in stable and progressive disease, and identified a set of 102 transcripts that were at least 5-fold up regulated and a set of 89 transcripts that were at least 5-fold down regulated in the progressive group (P-valueregulate cigarette-smoke induced inflammation, and Plunc (palate, lung and nasal epithelium associated, a gene not previously implicated in IPF. Interestingly, 26 of the up regulated genes are also increased in lung adenocarcinomas and have low or no expression in normal lung tissue. More importantly, we defined a SAGE molecular expression signature of 134 transcripts that sufficiently distinguished relatively stable from progressive IPF. CONCLUSIONS: These findings indicate that molecular signatures from lung parenchyma at the time of diagnosis could prove helpful in predicting the

  20. 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.[...

  1. Studies in developmental immunogenetics. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Owen, R D

    1976-05-26

    Progress is reported on studies of genetic regulation, mainly in complex organisms, and with an emphasis on the immune system as a model for developmental analysis and as a tool for following the development of other systems, especially the brain. Results are reported from studies of biochemical genetics, primarily from a developmental viewpoint and with particular regard to defense mechanisms; cellular aspects of the immune system; the area of cancer immunology and cell specificities as related to tumor systems, primarily from an immunogenetic viewpoint and with particular reference to leukemias in the mouse; and the disruptions of genetic control mechanisms in tumor development, especially as approached through the reappearance of fetal antigens associated with tumor development.

  2. [Progress on epigenetics applications in forensic science].

    Science.gov (United States)

    Yang, Ya-ran; Wang, Peng-xiang; Fang, Xiang-dong; Yan, Jiang-wei

    2012-10-01

    Epigenetics is the study of heritable changes in gene expression other than changes in the underlying DNA sequence. Such changes include DNA methylation, histone modification, chromatin remodeling, genomic imprinting, X chromosome inactivation and non-coding RNA regulation. Recent progresses on epigenetics open new possibilities in tackling these challenging problems in forensic science, including identification of fetal paternity testing in embryonic period, determination of the necessary allele in paternity testing, discrimination of identical twins, origination analysis of micro tissue, verification of forged DNA. This review focuses on epigenetics concept and its latest application in the field of paternity testing, age estimation, discrimination between the twins, identification of tissue of origin, and estimation of postmortem interval.

  3. Caveolin-1 and prostate cancer progression.

    Science.gov (United States)

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores

    2012-01-01

    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  4. Proposed Modification of the Progressive Retirement Programme

    CERN Document Server

    2003-01-01

    After discussion at TREF on 29 October 2003, the Management proposes in this document a modification affecting one of the general principles of the Progressive Retirement Programme (PRP), decided by the Council in December 1996 and introduced in April 1997. This modification would authorise the Director-General, in exceptional cases, as indicated in section 3 below, and, with the staff member's consent, to cancel his or her participation in the PRP and to reinstate the staff member in his or her original contractual situation. No modifications to the Staff Rules and Regulations are required. The proposal set out in section 3 of the present document is submitted by the Management, after consultation of the Governing Board of the Pension Fund, for recommendation by the Finance Committee to the Council and for approval by the Council, to enter into force as of 1 January 2004.

  5. 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

  6. [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

  7. 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

  8. 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.

  9. Progressive-Relapsing MS (PRMS)

    Science.gov (United States)

    ... a Local Support Group Ask an MS Navigator Edward M. Dowd Personal Advocate Program Connect with Peers ... relapsing MS (PRMS) Types of MS Clinically Isolated Syndrome (CIS) Relapsing-remitting MS (RRMS) Primary progressive MS ( ...

  10. Arsenic | Cancer Trends Progress Report

    Science.gov (United States)

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  11. Nitrate | Cancer Trends Progress Report

    Science.gov (United States)

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  12. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  13. Human Cpr (Cell Cycle Progression Restoration) Genes Impart a Far(-) Phenotype on Yeast Cells

    OpenAIRE

    Edwards, M. C.; Liegeois, N.; Horecka, J.; DePinho, R A; Sprague-Jr., G. F.; Tyers, M; Elledge, S J

    1997-01-01

    Regulated cell cycle progression depends on the proper integration of growth control pathways with the basic cell cycle machinery. While many of the central molecules such as cyclins, CDKs, and CKIs are known, and many of the kinases and phosphatases that modify the CDKs have been identified, little is known about the additional layers of regulation that impinge upon these molecules. To identify new regulators of cell proliferation, we have selected for human and yeast cDNAs that when overexp...

  14. Monomelic amyotrophy with late progression.

    Science.gov (United States)

    Rowin, J; Meriggioli, M N; Cochran, E J

    2001-04-01

    Monomelic amyotrophy is a sporadic juvenile-onset disease that presents with gradual onset of weakness and atrophy in the hand muscles unilaterally. Generally, this disease is considered a 'benign' and non-progressive motor neuron disease, which stabilizes within five years of onset. We discuss a case that illustrates that monomelic amyotrophy may rarely exhibit late clinical progression to the lower extremities after a prolonged period of disease stability.

  15. 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.

  16. Targeting ECM Disrupts Cancer Progression

    OpenAIRE

    Venning, Freja A; Wullkopf, Lena; Janine T. Erler

    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 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 casc...

  17. Recent Progress in Regge Calculus

    OpenAIRE

    1997-01-01

    While there has been some advance in the use of Regge calculus as a tool in numerical relativity, the main progress in Regge calculus recently has been in quantum gravity. After a brief discussion of this progress, attention is focussed on two particular, related aspects. Firstly, the possible definitions of diffeomorphisms or gauge transformations in Regge calculus are examined and examples are given. Secondly, an investigation of the signature of the simplicial supermetric is described. Thi...

  18. 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.

  19. 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.

  20. Scientific progress as increasing verisimilitude.

    Science.gov (United States)

    Niiniluoto, Ilkka

    2014-06-01

    According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

  1. 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 ( ...

  2. 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

  3. Molecular regulators of phosphate homeostasis in plants.

    Science.gov (United States)

    Lin, Wei-Yi; Lin, Shu-I; Chiou, Tzyy-Jen

    2009-01-01

    An appropriate cellular phosphate (Pi) concentration is indispensable for essential physiological and biochemical processes. To maintain cellular Pi homeostasis, plants have developed a series of adaptive responses to facilitate external Pi acquisition and to limit Pi consumption and to adjust Pi recycling internally when the Pi supply is inadequate. Over the past decade, significant progress has been made toward understanding such regulation at the molecular level. In this review, the focus is on the molecular regulators that mediate cellular Pi concentrations. The regulators are introduced and organized according to their original identification procedures, by the forward genetic approach of mutant screening or by reverse genetic analysis. These genes are involved in Pi uptake, allocation or remobilization or are upstream regulators, such as transcriptional factors or signalling molecules. In the future, integration of current knowledge and exploration of new technology is expected to offer new insights into molecular mechanisms that maintain Pi homeostasis.

