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Sample records for regulate phagosome maturation

  1. Class IA phosphatidylinositol 3-kinase p110α regulates phagosome maturation.

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    Emily P Thi

    Full Text Available Of the various phosphatidylinositol 3- kinases (PI3Ks, only the class III enzyme Vps34 has been shown to regulate phagosome maturation. During studies of phagosome maturation in THP-1 cells deficient in class IA PI3K p110α, we discovered that this PI3K isoform is required for vacuole maturation to progress beyond acquisition of Rab7 leading to delivery of lysosomal markers. Bead phagosomes from THP-1 cells acquired p110α and contained PI3P and PI(3,4,5P3; however, p110α and PI(3,4,5P3 levels in phagosomes from p110α knockdown cells were decreased. Phagosomes from p110α knock down cells showed normal acquisition of both Rab5 and EEA-1, but were markedly deficient in the lysosomal markers LAMP-1 and LAMP-2, and the lysosomal hydrolase, β-galactosidase. Phagosomes from p110α deficient cells also displayed impaired fusion with Texas Red dextran-loaded lysosomes. Despite lacking lysosomal components, phagosomes from p110α deficient cells recruited normal levels of Rab7, Rab-interacting lysosomal protein (RILP and homotypic vacuole fusion and protein sorting (HOPs components Vps41 and Vps16. The latter observations demonstrated that phagosomal Rab7 was active and capable of recruiting effectors involved in membrane fusion. Nevertheless, active Rab7 was not sufficient to bring about the delivery of lysosomal proteins to the maturing vacuole, which is shown for the first time to be dependent on a class I PI3K.

  2. Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis.

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    Youhei Egami

    Full Text Available Rab20, a member of the Rab GTPase family, is known to be involved in membrane trafficking, however its implication in FcγR-mediated phagocytosis is unclear. We examined the spatiotemporal localization of Rab20 during phagocytosis of IgG-opsonized erythrocytes (IgG-Es in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused Rab20, it was shown that Rab20 was transiently associated with the phagosomal membranes. During the early stage of phagosome formation, Rab20 was not localized on the membranes of phagocytic cups, but was gradually recruited to the newly formed phagosomes. Although Rab20 was colocalized with Rab5 to some extent, the association of Rab20 with the phagosomes persisted even after the loss of Rab5 from the phagosomal membranes. Then, Rab20 was colocalized with Rab7 and Lamp1, late endosomal/lysosomal markers, on the internalized phagosomes. Moreover, our analysis of Rab20 mutant expression revealed that the maturation of phagosomes was significantly delayed in cells expressing the GDP-bound mutant Rab20-T19N. These data suggest that Rab20 is an important component of phagosome and regulates the phagosome maturation during FcγR-mediated phagocytosis.

  3. A Drosophila Model to Image Phagosome Maturation

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    Douglas A. Brooks

    2013-03-01

    Full Text Available Phagocytosis involves the internalization of extracellular material by invagination of the plasma membrane to form intracellular vesicles called phagosomes, which have functions that include pathogen degradation. The degradative properties of phagosomes are thought to be conferred by sequential fusion with endosomes and lysosomes; however, this maturation process has not been studied in vivo. We employed Drosophila hemocytes, which are similar to mammalian professional macrophages, to establish a model of phagosome maturation. Adult Drosophila females, carrying transgenic Rab7-GFP endosome and Lamp1-GFP lysosome markers, were injected with E. coli DH5α and the hemocytes were collected at 15, 30, 45 and 60 minutes after infection. In wild-type females, E. coli were detected within enlarged Rab7-GFP positive phagosomes at 15 to 45 minutes after infection; and were also observed in enlarged Lamp1-GFP positive phagolysosomes at 45 minutes. Two-photon imaging of hemocytes in vivo confirmed this vesicle morphology, including enlargement of Rab7-GFP and Lamp1-GFP structures that often appeared to protrude from hemocytes. The interaction of endosomes and lysosomes with E. coli phagosomes observed in Drosophila hemocytes was consistent with that previously described for phagosome maturation in human ex vivo macrophages. We also tested our model as a tool for genetic analysis using 14-3-3e mutants, and demonstrated altered phagosome maturation with delayed E. coli internalization, trafficking and/or degradation. These findings demonstrate that Drosophila hemocytes provide an appropriate, genetically amenable, model for analyzing phagosome maturation ex vivo and in vivo.

  4. SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages1

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    Kamen, Lynn A.; Levinsohn, Jonathan; Cadwallader, Amy; Tridandapani, Susheela; Swanson, Joel A.

    2010-01-01

    Although the inositol phosphatase SHIP-1 is generally thought to inhibit signaling for Fc receptor-mediated phagocytosis, the product of its activity, phosphatidylinositol 3,4 bisphosphate (PI(3,4)P2) has been implicated in activation of the NADPH oxidase. This suggests that SHIP-1 positively regulates generation of reactive oxygen species after phagocytosis. To examine how SHIP-1 activity contributes to Fc receptor-mediated phagocytosis, we measured and compared phospholipid dynamics, membrane trafficking and the oxidative burst in macrophages from SHIP-1-deficient and wild-type mice. SHIP-1-deficient macrophages showed significantly elevated ratios of PI(3,4,5) P3 to PI(3,4)P2 on phagosomal membranes. Imaging reactive oxygen intermediate activities in phagosomes revealed decreased early NADPH oxidase activity in SHIP-1-deficient macrophages. SHIP-1-deficiency also altered later stages of phagosome maturation, as indicated by the persistent elevation of PI(3)P and the early localization of Rab5a to phagosomes. These direct measurements of individual organelles indicate that phagosomal SHIP-1 enhances the early oxidative burst through localized alteration of the membrane 3′ phosphoinositide composition. PMID:18490750

  5. The SecA2 pathway of Mycobacterium tuberculosis exports effectors that work in concert to arrest phagosome and autophagosome maturation.

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    Zulauf, Katelyn E; Sullivan, Jonathan Tabb; Braunstein, Miriam

    2018-04-30

    To subvert host defenses, Mycobacterium tuberculosis (Mtb) avoids being delivered to degradative phagolysosomes in macrophages by arresting the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. The SecA2 dependent protein export system is required for phagosome maturation arrest and consequently growth of Mtb in macrophages. To better understand the role of the SecA2 pathway in phagosome maturation arrest, we identified two effectors exported by SecA2 that contribute to this process: the phosphatase SapM and the kinase PknG. Then, utilizing the secA2 mutant of Mtb as a platform to study effector functions, we identified specific steps in phagosome maturation inhibited by SapM and/or PknG. By identifying a histidine residue that is essential for SapM phosphatase activity, we confirmed for the first time that the phosphatase activity of SapM is required for its effects on phagosome maturation in macrophages. We further demonstrated that SecA2 export of SapM and PknG contributes to the ability of Mtb to replicate in macrophages. Finally, we extended our understanding of the SecA2 pathway, SapM, and PknG by revealing that their contribution goes beyond preventing Mtb delivery to mature phagolysosomes and includes inhibiting Mtb delivery to autophagolysosomes. Together, our results revealed SapM and PknG to be two effectors exported by the SecA2 pathway of Mtb with distinct as well as cumulative effects on phagosome and autophagosome maturation. Our results further reveal that Mtb must have additional mechanisms of limiting acidification of the phagosome, beyond inhibiting recruitment of the V-ATPase proton pump to the phagosome, and they indicate differences between effects of Mtb on phagosome and autophagosome maturation.

  6. Molecular characterization of phagosomes

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    Desjardins, M.; Celis, J.E.; van Meer, G.; Dieplinger, H.; Jahraus, A.; Griffiths, G.; Huber, L.A.

    1994-01-01

    The transformation of newly formed phagosomes into mature phagolysosomes is a process that involves a complex series of interactions between phagosomes and other vacuolar organelles. The machinery required by phagosomes to mediate these interactions is poorly understood. In this study, we allowed

  7. Phagosome maturation in unicellular eukaryote Paramecium: the presence of RILP, Rab7 and LAMP-2 homologues

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    E Wyroba

    2009-08-01

    Full Text Available Phagosome maturation is a complex process enabling degradation of internalised particles. Our data obtained at the gene, protein and cellular level indicate that the set of components involved in this process and known up to now in mammalian cells is functioning in unicellular eukaryote. Rab7-interacting partners: homologues of its effector RILP (Rab-interacting lysosomal protein and LAMP-2 (lysosomal membrane protein 2 as well as a7 subunit of the 26S proteasome were revealed in Paramecium phagolysosomal compartment. We identified the gene/transcript fragments encoding RILP-related proteins (RILP1 and RILP2 in Paramecium by PCR/RT-PCR and sequencing. The deduced amino acid sequences of RILP1 and RILP2 show 60.5% and 58.3% similarity, respectively, to the region involved in regulating of lysosomal morphology and dynein-dynactin recruitment of human RILP. RILP colocalised with Rab7 in Paramecium lysosomes and at phagolysosomal membrane during phagocytosis of both the latex beads and bacteria. In the same compartment LAMP-2 was present and its expression during latex internalisation was 2.5-fold higher than in the control when P2 protein fractions (100 000 x g of equal load were quantified by immunoblotting. LAMP-2 crossreacting polypeptide of ~106 kDa was glycosylated as shown by fluorescent and Western analysis of the same blot preceded by PNGase F treatment. The a7 subunit of 26S proteasome was detected close to the phagosomal membrane in the small vesicles, in some of which it colocalised with Rab7. Immunoblotting confirmed presence of RILPrelated polypeptide and a7 subunit of 26S proteasome in Paramecium protein fractions. These results suggest that Rab7, RILP and LAMP-2 may be involved in phagosome maturation in Paramecium.

  8. Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3P critical for the degradation of apoptotic cells.

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    Nan Lu

    2012-01-01

    Full Text Available Phosphatidylinositol 3-phosphate (PtdIns(3P is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K Vps34 is regarded as the only kinase that produces PtdIns(3P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3P in a manner dependent on the large GTPase dynamin (DYN-1. PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.

  9. Lysophosphatidylcholine Promotes Phagosome Maturation and Regulates Inflammatory Mediator Production Through the Protein Kinase A–Phosphatidylinositol 3 Kinase–p38 Mitogen-Activated Protein Kinase Signaling Pathway During Mycobacterium tuberculosis Infection in Mouse Macrophages

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    Hyo-Ji Lee

    2018-04-01

    Full Text Available Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb. Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb. In macrophages infected with Mtb strain, H37Ra or H37Rv, LPC suppressed bacterial growth; however, this effect was suppressed in bone marrow-derived macrophages (BMDMs isolated from G2A (a G protein-coupled receptor involved in some LPC actions knockout mice. LPC also promoted phagosome maturation via phosphatidylinositol 3 kinase (PI3K–p38 mitogen-activated protein kinase (MAPK-mediated reactive oxygen species production and intracellular Ca2+ release during Mtb infection. In addition, LPC induced increased levels of intracellular cyclic adenosine monophosphate (cAMP and phosphorylated glycogen synthase kinase 3 beta (GSK3β in Mtb-infected macrophages. Protein kinase A (PKA-induced phosphorylation of GSK3β suppressed activation of NF-κB in LPC-treated macrophages during Mtb infection, leading to decreased secretion of pro-inflammatory cytokines and increased secretion of anti-inflammatory cytokines. These results suggest that LPC can effectively control Mtb growth by promoting phagosome maturation via cAMP-induced activation of the PKA–PI3K–p38 MAPK pathway. Moreover, LPC can regulate excessive production of pro-inflammatory cytokines associated with bacterial infection of macrophages.

  10. Membrane proteomics of phagosomes suggests a connection to autophagy

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    Shui, Wenqing; Sheu, Leslie; Liu, Jun; Smart, Brian; Petzold, Christopher J.; Hsieh, Tsung-yen; Pitcher, Austin; Keasling*, Jay D.; Bertozzi*, Carolyn R.

    2008-11-25

    Phagocytosis is the central process by which macrophage cellsinternalize and eliminate infectious microbes as well as apoptoticcells. During maturation, phagosomes containing engulfed particlesfuse with various endosomal compartments through theaction of regulatory molecules on the phagosomal membrane. Inthis study, we performed a proteomic analysis of the membranefraction from latex bead-containing (LBC) phagosomes isolatedfrom macrophages. The profile, which comprised 546 proteins,suggests diverse functions of the phagosome and potential connectionsto secretory processes, toll-like receptor signaling, andautophagy. Many identified proteins were not previously knownto reside in the phagosome. We characterized several proteins inLBC phagosomes that change in abundance on induction of autophagy,a process that has been previously implicated in the hostdefense against microbial pathogens. These observations suggestcrosstalk between autophagy and phagocytosis that may be relevantto the innate immune response of macrophages.

  11. Quantitative and dynamic assessment of the contribution of the ER to phagosome formation

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    Touret, Nicolas; Paroutis, Paul; Terebiznik, Mauricio; Harrison, Rene E.; Trombetta, Sergio; Pypaert, Marc; Chow, Amy; Jiang, Aimin; Shaw, James; Yip, Christopher; Moore, Hsiao-Ping; van der Wel, Nicole; Houben, Diane; Peters, Peter J.; de Chastellier, Chantal; Mellman, Ira; Grinstein, Sergio

    2005-01-01

    Phagosomes were traditionally thought to originate from an invagination and scission of the plasma membrane to form a distinct intracellular vacuole. An alternative model implicating the endoplasmic reticulum (ER) as a major component of nascent and maturing phagosomes was recently proposed (Gagnon

  12. Modelling phagosomal lipid networks that regulate actin assembly

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    Schwarz Roland

    2008-12-01

    Full Text Available Abstract Background When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator. However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion By establishing an active 'dialogue' between an

  13. Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages.

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    Lydia Kasper

    Full Text Available Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine, differentiation (M1-/M2-type or activation status (vitamin D3 stimulation. We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore

  14. Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

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    Rai, Ashim; Pathak, Divya; Thakur, Shreyasi; Singh, Shampa; Dubey, Alok Kumar; Mallik, Roop

    2016-02-11

    Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Mycobacterial mutants with defective control of phagosomal acidification.

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    2005-11-01

    Full Text Available The pathogenesis of mycobacterial infection is associated with an ability to interfere with maturation of the phagosomal compartment after ingestion by macrophages. Identification of the mycobacterial components that contribute to this phenomenon will allow rational design of novel approaches to the treatment and prevention of tuberculosis. Microarray-based screening of a transposon library was used to identify mutations that influence the fate of Mycobacterium bovis bacille Calmette-Guérin (BCG following uptake by macrophages. A screen based on bacterial survival during a 3-d infection highlighted genes previously implicated in growth of Mycobacterium tuberculosis in macrophages and in mice, together with a number of other virulence genes including a locus encoding virulence-associated membrane proteins and a series of transporter molecules. A second screen based on separation of acidified and non-acidified phagosomes by flow cytometry identified genes involved in mycobacterial control of early acidification. This included the KefB potassium/proton antiport. Mutants unable to control early acidification were significantly attenuated for growth during 6-d infections of macrophages. Early acidification of the phagosome is associated with reduced survival of BCG in macrophages. A strong correlation exists between genes required for intracellular survival of BCG and those required for growth of M. tuberculosis in mice. In contrast, very little correlation exists between genes required for intracellular survival of BCG and those that are up-regulated during intracellular adaptation of M. tuberculosis. This study has identified targets for interventions to promote immune clearance of tuberculosis infection. The screening technologies demonstrated in this study will be useful to the study of pathogenesis in many other intracellular microorganisms.

  16. Single-cell Raman and fluorescence microscopy reveal the association of lipid bodies with phagosomes in leukocytes

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    van Manen, Henk-Jan; Kraan, Yvonne M.; Roos, Dirk; Otto, Cees

    2005-01-01

    Cellular imaging techniques based on vibrational spectroscopy have become powerful tools in cell biology because the molecular composition of subcellular compartments can be visualized without the need for labeling. Using high-resolution, nonresonant confocal Raman microscopy on individual cells, we demonstrate here that lipid bodies (LBs) rich in arachidonate as revealed by their Raman spectra associate with latex bead-containing phagosomes in neutrophilic granulocytes. This finding was corroborated in macrophages and in PLB-985 cells, which can be induced to differentiate into neutrophil-like cells, by selective staining of LBs and visualization by confocal fluorescence microscopy. We further show that the accumulation of LBs near phagosomes is mediated at least in part by the flavohemoprotein gp91phox (in which “phox” is phagocyte oxidase), because different LB distributions around phagocytosed latex beads were observed in WT and gp91phox-deficient PLB-985 cells. gp91phox, which accumulates in the phagosomal membrane, is the catalytic subunit of the leukocyte NADPH oxidase, a critical enzyme in the innate immune response. Finally, time-lapse fluorescence microscopy experiments on neutrophils revealed that the LB-phagosome association is transient, similar to the “kiss-and-run” behavior displayed by endosomes involved in phagosome maturation. Because arachidonic acid (AA) has been shown to be involved in NADPH oxidase activation and phagosome maturation in neutrophils and macrophages, respectively, the findings reported here suggest that LBs may provide a reservoir of AA for local activation of these essential leukocyte functions. PMID:16002471

  17. The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle.

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    Jeff E Grotzke

    2009-04-01

    Full Text Available Mycobacterium tuberculosis (Mtb resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+ T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib. Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.

  18. Voltage-gated proton channel is expressed on phagosomes

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    Okochi, Yoshifumi; Sasaki, Mari; Iwasaki, Hirohide; Okamura, Yasushi

    2009-01-01

    Voltage-gated proton channel has been suggested to help NADPH oxidase activity during respiratory burst of phagocytes through its activities of compensating charge imbalance and regulation of pH. In phagocytes, robust production of reactive oxygen species occurs in closed membrane compartments, which are called phagosomes. However, direct evidence for the presence of voltage-gated proton channels in phagosome has been lacking. In this study, the expression of voltage-gated proton channels was studied by Western blot with the antibody specific to the voltage-sensor domain protein, VSOP/Hv1, that has recently been identified as the molecular correlate for the voltage-gated proton channel. Phagosomal membranes of neutrophils contain VSOP/Hv1 in accordance with subunits of NADPH oxidases, gp91, p22, p47 and p67. Superoxide anion production upon PMA activation was significantly reduced in neutrophils from VSOP/Hv1 knockout mice. These are consistent with the idea that voltage-gated proton channels help NADPH oxidase in phagocytes to produce reactive oxygen species.

  19. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling

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    Christophe J. Queval

    2017-09-01

    Full Text Available Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH, which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive.

  20. Decoupling internalization, acidification and phagosomal-endosomal/lysosomal fusion during phagocytosis of InlA coated beads in epithelial cells.

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    Craig D Blanchette

    Full Text Available BACKGROUND: Phagocytosis has been extensively examined in 'professional' phagocytic cells using pH sensitive dyes. However, in many of the previous studies, a separation between the end of internalization, beginning of acidification and completion of phagosomal-endosomal/lysosomal fusion was not clearly established. In addition, very little work has been done to systematically examine phagosomal maturation in 'non-professional' phagocytic cells. Therefore, in this study, we developed a simple method to measure and decouple particle internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in Madin-Darby Canine Kidney (MDCK and Caco-2 epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Our method was developed using a pathogen mimetic system consisting of polystyrene beads coated with Internalin A (InlA, a membrane surface protein from Listeria monocytogenes known to trigger receptor-mediated phagocytosis. We were able to independently measure the rates of internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in epithelial cells by combining the InlA-coated beads (InlA-beads with antibody quenching, a pH sensitive dye and an endosomal/lysosomal dye. By performing these independent measurements under identical experimental conditions, we were able to decouple the three processes and establish time scales for each. In a separate set of experiments, we exploited the phagosomal acidification process to demonstrate an additional, real-time method for tracking bead binding, internalization and phagosomal acidification. CONCLUSIONS/SIGNIFICANCE: Using this method, we found that the time scales for internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion ranged from 23-32 min, 3-4 min and 74-120 min, respectively, for MDCK and Caco-2 epithelial cells. Both the static and real-time methods developed here are expected to be readily and broadly applicable, as they simply

  1. Transfer of phagocytosed particles to the parasitophorous vacuole of Leishmania mexicana is a transient phenomenon preceding the acquisition of annexin I by the phagosome.

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    Collins, H L; Schaible, U E; Ernst, J D; Russell, D G

    1997-01-01

    The eukaryotic intracellular pathogen Leishmania mexicana resides inside macrophages contained within a membrane bound parasitophorous vacuole which, as it matures, acquires the characteristics of a late endosomal compartment. This study reports the selectivity of fusion of this compartment with other particle containing vacuoles. Phagosomes containing zymosan or live Listeria monocytogenes rapidly fused with L. mexicana parasitophorous vacuoles, while those containing latex beads or heat killed L. monocytogenes failed to do so. Fusigenicity of phagosomes was not primarily dependent on the receptor utilized for ingestion, as opsonization with defined ligands could not overcome the exclusion of either latex beads or heat killed organisms. However modulation of intracellular pH by pharmacological agents such as chloroquine and ammonium chloride increased delivery of live Listeria and also induced transfer of previously excluded particles. The absence of fusion correlated with the acquisition of annexin I, a putative lysosomal targeting, molecule, on the phagosome membrane. We propose that the acquisition of cellular membrane constituents such as annexin I during phagosome maturation can ultimately direct the fusion pathway of the vesicles formed and have described a model system to further document changes in vesicle fusigenicity within cells.

  2. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling.

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    Queval, Christophe J; Song, Ok-Ryul; Carralot, Jean-Philippe; Saliou, Jean-Michel; Bongiovanni, Antonino; Deloison, Gaspard; Deboosère, Nathalie; Jouny, Samuel; Iantomasi, Raffaella; Delorme, Vincent; Debrie, Anne-Sophie; Park, Sei-Jin; Gouveia, Joana Costa; Tomavo, Stanislas; Brosch, Roland; Yoshimura, Akihiko; Yeramian, Edouard; Brodin, Priscille

    2017-09-26

    Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS) protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. aprABC: A Mycobacterium tuberculosis complex-specific locus that modulates pH-driven adaptation to the macrophage phagosome

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    Abramovitch, Robert B.; Rohde, Kyle H.; Hsu, Fong-Fu; Russell, David G.