  4. Regulation of Bim in Health and Disease.

    Science.gov (United States)

    Sionov, Ronit Vogt; Vlahopoulos, Spiros A; Granot, Zvi

    2015-09-15

    The BH3-only Bim protein is a major determinant for initiating the intrinsic apoptotic pathway under both physiological and pathophysiological conditions. Tight regulation of its expression and activity at the transcriptional, translational and post-translational levels together with the induction of alternatively spliced isoforms with different pro-apoptotic potential, ensure timely activation of Bim. Under physiological conditions, Bim is essential for shaping immune responses where its absence promotes autoimmunity, while too early Bim induction eliminates cytotoxic T cells prematurely, resulting in chronic inflammation and tumor progression. Enhanced Bim induction in neurons causes neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's diseases. Moreover, type I diabetes is promoted by genetically predisposed elevation of Bim in β-cells. On the contrary, cancer cells have developed mechanisms that suppress Bim expression necessary for tumor progression and metastasis. This review focuses on the intricate network regulating Bim activity and its involvement in physiological and pathophysiological processes.

  5. Regulation of Rad51 promoter

    Science.gov (United States)

    Hine, Christopher M; Li, Hongjie; Xie, Li; Mao, Zhiyong; Seluanov, Andrei; Gorbunova, Vera

    2014-01-01

    The DNA double-strand break repair and homologous recombination protein Rad51 is overexpressed in the majority of human cancers. This correlates with therapy resistance and decreased patient survival. We previously showed that constructs containing Rad51 promoter fused to a reporter gene are, on average, 850-fold more active in cancer cells than in normal cells. It is not well understood what factors and sequences regulate the Rad51 promoter and cause its high activity in cancerous cells. Here we characterized regulatory regions and examined genetic requirements for oncogenic stimulation of the Rad51 promoter. We identified specific regions responsible for up- and downregulation of the Rad51 promoter in cancerous cells. Furthermore, we show that Rad51 expression is positively regulated by EGR1 transcription factor. We then modeled the malignant transformation process by expressing a set of oncoproteins in normal human fibroblasts. Expression of different combinations of SV40 large T antigen, oncogenic Ras and SV40 small T antigen resulted in step-wise increase in Rad51 promoter activity, with all the 3 oncoproteins together leading to a 47-fold increase in expression. Cumulatively, these results suggest that Rad51 promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy. PMID:24781030

  6. 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.

  7. 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.

  8. 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.

  9. "Human potential" and progressive pedagogy

    DEFF Research Database (Denmark)

    Øland, Trine

    2012-01-01

    This article examines the cultural constructs of progressive pedagogy in Danish school pedagogy and its emerging focus on the child’s human potential from the 1920s to the 1950s. It draws on Foucault’s notion of ‘dispositifs’ and the ‘elements of history’, encircling a complex transformation...... of continuity and discontinuity of progressive pedagogy. The Danish context is identified as being part of an international and scientific enlightenment movement circulating in, e.g., the New Education Fellowship (NEF). The cultural constructs embedded in progressivism are clarified in the article...

  10. Recent progress on intrinsic charm

    Science.gov (United States)

    Hobbs, T. J.

    2017-03-01

    Over the past ˜10 years, the topic of the nucleon's nonperturbative or intrinsic charm (IC) content has enjoyed something of a renaissance, largely motivated by theoretical developments involving quark modelers and PDF-fitters. In this talk I will briefly describe the importance of intrinsic charm to various issues in high-energy phenomenology, and survey recent progress in constraining its overall normalization and contribution to the momentum sum rule of the nucleon. I end with the conclusion that progress on the side of calculation has now placed the onus on experiment to unambiguously resolve the proton's intrinsic charm component.

  11. 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...

  12. 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...

  13. Scientific Progress in Strategic Management

    DEFF Research Database (Denmark)

    Foss, Nicolai

    , the RBV represents an "unfinished revolution" as there is still considerable potential to dig deeper in the deep structure of competitive advantage. Keywords: Resource-based view, mechanisms, reductionism, competitive advantage, transaction costs, property rights. JEL Code: L2, M1...... 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...

  14. 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.

  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. 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.

  17. 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

  18. Symmetrical progressive erythro-keratoderma

    Directory of Open Access Journals (Sweden)

    Sunil Gupta

    1999-01-01

    Full Text Available A 13-year-old male child had gradually progressive, bilaterall, symmetrical, erythematous hyperkeratotic plaques over knees, elbows, natal cleft, dorsa of hands and feet with palmoplantar keratoderma. High arched palate, fissured tongue and sternal depression (pectus-excavatum were unusual associations.

  19. Skills Underlying Coloured Progressive Matrices

    Science.gov (United States)

    Kirby, J. R.; Das, J. P.

    1978-01-01

    Raven's Coloured Progressive Matrices and a battery of ability tests were administered to a sample of 104 male fourth graders for purposes of investigating the relationships between 2 previously identified subscales of the Raven and the ability tests. Results indicated use of a spatial strategy and to a lesser extent, use of reasoning, indicating…

  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. 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).

  2. Research Progress of Isotope Technology

    Institute of Scientific and Technical Information of China (English)

    Department; of; Isotope

    2015-01-01

    Radioactive isotope is one of the origins of nonnuclear power technology.In the 12th Five Year Plan period,CIAE made breakthrough progresses on several important fields such as research and development of preparation of radioactive nuclides,preparation of radioactive source and study of radiopharmaceuticals relied on different financial support,successfully

  3. 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.

  4. Assessing Pupils' Progress in Science

    Science.gov (United States)

    Slade, Peter

    2009-01-01

    Good assessment practice is a fundamental part of good teaching and learning. It puts learners at the heart of the process, helping them to recognise achievement and make progress, and enables teachers to shape and adapt their teaching to individual needs and aspirations. Over the past year, the Qualifications and Curriculum Authority (QCA) has…

  5. Minority Student Progress Report, 1991.

    Science.gov (United States)

    Diaz, Porfirio R.; Luan, Jing

    This report offers a consolidated systemwide analysis of key issues and recommendations for improvement of minority recruitment and retention at Arizona State Universities and an evaluation of progress toward achieving Arizona Board of Regents (ABOR) approved recruitment and graduation goals. A description of ABOR system goals notes three goals:…

  6. 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.

  7. [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.

  8. 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...

  9. DSM-IV Progress Report.

    Science.gov (United States)

    Hohenshil, Thomas H.

    1992-01-01

    Notes that Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) will become one of most frequently used reference documents in counseling profession. Describes progress being made in development of DSM-IV, scheduled for publication in 1994. Describes revision process and proposed organizational changes and new diagnostic…

  10. 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.

  11. The cell cycle regulated transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stuart K Archer

    Full Text Available Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a "double-cut" elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several co-regulated transcript groups and were conserved in other kinetoplastids. Furthermore, we found evidence for cell-cycle regulation of a flagellar protein regulon with a highly conserved sequence motif, bearing similarity to consensus PUF-protein binding motifs. RNA sequence motifs that are functional in cell-cycle regulation were more widespread than previously expected and conserved within kinetoplastids. These findings highlight the central importance of post-transcriptional regulation in the proliferation of parasitic kinetoplastids.

  12. Regulated Hyaluronan Synthesis by Vascular Cells

    Directory of Open Access Journals (Sweden)

    Manuela Viola

    2015-01-01

    Full Text Available Cellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of HA synthase 2 (HAS2 and other covalent modifications including ubiquitination and O-GlcNAcylation. Substrate availability is important in HA synthesis control. Specific drugs reducing the UDP precursors are able to reduce HA synthesis whereas the hexosamine biosynthetic pathway (HBP increases the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc leading to an increase of HA synthesis. The flux through the HBP in the regulation of HA biosynthesis in human aortic vascular smooth muscle cells (VSMCs was reported as a critical aspect. In fact, inhibiting O-GlcNAcylation reduced HA production whereas increased O-GlcNAcylation augmented HA secretion. Additionally, O-GlcNAcylation regulates HAS2 gene expression resulting in accumulation of its mRNA after induction of O-GlcNAcylation with glucosamine treatments. The oxidized LDLs, the most common molecules related to atherosclerosis outcome and progression, are also able to induce a strong HA synthesis when they are in contact with vascular cells. In this review, we present recent described mechanisms involved in HA synthesis regulation and their role in atherosclerosis outcome and development.

  13. 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.

  14. Geothermal Progress Monitor report No. 8. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1983-11-01

    Geothermal Progress Monitor (GPM) Report Number 8 presents information concerning ongoing technology transfer activities and the mechanisms used to support these activities within geothermal R and D programs. A state-by-state review of major geothermal development activities for the reporting period 1 February 1983 through 31 July 1983 is provided. Recent drilling and exploration efforts and the current status of geothermal electric power plant development in the United States are summarized.

  15. Demyelination versus remyelination in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

    2010-01-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  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. Cultural Neuroscience: Progress and Promise.

    Science.gov (United States)

    Chiao, Joan Y; Cheon, Bobby K; Pornpattanangkul, Narun; Mrazek, Alissa J; Blizinsky, Katherine D

    2013-01-01

    The nature and origin of human diversity has been a source of intellectual curiosity since the beginning of human history. Contemporary advances in cultural and biological sciences provide unique opportunities for the emerging field of cultural neuroscience. Research in cultural neuroscience examines how cultural and genetic diversity shape the human mind, brain and behavior across multiple time scales: situation, ontogeny and phylogeny. Recent progress in cultural neuroscience provides novel theoretical frameworks for understanding the complex interaction of environmental, cultural and genetic factors in the production of adaptive human behavior. Here, we provide a brief history of cultural neuroscience, theoretical and methodological advances, as well as empirical evidence of the promise of and progress in the field. Implications of this research for population health disparities and public policy are discussed.

  3. 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

  4. Novel Insights into Fur Regulation in Helicobacter pylori

    Science.gov (United States)

    2013-01-10

    Pseudomonas aeruginosa (129), Vibrio cholerae (143), and more recently H. pylori (10), progress has been made in understanding the important features of Fe...of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co-ordination. Mol Microbiol 72:1208-20. 144. Smith, M. G., T. A...genes encoding iron-containing proteins. For example, in Gram-negative species such as E. coli and V. cholerae , genes that are regulated by classic

  5. Serotonin and the regulation of mammalian energy balance

    OpenAIRE

    Michael H Donovan; 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...

  6. 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.

  7. 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.

  8. Progress in breast cancer: overview.

    Science.gov (United States)

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed.

  9. 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).

  10. 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.

  11. Progress Toward Heavy Ion IFE

    Energy Technology Data Exchange (ETDEWEB)

    Meier, W R; Logan, B G; Waldron, W L; Sabbi, G L; Callahan-Miller, D A; Peterson, P F; Goodin, D T

    2002-01-17

    Successful development of Heavy Ion Fusion (HIF) will require scientific and technology advances in areas of targets, drivers and chambers. Design work on heavy ion targets indicates that high gain (60-130) may be possible with a -3-6 MJ driver depending on the ability to focus the beams to small spot sizes. Significant improvements have been made on key components of heavy ion drivers, including sources, injectors, insulators and ferromagnetic materials for long-pulse induction accelerator cells, solid-state pulsers, and superconducting quadrupole magnets. The leading chamber concept for HIF is the thick-liquid-wall HYLEE-II design, which uses an array of flibe jets to protect chamber structures from x-ray, debris, and neutron damage. Significant progress has been made in demonstrating the ability to create and control the types of flow needed to form the protective liquid blanket. Progress has also been made on neutron shielding for the final focus magnet arrays with predicted lifetimes now exceeding the life of the power plant. Safety analyses have been completed for the HYLEE-II design using state-of-the-art codes. Work also continues on target fabrication and injection for HE. A target injector experiment capable of > 5 Hz operation has been designed and construction will start in 2002. Methods for mass production of hohlraum targets are being evaluated with small-scale experiments and analyses. Progress in these areas will be reviewed.

  12. Hepcidin: regulation of the master iron regulator

    Science.gov (United States)

    Rishi, Gautam; Wallace, Daniel F.; Subramaniam, V. Nathan

    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 (FPN), inducing its internalization and degradation, thus limiting the amount of iron released into the blood. The major factors that are implicated in hepcidin regulation include iron stores, hypoxia, inflammation and erythropoiesis. The present review summarizes our present knowledge about the molecular mechanisms and signalling pathways contributing to hepcidin regulation by these factors. PMID:26182354

  13. 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

  14. Transcriptional network of androgen receptor in prostate cancer progression.

    Science.gov (United States)

    Takayama, Ken-ichi; Inoue, Satoshi

    2013-08-01

    The androgen receptor belongs to the nuclear receptor superfamily and functions as a ligand-dependent transcription factor. It binds to the androgen responsive element and recruits coregulatory factors to modulate gene transcription. In addition, the androgen receptor interacts with other transcription factors, such as forkhead box A1, and other oncogenic signaling pathway molecules that bind deoxyribonucleic acid and regulate transcription. Androgen receptor signaling plays an important role in the development of prostate cancer. Prostate cancer cells proliferate in an androgen-dependent manner, and androgen receptor blockade is effective in prostate cancer therapy. However, patients often progress to castration-resistant prostate cancer with elevated androgen receptor expression and hypersensitivity to androgen. Recently, comprehensive analysis tools, such as complementary DNA microarray, chromatin immunoprecipitation-on-chip and chromatin immunoprecipitation-sequence, have described the androgen-mediated diverse transcriptional program and gene networks in prostate cancer. Furthermore, functional and clinical studies have shown that some of the androgen receptor-regulated genes could be prognostic markers and potential therapeutic targets for the treatment of prostate cancer, particularly castration-resistant prostate cancer. Thus, identifying androgen receptor downstream signaling events and investigating the regulation of androgen receptor activity is critical for understanding the mechanism of carcinogenesis and progression to castration-resistant prostate cancer.