    2011-01-01

    Summary Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in the phagosome. We have identified an Acid and Phagosome Regulated (aprABC) locus that is unique to the Mtb complex and whose gene expression is induced during growth in acidic environments in vitro and in macrophages. Using the aprA promoter, we generated a strain that exhibits high levels of inducible fluorescence in response to growth in acidic medium in vitro and in macrophages. aprABC expression is dependent on the two-component regulator phoPR, linking phoPR signaling to pH sensing. Deletion of the aprABC locus causes defects in gene expression that impact aggregation, intracellular growth, and the relative levels of storage and cell wall lipids. We propose a model where phoPR senses the acidic pH of the phagosome and induces aprABC expression to fine-tune processes unique for intracellular adaptation of Mtb complex bacteria. PMID:21401735

  4. Autophagosome and phagosome.

    Science.gov (United States)

    Deretic, Vojo

    2008-01-01

    Autophagy and phagocytosis are evolutionarily ancient processes functioning in capture and digestion of material found in the cellular interior and exterior, respectively. In their most primordial form, both processes are involved in cellular metabolism and feeding, supplying cells with externally obtained particulate nutrients or using portions of cell's own cytoplasm to generate essential nutrients and energy at times of starvation. Although autophagy and phagocytosis are commonly treated as completely separate biological phenomena, they are topologically similar and can be, at least morphologically, viewed as different manifestations of a spectrum of related processes. Autophagy is the process of sequestering portions of cellular interior (cytosol and intracellular organelles) into a membranous organelle (autophagosome), whereas phagocystosis is its topological equivalent engaged in sequestering cellular exterior. Both autophagosomes and phagosomes mature into acidified, degradative organelles, termed autolysosomes and phagolysosomes, respectively. The basic role of autophagy as a nutritional process, and that of phagocytosis where applicable, has survived in present-day organisms ranging from yeast to man. It has in addition evolved into a variety of specialized processes in metazoans, with a major role in cellular/cytoplasmic homeostasis. In humans, autophagy has been implicated in many health and disease states, including cancer, neurodegeneration, aging and immunity, while phagocytosis plays a role in immunity and tissue homeostasis. Autophagy and phagocytosis cooperate in the latter two processes. In this chapter, we briefly review the regulatory and execution stages of both autophagy and phagocytosis.

  5. Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes

    Science.gov (United States)

    Maxson, Michelle E; Naj, Xenia; O'Meara, Teresa R; Plumb, Jonathan D; Cowen, Leah E

    2018-01-01

    Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae. PMID:29553370

  6. Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes

    Directory of Open Access Journals (Sweden)

    Brzezinska Agnieszka A

    2006-12-01

    Full Text Available Abstract Background Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. Results Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX domain of p47phox localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47phox, is translocated to the membrane of mature phagosomes. Conclusion We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.

  7. 7 CFR 915.332 - Florida avocado maturity regulation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Florida avocado maturity regulation. 915.332 Section... SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA Container and Pack Regulations § 915.332 Florida avocado maturity regulation. (a...

  8. 7 CFR 944.31 - Avocado import maturity regulation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Avocado import maturity regulation. 944.31 Section 944...; IMPORT REGULATIONS § 944.31 Avocado import maturity regulation. (a) Pursuant to section 8e [7 U.S.C. 608e...—Fruits; Import Regulations, the importation into the United States of any avocados, except the Hass...

  9. Rab39a interacts with phosphatidylinositol 3-kinase and negatively regulates autophagy induced by lipopolysaccharide stimulation in macrophages.

    Directory of Open Access Journals (Sweden)

    Shintaro Seto

    Full Text Available Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation and neuritogenesis. Here, we characterized Rab39a function in membrane trafficking of phagocytosis and autophagy induction in macrophages. Rab39a localized to the periphery of LAMP2-positive vesicles and showed the similar kinetics on the phagosome to that of LAMP1. The depletion of Rab39a did not influence the localization of LAMP2 to the phagosome, but it augments the autophagosome formation and LC3 processing by lipopolysaccharide (LPS stimulation. The augmentation of autophagosome formation in Rab39a-knockdown macrophages was suppressed by Atg5 depletion or an inhibitor for phosphatidylinostol 3-kinase (PI3K. Immunoprecipitation analysis revealed that Rab39a interacts with PI3K and that the amino acid residues from 34(th to 41(st in Rab39a were indispensable for this interaction. These results suggest that Rab39a negatively regulates the LPS-induced autophagy in macrophages.

  10. Molecular identification of Rab7 (ApRab7) in Aiptasia pulchella and its exclusion from phagosomes harboring zooxanthellae.

    Science.gov (United States)

    Chen, Ming-Chyuan; Cheng, Ying-Min; Sung, Ping-Jyun; Kuo, Cham-En; Fang, Lee-Shing

    2003-08-29

    The establishment and maintenance of the intracellular association between marine cnidarians and their symbiotic microalgae is essential to the well being of coral reef ecosystems; however, little is known concerning its underlying molecular mechanisms. In light of the critical roles of the small GTPase, Rab7, as a key regulator of vesicular trafficking, we cloned and characterized the Rab7 protein in the endosymbiosis system between the sea anemone, Aiptasia pulchella and its algal symbiont, Symbiodinium spp. The Aiptasia homologue of Rab7 proteins, ApRab7 is 88% identical to human Rab7 protein and contains all Rab-specific signature motifs. Results of EGFP reporter analysis, protein fractionation, and immunocytochemistry support that ApRab7 is located in late endocytic and phagocytic compartments and is able to promote their fusion. Significantly, the majority of phagosomes containing live symbionts that either have taken long residency in, or were newly internalized by Aiptasia digestive cells did not contain detectable levels of ApRab7, while most phagosomes containing either heat-killed or photosynthesis-impaired symbionts were positive for ApRab7 staining. Overall, our data suggest that live algal symbionts persist inside their host cells by actively excluding ApRab7 from their phagosomes, and thereby, establish and/or maintain an endosymbiotic relationship with their cnidarian hosts.

  11. Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes.

    Science.gov (United States)

    Sanghavi, Paulomi; D'Souza, Ashwin; Rai, Ashim; Rai, Arpan; Padinhatheeri, Ranjith; Mallik, Roop

    2018-05-07

    How the opposing activity of kinesin and dynein motors generates polarized distribution of organelles inside cells is poorly understood and hotly debated [1, 2]. Possible explanations include stochastic mechanical competition [3, 4], coordinated regulation by motor-associated proteins [5-7], mechanical activation of motors [8], and lipid-induced organization [9]. Here, we address this question by using phagocytosed latex beads to generate early phagosomes (EPs) that move bidirectionally along microtubules (MTs) in an in vitro assay [9]. Dynein/kinesin activity on individual EPs is recorded as real-time force generation of the motors against an optical trap. Activity of one class of motors frequently coincides with, or is rapidly followed by opposite motors. This leads to frequent and rapid reversals of EPs in the trap. Remarkably, the choice between dynein and kinesin can be explained by the tossing of a coin. Opposing motors therefore appear to function stochastically and independently of each other, as also confirmed by observing no effect on kinesin function when dynein is inhibited on the EPs. A simple binomial probability calculation based on the geometry of EP-microtubule contact explains the observed activity of dynein and kinesin on phagosomes. This understanding of intracellular transport in terms of a hypothetical coin, if it holds true for other cargoes, provides a conceptual framework to explain the polarized localization of organelles inside cells. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.

    Directory of Open Access Journals (Sweden)

    Kristine Porter

    Full Text Available Cells in the trabecular meshwork (TM, a tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic activity in TM cells is thought to play an important role in outflow pathway physiology. However, the molecular mechanisms triggered by phagocytosis in TM cells are unknown. Here we investigated the effects of chronic phagocytic stress on lysosomal function using different phagocytic ligands (E. coli, carboxylated beads, collagen I-coated beads, and pigment. Lysotracker red co-localization and electron micrographs showed the maturation of E. coli- and collagen I-coated beads-containing phagosomes into phagolysosomes. Maturation of phagosomes into phagolysosomes was not observed with carboxylated beads or pigment particles. In addition, phagocytosis of E. coli and collagen I-coated beads led to increased lysosomal mass, and the specific up-regulation and activity of cathepsin B (CTSB. Higher levels of membrane-bound and secreted CTSB were also detected. Moreover, in vivo zymography showed the intralysosomal degradation of ECM components associated with active CTSB, as well as an overall increased gelatinolytic activity in phagocytically challenged TM cells. This increased gelatinolytic activity with phagocytosis was partially blocked with an intracellular CTSB inhibitor. Altogether, these results suggest a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  13. The cellular prion protein negatively regulates phagocytosis and cytokine expression in murine bone marrow-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Min Wang

    Full Text Available The cellular prion protein (PrP(C is a glycosylphosphatidylinositol (GPI-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrP(C in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrP(C in phagocytosis and cytokine expression in bone marrow-derived macrophages infected with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA level. Knockout of PrP(C promoted bacterial uptake; upregulated Rab5, Rab7, and Eea1 mRNA expression; and increased the recruitment of lysosomal-associated membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity. Remarkably, knockout of PrP(C suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrP(C as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity.

  14. Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae.

    Science.gov (United States)

    Chen, Ming-Chyuan; Cheng, Ying-Min; Hong, Min-Chang; Fang, Lee-Shing

    2004-11-19

    The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts.

  15. Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae

    International Nuclear Information System (INIS)

    Chen, M.-C.; Cheng, Y.-M; Hong, M.-C.; Fang, L.-S.

    2004-01-01

    The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts

  16. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Regulation of oocyte maturation in fish.

    Science.gov (United States)

    Nagahama, Yoshitaka; Yamashita, Masakane

    2008-06-01

    A period of oocyte growth is followed by a process called oocyte maturation (the resumption of meiosis) which occurs prior to ovulation and is a prerequisite for successful fertilization. Our studies using fish models have revealed that oocyte maturation is a three-step induction process involving gonadotropin (LH), maturation-inducing hormone (MIH), and maturation-promoting factor (MPF). LH acts on the ovarian follicle layer to produce MIH (17alpha, 20beta-dihydroxy-4-pregnen-3-one, 17alpha, 20beta-DP, in most fishes). The interaction of ovarian thecal and granulosa cell layers (two-cell type model), is required for the synthesis of 17alpha,20beta-DP. The dramatic increase in the capacity of postvitellogenic follicles to produce 17alpha,20beta-DP in response to LH is correlated with decreases in P450c17 (P450c17-I) and P450 aromatase (oP450arom) mRNA and increases in the novel form of P450c17 (P450c17-II) and 20beta-hydroxysteroid dehydrogenase (20beta-HSD) mRNA. Transcription factors such as Ad4BP/SF-1, Foxl2, and CREB may be involved in the regulation of expression of these steroidogenic enzymes. A distinct family of G-protein-coupled membrane-bound MIH receptors has been shown to mediate non-genomic actions of 17alpha, 20beta-DP. The MIH signal induces the de novo synthesis of cyclin B from the stored mRNA, which activates a preexisting 35 kDa cdc2 kinase via phosphorylation of its threonine 161 by cyclin-dependent kinase activating kinase, thus producing the 34 kDa active cdc2 (active MPF). Upon egg activation, MPF is inactivated by degradation of cyclin B. This process is initiated by the 26S proteasome through the first cut in its NH(2) terminus at lysine 57.

  18. Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length.

    Science.gov (United States)

    Sydor, Tobias; von Bargen, Kristine; Hsu, Fong-Fu; Huth, Gitta; Holst, Otto; Wohlmann, Jens; Becken, Ulrike; Dykstra, Tobias; Söhl, Kristina; Lindner, Buko; Prescott, John F; Schaible, Ulrich E; Utermöhlen, Olaf; Haas, Albert

    2013-03-01

    Rhodococcus equi is a close relative of Mycobacterium spp. and a facultative intracellular pathogen which arrests phagosome maturation in macrophages before the late endocytic stage. We have screened a transposon mutant library of R. equi for mutants with decreased capability to prevent phagolysosome formation. This screen yielded a mutant in the gene for β-ketoacyl-(acyl carrier protein)-synthase A (KasA), a key enzyme of the long-chain mycolic acid synthesizing FAS-II system. The longest kasA mutant mycolic acid chains were 10 carbon units shorter than those of wild-type bacteria. Coating of non-pathogenic E. coli with purified wild-type trehalose dimycolate reduced phagolysosome formation substantially which was not the case with shorter kasA mutant-derived trehalose dimycolate. The mutant was moderately attenuated in macrophages and in a mouse infection model, but was fully cytotoxic.Whereas loss of KasA is lethal in mycobacteria, R. equi kasA mutant multiplication in broth was normal proving that long-chain mycolic acid compounds are not necessarily required for cellular integrity and viability of the bacteria that typically produce them. This study demonstrates a central role of mycolic acid chain length in diversion of trafficking by R. equi. © 2012 Blackwell Publishing Ltd.

  19. Comparative proteomic exploration of whey proteins in human and bovine colostrum and mature milk using iTRAQ-coupled LC-MS/MS.

    Science.gov (United States)

    Yang, Mei; Cao, Xueyan; Wu, Rina; Liu, Biao; Ye, Wenhui; Yue, Xiqing; Wu, Junrui

    2017-09-01

    Whey, an essential source of dietary nutrients, is widely used in dairy foods for infants. A total of 584 whey proteins in human and bovine colostrum and mature milk were identified and quantified by the isobaric tag for relative and absolute quantification (iTRAQ) proteomic method. The 424 differentially expressed whey proteins were identified and analyzed according to gene ontology (GO) annotation, Kyoto encyclopedia of genes and genomes (KEGG) pathway, and multivariate statistical analysis. Biological processes principally involved biological regulation and response to stimulus. Major cellular components were extracellular region part and extracellular space. The most prevalent molecular function was protein binding. Twenty immune-related proteins and 13 proteins related to enzyme regulatory activity were differentially expressed in human and bovine milk. Differentially expressed whey proteins participated in many KEGG pathways, including major complement and coagulation cascades and in phagosomes. Whey proteins show obvious differences in expression in human and bovine colostrum and mature milk, with consequences for biological function. The results here increase our understanding of different whey proteomes, which could provide useful information for the development and manufacture of dairy products and nutrient food for infants. The advanced iTRAQ proteomic approach was used to analyze differentially expressed whey proteins in human and bovine colostrum and mature milk.

  20. Foxa2 and Pdx1 cooperatively regulate postnatal maturation of pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Aimée Bastidas-Ponce

    2017-06-01

    Full Text Available Objective: The transcription factors (TF Foxa2 and Pdx1 are key regulators of beta-cell (β-cell development and function. Mutations of these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes of the young (MODY, pancreas agenesis, or diabetes susceptibility in human. Although Foxa2 has been shown to directly regulate Pdx1 expression during mouse embryonic development, the impact of this gene regulatory interaction on postnatal β-cell maturation remains obscure. Methods: In order to easily monitor the expression domains of Foxa2 and Pdx1 and analyze their functional interconnection, we generated a novel double knock-in homozygous (FVFPBFDHom fluorescent reporter mouse model by crossing the previously described Foxa2-Venus fusion (FVF with the newly generated Pdx1-BFP (blue fluorescent protein fusion (PBF mice. Results: Although adult PBF homozygous animals exhibited a reduction in expression levels of Pdx1, they are normoglycemic. On the contrary, despite normal pancreas and endocrine development, the FVFPBFDHom reporter male animals developed hyperglycemia at weaning age and displayed a reduction in Pdx1 levels in islets, which coincided with alterations in β-cell number and islet architecture. The failure to establish mature β-cells resulted in loss of β-cell identity and trans-differentiation towards other endocrine cell fates. Further analysis suggested that Foxa2 and Pdx1 genetically and functionally cooperate to regulate maturation of adult β-cells. Conclusions: Our data show that the maturation of pancreatic β-cells requires the cooperative function of Foxa2 and Pdx1. Understanding the postnatal gene regulatory network of β-cell maturation will help to decipher pathomechanisms of diabetes and identify triggers to regenerate dedifferentiated β-cell mass. Keywords: Foxa2, Pdx1, β-Cell maturation, β-Cell identity, Trans-differentiation

  1. A Network of Local and Redundant Gene Regulation Governs Arabidopsis Seed Maturation

    Science.gov (United States)

    To, Alexandra; Valon, Christiane; Savino, Gil; Guilleminot, Jocelyne; Devic, Martine; Giraudat, Jérôme; Parcy, François

    2006-01-01

    In Arabidopsis thaliana, four major regulators (ABSCISIC ACID INSENSITIVE3 [ABI3], FUSCA3 [FUS3], LEAFY COTYLEDON1 [LEC1], and LEC2) control most aspects of seed maturation, such as accumulation of storage compounds, cotyledon identity, acquisition of desiccation tolerance, and dormancy. The molecular basis for complex genetic interactions among these regulators is poorly understood. By analyzing ABI3 and FUS3 expression in various single, double, and triple maturation mutants, we have identified multiple regulatory links among all four genes. We found that one of the major roles of LEC2 was to upregulate FUS3 and ABI3. The lec2 mutation is responsible for a dramatic decrease in ABI3 and FUS3 expression, and most lec2 phenotypes can be rescued by ABI3 or FUS3 constitutive expression. In addition, ABI3 and FUS3 positively regulate themselves and each other, thereby forming feedback loops essential for their sustained and uniform expression in the embryo. Finally, LEC1 also positively regulates ABI3 and FUS3 in the cotyledons. Most of the genetic controls discovered were found to be local and redundant, explaining why they had previously been overlooked. This works establishes a genetic framework for seed maturation, organizing the key regulators of this process into a hierarchical network. In addition, it offers a molecular explanation for the puzzling variable features of lec2 mutant embryos. PMID:16731585

  2. Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

    Science.gov (United States)

    Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

    2014-09-29

    Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

  3. Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

    Science.gov (United States)

    Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

    2015-01-01

    SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

  4. Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

    Science.gov (United States)

    LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

    2012-01-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  5. Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success Story

    Science.gov (United States)

    van Dam, Jesse C. J.; Martins dos Santos, Vitor A. P.

    2018-01-01

    Tuberculosis remains one of the deadliest diseases. Emergence of drug-resistant and multidrug-resistant M. tuberculosis strains makes treating tuberculosis increasingly challenging. In order to develop novel intervention strategies, detailed understanding of the molecular mechanisms behind the success of this pathogen is required. Here, we review recent literature to provide a systems level overview of the molecular and cellular components involved in divalent metal homeostasis and their role in regulating the three main virulence strategies of M. tuberculosis: immune modulation, dormancy and phagosomal rupture. We provide a visual and modular overview of these components and their regulation. Our analysis identified a single regulatory cascade for these three virulence strategies that respond to limited availability of divalent metals in the phagosome. PMID:29364195

  6. Intracellular events regulating cross-presentation

    Directory of Open Access Journals (Sweden)

    Peter eCresswell

    2012-06-01

    Full Text Available Cross-presentation plays a fundamental role in the induction of CD8-T cell immunity. However, although more than three decades have passed since its discovery, surprisingly little is known about the exact mechanisms involved. Here we give an overview of the components involved at different stages of this process. First, antigens must be internalized into the cross-presenting cell. The involvement of different receptors, method of antigen uptake, and nature of the antigen can influence intracellular trafficking and access to the cross-presentation pathway. Once antigens access the endocytic system, different requirements for endosomal/phagosomal processing arise, such as proteolysis and reduction of disulfide bonds. The majority of cross-presented peptides are generated by proteasomal degradation. Therefore, antigens must cross a membrane barrier in a manner analogous to the fate of misfolded proteins in the endoplasmic reticulum (ER that are retrotranslocated into the cytosol for degradation. Indeed, some components of the ER-associated degradation (ERAD machinery have been implicated in cross-presentation. Further complicating the matter, endosomal and phagosomal compartments have been suggested as alternative sites to the ER for loading of peptides on MHC class I molecules. Finally, the antigen presenting cells involved, particularly dendritic cell subsets and their state of maturation, influence the efficiency of cross-presentation.

  7. Rac1 switching at the right time and location is essential for Fcγ receptor-mediated phagosome formation.

    Science.gov (United States)

    Ikeda, Yuka; Kawai, Katsuhisa; Ikawa, Akira; Kawamoto, Kyoko; Egami, Youhei; Araki, Nobukazu

    2017-08-01

    Lamellipodia are sheet-like cell protrusions driven by actin polymerization mainly through Rac1, a GTPase molecular switch. In Fcγ receptor-mediated phagocytosis of IgG-opsonized erythrocytes (IgG-Es), Rac1 activation is required for lamellipodial extension along the surface of IgG-Es. However, the significance of Rac1 deactivation in phagosome formation is poorly understood. Our live-cell imaging and electron microscopy revealed that RAW264 macrophages expressing a constitutively active Rac1 mutant showed defects in phagocytic cup formation, while lamellipodia were formed around IgG-Es. Because activated Rac1 reduced the phosphorylation levels of myosin light chains, failure of the cup formation is probably due to inhibition of actin/myosin II contractility. Reversible photo-manipulation of the Rac1 switch in macrophages fed with IgG-Es could phenocopy two lamellipodial motilities: outward-extension and cup-constriction by Rac1 ON and OFF, respectively. In conjunction with fluorescence resonance energy transfer imaging of Rac1 activity, we provide a novel mechanistic model of phagosome formation spatiotemporally controlled by Rac1 switching within a phagocytic cup. © 2017. Published by The Company of Biologists Ltd.

  8. Yersinia pestis Requires Host Rab1b for Survival in Macrophages.

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    Michael G Connor

    2015-10-01

    Full Text Available Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.

  9. MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation.

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    James R Howe

    Full Text Available Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

  10. The crucial role of the proto-oncogene c-mos in regulation of oocyte maturation

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    Irena Jałocha

    2010-12-01

    Full Text Available Meiosis arrest before fertilization is a common and unique feature of oogenesis in many animal species. On account of the unclear biological significance of meiosis arrest at various stages and for different durations in different animal species, this process and its regulation are the subject of many scientific studies. Studies on the development of ovarian teratomas proved to be helpful in defining the role of particular genes and biochemical cycles in control of the cell cycle in animals. These benign tumors are a valuable source of information on oocyte maturation. The [i]c-mos[/i] proto-oncogene, which is specifically expressed in female and male germ cells, plays a crucial role in control of meiotic cell division in mammals. Its product – Mos protein kinase – acting through mitogen-activated protein kinases (MAPKs regulates critical cellular functions required for homeostasis and decides about cell survival or apoptosis. The MAPK kinase kinase – MAPK kinase – MAPK (MKKK-MKK-MAPK phosphorelay system, in view of its role in cells, seems to be the ideal target for therapeutic intervention in cancer and other diseases. The recent research on human oocytes suggests that the basic mechanisms regulating various stages of oocyte maturation are similar to those described in animals.

  11. Downregulation of host tryptophan-aspartate containing coat (TACO gene restricts the entry and survival of Leishmania donovani in human macrophage model

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    Venkateswara Reddy Gogulamudi

    2015-10-01

    Full Text Available Leishmania are obligate intracellular protozoan parasites of mammalian hosts. Promastigotes of Leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. Phagosomal maturation arrest is known to play a central role in the survival of pathogenic Leishmania within activated macrophages. Recently, tryptophan-aspartate containing coat (TACO gene has been recognized as playing a crucial role in the survival of Mycobacterium tuberculosis within human macrophages by arresting the phagosome maturation process. We postulated that a similar association of TACO gene with phagosomes would prevent the vacuole from maturation in the case of Leishmania. In this study we attempted to define the effect of TACO gene downregulation on the uptake/survival of Leishmania donovani intracellularly, by treatment with Vitamin D3/Retinoic acid (RA & Chenodeoxycholic acid (CDCA/Retinoic acid (RA combinations in human THP-1 macrophages (in vitro. Treatment with these molecules downregulated the TACO gene in macrophages, resulting in reduced parasite load and marked reduction of disease progression in L. donovani infected macrophages. Taken together, these results suggest that TACO gene downregulation may play a role in subverting macrophage machinery in establishing the L.donovani replicative niche inside the host. Our study is the first to highlight the importantrole of the TACO gene in Leishmania entry, and to identify TACO gene downregulation as potential drug target against leishmaniasis.

  12. Regulators of growth plate maturation

    NARCIS (Netherlands)

    Emons, Joyce Adriana Mathilde

    2010-01-01

    Estrogen is known to play an important role in longitudinal bone growth and growth plate maturation, but the mechanism by which estrogens exert their effect is not fully understood. In this thesis this role is further explored. Chapter 1 contains a general introduction to longitudinal bone growth

  13. Rab GTPases and the Autophagy Pathway: Bacterial Targets for a Suitable Biogenesis and Trafficking of Their Own Vacuoles

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    María Milagros López de Armentia

    2016-03-01

    Full Text Available Autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. Intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. To degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a process that is regulated by Rab GTPases. Interestingly, in order to survive and replicate in the phagosome, some pathogens employ different strategies to manipulate vesicular traffic, inhibiting phagolysosomal biogenesis (e.g., Staphylococcus aureus and Mycobacterium tuberculosis or surviving in acidic compartments and forming replicative vacuoles (e.g., Coxiella burnetti and Legionella pneumophila. The bacteria described in this review often use secretion systems to control the host’s response and thus disseminate. To date, eight types of secretion systems (Type I to Type VIII are known. Some of these systems are used by bacteria to translocate pathogenic proteins into the host cell and regulate replicative vacuole formation, apoptosis, cytokine responses, and autophagy. Herein, we have focused on how bacteria manipulate small Rab GTPases to control many of these processes. The growing knowledge in this field may facilitate the development of new treatments or contribute to the prevention of these types of bacterial infections.

  14. Importin 8 regulates the transport of mature microRNAs into the cell nucleus.

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    Wei, Yao; Li, Limin; Wang, Dong; Zhang, Chen-Yu; Zen, Ke

    2014-04-11

    Mature microRNAs (miRNAs), ∼ 22-nucleotide noncoding RNAs regulating target gene expression at the post-transcriptional level, have been recently shown to be transported into the nucleus where they modulate the biogenesis of other miRNAs or their own expression. However, the mechanism that governs the transport of mature miRNAs from cytoplasm to nucleus remains unknown. Here, we report that importin 8 (IPO8), a member of the karyopherin β (also named the protein import receptor importin β) family, plays a critical role in mediating the cytoplasm-to-nucleus transport of mature miRNAs. Specifically knocking down IPO8 but not other karyopherin β family proteins via siRNA significantly decreases the nuclear transport of various known nucleus-enriched miRNAs without affecting their total cellular levels. IPO8-mediated nuclear transport of mature miRNAs is also dependent on the association of IPO8 with the Argonaute 2 (Ago2) complex. Cross-immunoprecipitation and Western blot analysis show that IPO8 is physically associated with Ago2. Knocking down IPO8 via siRNA markedly decreases the nuclear transport of Ago2 but does not affect the total cellular Ago2 level. Furthermore, dissociating the binding of miRNAs with Ago2 by trypaflavine strongly reduces the IPO8-mediated nuclear transport of miRNAs.

  15. Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

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    Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

    2012-10-01

    The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

  16. MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.

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    Wang, Jinli; Yang, Kun; Zhou, Lin; Minhaowu; Wu, Yongjian; Zhu, Min; Lai, Xiaomin; Chen, Tao; Feng, Lianqiang; Li, Meiyu; Huang, Chunyu; Zhong, Qiu; Huang, Xi

    2013-01-01

    Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

  17. MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.

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    Jinli Wang

    Full Text Available Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7 reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb, a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

  18. A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation

    Science.gov (United States)

    McGarvey, Alison C.; Souilhol, Céline; Rice, Ritva; Hills, David; Rice, David; Tomlinson, Simon R.

    2017-01-01

    In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development. We demonstrate that BMPER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMPER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture. PMID:29093060

  19. TBC-8, a putative RAB-2 GAP, regulates dense core vesicle maturation in Caenorhabditis elegans.

    Science.gov (United States)

    Hannemann, Mandy; Sasidharan, Nikhil; Hegermann, Jan; Kutscher, Lena M; Koenig, Sabine; Eimer, Stefan

    2012-01-01

    Dense core vesicles (DCVs) are thought to be generated at the late Golgi apparatus as immature DCVs, which subsequently undergo a maturation process through clathrin-mediated membrane remodeling events. This maturation process is required for efficient processing of neuropeptides within DCVs and for removal of factors that would otherwise interfere with DCV release. Previously, we have shown that the GTPase, RAB-2, and its effector, RIC-19, are involved in DCV maturation in Caenorhabditis elegans motoneurons. In rab-2 mutants, specific cargo is lost from maturing DCVs and missorted into the endosomal/lysosomal degradation route. Cargo loss could be prevented by blocking endosomal delivery. This suggests that RAB-2 is involved in retention of DCV components during the sorting process at the Golgi-endosomal interface. To understand how RAB-2 activity is regulated at the Golgi, we screened for RAB-2-specific GTPase activating proteins (GAPs). We identified a potential RAB-2 GAP, TBC-8, which is exclusively expressed in neurons and which, when depleted, shows similar DCV maturation defects as rab-2 mutants. We could demonstrate that RAB-2 binds to its putative GAP, TBC-8. Interestingly, TBC-8 also binds to the RAB-2 effector, RIC-19. This interaction appears to be conserved as TBC-8 also interacted with the human ortholog of RIC-19, ICA69. Therefore, we propose that a dynamic ON/OFF cycling of RAB-2 at the Golgi induced by the GAP/effector complex is required for proper DCV maturation.

  20. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

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    Jessberger Sebastian

    2006-11-01

    Full Text Available Abstract Background In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. Results We found that (1 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2 the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3 positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. Conclusion These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

  1. Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

    Science.gov (United States)

    Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

    2017-12-15

    Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. TBC-8, a Putative RAB-2 GAP, Regulates Dense Core Vesicle Maturation in Caenorhabditis elegans

    Science.gov (United States)

    Hannemann, Mandy; Sasidharan, Nikhil; Hegermann, Jan; Kutscher, Lena M.; Koenig, Sabine; Eimer, Stefan

    2012-01-01

    Dense core vesicles (DCVs) are thought to be generated at the late Golgi apparatus as immature DCVs, which subsequently undergo a maturation process through clathrin-mediated membrane remodeling events. This maturation process is required for efficient processing of neuropeptides within DCVs and for removal of factors that would otherwise interfere with DCV release. Previously, we have shown that the GTPase, RAB-2, and its effector, RIC-19, are involved in DCV maturation in Caenorhabditis elegans motoneurons. In rab-2 mutants, specific cargo is lost from maturing DCVs and missorted into the endosomal/lysosomal degradation route. Cargo loss could be prevented by blocking endosomal delivery. This suggests that RAB-2 is involved in retention of DCV components during the sorting process at the Golgi-endosomal interface. To understand how RAB-2 activity is regulated at the Golgi, we screened for RAB-2–specific GTPase activating proteins (GAPs). We identified a potential RAB-2 GAP, TBC-8, which is exclusively expressed in neurons and which, when depleted, shows similar DCV maturation defects as rab-2 mutants. We could demonstrate that RAB-2 binds to its putative GAP, TBC-8. Interestingly, TBC-8 also binds to the RAB-2 effector, RIC-19. This interaction appears to be conserved as TBC-8 also interacted with the human ortholog of RIC-19, ICA69. Therefore, we propose that a dynamic ON/OFF cycling of RAB-2 at the Golgi induced by the GAP/effector complex is required for proper DCV maturation. PMID:22654674

  3. TBC-8, a putative RAB-2 GAP, regulates dense core vesicle maturation in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Mandy Hannemann

    Full Text Available Dense core vesicles (DCVs are thought to be generated at the late Golgi apparatus as immature DCVs, which subsequently undergo a maturation process through clathrin-mediated membrane remodeling events. This maturation process is required for efficient processing of neuropeptides within DCVs and for removal of factors that would otherwise interfere with DCV release. Previously, we have shown that the GTPase, RAB-2, and its effector, RIC-19, are involved in DCV maturation in Caenorhabditis elegans motoneurons. In rab-2 mutants, specific cargo is lost from maturing DCVs and missorted into the endosomal/lysosomal degradation route. Cargo loss could be prevented by blocking endosomal delivery. This suggests that RAB-2 is involved in retention of DCV components during the sorting process at the Golgi-endosomal interface. To understand how RAB-2 activity is regulated at the Golgi, we screened for RAB-2-specific GTPase activating proteins (GAPs. We identified a potential RAB-2 GAP, TBC-8, which is exclusively expressed in neurons and which, when depleted, shows similar DCV maturation defects as rab-2 mutants. We could demonstrate that RAB-2 binds to its putative GAP, TBC-8. Interestingly, TBC-8 also binds to the RAB-2 effector, RIC-19. This interaction appears to be conserved as TBC-8 also interacted with the human ortholog of RIC-19, ICA69. Therefore, we propose that a dynamic ON/OFF cycling of RAB-2 at the Golgi induced by the GAP/effector complex is required for proper DCV maturation.

  4. Hypothalamic ER–associated degradation regulates POMC maturation, feeding, and age-associated obesity

    Science.gov (United States)

    Kim, Geun Hyang; Somlo, Diane R.M.; Haataja, Leena; Song, Soobin; Nillni, Eduardo A.

    2018-01-01

    Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism. Here, we report a pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated degradation (ERAD), within POMC neurons. Mice with POMC neuron–specific Sel1L deficiency developed age-associated obesity due, at least in part, to the ER retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a fraction of nascent POMC molecules for ubiquitination and proteasomal degradation, preventing accumulation of misfolded and aggregated POMC, thereby ensuring that another fraction of POMC can undergo normal posttranslational processing and trafficking for secretion. Moreover, we found that the disease-associated POMC-C28F mutant evades ERAD and becomes aggregated due to the presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this study not only identifies ERAD as an important mechanism regulating POMC maturation within the ER, but also provides insights into the pathogenesis of monogenic obesity associated with defective prohormone folding. PMID:29457782

  5. A marked animal-vegetal polarity in the localization of Na(+),K(+) -ATPase activity and its down-regulation following progesterone-induced maturation.

    Science.gov (United States)

    Mohanty, Basant Kumar; Gupta, Brij L

    2012-02-01

    The stage-VI Xenopus oocyte has a very distinct animal-vegetal polarity with structural and functional asymmetry. In this study, we show the expression and distribution pattern of Na(+),K(+) -ATPase in stage-VI oocytes, and its changes following progesterone-induced maturation. Using enzyme-specific electron microscopy phosphatase histochemistry, [(3) H]-ouabain autoradiography, and immunofluorescence cytochemistry at light microscopic level, we find that Na(+),K(+) -ATPase activity is mainly confined to the animal hemisphere. Electron microscopy histochemical results also suggest that polarized distribution of Na(+),K(+) -ATPase activity persists following progesterone-induced maturation, and it becomes gradually more polarized towards the animal pole. The time course following progesterone-induced maturation suggests that there is an initial up-regulation and then gradual down-regulation of Na(+),K(+) -ATPase activity leading to germinal vesicle breakdown (GVBD). By GVBD, the Na(+),K(+) -ATPase activity is completely down-regulated due to endocytotic removal of pump molecules from the plasma membrane into the sub-cortical region of the oocyte. This study provides the first direct evidence for a marked asymmetric localization of Na(+),K(+) -ATPase activity in any vertebrate oocyte. Here, we propose that such asymmetry in Na(+),K(+) -ATPase activity in stage-VI oocytes, and their down-regulation following progesterone-induced maturation, is likely to have a role in the active state of the germinal vesicle in stage-VI oocytes and chromosomal condensation after GVBD. Copyright © 2011 Wiley Periodicals, Inc.

  6. “Positive Regulation of RNA Metabolic Process” Ontology Group Highly Regulated in Porcine Oocytes Matured In Vitro: A Microarray Approach

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    Piotr Celichowski

    2018-01-01

    Full Text Available The cumulus-oocyte complexes (COCs growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in “oocytes RNA synthesis” in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM. Interactions between differentially expressed genes/proteins belonging to “positive regulation of RNA metabolic process” ontology group were investigated by STRING10 software. Using microarray assays, we found expression of 12258 porcine transcripts. Genes with fold change higher than 2 and with corrected p value lower than 0.05 were considered as differentially expressed. The ontology group “positive regulation of RNA metabolic process” involved differential expression of AR, INHBA, WWTR1, FOS, MEF2C, VEGFA, IKZF2, IHH, RORA, MAP3K1, NFAT5, SMARCA1, EGR1, EGR2, MITF, SMAD4, APP, and NR5A1 transcripts. Since all of the presented genes were downregulated after IVM, we suggested that they might be significantly involved in regulation of RNA synthesis before reaching oocyte MII stage. Higher expression of “RNA metabolic process” related genes before IVM indicated that they might be recognized as important markers and specific “transcriptomic fingerprint” of RNA template accumulation and storage for further porcine embryos growth and development.

  7. The Legionella Kinase LegK2 Targets the ARP2/3 Complex To Inhibit Actin Nucleation on Phagosomes and Allow Bacterial Evasion of the Late Endocytic Pathway

    Science.gov (United States)

    Michard, Céline; Sperandio, Daniel; Baïlo, Nathalie; Pizarro-Cerdá, Javier; LeClaire, Lawrence; Chadeau-Argaud, Elise; Pombo-Grégoire, Isabel; Hervet, Eva; Vianney, Anne; Gilbert, Christophe; Faure, Mathias; Cossart, Pascale

    2015-01-01

    ABSTRACT Legionella pneumophila, the etiological agent of legionellosis, replicates within phagocytic cells. Crucial to biogenesis of the replicative vacuole is the Dot/Icm type 4 secretion system, which translocates a large number of effectors into the host cell cytosol. Among them is LegK2, a protein kinase that plays a key role in Legionella infection. Here, we identified the actin nucleator ARP2/3 complex as a target of LegK2. LegK2 phosphorylates the ARPC1B and ARP3 subunits of the ARP2/3 complex. LegK2-dependent ARP2/3 phosphorylation triggers global actin cytoskeleton remodeling in cells, and it impairs actin tail formation by Listeria monocytogenes, a well-known ARP2/3-dependent process. During infection, LegK2 is addressed to the Legionella-containing vacuole surface and inhibits actin polymerization on the phagosome, as revealed by legK2 gene inactivation. Consequently, LegK2 prevents late endosome/lysosome association with the phagosome and finally contributes to remodeling of the bacterium-containing phagosome into a replicative niche. The inhibition of actin polymerization by LegK2 and its effect on endosome trafficking are ARP2/3 dependent since it can be phenocopied by a specific chemical inhibitor of the ARP2/3 complex. Thus, LegK2-ARP2/3 interplay highlights an original mechanism of bacterial virulence with an unexpected role in local actin remodeling that allows bacteria to control vesicle trafficking in order to escape host defenses. PMID:25944859

  8. Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina.

    Science.gov (United States)

    Irie, Shoichi; Sanuki, Rikako; Muranishi, Yuki; Kato, Kimiko; Chaya, Taro; Furukawa, Takahisa

    2015-08-01

    The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Ovarian follicle maturation and ovulation: An integrated perspective

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    Patino, R.; Thomas, P.; Yoshizaki, G.

    2003-01-01

    Numerous studies with teleosts have addressed the regulation and mechanisms of oocyte maturation, but largely at the exclusion of ovulation. A smaller but still considerable number of studies have focused on ovulation, and ignored maturation. Consequently, little is known about the mechanistic linkages between these two events. New information is presented here indicating that luteinizing hormone regulates the acquisition not only of oocyte maturational competence, but also ovulatory competence. The thesis is presented that maturation and ovulation are closely integrated and overlapping events that are best viewed conceptually and experimentally as parts of a functional whole. ?? 2004 Kluwer Academic Publishers.

  10. Transcriptional Programs Controlling Perinatal Lung Maturation

    Science.gov (United States)

    Xu, Yan; Wang, Yanhua; Besnard, Valérie; Ikegami, Machiko; Wert, Susan E.; Heffner, Caleb; Murray, Stephen A.; Donahue, Leah Rae; Whitsett, Jeffrey A.

    2012-01-01

    The timing of lung maturation is controlled precisely by complex genetic and cellular programs. Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS) and Broncho-Pulmonary Dysplasia (BPD), which are leading causes of mortality and morbidity in preterm infants. Mechanisms synchronizing gestational length and lung maturation remain to be elucidated. In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0) using lung RNAs from C57BL/6J (B6) and A/J mice that differ in gestational length by ∼30 hr (B6controlling lung maturation. We identified both temporal and strain dependent gene expression patterns during lung maturation. For time dependent changes, cell adhesion, vasculature development, and lipid metabolism/transport were major bioprocesses induced during the saccular stage of lung development at E16.5–E17.5. CEBPA, PPARG, VEGFA, CAV1 and CDH1 were found to be key signaling and transcriptional regulators of these processes. Innate defense/immune responses were induced at later gestational ages (E18.5–20.5), STAT1, AP1, and EGFR being important regulators of these responses. Expression of RNAs associated with the cell cycle and chromatin assembly was repressed during prenatal lung maturation and was regulated by FOXM1, PLK1, chromobox, and high mobility group families of transcription factors. Strain dependent lung mRNA expression differences peaked at E18.5. At this time, mRNAs regulating surfactant and innate immunity were more abundantly expressed in lungs of B6 (short gestation) than in A/J (long gestation) mice, while expression of genes involved in chromatin assembly and histone modification were expressed at lower levels in B6 than in A/J mice. The present study systemically mapped key regulators, bioprocesses, and transcriptional networks controlling lung maturation, providing the basis for new therapeutic strategies to enhance lung function in preterm

  11. Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells.

    Directory of Open Access Journals (Sweden)

    Valeria Zampini

    2011-04-01

    Full Text Available Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.

  12. Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells.

    Science.gov (United States)

    Zampini, Valeria; Rüttiger, Lukas; Johnson, Stuart L; Franz, Christoph; Furness, David N; Waldhaus, Jörg; Xiong, Hao; Hackney, Carole M; Holley, Matthew C; Offenhauser, Nina; Di Fiore, Pier Paolo; Knipper, Marlies; Masetto, Sergio; Marcotti, Walter

    2011-04-01

    Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.

  13. IL-15 regulates homeostasis and terminal maturation of NKT cells1

    Science.gov (United States)

    Gordy, Laura E.; Bezbradica, Jelena S.; Flyak, Andrew I.; Spencer, Charles T.; Dunkle, Alexis; Sun, Jingchun; Stanic, Aleksandar K.; Boothby, Mark R.; He, You-Wen; Zhao, Zhongming; Van Kaer, Luc; Joyce, Sebastian

    2011-01-01

    Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic NKT cells. The loss of IL15 also resulted in poor expression of key effector molecules such as IFN-γ, granzyme A and C as well as several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is consistent with a role of T-bet in regulating terminal maturation. PMID:22084435

  14. A highly conserved amino acid in VP1 regulates maturation of enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yong-Xin Zhang

    2017-09-01

    Full Text Available Enterovirus 71 (EV71 is the major causative agent of hand, foot and mouth disease (HFMD in children, causing severe clinical outcomes and even death. Here, we report an important role of the highly conserved alanine residue at position 107 in the capsid protein VP1 (VP1A107 in the efficient replication of EV71. Substitutional mutations of VP1A107 significantly diminish viral growth kinetics without significant effect on viral entry, expression of viral genes and viral production. The results of mechanistic studies reveal that VP1A107 regulates the efficient cleavage of the VP0 precursor during EV71 assembly, which is required, in the next round of infection, for the transformation of the mature virion (160S into an intermediate or A-particle (135S, a key step of virus uncoating. Furthermore, the results of molecular dynamic simulations and hydrogen-bond networks analysis of VP1A107 suggest that flexibility of the VP1 BC loop or the region surrounding the VP1107 residue directly correlates with viral infectivity. It is possible that sufficient flexibility of the region surrounding the VP1107 residue favors VP0 conformational change that is required for the efficient cleavage of VP0 as well as subsequent viral uncoating and viral replication. Taken together, our data reveal the structural role of the highly conserved VP1A107 in regulating EV71 maturation. Characterization of this novel determinant of EV71 virulence would promote the study on pathogenesis of Enteroviruses.

  15. 7 CFR 51.2841 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... considered mature when harvested in accordance with good commercial practice at a stage which will not result...

  16. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Federico Battisti

    2017-09-01

    Full Text Available Dendritic cells (DCs are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  17. Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation.