  15. CHL1 is involved in human breast tumorigenesis and progression

    Energy Technology Data Exchange (ETDEWEB)

    He, Li-Hong [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ma, Qin [Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin (China); Shi, Ye-Hui [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie; Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Shu-Fen [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Tong, Zhong-Sheng, E-mail: 83352162@qq.com [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  16. K+ channels and cell cycle progression in tumor cells

    Directory of Open Access Journals (Sweden)

    HALIMA eOUADID-AHIDOUCH

    2013-08-01

    Full Text Available K+ ions play a major role in many cellular processes. The deregulation of K+ signaling is associated with a variety of diseases such as hypertension, atherosclerosis, or diabetes. K+ ions are important for setting the membrane potential, the driving force for Ca2+ influx, and regulate volume of growing cells. Moreover, it is increasingly recognized that K+ channels control cell proliferation through a novel signaling mechanisms triggered and modulated independently of ion fluxes. In cancer, aberrant expression, regulation and/or sublocalization of K+ channels can alter the downstream signals that converge on the cell cycle machinery. Various K+ channels are involved in cell cycle progression and are needed only at particular stages of the cell cycle. Consistent with this idea, the expression of Eag1 and HERG channels fluctuate along the cell cycle. Despite of acquired knowledge, our understanding of K+ channels functioning in cancer cells requires further studies. These include identifying the molecular mechanisms controling the cell cycle machinery. By understanding how K+ channels regulate cell cycle progression in cancer cells, we will gain insights into how cancer cells subvert the need for K+ signal and its downstream targets to proliferate.

  17. How pregnancy can affect autoimmune diseases progression?

    Science.gov (United States)

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio

    2016-01-01

    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.

  18. 维生素 D通过 Wnt信号通路对肠道发育调控机制的研究进展%Research Progress of Mechanism of Vitamin D Regulating Development of the Intestine through Wnt Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    石宝石; 徐玲; 张小龙; 赖星; 刘亚娟; 唐志如

    2015-01-01

    Wnt信号通路广泛存在于脊椎和无脊椎动物体内,对动物机体各组织器官发育,如肝脏、肾脏、肠道等起着至关重要的作用。维生素D是一组脂溶性类固醇衍生物,维生素D不直接作用于靶器官,而是通过与维生素D受体( VDR )结合从而发挥其生物学效应。近年来研究表明,VDR可以通过影响Wnt信号通路的传导进而影响肠道发育,本文就VDR对Wnt信号通路的影响、Wnt信号通路对肠道发育的调控机制等方面作一综述,以期为Wnt信号通路在肠道发育调控研究提供参考。%Wnt signaling pathway is widely present in both vertebrate and invertebrate animal’ s tissues and or-gans, it plays a very important role in many organs such as the liver, kidney and intestine. Vitamin D is a group of derivatives of fat-soluble steroid, it doesn’ t affect the target organ directly, and it works with the vita-min D receptor and exerts its biological effects. Many studies report that vitamin D receptor ( VDR) can regu-late the development of intestine through the Wnt signaling pathway. This paper reviewed the effect of VDR to Wnt signaling pathway and the Wnt signaling pathway regulating the development of intestine to make some reference for the study on regulating intestine development.

  19. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

    OpenAIRE

    Serena Bonomi; Stefania Gallo; Morena Catillo; Daniela Pignataro; Giuseppe Biamonti; Claudia Ghigna

    2013-01-01

    Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer ...

  20. Small RNA Transcriptome of the Oral Microbiome during Periodontitis Progression.

    Science.gov (United States)

    Duran-Pinedo, Ana E; Yost, Susan; Frias-Lopez, Jorge

    2015-10-01

    The oral microbiome is one of the most complex microbial communities in the human body, and due to circumstances not completely understood, the healthy microbial community becomes dysbiotic, giving rise to periodontitis, a polymicrobial inflammatory disease. We previously reported the results of community-wide gene expression changes in the oral microbiome during periodontitis progression and identified signatures associated with increasing severity of the disease. Small noncoding RNAs (sRNAs) are key players in posttranscriptional regulation, especially in fast-changing environments such as the oral cavity. Here, we expanded our analysis to the study of the sRNA metatranscriptome during periodontitis progression on the same samples for which mRNA expression changes were analyzed. We observed differential expression of 12,097 sRNAs, identifying a total of 20 Rfam sRNA families as being overrepresented in progression and 23 at baseline. Gene ontology activities regulated by the differentially expressed (DE) sRNAs included amino acid metabolism, ethanolamine catabolism, signal recognition particle-dependent cotranslational protein targeting to membrane, intron splicing, carbohydrate metabolism, control of plasmid copy number, and response to stress. In integrating patterns of expression of protein coding transcripts and sRNAs, we found that functional activities of genes that correlated positively with profiles of expression of DE sRNAs were involved in pathogenesis, proteolysis, ferrous iron transport, and oligopeptide transport. These findings represent the first integrated sequencing analysis of the community-wide sRNA transcriptome of the oral microbiome during periodontitis progression and show that sRNAs are key regulatory elements of the dysbiotic process leading to disease.

  1. Earnings progression, human capital and incentives

    DEFF Research Database (Denmark)

    Frederiksen, Anders

    progression by investigating the effects of on-the-job human capital acquisition, explicit short-run incentives and career concern incentives on earnings progression. The model leads to predictions about the incentive structure and the progression in both cross-sectional and individual earnings which...

  2. Research Progress in Tomato Responses to Abiotic Stress

    Institute of Scientific and Technical Information of China (English)

    Jianing XU; Gang LIU; Liyun ZHANG

    2016-01-01

    Tomato is a kind of vegetable with high economic benefits in protected farmland.Accounting for 30% of vegetable planting area in the entire protected farmland,tomato plays an essential role in cultivation of protected vegetable.Different abiotic stresses have different degrees of influence on growth and development,yield,and fruit quality of tomatoes.Therefore,finding out life activity rules of tomatoes under different abiotic stresses will be of great significance to breeding for stress tolerance and increasing tomato yield and income.This paper made an overview of research progress in tomato responses to abiotic stress in growth and development,physiology and biochemistry,and gene regulation.

  3. [Regulation of terpene metabolism]. [Mentha piperita, Mentha spicata

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-01-01

    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.

  4. Infrastructures of progress and dispossession

    DEFF Research Database (Denmark)

    Andersen, Astrid Oberborbeck

    2016-01-01

    Abstract: Th is article examines what economic growth and state versions of progress have done to small and medium-scale farmers in an urban setting, in Arequipa in southern Peru. Th e general reorganization of production, resources, and labor in the Peruvian economy has generated a discursive move...... and organizational infrastructures and practices into account, and situates these in specifi c historical processes, the article argues that farmers within the urban landscape of Arequipa struggle to reclaim land and water, and reassert a status that they experience to be losing. Such a historical focus on material...

  5. Recent cryocooler progress in Japan

    Science.gov (United States)

    Matsubara, Y.

    1985-05-01

    The progress of cryocoolers and related devices in Japan is reviewed. The Japanese National Railways has developed the light weight 4 K on-board refrigerators since 1977 as part of the MAGLEV train program. Superconducting and cryogenic fundamental technology was examined which included high performance cryocooler, magnetic refrigerator and superfluid refrigeration. Space cryogenics such as the cooling systems of IR-detectors was studied. Cryocooler for special applications such as cryopump, NMR-CT and JJ devices was investigated. Compact heat exchangers, high performance regenerators and reliable compressors are investigated as a critical component technology.

  6. [Research progress on wetland ecotourism].

    Science.gov (United States)

    Wang, Li-Long; Lu, Lin

    2009-06-01

    Wetland is rich in biodiversity and cultural diversity, possessing higher tourism value and environmental education and community participation functions. Wetland ecotourism reflects the sustainable development of tourism economy and wetland protection, having received great concern from governments and scholars at home and abroad. This paper summarized the related theories and practices, discussed the research advances in wetland ecotourism from the aspects of significance, progress, contents, methods and results, and pointed out the important research fields in the future, aimed to accelerate the development of wetland ecotourism research and to provide reference about the resources exploitation, environment protection, and scientific administration of wetland and related scenic areas.

  7. Progress in polymer solar cell

    Institute of Scientific and Technical Information of China (English)

    LI LiGui; LU GuangHao; YANG XiaoNiu; ZHOU EnLe

    2007-01-01

    This review outlines current progresses in polymer solar cell. Compared to traditional silicon-based photovoltaic (PV) technology, the completely different principle of optoelectric response in the polymer cell results in a novel configuration of the device and more complicated photovoltaic generation process. The conception of bulk-heterojunction (BHJ) is introduced and its advantage in terms of morphology is addressed. The main aspects including the morphology of photoactive layer, which limit the efficiency and stability of polymer solar cell, are discussed in detail. The solutions to boosting up both the efficiency and stability (lifetime) of the polymer solar cell are highlighted at the end of this review.

  8. Bilateral Progressive Obliterative Retinal Vasculitis

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    In this paper, 10 cases of a special type of retinal vasculitis are reported, which was characterized by progressive obliteration of vessels in both eyes, developed from the periphery to the posterior ploe, and was complicated by vitreous hemorrhage (5 eyes) and neovascular glaucoma (5 eyes) in later stage. The visual acuity was 0. 05 in 10 eyes (50%). Argon laser pho-tocoagulation seemed to be able to retard the natural course of the disease. Fundus changes, differential diagnosis and treatment etc are...

  9. PROGRESS ON ACTIVATED CARBON FIBERS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Activated carbon fiber is one kind of important adsorption materials. These novel fibrousadsorbents have high specific surface areas or abundant functional groups, which make them havegreater adsorption/desorption rates and larger adsorption capacities than other adsorbents. They canbe prepared as bundle, paper, cloth and felt to meet various technical requirement. They also showreduction property. In this paper the latest progress on the studies of the preparation and adsorptionproperties of activated carbon fibers is reviewed. The application of these materials in drinking waterpurification, environmental control, resource recovery, chemical industry, and in medicine and healthcare is also presented.

  10. Genetic progression of malignant melanoma.

    Science.gov (United States)

    Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

    2016-03-01

    Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

  11. Progress toward hydrogen peroxide micropulsion

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, J C; Dittman, M D; Ledebuhr, A G

    1999-07-08

    A new self-pressurizing propulsion system has liquid thrusters and gas jet attitude control without heavy gas storage vessels. A pump boosts the pressure of a small fraction of the hydrogen peroxide, so that reacted propellant can controllably pressurize its own source tank. The warm decomposition gas also powers the pump and is supplied to the attitude control jets. The system has been incorporated into a prototype microsatellite for terrestrial maneuvering tests. Additional progress includes preliminary testing of a bipropellant thruster, and storage of unstabilized hydrogen peroxide in small sealed tanks.

  12. Nuclear spectroscopic studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.

    1996-01-16

    This report describes progress in the experimental nuclear physics program of the University of Tennessee, Knoxville. It presents findings related to properties of high-spin states, low-energy levels of nuclei far from stability, and high-energy heavy-ion physics, as well as a brief description of the Joint Institute of Heavy Ion Research (a collaboration between the University of Tennessee, Vanderbilt University, and Oak Ridge National Laboratory) and its activities (particularly those of the last few years), and a list of publications. 89 refs., 18 figs., 5 tabs.

  13. 高温和干旱胁迫下,植物叶片光合系统变化、气孔运动及其调控研究进展%Research Progress of Photosystem Variation, Stoma Movement and Its Regulation of Plant Leaf under High Temperature and Drought Stress

    Institute of Scientific and Technical Information of China (English)

    肖万欣; 王延波; 谢甫绨; 赵海岩

    2012-01-01

    The frequency of catastrophic weather which caused by global climate warming was increased. The rate of high temperature and drought happened simultaneous was increased year by year. A detailed description on photosystem, stoma movement, signal transduction of adversity stress and regulation of stomatal open and close of plant leaf was discussed, as effect of high temperature and drought. The motion law of plant leaf stoma movement and regulation of stomatal open and close used by ABA was discussed from the angle of plant physiology and cell biology, which to provide theoretical basis of new plant variety breeding for drought and high temperature resistance, and for scientific, economic and high effective regulation stoma movement of plant leaf, which could defense short- and long-term adversity stress and guarantee grain stable and high yield finally.%全球气候变暖导致灾难性天气发生频率增高,高温和干旱同时发生的几率逐年增加,针对高温和干旱给植物带来的影响,本文从植物叶片光合系统、气孔运动、逆境胁迫信号传导和叶片气孔开闭调控4个方面进行详细阐述,从植物生理学和细胞生物学角度,讨论了植物叶片气孔运动规律及应用脱落酸对气孔开闭进行调控的研究进展,为抗旱耐高温型植物新品种选育提供理论基础,为科学、经济、高效调控植物叶片气孔运动,防御短暂和长期性逆境胁迫,保证粮食稳产、高产提供科学依据.