    Science.gov (United States)

    Lee, Patrick Kia Ming; Goh, Wilson Wen Bin; Sng, Judy Chia Ghee

    2017-02-01

    The brain adapts to dynamic environmental conditions by altering its epigenetic state, thereby influencing neuronal transcriptional programs. An example of an epigenetic modification is protein methylation, catalyzed by protein arginine methyltransferases (PRMT). One member, Prmt8, is selectively expressed in the central nervous system during a crucial phase of early development, but little else is known regarding its function. We hypothesize Prmt8 plays a role in synaptic maturation during development. To evaluate this, we used a proteome-wide approach to characterize the synaptic proteome of Prmt8 knockout versus wild-type mice. Through comparative network-based analyses, proteins and functional clusters related to neurite development were identified to be differentially regulated between the two genotypes. One interesting protein that was differentially regulated was tenascin-R (TNR). Chromatin immunoprecipitation demonstrated binding of PRMT8 to the tenascin-r (Tnr) promoter. TNR, a component of perineuronal nets, preserves structural integrity of synaptic connections within neuronal networks during the development of visual-somatosensory cortices. On closer inspection, Prmt8 removal increased net formation and decreased inhibitory parvalbumin-positive (PV+) puncta on pyramidal neurons, thereby hindering the maturation of circuits. Consequently, visual acuity of the knockout mice was reduced. Our results demonstrated Prmt8's involvement in synaptic maturation and its prospect as an epigenetic modulator of developmental neuroplasticity by regulating structural elements such as the perineuronal nets. © 2016 International Society for Neurochemistry.

  18. Bicarbonate Transport During Enamel Maturation.

    Science.gov (United States)

    Yin, Kaifeng; Paine, Michael L

    2017-11-01

    Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features. During the secretory stage, the inner epithelium of the enamel organ (i.e., the ameloblast cells) synthesizes and secretes enamel matrix proteins (EMPs) into the enamel space. The protein-rich enamel matrix forms a highly organized architecture in a pH-neutral microenvironment. As amelogenesis transitions to maturation stage, EMPs are degraded and internalized by ameloblasts through endosomal-lysosomal pathways. Enamel crystallite formation is initiated early in the secretory stage, however, during maturation stage the more rapid deposition of calcium and phosphate into the enamel space results in a rapid expansion of crystallite length and mineral volume. During maturation-stage amelogenesis, the pH value of enamel varies considerably from slightly above neutral to acidic. Extracellular acid-base balance during enamel maturation is tightly controlled by ameloblast-mediated regulatory networks, which include significant synthesis and movement of bicarbonate ions from both the enamel papillary layer cells and ameloblasts. In this review we summarize the carbonic anhydrases and the carbonate transporters/exchangers involved in pH regulation in maturation-stage amelogenesis. Proteins that have been shown to be instrumental in this process include CA2, CA6, CFTR, AE2, NBCe1, SLC26A1/SAT1, SLC26A3/DRA, SLC26A4/PDS, SLC26A6/PAT1, and SLC26A7/SUT2. In addition, we discuss the association of miRNA regulation with bicarbonate transport in tooth enamel formation.

  19. The role of lipids in host microbe interactions.

    Science.gov (United States)

    Lang, Roland; Mattner, Jochen

    2017-06-01

    Lipids are one of the major subcellular constituents and serve as signal molecules, energy sources, metabolic precursors and structural membrane components in various organisms. The function of lipids can be modified by multiple biochemical processes such as (de-)phosphorylation or (de-)glycosylation, and the organization of fatty acids into distinct cellular pools and subcellular compartments plays a pivotal role for the morphology and function of various cell populations. Thus, lipids regulate, for example, phagosome formation and maturation within host cells and thus, are critical for the elimination of microbial pathogens. Vice versa, microbial pathogens can manipulate the lipid composition of phagosomal membranes in host cells, and thus avoid their delivery to phagolysosomes. Lipids of microbial origin belong also to the strongest and most versatile inducers of mammalian immune responses upon engagement of distinct receptors on myeloid and lymphoid cells. Furthermore, microbial lipid toxins can induce membrane injuries and cell death. Thus, we will review here selected examples for mutual host-microbe interactions within the broad and divergent universe of lipids in microbial defense, tissue injury and immune evasion.

  20. Regulation of Oligodendrocyte Progenitor Cell Maturation by PPARδ: Effects on Bone Morphogenetic Proteins

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Simonini

    2009-12-01

    Full Text Available In EAE (experimental autoimmune encephalomyelitis, agonists of PPARs (peroxisome proliferator-activated receptors provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells, and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins. We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ-null mice. In OPCs derived from E13 mice (where E is embryonic day, GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ-null compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

  1. 7 CFR 1427.174 - Maturity of seed cotton loans.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Maturity of seed cotton loans. 1427.174 Section 1427.174 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION... Maturity of seed cotton loans. Seed cotton loans mature on demand by CCC but no later than May 31 following...

  2. Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan

    2009-01-01

    Monocyte-derived dendritic cells (DCs) are used as adjuvant cells in cancer immunotherapy and have shown promising results. In order to obtain full functional capacity, these DCs need to be maturated, and the current "gold standard" for this process is maturation with TNF-alpha, IL-1beta, IL-6...... a functional relationship between CD38, IFN-alpha and TLR3. Thus, CD38 appear to be a relevant marker for activation by TLR3 or IFN-alpha. Addition of IFN-alpha to the sDC cocktail results in up-regulation of both CD38 and CD83 and improved capacity for induction of autologous T-cell responses despite few...... other changes in DC phenotype and cytokine secretion. Our observations suggest that IFN-alpha could be included in maturation protocols for clinical grade DCs used for immunotherapy against cancer and should be included if DCs are used for CD8+ T-cell stimulation in vitro....

  3. Mycobacteria, Metals, and the Macrophage

    Science.gov (United States)

    Niederweis, Michael; Wolschendorf, Frank; Mitra, Avishek; Neyrolles, Olivier

    2015-01-01

    Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  4. The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.

    Science.gov (United States)

    Wijayatunge, Ranjula; Liu, Fang; Shpargel, Karl B; Wayne, Nicole J; Chan, Urann; Boua, Jane-Valeriane; Magnuson, Terry; West, Anne E

    2018-03-01

    The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neurons of the developing postnatal mouse cerebellum. At postnatal day 7, Kdm6b is expressed throughout the layers of the developing cerebellar cortex, but its expression is upregulated in newborn cerebellar granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN precursors either alone or in combination with Kdm6a did not disturb the gross morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown of Kdm6b in cultured CGN precursors did not alter the induced expression of early neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b significantly impaired the induction of a mature neuronal gene expression program, which includes gene products required for functional synapse maturation. Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, these data reveal a previously unknown role for Kdm6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

    Science.gov (United States)

    Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

    2004-05-01

    Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

  6. Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin signal transduction pathway.

    Science.gov (United States)

    Mimura, Manaki; Nagato, Yasuo; Itoh, Jun-Ichi

    2012-05-01

    Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and plastochron, and their loss-of-function mutants exhibit small organs and rapid leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding protein, respectively. Their homologs in Arabidopsis and maize are also associated with plant development/organ size. Despite the importance of PLA genes in plant development, their molecular functions remain unknown. Here, we investigated how PLA1 and PLA2 genes are related to phytohormones. We found that gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2 expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings, expression levels of GA biosynthesis genes and the signal transduction gene were similar to those in wild-type seedlings. GA treatment slightly down-regulated the GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4, whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down-regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal transduction affects the expression of PLA1 and PLA2, PLA expression in GA-signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand, the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive-active mutant, slr1-1, causing ectopic overexpression. These results indicate that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to regulate leaf development.

  7. Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the B cell receptor by regulating calcium and calmodulin.

    Directory of Open Access Journals (Sweden)

    Elaine F Kenny

    Full Text Available B cells signal through both the B cell receptor (BCR which binds antigens and Toll-like receptors (TLRs including TLR9 which recognises CpG DNA. Activation of TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase (BTK is required for synergistic IL6 production and up-regulation of surface expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells. We show that BTK is essential for co-localisation of the BCR and TLR9 within a potential auto-phagosome-like compartment in the Namalwa human B cell line. Downstream of BTK we find that calcium acting via calmodulin is required for this process. These data provide new insights into the role of BTK, an important target for autoimmune diseases, in B cell activation.

  8. The Tec kinase ITK regulates thymic expansion, emigration, and maturation of γδ NKT cells.

    Science.gov (United States)

    Yin, Catherine C; Cho, Ok Hyun; Sylvia, Katelyn E; Narayan, Kavitha; Prince, Amanda L; Evans, John W; Kang, Joonsoo; Berg, Leslie J

    2013-03-15

    The Tec family tyrosine kinase, Itk, regulates signaling downstream of the TCR. The absence of Itk in CD4(+) T cells results in impaired Th2 responses along with defects in maturation, cytokine production, and survival of iNKT cells. Paradoxically, Itk(-/-) mice have spontaneously elevated serum IgE levels, resulting from an expansion of the Vγ1.1(+)Vδ6.3(+) subset of γδ T cells, known as γδ NKT cells. Comparisons between γδ NKT cells and αβ iNKT cells showed convergence in the pattern of cell surface marker expression, cytokine profiles, and gene expression, suggesting that these two subsets of NKT cells undergo similar differentiation programs. Hepatic γδ NKT cells have an invariant TCR and are derived predominantly from fetal progenitors that expand in the thymus during the first weeks of life. The adult thymus contains these invariant γδ NKT cells plus a heterogeneous population of Vγ1.1(+)Vδ6.3(+) T cells with diverse CDR3 sequences. This latter population, normally excluded from the liver, escapes the thymus and homes to the liver when Itk is absent. In addition, Itk(-/-) γδ NKT cells persistently express high levels of Zbtb16 (PLZF) and Il4, genes that are normally downregulated in the most mature subsets of NKT cells. These data indicate that Itk signaling is required to prevent the expansion of γδ NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation.

  9. The dynamics of connexin expression, degradation and localisation are regulated by gonadotropins during the early stages of in vitro maturation of swine oocytes.

    Directory of Open Access Journals (Sweden)

    Nicolas Santiquet

    Full Text Available Gap junctional communication (GJC plays a primordial role in oocyte maturation and meiotic resumption in mammals by directing the transfer of numerous molecules between cumulus cells and the oocyte. Gap junctions are made of connexins (Cx, proteins that regulate GJC in numerous ways. Understanding the dynamic regulation of connexin arrangements during in vitro maturation (IVM could provide a powerful tool for controlling meiotic resumption and consequently in vitro development of fully competent oocytes. However, physiological events happening during the early hours of IVM may still be elucidated. The present study reports the dynamic regulation of connexin expression, degradation and localization during this stage. Cx43, Cx45 and Cx60 were identified as the main connexins expressed in swine COC. Cx43 and Cx45 transcripts were judged too static to be a regulator of GJC, while Cx43 protein expression was highly responsive to gonadotropins, suggesting that it might be the principal regulator of GJC. In addition, the degradation of Cx43 expressed after 4.5 h of IVM in response to equine chorionic gonadotropin appeared to involve the proteasomal complex. Cx43 localisation appeared to be associated with GJC. Taken together, these results show for the first time that gonadotropins regulate Cx43 protein expression, degradation and localisation in porcine COC during the first several hours of IVM. Regulation of Cx43 may in turn, via GJC, participate in the development of fully competent oocytes.

  10. Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary

    Directory of Open Access Journals (Sweden)

    Sandy B. Serizier

    2017-11-01

    Full Text Available For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells. Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

  11. Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary.

    Science.gov (United States)

    Serizier, Sandy B; McCall, Kimberly

    2017-01-01

    For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

  12. Sustaining Exploration in Mature Basins

    International Nuclear Information System (INIS)

    Bayo, A.

    2002-01-01

    Exploration is a business like any other business driven by opportunity, resources and expectation of profit. Therefore, exploration will thrive anywhere the opportunities are significant, the resources are available and the outlook for profit (or value creation) is good. To sustain exploration activities anywhere, irrespective of the environment, there must be good understanding of the drivers of these key investment criteria. This paper will examine these investment criteria as they relate to exploration business and address the peculiarity of exploration in mature basin. Mature basins are unique environment that lends themselves a mix of fears, paradigms and realities, particularly with respect to the perception of value. To sustain exploration activities in a mature basin, we need to understand these perceptions relative to the true drivers of profitability. Exploration in the mature basins can be as profitable as exploration in emerging basins if the dynamics of value definition-strategic and fiscal values are understood by operators, regulators and co ventures alike. Some suggestions are made in this presentation on what needs to be done in addressing these dynamic investment parameters and sustaining exploration activities in mature basins

  13. MiR-29b inhibits collagen maturation in hepatic stellate cells through down-regulating the expression of HSP47 and lysyl oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yifei; Ghazwani, Mohammed; Li, Jiang [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Sun, Ming; Stolz, Donna B. [Department of Cell Biology and Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261 (United States); He, Fengtian [Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038 (China); Fan, Jie [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Xie, Wen [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Li, Song, E-mail: sol4@pitt.edu [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States)

    2014-04-18

    Highlights: • Enhanced HSP47 and LOX expression is associated with decreased miR-29b level in liver fibrosis. • miR-29b down-regulates HSP47 and LOX expression. • The suppression of HSP47 and LOX by miR-29b is mediated by putative sites at their 3′-UTRs. • miR-29b inhibits extracellular LOX activity and collagen maturation. - Abstract: Altered expression of miR-29b is implicated in the pathogenesis and progression of liver fibrosis. We and others previously demonstrated that miR-29b down-regulates the expression of several extracellular-matrix (ECM) genes including Col 1A1, Col 3A1 and Elastin via directly targeting their 3′-UTRs. However, whether or not miR-29b plays a role in the post-translational regulation of ECM biosynthesis has not been reported. Heat shock protein 47 (HSP47) and lysyl oxidase (LOX) are known to be essential for ECM maturation. In this study we have demonstrated that expression of HSP47 and LOX was significantly up-regulated in culture-activated primary rat hepatic stellate cells (HSCs), TGF-β stimulated LX-2 cells and liver tissue of CCl{sub 4}-treated mice, which was accompanied by a decrease of miR-29b level. In addition, over-expression of miR-29b in LX-2 cells resulted in significant inhibition on HSP47 and LOX expression. Mechanistically, miR-29b inhibited the expression of a reporter gene that contains the respective full-length 3′-UTR from HSP47 and LOX gene, and this inhibitory effect was abolished by the deletion of a putative miR-29b targeting sequence from the 3′-UTRs. Transfection of LX-2 cells with miR-29b led to abnormal collagen structure as shown by electron-microscopy, presumably through down-regulation of the expression of molecules involved in ECM maturation including HSP47 and LOX. These results demonstrated that miR-29b is involved in regulating the post-translational processing of ECM and fibril formation.

  14. MiR-29b inhibits collagen maturation in hepatic stellate cells through down-regulating the expression of HSP47 and lysyl oxidase

    International Nuclear Information System (INIS)

    Zhang, Yifei; Ghazwani, Mohammed; Li, Jiang; Sun, Ming; Stolz, Donna B.; He, Fengtian; Fan, Jie; Xie, Wen; Li, Song

    2014-01-01

    Highlights: • Enhanced HSP47 and LOX expression is associated with decreased miR-29b level in liver fibrosis. • miR-29b down-regulates HSP47 and LOX expression. • The suppression of HSP47 and LOX by miR-29b is mediated by putative sites at their 3′-UTRs. • miR-29b inhibits extracellular LOX activity and collagen maturation. - Abstract: Altered expression of miR-29b is implicated in the pathogenesis and progression of liver fibrosis. We and others previously demonstrated that miR-29b down-regulates the expression of several extracellular-matrix (ECM) genes including Col 1A1, Col 3A1 and Elastin via directly targeting their 3′-UTRs. However, whether or not miR-29b plays a role in the post-translational regulation of ECM biosynthesis has not been reported. Heat shock protein 47 (HSP47) and lysyl oxidase (LOX) are known to be essential for ECM maturation. In this study we have demonstrated that expression of HSP47 and LOX was significantly up-regulated in culture-activated primary rat hepatic stellate cells (HSCs), TGF-β stimulated LX-2 cells and liver tissue of CCl 4 -treated mice, which was accompanied by a decrease of miR-29b level. In addition, over-expression of miR-29b in LX-2 cells resulted in significant inhibition on HSP47 and LOX expression. Mechanistically, miR-29b inhibited the expression of a reporter gene that contains the respective full-length 3′-UTR from HSP47 and LOX gene, and this inhibitory effect was abolished by the deletion of a putative miR-29b targeting sequence from the 3′-UTRs. Transfection of LX-2 cells with miR-29b led to abnormal collagen structure as shown by electron-microscopy, presumably through down-regulation of the expression of molecules involved in ECM maturation including HSP47 and LOX. These results demonstrated that miR-29b is involved in regulating the post-translational processing of ECM and fibril formation

  15. Chloride flux in phagocytes.

    Science.gov (United States)

    Wang, Guoshun

    2016-09-01

    Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 7 CFR 51.767 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Florida Citrus Industry, Part 1, Chapter 20-13 Market Classification, Maturity Standards and Processing or... 2065-S, 14th and Independence Ave., Washington, DC 20250 or at the National Archives and Records...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. ...

  17. 7 CFR 51.1158 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Citrus Industry, Part 1, Chapter 20-13 Market Classification, Maturity Standards and Processing or... 2065-S, 14th and Independence Ave., Washington, DC 20250 or at the National Archives and Records...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. ...

  18. MatureBayes: a probabilistic algorithm for identifying the mature miRNA within novel precursors.

    Directory of Open Access Journals (Sweden)

    Katerina Gkirtzou

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are small, single stranded RNAs with a key role in post-transcriptional regulation of thousands of genes across numerous species. While several computational methods are currently available for identifying miRNA genes, accurate prediction of the mature miRNA remains a challenge. Existing approaches fall short in predicting the location of mature miRNAs but also in finding the functional strand(s of miRNA precursors. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present a computational tool that incorporates a Naive Bayes classifier to identify mature miRNA candidates based on sequence and secondary structure information of their miRNA precursors. We take into account both positive (true mature miRNAs and negative (same-size non-mature miRNA sequences examples to optimize sensitivity as well as specificity. Our method can accurately predict the start position of experimentally verified mature miRNAs for both human and mouse, achieving a significantly larger (often double performance accuracy compared with two existing methods. Moreover, the method exhibits a very high generalization performance on miRNAs from two other organisms. More importantly, our method provides direct evidence about the features of miRNA precursors which may determine the location of the mature miRNA. We find that the triplet of positions 7, 8 and 9 from the mature miRNA end towards the closest hairpin have the largest discriminatory power, are relatively conserved in terms of sequence composition (mostly contain a Uracil and are located within or in very close proximity to the hairpin loop, suggesting the existence of a possible recognition site for Dicer and associated proteins. CONCLUSIONS: This work describes a novel algorithm for identifying the start position of mature miRNA(s produced by miRNA precursors. Our tool has significantly better (often double performance than two existing approaches and provides new insights about the potential use

  19. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

    Science.gov (United States)

    Spencer, William C; Deneris, Evan S

    2017-01-01

    The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

  20. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

    Science.gov (United States)

    Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F.; Roy, Anna R.; Galjart, Niels; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis

    2017-01-01

    Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PMID:28846746

  1. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

    Directory of Open Access Journals (Sweden)

    Melisa Gomez-Velazquez

    2017-08-01

    Full Text Available Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

  2. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

    Science.gov (United States)

    Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Tena, Juan J; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F; Roy, Anna R; Galjart, Niels; Delgado-Olguin, Paul; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis; Manzanares, Miguel

    2017-08-01

    Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

  3. Carbon sequestration and water flow regulation services in mature Mediterranean Forest

    Science.gov (United States)

    Beguería, S.; Ovando, P.