  14. Progress as Compositional Lock-Freedom

    DEFF Research Database (Denmark)

    Carbone, Marco; Dardha, Ornela; Montesi, Fabrizio

    2014-01-01

    such definition to capture a more intuitive notion of context adequacy for checking progress. Interestingly, our new catalysers lead to a novel characterisation of progress in terms of the standard notion of lock-freedom. Guided by this discovery, we also develop a conservative extension of catalysers that does...... not depend on types, generalising the notion of progress to untyped session-based processes. We combine our results with existing techniques for lock-freedom, obtaining a new methodology for proving progress. Our methodology captures new processes wrt previous progress analysis based on session types....

  15. Carotenoid Metabolism: Biosynthesis, Regulation,and Beyond

    Institute of Scientific and Technical Information of China (English)

    Shan Lu; Li Li

    2008-01-01

    Carotenoids are Indispensable to plants and play a critical role in human nutrition and health. Significant progress has been made in our understanding of carotenoid metabolism in plants. The biosynthetic pathway has been extensively studied.Nearly all the genes encoding the biosynthetic enzymes have been isolated and characterized from various organisms. In recent years, there is an increasing body of work on the signaling pathways and plastid development, which might provide global control of carotenoid biosynthesis and accumulation. Herein, we will highlight recent progress on the biosynthesis,regulation, and metabolic engineering of carotenoids in plants, as well as the future research towards elucidating the regulatory mechanisms and metabolic network that control carotenoid metabolism.

  16. Auxin-Cytokinin Interaction Regulates Meristem Development

    Institute of Scientific and Technical Information of China (English)

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

    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 in auxin and cytokinin biosynthesis, auxin transport, and auxin and cytokinin signaling.The frameworks for the complicated interaction of these two hormones in the control of shoot apical meristem and root apical meristem formation as well as their roles in in vitro organ regeneration are the major focus of this review.

  17. Long Non-coding RNAs In Cancer Progression

    Directory of Open Access Journals (Sweden)

    Keiko eTano

    2012-10-01

    Full Text Available Recent large-scale transcriptome analyses have revealed that transcription is spread throughout the mammalian genomes, yielding large numbers of transcripts, including long non-coding (lnc RNAs with little or no protein-coding capacity. Dozens of lncRNAs have been identified as biologically significant. In many cases, lncRNAs act as key molecules in the regulation of processes such as chromatin remodeling, transcription and post-transcriptional processing. Several lncRNAs (e.g., MALAT1, HOTAIR and ANRIL are associated with human diseases, including cancer. Those lncRNAs associated with cancer are often aberrantly expressed. Although the underlying molecular mechanisms by which lncRNAs regulate cancer development are unclear, recent studies have revealed that such aberrant expression of lncRNAs affects the progression of cancers. In this review, we highlight recent findings regarding the roles of lncRNAs in cancer biology.

  18. Epigenetic regulation of cystatins in cancer.

    Science.gov (United States)

    Rivenbark, Ashley G; Coleman, William B

    2009-01-01

    Cystatins function as cysteine protease inhibitors, are expressed in numerous cell types, and regulate a number of physiological processes. Four cystatins have been extensively studied: cystatin A, cystatin B, cystatin C, and cystatin M. Aberrant regulation of cystatins occurs in a number of diseases, including cancer and certain neurodegenerative disorders. Recent advances in the understanding of cystatin function suggest that these proteins may regulate promotion or suppression of tumor growth, invasion, and metastasis. Cancer is a disease of abnormal gene expression and cancer cells exhibit aberrant epigenetic events (such as DNA methylation), leading to gene silencing. Cystatins are epigenetically silenced through DNA methylation-dependent mechanisms in several forms of cancer, including breast, pancreatic, brain, and lung. These findings suggest that DNA methylation-dependent epigenetic mechanisms may play an important role in the loss of cystatin gene expression and protein function during neoplastic transformation and/or tumor progression. This review summarizes the biological processes in which cystatins function, focuses on the neoplastic events that involve aberrant regulation of cystatins, and discusses the possible epigenetic regulation of cystatins in cancer.

  19. [Growth and nonlinearity]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Savit, R.

    1993-12-31

    The research centered on the physics of growth. One particular focus was the spiral patterns seen in excitable media, such as the chemical reaction of Belousov and Zhabatinskii, and the aggregation of the slime mold, Dictyostelium Discoideum. Another area of interest is the statistical roughness of the growth front itself. For example, when growing thin films, the roughness of the surface is very important for the ultimate quality of the film. Besides its direct technological relevance, this problem is intimately connected to many fundamental problems in statistical physics. In addition work was done in the related area of statistical properties of flux-flow motion in superconductors. Substantial progress was also made on techniques and applications of the analysis of complex systems. Methods of time series analysis were generalized to the analysis of complex spatio-temporal patterns. In the examples studied most, turbulence and electroencephalograms, the spatio-temporal patterns are very complex and fleeting, and can easily be misken for random noise. Nevertheless, substantial progress was made in developing and applying methods to these systems that indicate the presence of nonrandom time-varying spatial patterns.

  20. Alternative energies. Updates on progress

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, German (ed.) [CIRCE - Centre of Research for Energy Resources and Consumption, Zaragoza (Spain)

    2013-07-01

    Presents fundamental and applied research of alternative energies. Address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress. Includes the life cycle assessment and thermoeconomic analysis as tools for evaluating and optimising environmental and cost subjects. This book presents nine chapters based on fundamental and applied research of alternative energies. At the present time, the challenge is that technology has to come up with solutions that can provide environmentally friendly energy supply options that are able to cover the current world energy demand. Experts around the world are working on these issues for providing new solutions that will break the existing technological barriers. This book aims to address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress for each pillar. It also includes the life cycle assessment (LCA) and thermoeconomic analysis (TA) as tools for evaluating and optimising environmental and cost subjects. Chapters are organized into fundamental research, applied research and future trends; and written for engineers, academic researches and scientists.

  1. Progress on DCLL Blanket Concept

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Clement; Abdou, M.; Katoh, Yutai; Kurtz, Richard J.; Lumsdaine, A.; Marriott, Edward P.; Merrill, Brad; Morley, Neil; Pint, Bruce A.; Sawan, M.; Smolentsev, S.; Williams, Brian; Willms, Scott; Youssef, M.