    2015-12-01

    We develop a forestland use and management model that integrates spatially-explicit biophysical and economic data, to estimate the expected pattern of climate regulation services through carbon dioxide (CO2) sequestration in tree and shrubs biomass, and water flow regulation. We apply this model to examine the potential trade-offs and synergies in the supply of CO2 sequestration and water flow services in mature Mediterranean forest, considering two alternative forest management settings. A forest restoration scenario through investments in facilitating forest regeneration, and a forestry activity abandonment scenario as result of unprofitable forest regeneration investment. The analysis is performed for different discount rates and price settings for carbon and water. The model is applied at the farm level in a group of 567 private silvopastoral farms across Andalusia (Spain), considering the main forest species in this region: Quercus ilex, Q. suber, Pinus pinea, P. halepensis, P. pinaster and Eucalyptus sp., as well as for tree-less shrubland and pastures. The results of this research are provided by forest land unit, vegetation, farm and for the group of municipalities where the farms are located. Our results draw attention to the spatial variability of CO2 and water flow regulation services, and point towards a trade-off between those services. The pattern of economic benefits associated to water and carbon services fluctuates according to the assumptions regarding price levels and discounting rates, as well as in connection to the expected forest management and tree growth models, and to spatially-explicit forest attributes such as existing tree and shrubs inventories, the quality of the sites for growing different tree species, soil structure or the climatic characteristics. The assumptions made regarding the inter-temporal preferences and relative prices have a large effect on the estimated economic value of carbon and water services. These results

  4. A Conserved Cytochrome P450 Evolved in Seed Plants Regulates Flower Maturation.

    Science.gov (United States)

    Liu, Zhenhua; Boachon, Benoît; Lugan, Raphaël; Tavares, Raquel; Erhardt, Mathieu; Mutterer, Jérôme; Demais, Valérie; Pateyron, Stéphanie; Brunaud, Véronique; Ohnishi, Toshiyuki; Pencik, Ales; Achard, Patrick; Gong, Fan; Hedden, Peter; Werck-Reichhart, Danièle; Renault, Hugues

    2015-12-07

    Global inspection of plant genomes identifies genes maintained in low copies across taxa and under strong purifying selection, which are likely to have essential functions. Based on this rationale, we investigated the function of the low-duplicated CYP715 cytochrome P450 gene family that appeared early in seed plants and evolved under strong negative selection. Arabidopsis CYP715A1 showed a restricted tissue-specific expression in the tapetum of flower buds and in the anther filaments upon anthesis. cyp715a1 insertion lines showed a strong defect in petal development, and transient alteration of pollen intine deposition. Comparative expression analysis revealed the downregulated expression of genes involved in pollen development, cell wall biogenesis, hormone homeostasis, and floral sesquiterpene biosynthesis, especially TPS21 and several key genes regulating floral development such as MYB21, MYB24, and MYC2. Accordingly, floral sesquiterpene emission was suppressed in the cyp715a1 mutants. Flower hormone profiling, in addition, indicated a modification of gibberellin homeostasis and a strong disturbance of the turnover of jasmonic acid derivatives. Petal growth was partially restored by the active gibberellin GA3 or the functional analog of jasmonoyl-isoleucine, coronatine. CYP715 appears to function as a key regulator of flower maturation, synchronizing petal expansion and volatile emission. It is thus expected to be an important determinant of flower-insect interaction. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  5. ORGANIZATIONAL PROJECT MANAGEMENT MATURITY

    Directory of Open Access Journals (Sweden)

    Yana Derenskaya

    2017-11-01

    Full Text Available The present article is aimed at developing a set of recommendations for achieving a higher level of organizational project maturity at a given enterprise. Methodology. For the purposes of the current research, the available information sources on the components of project management system are analysed; the essence of “organizational maturity” and the existing models of organizational maturity are studied. The method of systemic and structural analysis, as well as the method of logical generalization, are employed in order to study the existing models of organizational maturity, to describe levels of organizational maturity, and finally to develop a set of methodological recommendations for achieving a higher level of organizational project maturity at a given enterprise. The results of the research showed that the core elements of project management system are methodological, organizational, programtechnical, and motivational components. Project management encompasses a wide range of issues connected with organizational structure, project team, communication management, project participants, etc. However, the fundamental basis for developing project management concept within a given enterprise starts with defining its level of organizational maturity. The present paper describes various models of organizational maturity (staged, continuous, petal-shaped and their common types (H. Кеrzner Organizational Maturity Model, Berkeley PM Maturity Model, Organizational Project Management Maturity Model, Portfolio, Program & Project Management Maturity Model. The analysis of available theoretic works showed that the notion “organizational project maturity” refers to the capability of an enterprise to select projects and manage them with the intention of achieving its strategic goals in the most effective way. Importantly, the level of maturity can be improved by means of formalizing the acquired knowledge, regulating project-related activities

  6. Regulating gonad inhibition and vitellogenin/vitellin induction in Penaeus monodon using mature GIH fusion protein and polyclonal antisera

    Digital Repository Service at National Institute of Oceanography (India)

    Vrinda, S.; Jasmin, C.; Sivakumar, K.C.; Jose, S.; Jose, B.; Philip, R; BrightSingh, I

    September 2016 Available online 15 September 2016 Keywords: Gonad-inhibiting hormone (GIH) Fusion/chimeric proteinaa r t i c l e i n f o b s t r a c tRegulating gonad inhibition and vitellogen Penaeus monodon using mature GIH fusion polyclonal antisera... restriction site overhangs to match with that of the expression vector; pET32a+. The forward primer (GIH-F- 5′-GAAT TCAACATCCTGGACAGCAAATGCAGGGGTGC-3′) contained EcoR I site (italics) and 29 nucleotide residues encoding the N terminal amino acid residues...

  7. MSX2 stimulates chondrocyte maturation by controlling Ihh expression.

    Science.gov (United States)

    Amano, Katsuhiko; Ichida, Fumitaka; Sugita, Atsushi; Hata, Kenji; Wada, Masahiro; Takigawa, Yoko; Nakanishi, Masako; Kogo, Mikihiko; Nishimura, Riko; Yoneda, Toshiyuki

    2008-10-24

    Several studies indicated that a homeobox gene, Msx2, is implicated in regulation of skeletal development by controlling enchondral ossification as well as membranous ossification. However, the molecular basis by which Msx2 conducts chondrogenesis is currently unclear. In this study, we examined the role of Msx2 in chondrocyte differentiation using mouse primary chondrocytes and embryonic metatarsal explants. Treatment with BMP2 up-regulated the expression of Msx2 mRNA along with chondrocyte differentiation in murine primary chondrocytes. Overexpression of wild-type Msx2 stimulated calcification of primary chondrocytes in the presence of BMP2. We also found that constitutively active Msx2 (caMsx2) enhanced BMP2-dependent calcification more efficiently than wild-type Msx2. Consistently, caMsx2 overexpression up-regulated the expression of alkaline phosphatase and collagen type X induced by BMP2. Furthermore, organ culture experiments using mouse embryonic metatarsals indicated that caMsx2 clearly stimulated the maturation of chondrocytes into the prehypertrophic and hypertrophic stages in the presence of BMP2. In contrast, knockdown of Msx2 inhibited maturation of primary chondrocytes. The stimulatory effect of Msx2 on chondrocyte maturation was enhanced by overexpression of Smad1 and Smad4 but inhibited by Smad6, an inhibitory Smad for BMP2 signaling. These data suggest that Msx2 requires BMP2/Smad signaling for its chondrogenic action. In addition, caMsx2 overexpression induced Ihh (Indian hedgehog) expression in mouse primary chondrocytes. Importantly, treatment with cyclopamine, a specific inhibitor for hedgehogs, blocked Msx2-induced chondrogenesis. Collectively, our results indicated that Msx2 promotes the maturation of chondrocytes, at least in part, through up-regulating Ihh expression.

  8. Transforming growth factor-β1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation

    International Nuclear Information System (INIS)

    Han Fei; Gilbert, James R.; Harrison, Gerald; Adams, Christopher S.; Freeman, Theresa; Tao Zhuliang; Zaka, Raihana; Liang Hongyan; Williams, Charlene; Tuan, Rocky S.; Norton, Pamela A.; Hickok, Noreen J.

    2007-01-01

    Fibronectin (FN) isoform expression is altered during chondrocyte commitment and maturation, with cartilage favoring expression of FN isoforms that includes the type II repeat extra domain B (EDB) but excludes extra domain A (EDA). We and others have hypothesized that the regulated splicing of FN mRNAs is necessary for the progression of chondrogenesis. To test this, we treated the pre-chondrogenic cell line ATDC5 with transforming growth factor-β1, which has been shown to modulate expression of the EDA and EDB exons, as well as the late markers of chondrocyte maturation; it also slightly accelerates the early acquisition of a sulfated proteoglycan matrix without affecting cell proliferation. When chondrocytes are treated with TGF-β1, the EDA exon is preferentially excluded at all times whereas the EDB exon is relatively depleted at early times. This regulated alternative splicing of FN correlates with the regulation of alternative splicing of SRp40, a splicing factor facilitating inclusion of the EDA exon. To determine if overexpression of the SRp40 isoforms altered FN and FN EDA organization, cDNAs encoding these isoforms were overexpressed in ATDC5 cells. Overexpression of the long-form of SRp40 yielded an FN organization similar to TGF-β1 treatment; whereas overexpression of the short form of SRp40 (which facilitates EDA inclusion) increased formation of long-thick FN fibrils. Therefore, we conclude that the effects of TGF-β1 on FN splicing during chondrogenesis may be largely dependent on its effect on SRp40 isoform expression

  9. Decoupling Internalization, Acidification and Phagosmal-Endosomal/Iysosomal Phagocytosis of Internalin A coated Beads in epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Blanchette, C D; Woo, Y; Thomas, C; Shen, N; Sulchek, T A; Hiddessen, A L

    2008-12-22

    Phagocytosis has been extensively examined in 'professional' phagocytic cells using pH sensitive dyes. However, in many of the previous studies, a separation between the end of internalization, beginning of acidification and completion of phagosomal-endosomal/lysosomal fusion was not clearly established, and in several cases, it was treated as a one-step process. In addition, very little work has been done to systematically examine phagosomal maturation in 'non-professional' phagocytic cells, such as epithelial cells. Therefore, in this study, we developed a simple and novel method to decouple and accurately measure particle internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in Madin-Darby Canine Kidney (MDCK) and Caco-2 epithelial cells. Our method was developed using a pathogen mimetic system consisting of polystyrene beads coated with Internalin A (InlA), a membrane surface protein from Listeria monocytogenes known to trigger receptor-mediated internalization. We achieved independent measurements of the rates of internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in epithelial cells by combining the InlA-coated beads (InlA-beads) with antibody quenching, pH sensitive dyes and endosomal/lysosomal dyes, as follows: the rate of InlA bead internalization was measured via antibody quenching of a pH independent dye (Alexa488) conjugated to InlA-beads, the rate at which phagosomes containing internalized InlA beads became acidified was measured using a pH dependent dye (FITC) conjugated to the beads and the rate of phagosomal-endosomal/lysosomal fusion was measured using a combination of unlabeled InlA-beads and an endosomal/lysosomal dye. By performing these independent measurements under identical experimental conditions, we were able to decouple the three processes and establish time scales for each. In a separate set of experiments, we also exploited the phagosomal acidification

  10. Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Houeix Benoit

    2010-03-01

    Full Text Available Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1, which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein beta polypeptide 2-like 1 (GNB2L1 were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For

  11. Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons

    Science.gov (United States)

    Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi

    2017-01-01

    Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549

  12. Posttesticular sperm maturation, infertility, and hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Marjorie Whitfield

    2015-01-01

    Full Text Available Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.

  13. Two Novel Rab2 Interactors Regulate Dense-core Vesicle Maturation

    Science.gov (United States)

    Ailion, Michael; Hannemann, Mandy; Dalton, Susan; Pappas, Andrea; Watanabe, Shigeki; Hegermann, Jan; Liu, Qiang; Han, Hsiao-Fen; Gu, Mingyu; Goulding, Morgan Q.; Sasidharan, Nikhil; Schuske, Kim; Hullett, Patrick; Eimer, Stefan; Jorgensen, Erik M.

    2014-01-01

    Summary Peptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi, and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1 and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a new pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network. PMID:24698274

  14. Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.

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    Lu Wang

    Full Text Available Casein kinase I alpha (CK1α is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1α mRNA and protein expression, as well as its subcellular localization in mouse oocytes from germinal vesicle to the late 1-cell stage. Our results showed that the expression level of CK1α was increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1α specific morpholino injection to block the function of CK1α. This functional blocking leads to failure of polar body 1 (PB1 extrusion, chromosome misalignment and MII plate incrassation. We further found that D4476, a specific and efficient CK1 inhibitor, decreased the rate of PB1 extrusion. Moreover, D4476 resulted in giant polar body extrusion, oocyte pro-MI arrest, chromosome congression failure and impairment of embryo developmental potential. In addition, we employed pyrvinium pamoate (PP, an allosteric activator of CK1α, to enhance CK1α activity in oocytes. Supplementation of PP induced oocyte meiotic maturation failure, severe congression abnormalities and misalignment of chromosomes. Taken together, our study for the first time demonstrates that CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.

  15. Correlation between dental maturity and cervical vertebral maturity.

    Science.gov (United States)

    Chen, Jianwei; Hu, Haikun; Guo, Jing; Liu, Zeping; Liu, Renkai; Li, Fan; Zou, Shujuan

    2010-12-01

    The aim of this study was to investigate the association between dental and skeletal maturity. Digital panoramic radiographs and lateral skull cephalograms of 302 patients (134 boys and 168 girls, ranging from 8 to 16 years of age) were examined. Dental maturity was assessed by calcification stages of the mandibular canines, first and second premolars, and second molars, whereas skeletal maturity was estimated by the cervical vertebral maturation (CVM) stages. The Spearman rank-order correlation coefficient was used to measure the association between CVM stage and dental calcification stage of individual teeth. The mean chronologic age of girls was significantly lower than that of boys in each CVM stage. The Spearman rank-order correlation coefficients between dental maturity and cervical vertebral maturity ranged from 0.391 to 0.582 for girls and from 0.464 to 0.496 for boys (P cervical vertebral maturation stage. The development of the mandibular second molar in females and that of the mandibular canine in males had the strongest correlations with cervical vertebral maturity. Therefore, it is practical to consider the relationship between dental and skeletal maturity when planning orthodontic treatment. Copyright © 2010 Mosby, Inc. All rights reserved.

  16. Regulate or deregulate. Influencing network interconnection charges

    Energy Technology Data Exchange (ETDEWEB)

    Van De Wielle, B.

    2003-06-01

    We study the choice between regulating interconnection charges or delegating their determination to the operators, both in a non-mature and a mature market. Three regulatory regimes are considered: full, cost-based and bill-and-keep. Delegation corresponds to bargaining about the interconnection charges using the regulatory schemes as disagreement outcomes. Applying regulation benefits the consumers. Under full regulation, access charges account for asymmetries and allow a unique Ramsey price. Delegation benefits the operators. In a mature market delegation robs the government of any market influence. In a non-mature market government preferences coincide with those of the largest operator and are disadvantageous for entry.

  17. Plastic downregulation of the transcriptional repressor BCL6 during maturation of human dendritic cells

    International Nuclear Information System (INIS)

    Pantano, Serafino; Jarrossay, David; Saccani, Simona; Bosisio, Daniela; Natoli, Gioacchino

    2006-01-01

    Dendritic cell (DC) maturation links peripheral events initiated by the encounter with pathogens to the activation and expansion of antigen-specific T lymphocytes in secondary lymphoid organs. Here, we describe an as yet unrecognized modulator of human DC maturation, the transcriptional repressor BCL6. We found that both myeloid and plasmacytoid DCs constitutively express BCL6, which is rapidly downregulated following maturation triggered by selected stimuli. Both in unstimulated and maturing DCs, control of BCL6 protein levels reflects the convergence of several mechanisms regulating BCL6 stability, mRNA transcription and nuclear export. By regulating the induction of several genes implicated in the immune response, including inflammatory cytokines, chemokines and survival genes, BCL6 may represent a pivotal modulator of the afferent branch of the immune response

  18. Capability maturity models for offshore organisational management.

    Science.gov (United States)

    Strutt, J E; Sharp, J V; Terry, E; Miles, R

    2006-12-01

    The goal setting regime imposed by the UK safety regulator has important implications for an organisation's ability to manage health and safety related risks. Existing approaches to safety assurance based on risk analysis and formal safety assessments are increasingly considered unlikely to create the step change improvement in safety to which the offshore industry aspires and alternative approaches are being considered. One approach, which addresses the important issue of organisational behaviour and which can be applied at a very early stage of design, is the capability maturity model (CMM). The paper describes the development of a design safety capability maturity model, outlining the key processes considered necessary to safety achievement, definition of maturity levels and scoring methods. The paper discusses how CMM is related to regulatory mechanisms and risk based decision making together with the potential of CMM to environmental risk management.

  19. Regulated Assembly of Vacuolar ATPase Is Increased during Cluster Disruption-induced Maturation of Dendritic Cells through a Phosphatidylinositol 3-Kinase/mTOR-dependent Pathway*

    Science.gov (United States)

    Liberman, Rachel; Bond, Sarah; Shainheit, Mara G.; Stadecker, Miguel J.; Forgac, Michael

    2014-01-01

    The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps composed of a peripheral V1 domain and a membrane-embedded V0 domain. Regulated assembly of V1 and V0 represents an important regulatory mechanism for controlling V-ATPase activity in vivo. Previous work has shown that V-ATPase assembly increases during maturation of bone marrow-derived dendritic cells induced by activation of Toll-like receptors. This increased assembly is essential for antigen processing, which is dependent upon an acidic lysosomal pH. Cluster disruption of dendritic cells induces a semi-mature phenotype associated with immune tolerance. Thus, semi-mature dendritic cells are able to process and present self-peptides to suppress autoimmune responses. We have investigated V-ATPase assembly in bone marrow-derived, murine dendritic cells and observed an increase in assembly following cluster disruption. This increased assembly is not dependent upon new protein synthesis and is associated with an increase in concanamycin A-sensitive proton transport in FITC-loaded lysosomes. Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. These results suggest that the phosphatidylinositol 3-kinase/mTOR pathway is involved in controlling V-ATPase assembly during dendritic cell maturation. PMID:24273170

  20. Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs are often produced by granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-4 (IL-4 stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS and interferon-γ (IFN-γ induction in order to characterize the usefulness of mature DCs (mDCs for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-γ and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA expression analysis. Results After 24 hours of LPS and IFN-γ stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion DCs, matured with LPS and IFN-γ, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.

  1. Maturity and maturity models in lean construction

    Directory of Open Access Journals (Sweden)

    Claus Nesensohn

    2014-03-01

    Full Text Available In recent years there has been an increasing interest in maturity models in management-related disciplines; which reflects a growing recognition that becoming more mature and having a model to guide the route to maturity can help organisations in managing major transformational change. Lean Construction (LC is an increasingly important improvement approach that organisations seek to embed. This study explores how to apply the maturity models to LC. Hence the attitudes, opinions and experiences of key industry informants with high levels of knowledge of LC were investigated. To achieve this, a review of maturity models was conducted, and data for the analysis was collected through a sequential process involving three methods. First a group interview with seven key informants. Second a follow up discussion with the same individuals to investigate some of the issues raised in more depth. Third an online discussion held via LinkedIn in which members shared their views on some of the results. Overall, we found that there is a lack of common understanding as to what maturity means in LC, though there is general agreement that the concept of maturity is a suitable one to reflect the path of evolution for LC within organisations.

  2. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

    Science.gov (United States)

    Qu, Yan; Dubyak, George R

    2009-06-01

    Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

  3. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    Science.gov (United States)

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  4. Maturation and integration of adult born hippocampal neurons: signal convergence onto small Rho GTPases

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    Krishna eVadodaria

    2013-08-01

    Full Text Available Adult neurogenesis, restricted to specific regions in the mammalian brain, represents one of the most interesting forms of plasticity in the mature nervous system. Adult-born hippocampal neurons play important roles in certain forms of learning and memory, and altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases such as major depression and epilepsy. Newborn neurons go through distinct developmental steps from a dividing neurogenic precursor to a synaptically integrated mature neuron. Previous studies have uncovered several molecular signaling pathways involved in distinct steps of this maturational process. In this context, the small Rho GTPases, Cdc42, Rac1 and RhoA have recently been shown to regulate the morphological and synaptic maturation of adult-born dentate granule cells in vivo. Distinct upstream regulators, including several growth factors that modulate maturation and integration of newborn neurons have been shown to also recruit the small Rho GTPases. Here we review recent findings and highlight the possibility that small Rho GTPases may act as central assimilators, downstream of critical input onto adult-born hippocampal neurons contributing to their maturation and integration into the existing dentate gyrus circuitry.

  5. Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Sebastian Jessberger

    2008-11-01

    Full Text Available Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5 activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.

  6. Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner.

    Science.gov (United States)

    Wu, Biming; Durisin, Emily K; Decker, Joseph T; Ural, Evran E; Shea, Lonnie D; Coleman, Rhima M

    Inorganic phosphate (Pi) has been recognized as an important signaling molecule that modulates chondrocyte maturation and cartilage mineralization. However, conclusive experimental evidence for its involvement in early chondrogenesis is still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi does not correlate with the Pi concentration in the culture medium but is better predicted by the availability of Pi on a per cell basis (Pi abundance). Both culture models were treated with ITS+, 10mM β-glycerophosphate (βGP), or ITS+/10mM βGP, which resulted in three levels of Pi abundance in cultures: basal (Pi/DNA 60ng/µg). In chondrogenic medium alone, the abundance levels were at the basal level in 2D culture and moderate in 3D cultures. The addition of 10mM βGP resulted in moderate abundance in 2D and high abundance in 3D cultures. Moderate Pi abundance enhanced early chondrogenesis and production of aggrecan and type II collagen whereas high Pi abundance inhibited chondrogenic differentiation and induced rapid mineralization. Inhibition of sodium phosphate transporters reduced phosphate-induced expression of chondrogenic markers. When 3D ITS+/βGP cultures were treated with levamisole to reduce ALP activity, Pi abundance was decreased to moderate levels, which resulted in significant upregulation of chondrogenic markers, similar to the response in 2D cultures. Delay of phosphate delivery until after early chondrogenesis occurs (7 days) no longer enhanced chondrogenesis, but instead accelerated hypertrophy and mineralization. Together, our data highlights the dependence of chondroprogenitor cell response to Pi on its availability to individual cells and the chondrogenic maturation stage of these cells and suggest that appropriate temporal delivery of phosphate to ATDC5 cells in 3D cultures represents a rapid model for mechanistic studies into the effects of

  7. Endogenous laminin is required for human airway smooth muscle cell maturation

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    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  8. Terminal Maturation of Orthochromatic Erythroblasts Is Impaired in Burn Patients.

    Science.gov (United States)

    Hasan, Shirin; Mosier, Michael J; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

    2018-02-20

    Mechanisms of erythropoietin (Epo)-resistant anemia in burn patients are poorly understood. We have recently found that administering a nonselective beta 1,2-adrenergic blocker propranolol (PR) was effective in reversing myelo-erythroid commitment through MafB regulation and increase megakaryocyte erythrocyte progenitors in burn patients' peripheral blood mononuclear cell (PBMC)-derived ex vivo culture system. Having known that Epo-dependent proliferation of early erythroblasts is intact after burn injury, here we inquired whether or not Epo-independent maturation stage of erythropoiesis is affected by burn injury and the relative role of PR on late-stage erythropoiesis. While majority of erythropoiesis occurs in the bone marrow, maturation into reticulocytes is crucial for their release into sinusoids to occupy the peripheral circulation for which enucleation is vital. peripheral blood mononuclear cells (PBMCs) from burn patients were extended beyond commitment and proliferation stages to late maturation stage in ex vivo culture to understand the role of PR in burn patients. Burn impedes late maturation of orthochromatic erythroblasts into reticulocytes by restricting the enucleation step. Late-stage erythropoiesis is impaired in burn patients irrespective of PR treatment. Further, substituting the microenvironment with control plasma (homologous) in place of autologous plasma rescues the conversion of orthochromatic erythroblasts to reticulocytes. Results show promise in formulating interventions to regulate late-stage erythropoiesis, which can be used in combination with PR to reduce the number of transfusions.

  9. Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

    Science.gov (United States)

    Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

    2013-11-01

    Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

  10. MRP8/14 induces autophagy to eliminate intracellular Mycobacterium bovis BCG.

    Science.gov (United States)

    Wang, Jinli; Huang, Chunyu; Wu, Minhao; Zhong, Qiu; Yang, Kun; Li, Miao; Zhan, Xiaoxia; Wen, Jinsheng; Zhou, Lin; Huang, Xi

    2015-04-01

    To explore the role of myeloid-related protein 8/14 in mycobacterial infection. The mRNA and protein expression levels of MRP8 or MRP14 were measured by real-time PCR and flow cytometry, respectively. Role of MRP8/14 was tested by overexpression or RNA interference assays. Flow cytometry and colony forming unit were used to test the phagocytosis and the survival of intracellular Mycobacterium bovis BCG (BCG), respectively. Autophagy mediated by MRP8/14 was detected by Western blot and immunofluorescence. The colocalization of BCG phagosomes with autophagosomes or lysosomes was by detected by confocal microscopy. ROS production was detected by flow cytometry. MRP8/14 expressions were up-regulated in human monocytic THP1 cells and primary macrophages after mycobacterial challenge. Silencing of MRP8/14 suppressed bacterial killing, but had no influence on the phagocytosis of BCG. Importantly, silencing MRP8/14 decreased autophagy and BCG phagosome maturation in THP1-derived macrophages, thereby increasing the BCG survival. Additionally, we demonstrated that MRP8/14 promoted autophagy in a ROS-dependent manner. The present study revealed a novel role of MRP8/14 in the autophagy-mediated elimination of intracellular BCG by promoting ROS generation, which may provide a promising therapeutic target for tuberculosis and other intracellular bacterial infectious diseases. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  11. Glia maturation factor gamma regulates the migration and adherence of human T lymphocytes

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    Lippert Dustin ND

    2012-04-01

    Full Text Available Abstract Background Lymphocyte migration and chemotaxis are essential for effective immune surveillance. A critical aspect of migration is cell polarization and the extension of pseudopodia in the direction of movement. However, our knowledge of the underlying molecular mechanisms responsible for these events is incomplete. Proteomic analysis of the isolated leading edges of CXCL12 stimulated human T cell lines was used to identify glia maturation factor gamma (GMFG as a component of the pseudopodia. This protein is predominantly expressed in hematopoietic cells and it has been shown to regulate cytoskeletal branching. The present studies were undertaken to examine the role of GMFG in lymphocyte migration. Results Microscopic analysis of migrating T-cells demonstrated that GMFG was distributed along the axis of movement with enrichment in the leading edge and behind the nucleus of these cells. Inhibition of GMFG expression in T cell lines and IL-2 dependent human peripheral blood T cells with shRNAmir reduced cellular basal and chemokine induced migration responses. The failure of the cells with reduced GMFG to migrate was associated with an apparent inability to detach from the substrates that they were moving on. It was also noted that these cells had an increased adherence to extracellular matrix proteins such as fibronectin. These changes in adherence were associated with altered patterns of β1 integrin expression and increased levels of activated integrins as detected with the activation specific antibody HUTS4. GMFG loss was also shown to increase the expression of the β2 integrin LFA-1 and to increase the adhesion of these cells to ICAM-1. Conclusions The present studies demonstrate that GMFG is a component of human T cell pseudopodia required for migration. The reduction in migration and increased adherence properties associated with inhibition of GMFG expression suggest that GMFG activity influences the regulation of integrin mediated

  12. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

    NARCIS (Netherlands)

    M. Gomez-Velazquez (Melisa); C. Badia-Careaga (Claudio); Lechuga-Vieco, A.V. (Ana Victoria); Nieto-Arellano, R. (Rocio); Tena, J.J. (Juan J.); Rollan, I. (Isabel); Alvarez, A. (Alba); Torroja, C. (Carlos); Caceres, E.F. (Eva F.); Roy, A. (Anna); N.J. Galjart (Niels); Delgado-Olguin, P. (Paul); F. Sánchez-Cabo (Fátima); Enriquez, J.A. (Jose Antonio); Gomez-Skarmeta, J.L. (Jose Luis); M. Manzanares (Miguel)

    2017-01-01

    textabstractCardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such

  13. Comparative Proteomic Analysis of Mature and Immature Oocytes of the Swamp Buffalo (Bubalus bubalis

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    Qiang Fu

    2016-01-01

    Full Text Available Maternal protein components change markedly during mammalian oogenesis. Many of these proteins have yet to be characterized and verified. In this study, a proteomics approach was used to evaluate changes in proteins during oogenesis in the Swamp Buffalo (Bubalus bubalis. Proteins from 500 immature oocytes and 500 in vitro matured oocytes were subjected to two-dimensional electrophoresis, and more than 400 spots were detected. Image analysis indicated that 17 proteins were differentially expressed between the two groups. Eight proteins were identified by mass spectrometry. In mature oocytes, three proteins were down-regulated: major vault protein (MVP, N-acetyllactosaminide β-1,6-N-acetylglucosaminyl-transferase (GCNT-2, and gem-associated protein (GEMIN8, whereas five other proteins, heat shock protein (HSP60, Ras-responsive element-binding protein 1 (RREB-1, heat shock cognate 71 kDa protein (HSC71, hemoglobin subunit α (HBA, and BMP-2-inducible protein kinase (BMP-2K, were up-regulated. The expression profiles of HSP60 and GEMIN8 were further verified by Western blotting. The changes in HSP60 protein expression demonstrate the increasing need for mitochondrial protein importation to facilitate macromolecular assembly during oocyte maturation. The down-regulation of GEMIN8 production implies that RNA splicing is impaired in mature oocytes.

  14. DMPD: Linking inflammasome activation and phagosome maturation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available ml file with CIOPlayer Open .csml file with CIOPlayer - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  15. Enterprise Risk Management Implementation Maturity in Non Bank and Financial Companies

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    Subagio Tjahjono

    2017-07-01

    Full Text Available Previous studies of ERM implementation mostly using dummy variable to figure out relation with its determinant. Until today, studies that using risk management maturity as real variable are limited. Therefore, this study intends to determine the maturity level of ERM implementation in non-financial companies listed on Indonesia Stock Exchange during period 2015 and influence of firm’s total assets, total employee, leverage and public ownership to the ERM maturity. The method use are qualitative and multiple regression analysis. The result of data analysis showed that ERM implementation in selected sample during 2015 are still low (majority in initial and repeatable level. In addition, from determinant factors only total asset that have significant influence to the ERM maturity. This result implies that non-financial listed companies are vulnerable to risks. Management should consider future benefit of a mature ERM, not only to comply with regulation.DOI: 10.15408/etk.v16i2.5440 

  16. Long-range correlations in rectal temperature fluctuations of healthy infants during maturation.

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    Georgette Stern

    Full Text Available BACKGROUND: Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (T(rec patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS: We measured T(rec fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, alpha using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that T(rec fluctuations exhibit fractal long-range correlations with a mean (SD alpha of 1.51 (0.11, indicating that T(rec is regulated in a highly correlated and hence deterministic manner. A significant increase in alpha with age from 1.42 (0.07 at 4 weeks to 1.58 (0.04 at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. alpha was not associated with mean room temperature or influenced by immunization CONCLUSIONS: This study shows that the quantification of long-range correlations using alpha derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time T(rec pattern in young infants, reflective of maturation of

  17. "Mature Regionalism" and the Genesis of "Functional Projects": "Educational Regionalism" in Small (and Micro-States)

    Science.gov (United States)

    Jules, Tavis D.

    2017-01-01

    This article advances that the movement towards "deeper" Caribbean integration has generated a shift from "immature" regionalism to a "mature" form of regionalism. Thus, mature regionalism, a new governance mechanism, in regulating the institutional and legal framework of Caribbean Single Market and Economy is…

  18. Maturity group classification and maturity locus genotyping of early-maturing soybean varieties from high-latitude cold regions.

    Science.gov (United States)

    Jia, Hongchang; Jiang, Bingjun; Wu, Cunxiang; Lu, Wencheng; Hou, Wensheng; Sun, Shi; Yan, Hongrui; Han, Tianfu

    2014-01-01

    With the migration of human beings, advances of agricultural sciences, evolution of planting patterns and global warming, soybeans have expanded to both tropical and high-latitude cold regions (HCRs). Unlike other regions, HCRs have much more significant and diverse photoperiods and temperature conditions over seasons or across latitudes, and HCR soybeans released there show rich diversity in maturity traits. However, HCR soybeans have not been as well classified into maturity groups (MGs) as other places. Therefore, it is necessary to identify MGs in HCRs and to genotype the maturity loci. Local varieties were collected from the northern part of Northeast China and the far-eastern region of Russia. Maturity group reference (MGR) soybeans of MGs MG000, MG00, and MG0 were used as references during field experiments. Both local varieties and MGR soybeans were planted for two years (2010-2011) in Heihe (N 50°15', E 127°27', H 168.5 m), China. The days to VE (emergence), R1 (beginning bloom) and R7 (beginning maturity) were recorded and statistically analyzed. Furthermore, some varieties were further genotyped at four molecularly-identified maturity loci E1, E2, E3 and E4. The HCR varieties were classified into MG0 or even more early-maturing. In Heihe, some varieties matured much earlier than MG000, which is the most early-maturing known MG, and clustered into a separate group. We designated the group as MG0000, following the convention of MGs. HCR soybeans had relatively stable days to beginning bloom from emergence. The HCR varieties diversified into genotypes of E1, E2, E3 and E4. These loci had different effects on maturity. HCRs diversify early-maturing MGs of soybean. MG0000, a new MG that matures much earlier than known MGs, was developed. HCR soybean breeding should focus more on shortening post-flowering reproductive growth. E1, E2, E3, and E4 function differentially.

  19. Genetic and Hormonal Regulation of Chlorophyll Degradation during Maturation of Seeds with Green Embryos.

    Science.gov (United States)

    Smolikova, Galina; Dolgikh, Elena; Vikhnina, Maria; Frolov, Andrej; Medvedev, Sergei

    2017-09-16

    The embryos of some angiosperms (usually referred to as chloroembryos) contain chlorophylls during the whole period of embryogenesis. Developing embryos have photochemically active chloroplasts and are able to produce assimilates, further converted in reserve biopolymers, whereas at the late steps of embryogenesis, seeds undergo dehydration, degradation of chlorophylls, transformation of chloroplast in storage plastids, and enter the dormancy period. However, in some seeds, the process of chlorophyll degradation remains incomplete. These residual chlorophylls compromise the quality of seed material in terms of viability, nutritional value, and shelf life, and represent a serious challenge for breeders and farmers. The mechanisms of chlorophyll degradation during seed maturation are still not completely understood, and only during the recent decades the main pathways and corresponding enzymes could be characterized. Among the identified players, the enzymes of pheophorbide a oxygenase pathway and the proteins encoded by STAY GREEN ( SGR ) genes are the principle ones. On the biochemical level, abscisic acid (ABA) is the main regulator of seed chlorophyll degradation, mediating activity of corresponding catabolic enzymes on the transcriptional level. In general, a deep insight in the mechanisms of chlorophyll degradation is required to develop the approaches for production of chlorophyll-free high quality seeds.

  20. The Effect of Fetal Maturity on the Regulation of Fetoplacental Unit ...

    African Journals Online (AJOL)

    ... suppressed from 12.4676 + 2.66ng/ml to 5.4 + 0.91ng/ml [P<0.001] The suppression of oestriol in the group II [38th week] markedly exceed that of group I [32nd week]. Our results show that the hypothalamic-pituitary system of mature fetuses exhibits a high sensitivity to the feedback action of cortisol than immature fetuses.

  1. The anion exchanger Ae2 is required for enamel maturation in mouse teeth

    NARCIS (Netherlands)

    Lyaruu, D.M.; Bronckers, A.L.J.J.; Mulder, L.; Mardones, P.; Medina, J.F.; Kellokumpu, S.; Oude Elferink, R.P.J.; Everts, V.

    2008-01-01

    One of the mechanisms by which epithelial cells regulate intracellular pH is exchanging bicarbonate for Cl-. We tested the hypothesis that in ameloblasts the anion exchanger-2 (Ae2) is involved in pH regulation during maturation stage amelogenesis. Quantitative X-ray microprobe mineral content

  2. The anion exchanger Ae2 is required for enamel maturation in mouse teeth

    NARCIS (Netherlands)

    Lyaruu, D. M.; Bronckers, A. L. J. J.; Mulder, L.; Mardones, P.; Medina, J. F.; Kellokumpu, S.; Oude Elferink, R. P. J.; Everts, V.

    2008-01-01

    One of the mechanisms by which epithelial cells regulate intracellular pH is exchanging bicarbonate for Cl(-). We tested the hypothesis that in ameloblasts the anion exchanger-2 (Ae2) is involved in pH regulation during maturation stage amelogenesis. Quantitative X-ray microprobe mineral content

  3. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  4. Intraovarian markers of follicular and oocyte maturation.

    Science.gov (United States)

    Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

    1987-08-01

    The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

  5. Pharmaceutical Options for Triggering of Final Oocyte Maturation in ART

    Directory of Open Access Journals (Sweden)

    Juan Carlos Castillo

    2014-01-01

    Full Text Available Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages over hCG trigger. GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle surge of gonadotropins, without the prolonged action of hCG, resulting in the retrieval of more mature oocytes and a significant reduction in or elimination of OHSS as compared to hCG triggering. The induction of final follicular maturation using GnRHa represents a paradigm shift in the ovulation triggering concept in ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key central regulators of the neuroendocrine mechanisms of human reproduction, who have been shown to effectively elicit an LH surge and to induce final oocyte maturation in IVF cycles. This new trigger concept may, therefore, offer a completely new, “natural” pharmacological option for ovulation induction. Whether kisspeptins will be the future agent to trigger ovulation remains to be further explored.

  6. Genetic and Hormonal Regulation of Chlorophyll Degradation during Maturation of Seeds with Green Embryos

    Directory of Open Access Journals (Sweden)

    Galina Smolikova

    2017-09-01

    Full Text Available The embryos of some angiosperms (usually referred to as chloroembryos contain chlorophylls during the whole period of embryogenesis. Developing embryos have photochemically active chloroplasts and are able to produce assimilates, further converted in reserve biopolymers, whereas at the late steps of embryogenesis, seeds undergo dehydration, degradation of chlorophylls, transformation of chloroplast in storage plastids, and enter the dormancy period. However, in some seeds, the process of chlorophyll degradation remains incomplete. These residual chlorophylls compromise the quality of seed material in terms of viability, nutritional value, and shelf life, and represent a serious challenge for breeders and farmers. The mechanisms of chlorophyll degradation during seed maturation are still not completely understood, and only during the recent decades the main pathways and corresponding enzymes could be characterized. Among the identified players, the enzymes of pheophorbide a oxygenase pathway and the proteins encoded by STAY GREEN (SGR genes are the principle ones. On the biochemical level, abscisic acid (ABA is the main regulator of seed chlorophyll degradation, mediating activity of corresponding catabolic enzymes on the transcriptional level. In general, a deep insight in the mechanisms of chlorophyll degradation is required to develop the approaches for production of chlorophyll-free high quality seeds.

  7. Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation.

    Science.gov (United States)

    Plank, Jennifer L; Mundell, Nathan A; Frist, Audrey Y; LeGrone, Alison W; Kim, Thomas; Musser, Melissa A; Walter, Teagan J; Labosky, Patricia A

    2011-01-15

    Interactions between cells from the ectoderm and mesoderm influence development of the endodermally-derived pancreas. While much is known about how mesoderm regulates pancreatic development, relatively little is understood about how and when the ectodermally-derived neural crest regulates pancreatic development and specifically, beta cell maturation. A previous study demonstrated that signals from the neural crest regulate beta cell proliferation and ultimately, beta cell mass. Here, we expand on that work to describe timing of neural crest arrival at the developing pancreatic bud and extend our knowledge of the non-cell autonomous role for neural crest derivatives in the process of beta cell maturation. We demonstrated that murine neural crest entered the pancreatic mesenchyme between the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with pancreatic progenitors as the epithelium branched into the surrounding mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium. Consistent with previous data, in the absence of Foxd3, and therefore the absence of neural crest cells, proliferation of insulin-expressing cells and insulin-positive area are increased. Analysis of endocrine cell gene expression in the absence of neural crest demonstrated that, although the number of insulin-expressing cells was increased, beta cell maturation was significantly impaired. Decreased MafA and Pdx1 expression illustrated the defect in beta cell maturation; we discovered that without neural crest, there was a reduction in the percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to controls. In addition, transmission electron microscopy analyses revealed decreased numbers of characteristic insulin granules and the presence of abnormal granules in insulin-expressing cells from mutant embryos. Together, these data demonstrate that

  8. Rac1 is dispensable for oocyte maturation and female fertility in vivo.

    Science.gov (United States)

    Hao, Jian-Xiu; Meng, Tie-Gang; Fan, Li-Hua; Yao, Yuan-Qing

    2017-01-01

    Oocyte maturation, the important process to produce female haploid gamete, accompanies with polarity establishment and highly asymmetric cell division to emit minor polar body within little cytoplasm. Microfilaments play central roles in polarity establishment and asymmetric cell division. Several actin regulators like WASP protein family as well as small GTPases function in microfilament dynamics, involving the process. Rac1, one member of RhoGTPases, has been reported to regulate the polarity and asymmetric cell division in mouse oocytes in vitro. The physiological role of Rac1 in mouse oocyte remains unknown. By conditional knockout technology, we specifically deleted Rac1 gene in mouse oocyte, and found that Rac1 deletion exerted little effect on mouse oocyte maturation including polarity establishment and asymmetric division, and the mutant mice showed normal fertility.

  9. Intracellular invasion of Orientia tsutsugamushi activates inflammasome in asc-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jung-Eun Koo

    Full Text Available Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β, which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1β maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1β and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1β production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense.

  10. Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

    Science.gov (United States)

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Inoue, Makoto; Tonthat, Nam K; Bain, Judith M; Louw, Johanna; Shinohara, Mari L; Erwig, Lars P; Schumacher, Maria A; Ko, Dennis C; Heitman, Joseph

    2015-09-01

    Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-locked phenotype indicating that calcineurin governs the dimorphic transition. Genetic analysis in this study reveals that two calcineurin A catalytic subunits (out of three) are functionally diverged. Homology modeling illustrates modes of resistance resulting from amino substitutions in the interface between each calcineurin subunit and the inhibitory drugs. In addition, we show how the dimorphic transition orchestrated by calcineurin programs different outcomes during host-pathogen interactions. For example, when macrophages phagocytose Mucor yeast, subsequent phagosomal maturation occurs, indicating host cells respond appropriately to control the pathogen. On the other hand, upon phagocytosis of spores, macrophages fail to form mature phagosomes. Cytokine production from immune cells differs following exposure to yeast versus spores (which germinate into hyphae). Thus, the morphogenic transition can be targeted as an efficient treatment option against Mucor infection. In addition, genetic analysis (including gene disruption and mutational studies) further strengthens the understanding of calcineurin and provides a foundation to develop antifungal agents targeting calcineurin to deploy against Mucor and other pathogenic fungi. © 2015 John Wiley & Sons Ltd.

  11. Heme Oxygenase-1/Carbon Monoxide System and Embryonic Stem Cell Differentiation and Maturation into Cardiomyocytes

    Science.gov (United States)

    Suliman, Hagir B.; Zobi, Fabio

    2016-01-01

    Abstract Aims: The differentiation of embryonic stem (ES) cells into energetically efficient cardiomyocytes contributes to functional cardiac repair and is envisioned to ameliorate progressive degenerative cardiac diseases. Advanced cell maturation strategies are therefore needed to create abundant mature cardiomyocytes. In this study, we tested whether the redox-sensitive heme oxygenase-1/carbon monoxide (HO-1/CO) system, operating through mitochondrial biogenesis, acts as a mechanism for ES cell differentiation and cardiomyocyte maturation. Results: Manipulation of HO-1/CO to enhance mitochondrial biogenesis demonstrates a direct pathway to ES cell differentiation and maturation into beating cardiomyocytes that express adult structural markers. Targeted HO-1/CO interventions up- and downregulate specific cardiogenic transcription factors, transcription factor Gata4, homeobox protein Nkx-2.5, heart- and neural crest derivatives-expressed protein 1, and MEF2C. HO-1/CO overexpression increases cardiac gene expression for myosin regulatory light chain 2, atrial isoform, MLC2v, ANP, MHC-β, and sarcomere α-actinin and the major mitochondrial fusion regulators, mitofusin 2 and MICOS complex subunit Mic60. This promotes structural mitochondrial network expansion and maturation, thereby supporting energy provision for beating embryoid bodies. These effects are prevented by silencing HO-1 and by mitochondrial reactive oxygen species scavenging, while disruption of mitochondrial biogenesis and mitochondrial DNA depletion by loss of mitochondrial transcription factor A compromise infrastructure. This leads to failure of cardiomyocyte differentiation and maturation and contractile dysfunction. Innovation: The capacity to augment cardiomyogenesis via a defined mitochondrial pathway has unique therapeutic potential for targeting ES cell maturation in cardiac disease. Conclusion: Our findings establish the HO-1/CO system and redox regulation of mitochondrial biogenesis as

  12. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

    International Nuclear Information System (INIS)

    Lopez, Soledad; Gomez, Enrique; Torres, Maria J.; Pozo, David; Fernandez, Tahia D.; Ariza, Adriana; Sanz, Maria L.; Blanca, Miguel; Mayorga, Cristobalina

    2015-01-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

  13. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Soledad [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Gomez, Enrique [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Torres, Maria J. [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Pozo, David [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Fernandez, Tahia D.; Ariza, Adriana [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Sanz, Maria L. [Department of Allergology and Clinical Immunology, University Clinic of Navarra, Pamplona (Spain); Blanca, Miguel [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Mayorga, Cristobalina, E-mail: lina.mayorga@ibima.eu [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain)

    2015-11-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

  14. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    Energy Technology Data Exchange (ETDEWEB)

    Fogliarini, Celine [Faculte Timone, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Chaumoitre, Katia [Hopital Nord, Department of Radiology, Marseille (France); Chapon, Frederique; Levrier, Olivier; Girard, Nadine [Hopital Timone, Department of Neuroradiology, Marseille Cedex 5 (France); Fernandez, Carla; Figarella-Branger, Dominique [Hopital Timone, Department of Pathology, Marseille (France)

    2005-08-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  15. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    International Nuclear Information System (INIS)

    Fogliarini, Celine; Chaumoitre, Katia; Chapon, Frederique; Levrier, Olivier; Girard, Nadine; Fernandez, Carla; Figarella-Branger, Dominique

    2005-01-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  16. Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets.