    2013-09-01

    Under the US Fusion Nuclear Science and Technology Development program, we have selected the Dual Coolant Lead Lithium concept (DCLL) as a reference blanket, which has the potential to be a high performance DEMO blanket design with a projected thermal efficiency of >40%. Reduced activation ferritic/martensitic (RAF/M) steel is used as the structural material. The self-cooled breeder PbLi is circulated for power conversion and for tritium breeding. A SiC-based flow channel insert (FCI) is used as a means for magnetohydrodynamic pressure drop reduction from the circulating liquid PbLi and as a thermal insulator to separate the high-temperature PbLi (~700°C) from the helium-cooled RAF/M steel structure. We are making progress on related R&D needs to address critical Fusion Nuclear Science and Facility (FNSF) and DEMO blanket development issues. When performing the function as the Interface Coordinator for the DCLL blanket concept, we had been developing the mechanical design and performing neutronics, structural and thermal hydraulics analyses of the DCLL TBM module. We had estimated the necessary ancillary equipment that will be needed at the ITER site and a detailed safety impact report has been prepared. This provided additional understanding of the DCLL blanket concept in preparation for the FNSF and DEMO. This paper will be a summary report on the progress of the DCLL TBM design and R&Ds for the DCLL blanket concept.

  2. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  3. Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Masataka Kikuchi

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

  4. DNA copy-number control through inhibition of replication fork progression

    NARCIS (Netherlands)

    J.T. Nordman (Jared T.); E. Kozhevnikova (Elena); C.P. Verrijzer (Peter); A.V. Pindyurin (Alexey); E.N. Andreyeva (Evgeniya); V.V. Shloma (Victor); I.F. Zhimulev (Igor); T. Orr-Weaver (T.)

    2014-01-01

    textabstractProper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell

  5. Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

    Science.gov (United States)

    BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

  6. Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

    Science.gov (United States)

    Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

  7. FY2011 Annual Progress Report for Advanced Combustion Engine Research and Development

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2011-12-01

    Annual Progress Report for the Advanced Combustion Engine Research and Development (R&D) subprogram supporting the mission of the Vehicle Technologies Program by removing the critical technical barriers to commercialization of advanced internal combustion engines (ICEs) for passenger and commercial vehicles that meet future federal emissions regulations.

  8. Dissolved organic matter and lake metabolism. Technical progress report, 1 July 1975--30 June 1976

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, R. G.

    1976-01-01

    Progress is reported in the following areas of research: interactions of dissolved organic matter with inorganic nutrient cycling; regulation of the photosynthetic and decompositional metabolism of micro- and macroflora; regulatory mechanisms of growth and rates of carbon cycling; and fate of detrital dissolved and particulate organic matter. (HLW)

  9. 48 CFR 32.503-3 - Initiation of progress payments and review of accounting system.

    Science.gov (United States)

    2010-10-01

    ... payments and review of accounting system. 32.503-3 Section 32.503-3 Federal Acquisition Regulations System... on Costs 32.503-3 Initiation of progress payments and review of accounting system. (a) For..., (2) possessed of an adequate accounting system and controls, and (3) in sound financial...

  10. Integrated extracellular matrix signaling in mammary gland development and breast cancer progression.

    Science.gov (United States)

    Zhu, Jieqing; Xiong, Gaofeng; Trinkle, Christine; Xu, Ren

    2014-09-01

    Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.

  11. Novel regulators of spermatogenesis.

    Science.gov (United States)

    Fok, Kin Lam; Chen, Hao; Ruan, Ye Chun; Chan, Hsiao Chang

    2014-05-01

    Spermatogenesis is a multistep process that supports the production of millions of sperm daily. Understanding of the molecular mechanisms that regulate spermatogenesis has been a major focus for decades. Yet, the regulators involved in different cellular processes of spermatogenesis remain largely unknown. Human diseases that result in defective spermatogenesis have provided hints on the molecular mechanisms regulating this process. In this review, we have summarized recent findings on the function and signaling mechanisms of several genes that are known to be associated with disease or pathological processes, including CFTR, CD147, YWK-II and CT genes, and discuss their potential roles in regulating different processes of spermatogenesis.

  12. miR-148 regulates Mitf in melanoma cells.

    Directory of Open Access Journals (Sweden)

    Benedikta S Haflidadóttir

    Full Text Available The Microphthalmia associated transcription factor (Mitf is an important regulator in melanocyte development and has been shown to be involved in melanoma progression. The current model for the role of Mitf in melanoma assumes that the total activity of the protein is tightly regulated in order to secure cell proliferation. Previous research has shown that regulation of Mitf is complex and involves regulation of expression, splicing, protein stability and post-translational modifications. Here we show that microRNAs (miRNAs are also involved in regulating Mitf in melanoma cells. Sequence analysis revealed conserved binding sites for several miRNAs in the Mitf 3'UTR sequence. Furthermore, miR-148 was shown to affect Mitf mRNA expression in melanoma cells through a conserved binding site in the 3'UTR sequence of mouse and human Mitf. In addition we confirm the previously reported effects of miR-137 on Mitf. Other miRNAs, miR-27a, miR-32 and miR-124 which all have conserved binding sites in the Mitf 3'UTR sequence did not have effects on Mitf. Our data show that miR-148 and miR-137 present an additional level of regulating Mitf expression in melanocytes and melanoma cells. Loss of this regulation, either by mutations or by shortening of the 3'UTR sequence, is therefore a likely factor in melanoma formation and/or progression.

  13. Transcriptional responses and regulations to deficient phosphorus in plants

    Institute of Scientific and Technical Information of China (English)

    Jinxiang BAO; Shuhua ZHANG; Wenjing LU; Chengjin GUO; Juntao GU; Kai XIAO

    2009-01-01

    Significant progress has been made over the past several years in the understanding of phosphorus (Pi)-starvation responses in plants and their regulation. The transcriptional changes that occur in response to Pi starvation are beginning to be revealed, although much is left to understand about their significance. In this paper, the recent progresses on the gene expression changes under deficient-Pi, cis-regulatory elements involved in response to deficient-Pi, the transcriptional control of Pi-starvation responses in eukaryotes, transcription factors involved in response to Pi-starvation, the role of MicroRNA on regulation of phosphate homeostasis, and phosphate sensing and signal transduction in plants have been summarized. The purpose of this review is to provide some basis for further elucidation of the transcriptional responses and regulations, and the networks of Pi sensing and signal transduction under deficient-Pi in plants in the future.