    Science.gov (United States)

    Long, Baisheng; Yin, Cong; Fan, Qiwen; Yan, Guokai; Wang, Zhichang; Li, Xiuzhi; Chen, Changqing; Yang, Xingya; Liu, Lu; Zheng, Zilong; Shi, Min; Yan, Xianghua

    2016-04-01

    Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in postnatal life. However, the underlying mechanisms by which IUGR affects fetal liver development and metabolism remain incompletely understood. Here, we applied a high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on the liver of newborn piglets. As a result, we identified 78 differentially expressed proteins in the three biological replicates, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Among them, a majority of differentially expressed proteins were related to nutrient metabolism and mitochondrial function. Additionally, many significantly down-regulated proteins participated in the mTOR signaling pathway and the phagosome maturation signaling pathway. Further analysis suggested that glucose concentration and hepatic glycogen storage were both reduced in IUGR newborn piglets, which may contribute to AMPK activation and mTORC1 inhibition. However, AMPK activation and mTORC1 inhibition failed to induce autophagy in the liver of IUGR neonatal pigs. A possible reason is that PP2Ac, a potential candidate in autophagy regulation, is significantly down-regulated in the liver of IUGR newborn piglets. These findings may provide implications for preventing and treating IUGR in human beings and domestic animals.

  17. Regulation of mature oil fields: a constitutional analysis; Regulacao de campos maduros de petroleo: uma analise a luz da Constituicao Federal de 1988

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Mariana de; Xavier, Yanko Marcius de Alencar [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2008-07-01

    The oil activities in Brazil had been started in an intensive way by the years 30 and 40. During approximately 40 years only one agent had been executed the oil activities in this country: the PETROBRAS. Many of the fields explored in the past are nowadays in decline. These fields, not interesting for the majors, would be interesting for the small and medium enterprises. The present research analyses the mature oil fields and its regulation in Brazil, looking to the 'Constituicao Federal de 1988' and to the idea of social and economic development. (author)

  18. Measurement of bacterial capture and phagosome maturation of Kupffer cells by intravital microscopy

    NARCIS (Netherlands)

    Surewaard, Bas G.J.; Kubes, Paul

    2017-01-01

    It is central to the field of bacterial pathogenesis to define how bacteria are killed by phagocytic cells. During phagocytosis, the microbe is localized to the phagolysosome where crucial defense mechanisms such as acidification and production of reactive oxygen species (ROS) are initiated. This

  19. Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

    Science.gov (United States)

    McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

    2017-01-01

    More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

  20. Maturation of the adolescent brain

    Directory of Open Access Journals (Sweden)

    Arain M

    2013-04-01

    significantly impact maturation of the adolescent brain. Pharmacological interventions to regulate adolescent behavior have been attempted with limited success. Since several factors, including age, sex, disease, nutritional status, and substance abuse have a significant impact on the maturation of the adolescent brain, we have highlighted the influence of these clinically significant and socially important aspects in this report. Keywords: myelinogenesis, neurocircuitry, molecular imaging, drug addiction, behavior, social adjustment

  1. Regulate or Deregulate : Influencing Network Interconnenction Charges

    NARCIS (Netherlands)

    van de Wielle, B.

    2003-01-01

    We study the choice between regulating interconnection charges or delegating their determination to the operators, both in a non-mature and a mature market. Three regulatory regimes are considered: full, cost-based and bill-and-keep. Delegation corresponds to bargaining about the interconnection

  2. Assessing healthcare process maturity: challenges of using a business process maturity model

    NARCIS (Netherlands)

    Tarhan, A.; Turetken, O.; van den Biggelaar, F.J.H.M.

    2015-01-01

    Doi: 10.4108/icst.pervasivehealth.2015.259105 The quality of healthcare services is influenced by the maturity of healthcare processes used to develop it. A maturity model is an instrument to assess and continually improve organizational processes. In the last decade, a number of maturity models

  3. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  4. Diagnostic assessment of skeletal maturity through dental maturation in Hispanic growing individuals

    Directory of Open Access Journals (Sweden)

    Alejandra Cisternas

    2017-01-01

    Full Text Available Background: The aim of this study was to explore dental maturation as a diagnostic test for skeletal maturation. Materials and Methods: Six hundred and fifty-seven growing individuals were classified according to their cervical vertebral maturity and dental maturity, both determined in lateral cephalograms and panoramic radiographs, respectively. The correlation between cervical and dental stages was established for each gender. A receiver operating characteristic curve analysis was made, and sensitivity and specificity values were established. Results: Correlation was found between cervical and dental maturation for females (r = 0.73; P<0.001 and males (r = 0.60; P<0.001. Sensitivity for dental Stage F, as an indicator of a postmaturation peak stage, was 87.21% for females and 97.1% for males, whereas specificity for the same stage was 82.92% and 72.3% for females and males, respectively. Conclusions: Dental maturation evaluation could contribute determining whether a patient is in a pre- or post-growth spurt stage.

  5. Correlation between Dental Maturity by Demirjian Method and Skeletal Maturity by Cervical Vertebral Maturity Method using Panoramic Radiograph and Lateral Cephalogram

    Directory of Open Access Journals (Sweden)

    Madhusudhanan Mallika Mini

    2017-01-01

    Full Text Available Introduction: Radiographs are effective tools in assessing the stages of bone maturation in dentistry. The cervical vertebral maturation method is a proven effective tool in assessing the adolescent growth spurt than hand-wrist radiographs in an individual. Assessment of dental calcification stages are a reliable method for determining dental maturity. Panoramic imaging can be used as the primary imaging modality for assessing maturity if a correlation can be found out between tooth calcification stages and cervical vertebral maturation stages. This study was conducted to determine the correlation between dental maturity stage and cervical vertebral maturity stage and to estimate predictor variables for cervical vertebral maturation stages (CVMS stratified by gender in a tertiary hospital setting. Materials and Methods: A descriptive study was conducted among patients accessing orthodontic care in radiology outpatient clinic, Oral Medicine and Radiology department, Government Dental College Thiruvananthapuram for a period of 15 months. Participants were selected between the ages of 8 and 16 years. Panoramic radiographs and lateral cephalograms were used to determine dental maturity stages using Demirjian method and CVMS using Bacetti and Franchi method, respectively. Results: One hundred patients (males = 46, females = 54 were included in the study; the spearman rank order correlation revealed significant relationship. The correlation ranged from 0.61 to 0.74 for females and 0.48 to 0.51 for males. Second premolar showed highest correlation and canine the lowest for both females and males. Stage G of mandibular second premolar signifies the pubertal growth period in this study population. By ordinal regression model, G stage of second premolar was found to be a significant predictor in males and stage H followed by G and F in females for the age group of 12–14 years. Conclusion: Dental maturation stages were significantly correlated with CVMS

  6. Small GTPases and formins in mammalian oocyte maturation: cytoskeletal organizers.

    Science.gov (United States)

    Kwon, Sojung; Lim, Hyunjung J

    2011-03-01

    The maturation process of mammalian oocytes accompanies an extensive rearrangement of the cytoskeleton and associated proteins. As this process requires a delicate interplay between the cytoskeleton and its regulators, it is often targeted by various external and internal adversaries that affect the congression and/or segregation of chromosomes. Asymmetric cell division in oocytes also requires specific regulators of the cytoskeleton, including formin-2 and small GTPases. Recent literature providing clues regarding how actin filaments and microtubules interact during spindle migration in mouse oocytes are highlighted in this review.

  7. Identification of a potent small molecule capable of regulating polyploidization, megakaryocyte maturation, and platelet production.

    Science.gov (United States)

    Huang, Nick; Lou, Mabel; Liu, Hua; Avila, Cecilia; Ma, Yupo

    2016-12-08

    Megakaryocytic cell maturation involves polyploidization, and megakaryocyte (MK) ploidy correlates with their maturation and platelet production. Retardation of MK maturation is closely associated with poor MK engraftment after cord blood transplantation and neonatal thrombocytopenia. Despite the high prevalence of thrombocytopenia in a range of setting that affect infants to adults, there are still very limited modalities of treatment. Human CD34 + cells were isolated from cord blood or bone marrow samples acquired from consenting patients. Cells were cultured and induced using 616452 and compared to current drugs on the market such as rominplostim or TPO. Ploidy analysis was completed using propidium iodide staining and flow cytometry analysis. Animal studies consisted of transplanting human CD34 + cells into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice followed by daily injections of 15 mg/kg of 616452. Within one week of culture, the chemical was able to induce polyploidization, the process required for megakaryocyte maturation with the accumulation of DNA content, to 64 N or greater to achieve a relative adult size. We observed fold increases as high as 200-fold in cells of 16 N or greater compared to un-induced cells with a dose-dependent manner. In addition, MK differentiated in the presence of 616452 demonstrated a more robust capacity of MK differentiation than that of MKs cultured with rominplostim used for adult idiopathic thrombocytopenic purpura (ITP) patients. In mice transplanted with human cord blood, 616452 strikingly enhanced MK reconstitution in the marrow and human peripheral platelet production. The molecular therapeutic actions for this chemical may be through TPO-independent pathways. Our studies may have an important impact on our fundamental understanding of fetal MK biology, the clinical management of thrombocytopenic neonates and leukemic differentiation therapy.

  8. An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells

    Science.gov (United States)

    Wei, Tingyi; Chen, Wen; Wang, Xiukun; Zhang, Man; Chen, Jiayu; Zhu, Songcheng; Chen, Long; Yang, Dandan; Wang, Guiying; Jia, Wenwen; Yu, Yangyang; Duan, Tao; Wu, Minjuan; Liu, Houqi; Gao, Shaorong; Kang, Jiuhong

    2015-01-01

    The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation. PMID:25934799

  9. 7 CFR 1436.13 - Loan installments, delinquency, and acceleration of maturity date.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Loan installments, delinquency, and acceleration of... FACILITY LOAN PROGRAM REGULATIONS § 1436.13 Loan installments, delinquency, and acceleration of maturity... delinquency, CCC may permit a rescheduling of the debt or other measures consistent with the collection of...

  10. The Effect of Growth Hormone on Lipid Accumulation or Maturation in Adipocytes

    Directory of Open Access Journals (Sweden)

    Yuchao Zhang

    2016-11-01

    Full Text Available Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH on lipids accumulation or maturation of adipocytes remains elusive. Methods: In the present study, effect of GH on lipid accumulation in vitro and in vivo was examined. cDNA microarray, quantitative real time-PCR (qPCR and western blotting was used to analyze the expression of genes related to adipocyte lipid accumulation or degradation in pre- or mature 3T3-F442A adipocytes treated with GH and in epididymal adipose tissue of C57BL/6 mice administrated with GH. Level of adiponectin in supernatants of cultured F442A adipocytes was determined by enzyme-linked immune-sorbent assay. Results: We found that in 3T3-F442A especially 6 days post initiation of adipogenesis, GH intervention resulted in decreased expression of adipocyte maturation regulators (C/EBPα, PPARγ and prominent genes related to lipid synthesis such as FAS and FABP, while the expression of UCP1 was markedly enhanced. cDNA microarray analysis and qPCR showed that the expression of SOCS2 and Adipor2 was increased under GH-treatment in mature 3T3-F442A adipocytes. GH treatment increased the mRNA expression of adiponectin and UCP1 in mature adipocytes. The above results were confirmed by in vivo study. Conclusions: GH potentially negatively modulates the maturation and accumulation of lipid in adipocytes.

  11. On gonadic maturation and reproductive strategy in deep-sea benthic octopus Graneledone macrotyla

    Science.gov (United States)

    Guerra, Ángel; Sieiro, María Pilar; Roura, Álvaro; Portela, Julio M.; del Río, José Luís

    2013-09-01

    The new information reported in this paper is based on five maturing and mature females of the large-tuberculate octopus Graneledone macrotyla. These specimens were caught in bottom trawl surveys ATLANTIS 2009 (February 24 to April 1, 2009) and ATLANTIS 2010 (March 9 to April 5, 2010) carried out off the Argentinean Economic Exclusive Zone. Capture depth ranged from 475 to 921 m and sea bottom temperature between 2.8 and 3.1 °C. Development of the complex ovary, oviducts, and oviducal glands during gonadic maturation is described. The absence of spermathecae in the oviducal glands and the presence of fertilized eggs inside the ovary suggested that fertilization took place within the ovary. Histological techniques showed the presence of four types of oocytes. Maturing oocyte size-frequency distribution was polymodal. Fluorescence reaction showed that atresia occurred in both early and later oocyte maturation stages. Atresia affected 48-55 % of the initial number of oocytes. The maximum observed potential fecundity was estimated at 250-300 eggs. G. macrotyla showed a group-synchronous ovulation pattern, regulative atresia, and a batching spawning pattern with a few egg batches spawned intermittently over an extended period of spawning.

  12. Novel maturity parameters for mature to over-mature source rocks and oils based on the distribution of phenanthrene series compounds

    Directory of Open Access Journals (Sweden)

    Zixiang Wang

    2016-03-01

    Two additional novel and an optimized maturation parameters based on the distribution of phenanthrene series compounds are proposed and their relationships to EasyRo% (x are established: log(MPs/P = 0.19x + 0.08 (0.9% < EasyRo% < 2.1%; log(MPs/P = 0.64x − 0.86 (2.1% < EasyRo% < 3.4%; log(DMPs/TMPs = 0.71x − 0.55 (0.9% < EasyRo% < 3.4%; log(MTR = 0.84x − 0.75 (0.9% < EasyRo% < 3.4%. These significant positive correlations are strong argument for using log(MPs/P, log(DMPs/TMPs and log(MTR as maturity parameters, especially for mature to over-mature source rocks.

  13. Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues.

    Science.gov (United States)

    Qu, Feini; Li, Qing; Wang, Xiao; Cao, Xuan; Zgonis, Miltiadis H; Esterhai, John L; Shenoy, Vivek B; Han, Lin; Mauck, Robert L

    2018-02-19

    Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.

  14. Vitrification affects nuclear maturation and gene expression of immature human oocytes

    Directory of Open Access Journals (Sweden)

    Abbas Shahedi

    2017-02-01

    Full Text Available Background: Vitrification of oocytes is a fast-freezing technique, which may affect the quality of the human oocyte, and consequently affects the embryo development, pregnancy and birth. The aim of the current study was to investigate the consequence of in-vitro vitrification on maturation status of immature human oocytes, additionally, expression levels of stress, and apoptosis related genes. Materials and Methods: The total of 213 human immature oocytes which routinely discarded from assisted reproduction clinics were collected and divided into two groups including: (I fresh germinal vesicle (GV oocytes (n=106 (matured in-vitro  (fIVM , and  (II GV oocytes (n=107 that initially vitrified, then matured in  in-vitro (vIVM. After 36 hours of incubation, the oocytes were evaluated for nuclear maturation and expression level of DNA methyltransferase (DNMT1, stress related genes (Sod1 and Hsp70, and apoptotic related genes (Bax and Bcl-2 by quantitative Real-Time PCR. Results: Oocyte maturation rates were reduced in vIVM compared to fIVM oocytes (P=0.001. The expression of stress (Sod1 and Hsp70, and apoptotic-related genes (Bax and Bcl-2 in vIVM were significantly higher compared to the fIVM group. Additionally, pro-apoptotic gene up-regulated 4.3 times more than anti-apoptotic gene in vIVM oocyte. However, DNMT1 gene expression was reduced in vIVM oocyte (P = 0.047. Conclusions: The low survival rate of vitrified In-vitro matured GV oocytes could definitely be explained by the alterations of their gene expression profile. 

  15. Cryptococcus neoformans: Tripping on Acid in the phagolysosome

    Directory of Open Access Journals (Sweden)

    Carlos Miguel De Leon Rodriguez

    2016-02-01

    Full Text Available Cryptococcus neoformans (Cn is a basidiomycetous pathogenic yeast that is a frequent cause of meningoencephalitis in immunocompromised individuals. Cn is a facultative intracellular pathogen in mammals, insects and amoeba. Cn infection occurs after inhalation of spores or desiccated cells from the environment. After inhalation Cn localizes to the lungs where it can be phagocytosed by alveolar macrophages. Cn is surrounded by a polysaccharide capsule that helps the fungus survive in vivo by interfering with phagocytosis, quenching free radical bursts and shedding polysaccharides that negatively modulates the immune system. After phagocytosis, Cn resides within the phagosome that matures to become a phagolysosome, a process that results in the acidification of the phagolysosomal lumen. Cn replicates at a higher rate inside macrophages than in the extracellular environment, possibly as a result that the phagosomal pH is near that optimal for growth. Cn increases the phagolysosomal pH and modulates the dynamics of Rab GTPases interaction with the phagolysosome. Chemical manipulation of the phagolysosomal pH with drugs can result in direct and indirect killing of Cn and reduced non-lytic exocytosis. Phagolysosomal membrane damage after Cn infection occurs both in vivo and in vitro, and is required for Cn growth and survival. Macrophage treatment with IFN-γ reduces the phagolysosomal damage and increases intracellular killing of Cn. Studies on mice and humans show that treatment with IFN-γ can improve host control of the disease. However the mechanism by which Cn mediates phagolysosomal membrane damage remains unknown but likely candidates are phospholipases and mechanical damage from an enlarging capsule. Here we review Cn intracellular interaction with a particular emphasis on phagosomal interactions and develop the notion that the extent of damage of the phagosomal membrane is a key determinant of the outcome of the Cn-macrophage interaction.

  16. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming.

    Science.gov (United States)

    Dalod, Marc; Chelbi, Rabie; Malissen, Bernard; Lawrence, Toby

    2014-05-16

    Dendritic cells (DC) are key regulators of both protective immune responses and tolerance to self-antigens. Soon after their discovery in lymphoid tissues by Steinman and Cohn, as cells with the unique ability to prime naïve antigen-specific T cells, it was realized that DC can exist in at least two distinctive states characterized by morphological, phenotypic and functional changes-this led to the description of DC maturation. It is now well appreciated that there are several subsets of DC in both lymphoid and non-lymphoid tissues of mammals, and these cells show remarkable functional specialization and specificity in their roles in tolerance and immunity. This review will focus on the specific characteristics of DC subsets and how their functional specialization may be regulated by distinctive gene expression programs and signaling responses in both steady-state and in the context of inflammation. In particular, we will highlight the common and distinctive genes and signaling pathways that are associated with the functional maturation of DC subsets. © 2014 The Authors.

  17. Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

    Science.gov (United States)

    LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

    2012-01-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together

  18. Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation

    Science.gov (United States)

    Ho, Ming-Hua; Liao, Mei-Hsiu; Lin, Yi-Ling; Lai, Chien-Hao; Lin, Pei-I; Chen, Ruei-Ming

    2014-01-01

    Osteoblast maturation plays a key role in regulating osteogenesis. Electrospun nanofibrous products were reported to possess a high surface area and porosity. In this study, we developed chitosan nanofibers and examined the effects of nanofibrous scaffolds on osteoblast maturation and the possible mechanisms. Macro- and micro observations of the chitosan nanofibers revealed that these nanoproducts had a flat surface and well-distributed fibers with nanoscale diameters. Mouse osteoblasts were able to attach onto the chitosan nanofiber scaffolds, and the scaffolds degraded in a time-dependent manner. Analysis by scanning electron microscopy further showed mouse osteoblasts adhered onto the scaffolds along the nanofibers, and cell–cell communication was also detected. Mouse osteoblasts grew much better on chitosan nanofiber scaffolds than on chitosan films. In addition, human osteoblasts were able to adhere and grow on the chitosan nanofiber scaffolds. Interestingly, culturing human osteoblasts on chitosan nanofiber scaffolds time-dependently increased DNA replication and cell proliferation. In parallel, administration of human osteoblasts onto chitosan nanofibers significantly induced osteopontin, osteocalcin, and alkaline phosphatase (ALP) messenger (m)RNA expression. As to the mechanism, chitosan nanofibers triggered runt-related transcription factor 2 mRNA and protein syntheses. Consequently, results of ALP-, alizarin red-, and von Kossa-staining analyses showed that chitosan nanofibers improved osteoblast mineralization. Taken together, results of this study demonstrate that chitosan nanofibers can stimulate osteoblast proliferation and maturation via runt-related transcription factor 2-mediated regulation of osteoblast-associated osteopontin, osteocalcin, and ALP gene expression. PMID:25246786

  19. Correlation of Improved Version of Cervical Vertebral Maturation Indicator with Other Growth Maturity Indicators

    Directory of Open Access Journals (Sweden)

    Tripti Tikku

    2013-01-01

    Conclusion: The correlation between middle phalanx of 3rd finger (MP3 and cervical vertebral maturation method (CVMI and CVMS was higher as compared to the correlation of either of the cervical vertebral maturation method or MP3 with dental maturation indicator.

  20. The pivotal role of abscisic acid signaling during transition from seed maturation to germination.

    Science.gov (United States)

    Yan, An; Chen, Zhong

    2017-05-01

    Seed maturation and germination are two continuous developmental processes that link two distinct generations in spermatophytes; the precise genetic control of these two processes is, therefore, crucially important for the survival of the next generation. Pieces of experimental evidence accumulated so far indicate that a concerted action of endogenous signals and environmental cues is required to govern these processes. Plant hormone abscisic acid (ABA) has been suggested to play a predominant role in directing seed maturation and maintaining seed dormancy under unfavorable environmental conditions until antagonized by gibberellins (GA) and certain environmental cues to allow the commencement of seed germination when environmental conditions are favorable; therefore, the balance of ABA and GA is a major determinant of the timing of seed germination. Due to the advent of new technologies and system biology approaches, molecular studies are beginning to draw a picture of the sophisticated genetic network that drives seed maturation during the past decade, though the picture is still incomplete and many details are missing. In this review, we summarize recent advances in ABA signaling pathway in the regulation of seed maturation as well as the transition from seed maturation to germination, and highlight the importance of system biology approaches in the study of seed maturation.

  1. Developing maturity grids for assessing organisational capabilities

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2009-01-01

    Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment......Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment...