  14. Short-Term Activation of Hypoxia-Inducible Factor Slows Kidney Disease Progression in Rat Model of 5/6 ;Subtotal Nephrectomy by Up-regulating MiR-29c Expression%低氧诱导因子短期活化后诱导 miR-29c表达上调可延缓5/6肾切除大鼠的肾病进展

    Institute of Scientific and Technical Information of China (English)

    梁怡然; 衡艳艳; 俞小芳; 贾平; 方艺

    2016-01-01

    目的:探讨适度活化低氧诱导因子(hypoxia‐inducible factor ,HIF)对延缓残肾慢性肾脏病进展的作用及可能机制。方法:雄性SD大鼠采用二步法5/6肾大部切除术建立残肾模型,随机分为L‐mimosine (L‐Mim)治疗组(术后5~12周短期给予脯氨酸羟化酶抑制剂,隔日50 mg/kg腹腔给药)和未治疗残肾组,同时设立假手术对照组。术后12周末处死大鼠留取标本。结果:L‐Mim治疗组大鼠血肌酐水平[(82.4±6.3)比(130.1±24.1)μmol/L , P<0.05]、24 h尿蛋白水平[(0.7±0.1)比(1.7±0.5) g/d ,P<0.05]以及残肾病理改变较未治疗残肾组大鼠有显著改善。miRNA芯片分析结果提示:L‐Mim治疗组肾皮质miR‐29c丰度高于未治疗残肾组,伴 HIF‐1α和 HIF‐2α表达增强。经荧光素酶报告检测系统和体外突变实验明确原肌球蛋白1(TPM1)为miR‐29c靶基因之一。HK2细胞转染pre‐miR‐29c寡核苷酸后可以抑制 TGF‐β1(3 ng/mL ,24 h)诱导的原肌球蛋白水平上调(P<0.05或0.01)。结论:大鼠残肾肾间质纤维化病变明显并伴miR‐29c水平下调,适度活化 HIF水平可通过上调miR‐29c表达延缓残肾功能恶化。%Objective:To investigate the role and probable mechanism of moderate activation of hypoxia‐inducible factor(HIF) in slowing chronic kidney disease progression of remnant kidney .Methods :Rat models of remnant kidney were established by 5/6 subtotal nephrectomy in male Sprague‐Dawley rats . And then they were randomly allocated to L‐mimosine (L‐Mim ) treatment group ,in which the rats were treated with intraperitoneal injections of L‐Mim during 5‐12 week after operation ,and untreated remnant kidney group .Meanwhile ,sham operated rats were set as control group .All rats were sacrificed at the end of week 12 ,and the specimens were collected .Results:The serum creatinine level

  15. Global gene expression profile progression in Gaucher disease mouse models

    Directory of Open Access Journals (Sweden)

    Zhang Wujuan

    2011-01-01

    Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

  16. Aquaporin-2 regulation in health and disease

    DEFF Research Database (Denmark)

    Radin, M J; Yu, Ming-Jiun; Stødkilde-Jørgensen, Lene

    2012-01-01

    translation of AQP2 mRNA and removal via degradation or secretion into the urine in exosomes. AQP2 abundance increases in response to vasopressin chiefly due to increased translation subsequent to increases in AQP2 mRNA. Vasopressin-mediated regulation of AQP2 gene transcription is poorly understood, although...... several transcription factor-binding elements in the 5′ flanking region of the AQP2 gene have been identified, and candidate transcription factors corresponding to these elements have been discovered in proteomics studies. Here, we review progress in this area and discuss elements of vasopressin signaling...

  17. Correlation between Polyamines and Growth Regulators

    DEFF Research Database (Denmark)

    Gemici, Meliha; Unal, D.; Azeri, N.;

    2007-01-01

    Compounds of polyamines, considering to be essential for life, are found in prokaryotes and eukaryotes. Although their exact functions have not yet been identified, it is clear that the polyamines play important specific roles in a number of cellular processes such as replication and translation......, embryonic development, cell cycle, programmed cell death and cancer. In addition, the metabolic pathway of these compounds is lighten in recent years, the relationship between polyamines and hormones still remains unclear. In this study, we suggest that cytokinin and auxin, a plant growth hormone...... and regulating cell cycle progression, could be correlated with polyamines....

  18. Lignin biosynthesis and its molecular regulation

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Lignin biosynthesis has become increasingly highlighted because it plays an important role in the growth and development of plant, in the systematic evolution of plant and in the human life. Due to the progress in the field of lignin studies in recent years, the lignin biosynthesis pathway has been 修订日期:. Here we discuss some genetic engineering approaches on lignin biosynthesis, and conceive strategy to regulate lignin biosynthesis in order to use lignin resource more efficiently in agricultural and industrial productions.

  19. LuxS/AI-2型群体感应系统调控细菌生物被膜形成研究进展%Progress in Research on Biofilm Formation Regulated by LuxS/AI-2 Quorum Sensing

    Institute of Scientific and Technical Information of China (English)

    刘蕾; 桂萌; 武瑞赟; 李平兰

    2016-01-01

    Themajority of bacteriaform biofilms for growth and development and bacteria within biofilms may better adapt to environment than their planktonic counterparts. LuxS-dependent quorum sensing is a widespread system used by bacteria for cell-to-cell communication, which can regulate biofilm formation in a cell density-dependent manner. Autoinducer 2 (AI-2) produced by LuxS, is a species-nonspecific signal used by both gram-negative and gram-positive bacteria for biofilm formation. Currently, several inhibitors of LuxS/AI-2 quorum sensing have been determined to influence biofilm formation based on their anti-AI-2 communication mechanisms. Recently, there has been a surging interest in the mechanism of biofilm regulation by LuxS/AI-2 quorum sensing system, which is important to better understand the relationship between LuxS-dependent QS system and biofilm formation.%生物被膜是大多数细菌在自然状态下的一种生长方式,使菌体具有浮游态时不具有的优势。它的形成和发展受到群体感应系统的调控,该系统是细菌依赖于群体密度而调控其生理行为的一种机制。其中LuxS/2型自诱导物(autoinducer 2,AI-2)群体感应系统又称种间群体感应系统,广泛存在于G+及G-菌中。其信号分子AI-2被认为是种间通用的信号分子,参与调控多种细菌的生物被膜。此外,目前已发现多种LuxS/AI-2型群体感应系统抑制剂,它们可以影响许多细菌生物被膜的形成。目前研究人员已开始致力于揭示LuxS/AI-2型群体感应系统调控生物被膜形成的分子机制,这对于进一步理解LuxS/AI-2型群体感应系统与生物被膜的关系具有重要意义。

  20. Progress in Coal Liquefaction Technologies

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Worldwide primary energy consumption is entering an era of pluralism and high quality under the influence of rapid economic development, increasing energy shortage and strict environmental policies. Although renewable energy technology is developing rapidly, fossil fuels (coal, oil and gas) are still the dominant energy sources in the world. As a country rich in coal but short ofoil and gas, China's oil imports have soared in the past few years. Government, research organizations and enterprises in China are paying more and more attention to the processes of converting coal into clean liquid fuels. Direct and indirect coal liquefaction technologies are compared in this paper based on China's current energy status and technological progress not only in China itself but also in the world.