  2. miRNA-130a regulates C/EBP-ε expression during granulopoiesis

    DEFF Research Database (Denmark)

    Larsen, Maria T; Häger, Mattias; Glenthøj, Andreas

    2014-01-01

    cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors...... target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.......CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have...

  3. Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

    KAUST Repository

    Di Palma, Francesco; Tramontano, Anna

    2017-01-01

    The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

  4. Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

    KAUST Repository

    Di Palma, Francesco

    2017-08-03

    The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

  5. People Capability Maturity Model. SM.

    Science.gov (United States)

    1995-09-01

    tailored so it consumes less time and resources than a traditional software process assessment or CMU/SEI-95-MM-02 People Capability Maturity Model...improved reputation or customer loyalty. CMU/SEI-95-MM-02 People Capability Maturity Model ■ L5-17 Coaching Level 5: Optimizing Activity 1...Maturity Model CMU/SEI-95-MM-62 Carnegie-Mellon University Software Engineering Institute DTIC ELECTE OCT 2 7 1995 People Capability Maturity

  6. Adolescent emotional maturation through divergent models of brain organization

    Directory of Open Access Journals (Sweden)

    Jose Víctor Orón Semper

    2016-08-01

    Full Text Available In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA or a dynamic systems perspective (DSP is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning.

  7. Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis.

    Science.gov (United States)

    Nandi, Sayan; Alviña, Karina; Lituma, Pablo J; Castillo, Pablo E; Hébert, Jean M

    2018-01-15

    Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. IT Governance Maturity: Developing a Maturity Model Using the Delphi Method

    NARCIS (Netherlands)

    Smits, Daniël; van Hillegersberg, Jos

    2015-01-01

    To advance in maturity, organizations should pay attention to both the hard and soft sides of IT governance (ITG). The hard side is related to processes and structure, the soft side to social aspects like behavior and organizational culture. This paper describes a study to develop an ITG maturity

  9. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

    Science.gov (United States)

    Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

    2015-07-01

    Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

  10. DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral model Aiptasia

    KAUST Repository

    Li, Yong

    2017-11-03

    The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model system Aiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

  11. DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral model Aiptasia

    KAUST Repository

    Li, Yong; Liew, Yi Jin; Cui, Guoxin; Cziesielski, Maha J; Zahran, Noura Ibrahim Omar; Michell, Craig T; Voolstra, Christian R.; Aranda, Manuel

    2017-01-01

    The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model system Aiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

  12. Academic Achievement of High School Students in Relation to Their Anxiety, Emotional Maturity and Social Maturity

    Science.gov (United States)

    Puar, Surjit Singh

    2013-01-01

    The present study has been designed to investigate the non-cognitive variables like anxiety, emotional maturity and social maturity and their relationship with academic achievement and also to see the locale-wise differences on the basis of their anxiety, emotional maturity and social maturity. The study was conducted over a sample of 400 (200…

  13. Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

    Science.gov (United States)

    Buglione, Luigi

    During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

  14. Rapamycin-based inducible translocation systems for studying phagocytosis.

    Science.gov (United States)

    Bohdanowicz, Michal; Fairn, Gregory D

    2011-01-01

    Phagocytosis is an immune receptor-mediated process whereby cells engulf large particles. The process is dynamic and requires several localized factors acting in concert with and sequentially after the engagement of immune receptors to envelope the particle. Once the particle is internalized, the nascent -phagosome undergoes a series of events leading to its maturation to the microbicidal phagolysosome. Investigating these dynamic and temporally controlled series of events in live cells requires noninvasive methods. The ability to rapidly recruit the proteins of interest to the sites of phagocytosis or to nascent phagosomes would help dissect the regulatory mechanisms involved during phagocytosis. Here, we describe a general approach to express in RAW264.7 murine macrophages, a genetically encoded rapamycin--induced heterodimerization system. In the presence of rapamycin, tight association between FK506-binding protein (FKBP) and FKBP rapamycin-binding protein (FRB) is observed. Based on this principle, a synthetic system consisting of a targeting domain attached to FKBP can recruit a protein of interest fused to FRB upon the addition of rapamycin. Previously, this technique has been used to target lipid-modifying enzymes and small GTPases to the phagosome or plasma membrane. The recruitment of the FRB module can be monitored by fluorescent microscopy if a fluorescent protein is fused to the FRB sequence. While the focus of this chapter is on phagocytic events, this method can be employed to study any organelle of interest when the appropriate targeting sequence is used.

  15. Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

    Science.gov (United States)

    Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

    2014-01-01

    The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

  16. Maturity Models Development in IS Research

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi; Andersen, Kim Normann

    2015-01-01

    Maturity models are widespread in IS research and in particular, IT practitioner communities. However, theoretically sound, methodologically rigorous and empirically validated maturity models are quite rare. This literature review paper focuses on the challenges faced during the development...... literature reveals that researchers have primarily focused on developing new maturity models pertaining to domain-specific problems and/or new enterprise technologies. We find rampant re-use of the design structure of widely adopted models such as Nolan’s Stage of Growth Model, Crosby’s Grid, and Capability...... Maturity Model (CMM). Only recently have there been some research efforts to standardize maturity model development. We also identify three dominant views of maturity models and provide guidelines for various approaches of constructing maturity models with a standard vocabulary. We finally propose using...

  17. Modeling non-maturing liabilities

    OpenAIRE

    von Feilitzen, Helena

    2011-01-01

    Non‐maturing liabilities, such as savings accounts, lack both predetermined maturity and reset dates due to the fact that the depositor is free to withdraw funds at any time and that the depository institution is free to change the rate. These attributes complicate the risk management of such products and no standardized solution exists. The problem is important however since non‐maturing liabilities typically make up a considerable part of the funding of a bank. In this report different mode...

  18. Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand

    Science.gov (United States)

    Maddur, Mohan S.; Sharma, Meenu; Hegde, Pushpa; Stephen-Victor, Emmanuel; Pulendran, Bali; Kaveri, Srini V.; Bayry, Jagadeesh

    2015-01-01

    Dendritic cells (DCs) play a critical role in immune homeostasis by regulating the functions of various immune cells, including T and B cells. Notably, DCs also undergo education on reciprocal signalling by these immune cells and environmental factors. Various reports demonstrated that B cells have profound regulatory functions, although only few reports have explored the regulation of human DCs by B cells. Here we demonstrate that activated but not resting B cells induce maturation of DCs with distinct features to polarize Th2 cells that secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is contact dependent and implicates signalling of B-cell activation molecules CD69, B-cell-activating factor receptor, and transmembrane activator and calcium-modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2 cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our results suggest that B cells have the ability to control their own effector functions by enhancing the ability of human DCs to mediate Th2 differentiation. PMID:24910129

  19. Slab replacement maturity guidelines.

    Science.gov (United States)

    2014-04-01

    This study investigated the use of maturity method to determine early age strength of concrete in slab : replacement application. Specific objectives were (1) to evaluate effects of various factors on the compressive : maturity-strength relationship ...

  20. Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

    Directory of Open Access Journals (Sweden)

    Marlène Gallet

    Full Text Available ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation, but not early (commitment, negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

  1. Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

    Science.gov (United States)

    Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

    2013-01-01

    ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

  2. Maturity effects in energy futures

    Energy Technology Data Exchange (ETDEWEB)

    Serletis, Apostolos (Calgary Univ., AB (CA). Dept. of Economics)

    1992-04-01

    This paper examines the effects of maturity on future price volatility and trading volume for 129 energy futures contracts recently traded in the NYMEX. The results provide support for the maturity effect hypothesis, that is, energy futures prices to become more volatile and trading volume increases as futures contracts approach maturity. (author).

  3. Correlation between Cervical Vertebral Maturation Stages and Dental Maturation in a Saudi Sample

    Directory of Open Access Journals (Sweden)

    Nayef H Felemban

    2017-01-01

    Full Text Available Background: The aim of the present study was to compare the cervical vertebra maturation stages method and dental maturity using tooth calcification stages. Methods: The current study comprised of 405 subjects selected from orthodontic patients of Saudi origin coming to clinics of the specialized dental centers in western region of Saudi Arabia. Dental age was assessed according to the developmental stages of upper and lower third molars and skeletal maturation according to the cervical vertebrae maturation stage method. Statistical analysis was done using Kruskal-Wallis H, Mann-Whitney U test, Chi-Square test; t-test and Spearman correlation coefficient for inter group comparison. Results: The females were younger than males in all cervical stages. The CS1-CS2 show the period before the peak of growth, during CS3-CS5 it’s the pubertal growth spurt and CS6 is the period after the peak of the growth. The mean age and standard deviation for cervical stages of CS2, CS3 and CS4 were 12.09 ±1.72 years, 13.19 ±1.62 and 14.88 ±1.52 respectively. The Spearman correlation coefficients between cervical vertebrae and dental maturation were between 0.166 and 0.612, 0.243 and 0.832 for both sexes for upper and lower third molars. The significance levels for all coefficients were equal at 0.01 and 0.05. Conclusion: The results of this study showed that the skeletal maturity increased with the increase in dental ages for both genders. An early rate of skeletal maturation stage was observed in females. This study needs further analysis using a larger sample covering the entire dentition.

  4. Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation

    Directory of Open Access Journals (Sweden)

    Ho MH

    2014-09-01

    Full Text Available Ming-Hua Ho,1,2 Mei-Hsiu Liao,3 Yi-Ling Lin,2 Chien-Hao Lai,3 Pei-I Lin,3 Ruei-Ming Chen2–4 1Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Cell Physiology and Molecular Image Research Center and Department of Anesthesiology, Wan Fang Hospital, 3Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan; 4Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan Abstract: Osteoblast maturation plays a key role in regulating osteogenesis. Electrospun nanofibrous products were reported to possess a high surface area and porosity. In this study, we developed chitosan nanofibers and examined the effects of nanofibrous scaffolds on osteoblast maturation and the possible mechanisms. Macro- and micro observations of the chitosan nanofibers revealed that these nanoproducts had a flat surface and well-distributed fibers with nanoscale diameters. Mouse osteoblasts were able to attach onto the chitosan nanofiber scaffolds, and the scaffolds degraded in a time-dependent manner. Analysis by scanning electron microscopy further showed mouse osteoblasts adhered onto the scaffolds along the nanofibers, and cell–cell communication was also detected. Mouse osteoblasts grew much better on chitosan nanofiber scaffolds than on chitosan films. In addition, human osteoblasts were able to adhere and grow on the chitosan nanofiber scaffolds. Interestingly, culturing human osteoblasts on chitosan nanofiber scaffolds time-dependently increased DNA replication and cell proliferation. In parallel, administration of human osteoblasts onto chitosan nanofibers significantly induced osteopontin, osteocalcin, and alkaline phosphatase (ALP messenger (mRNA expression. As to the mechanism, chitosan nanofibers triggered runt-related transcription factor 2 mRNA and protein syntheses. Consequently, results of ALP-, alizarin red-, and von Kossa-staining analyses

  5. Kelch-like ECT2-interacting protein KLEIP regulates late-stage pulmonary maturation via Hif-2α in mice

    Directory of Open Access Journals (Sweden)

    Nicole Woik

    2014-06-01

    Full Text Available Respiratory distress syndrome (RDS caused by preterm delivery is a major clinical problem with limited mechanistic insight. Late-stage embryonic lung development is driven by hypoxia and the hypoxia-inducible transcription factors Hif-1α and Hif-2α, which act as important regulators for lung development. Expression of the BTB-and kelch-domain-containing (BTB-kelch protein KLEIP (Kelch-like ECT2-interacting protein; also named Klhl20 is controlled by two hypoxia response elements, and KLEIP regulates stabilization and transcriptional activation of Hif-2α. Based on the available data, we hypothesized an essential role for KLEIP in murine lung development and function. Therefore, we have performed a functional, histological, mechanistic and interventional study in embryonic and neonatal KLEIP−/− mice. Here, we show that about half of the KLEIP−/− neonates die due to respiratory failure that is caused by insufficient aeration, reduced septal thinning, reduced glycogenolysis, type II pneumocyte immaturity and reduced surfactant production. Expression analyses in embryonic day (E 18.5 lungs identified KLEIP in lung capillaries, and showed strongly reduced mRNA and protein levels for Hif-2α and VEGF; such reduced levels are associated with embryonic endothelial cell apoptosis and lung bleedings. Betamethasone injection in pregnant females prevented respiratory failure in KLEIP−/− neonates, normalized lung maturation, vascularization, aeration and function, and increased neonatal Hif-2α expression. Thus, the experimental study shows that respiratory failure in KLEIP−/− neonates is determined by insufficient angiocrine Hif-2α–VEGF signaling and that betamethasone activates this newly identified signaling cascade in late-stage embryonic lung development.

  6. Maturity models in supply chain sustainability

    DEFF Research Database (Denmark)

    Correia, Elisabete; Carvalho, Helena; Azevedo, Susana G.

    2017-01-01

    A systematic literature review of supply chain maturity models with sustainability concerns is presented. The objective is to give insights into methodological issues related to maturity models, namely the research objectives; the research methods used to develop, validate and test them; the scope...... of maturity levels. The comprehensive review, analysis, and synthesis of the maturity model literature represent an important contribution to the organization of this research area, making possible to clarify some confusion that exists about concepts, approaches and components of maturity models...

  7. INFLUENCE MATURATION OF VEAL ON THE MICROBIOLOGICAL AND PHYSICAL INDICATORS

    Directory of Open Access Journals (Sweden)

    Simona Kunová

    2015-06-01

    Full Text Available The aim of the present study was to evaluate microbial and pH changes in veal meat during maturation. Total viable counts, coliform bacteria and pH changes in chilling meat were evaluated after 24 hours, 7 days and 14 days of meat maturation. There were analysed 8 samples of veal meeat. Results of microbiological analysis were compared with Commission regulation (EC No 2073/2005 on microbiological criteria for foodstuffs. Total viable counts (TVC in samples after 24 hours of chilling ranged from 2.02 log CFU.cm-to 4.21 log CFU.cm-2 (1.64 . 104 CFU.cm-2. The average number of TVC after 24 hours of meat maturation was 3.27 log CFU.cm-2, coliform bacteria (CB after 24 hours were lower than than 1 log cfu.cm-2 in five samples, and the highest number of coliform bacteria was 1.65 log cfu.cm-2, average number of CB was 1.13 log cfu.cm-2. pH values in samples after 24 hours of maturation were in range from 6.6 to 7.0, average pH value was 6.8. TVC in samples after 7 days of chilling ranged from 3.09 log CFU.cm-2 to 4.01 log CFU.cm-2, the average number of TVC after 7 days of storage was 3.39 log CFU.cm-2. CB after 7 days of meat maturation were lower than 1 log CFU cm-2 in three samples, the highest value of CB was 2.07 log CFU cm-2, the average value of CB in samples after 7 days of meat chilling was 1.03 log CFU cm-2. pH values of meat after 7 days of maturation ranged from 5.5 to 6.1. The average pH value of samples after 7 days of storage was 5.73 pH values of meat after 14 days of maturation ranged from 6.0 to 6.4. The average pH value of samples after 14 days of storage was 6.16.

  8. Paxillin and embryonic PolyAdenylation Binding Protein (ePABP) engage to regulate androgen-dependent Xenopus laevis oocyte maturation - A model of kinase-dependent regulation of protein expression.

    Science.gov (United States)

    Miedlich, Susanne U; Taya, Manisha; Young, Melissa Rasar; Hammes, Stephen R

    2017-06-15

    Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues. Phosphoserine-paxillin then further augments Mos protein translation and downstream Erk2 activation, resulting in meiotic progression. We hypothesized that paxillin enhances Mos translation by interacting with embryonic PolyAdenylation Binding Protein (ePABP) on polyadenylated Mos mRNA. Knockdown of ePABP phenocopied paxillin knockdown, with reduced Mos protein expression, Erk2 and Cdk1 activation, as well as oocyte maturation. In both Xenopus oocytes and mammalian cells (HEK-293), paxillin and ePABP constitutively interacted. Testosterone (Xenopus) or EGF (HEK-293) augmented ePABP-paxillin binding, as well as ePABP binding to Mos mRNA (Xenopus), in an Erk-dependent fashion. Thus, ePABP and paxillin work together in an Erk-dependent fashion to enhance Mos protein translation and promote oocyte maturation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cloning and characterization of two 9-cis-epoxycarotenoid dioxygenase genes, differentially regulated during fruit maturation and under stress conditions, from orange (Citrus sinensis L. Osbeck).

    Science.gov (United States)

    Rodrigo, María-Jesús; Alquezar, Berta; Zacarías, Lorenzo

    2006-01-01

    There is now biochemical and genetic evidence that oxidative cleavage of cis-epoxycarotenoids by 9-cis-epoxycarotenoid dioxygenase (NCED) is the critical step in the regulation of abscisic acid (ABA) synthesis in higher plants. The peel of Citrus fruit accumulates large amounts of ABA during maturation. To understand the regulation of ABA biosynthesis in Citrus, two full-length cDNAs (CsNCED1 and CsNCED2) encoding NCEDs were isolated and characterized from the epicarp of orange fruits (Citrus sinensis L. Osbeck). Expression of the CsNCED1 gene increased in the epicarp during natural and ethylene-induced fruit maturation, and in water-stressed leaves, in a pattern consistent with the accumulation of ABA. The second gene, CsNCED2, was not detected in dehydrated leaves and, in fruits, exhibited a differential expression to that of CsNCED1. Taken together, these results suggests that CsNCED1 is likely to play a primary role in the biosynthesis of ABA in both leaves and fruits, while CsNCED2 appears to play a subsidiary role restricted to chromoplast-containing tissue. Furthermore, analysis of 9-cis-violaxanthin and 9'-cis-neoxanthin, as the two possible substrates for NCEDs, revealed that the former was the main carotenoid in the outer coloured part of the fruit peel as the fruit ripened or after ethylene treatment, whereas 9'-cis-neoxanthin was not detected or was in trace amounts. By contrast, turgid and dehydrated leaves contained 9'-cis-neoxanthin but 9-cis-violaxanthin was absent. Based on these results, it is suggested that 9-cis-violaxanthin may be the predominant substrate for NCED in the peel of Citrus fruits, whereas 9'-cis-neoxanthin would be the precursor of ABA in photosynthetic tissues.

  10. Protein trafficking and maturation regulate intramembrane proteolysis.

    Science.gov (United States)

    Morohashi, Yuichi; Tomita, Taisuke

    2013-12-01

    Intramembrane-cleaving proteases (I-CLiPs) are membrane embedded proteolytic enzymes. All substrates identified so far are also membrane proteins, involving a number of critical cellular signaling as well as human diseases. After synthesis and assembly at the endoplasmic reticulum, membrane proteins are exported to the Golgi apparatus and transported to their sites of action. A number of studies have revealed the importance of the intracellular membrane trafficking in i-CLiP-mediated intramembrane proteolysis, not only for limiting the unnecessary encounter between i-CLiPs and their substrate but also for their cleavage site preference. In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. A dynamic interplay between phytohormones is required for fruit development, maturation and ripening

    Directory of Open Access Journals (Sweden)

    Peter eMcAtee

    2013-04-01

    Full Text Available Plant species that bear fruit often utilise expansion of an ovary (carpel or accessory tissue as a vehicle for seed dispersal. While the seed(s develop, the tissue(s of the fruit follow a common progression of cell division and cell expansion, promoting growth of the fruit. Once the seed is fully developed, the fruit matures and the surrounding tissue either dries or ripens promoting the dissemination of the seed. As with many developmental processes in plants, plant hormones play an important role in the synchronisation of signals between the developing seed and its surrounding fruit tissue(s, regulating each phase of fruit development. Following pollination, fruit set is achieved through a de-repression of growth and an activation of cell division via the action of auxin and/or cytokinin and/or gibberellin. Following fruit set, growth of the fruit is facilitated through a relatively poorly studied period of cell expansion and endoreduplication that is likely regulated by similar hormones as in fruit set. Once the seeds reach maturity, fruit become ready to undergo ripening and during this period there is a major switch in relative hormone levels of the fruit, involving an overall decrease in auxin, gibberellin and cytokinin and a simultaneous increase in abscisic acid and ethylene. While the role of hormones in fruit set and ripening is well documented, the knowledge of the roles of other hormones during growth, maturation and some individual ripening components is sketchy.

  12. iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions

    OpenAIRE

    Wu, Jinhong; Yang, Jialong; Yang, Kai; Wang, Hongxia; Gorentla, Balachandra; Shin, Jinwook; Qiu, Yurong; Que, Loretta G.; Foster, W. Michael; Xia, Zhenwei; Chi, Hongbo; Zhong, Xiao-Ping

    2014-01-01

    Terminal maturation of invariant NKT (iNKT) cells from stage 2 (CD44+NK1.1–) to stage 3 (CD44+NK1.1+) is accompanied by a functional acquisition of a predominant IFN-γ–producing (iNKT-1) phenotype; however, some cells develop into IL-17–producing iNKT (iNKT-17) cells. iNKT-17 cells are rare and restricted to a CD44+NK1.1– lineage. It is unclear how iNKT terminal maturation is regulated and what factors mediate the predominance of iNKT-1 compared with iNKT-17. The tumor suppressor tuberous scl...

  13. Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi

    2016-01-01

    Recent advancements in set theory and readily available software have enabled social science researchers to bridge the variable-centered quantitative and case-based qualitative methodological paradigms in order to analyze multi-dimensional associations beyond the linearity assumptions, aggregate...... effects, unicausal reduction, and case specificity. Based on the developments in set theoretical thinking in social sciences and employing methods like Qualitative Comparative Analysis (QCA), Necessary Condition Analysis (NCA), and set visualization techniques, in this position paper, we propose...... and demonstrate a new approach to maturity models in the domain of Information Systems. This position paper describes the set-theoretical approach to maturity models, presents current results and outlines future research work....

  14. Seed maturation in Arabidopsis thaliana is characterized by nuclear size reduction and increased chromatin condensation.

    Science.gov (United States)

    van Zanten, Martijn; Koini, Maria A; Geyer, Regina; Liu, Yongxiu; Brambilla, Vittoria; Bartels, Dorothea; Koornneef, Maarten; Fransz, Paul; Soppe, Wim J J

    2011-12-13

    Most plant species rely on seeds for their dispersal and survival under unfavorable environmental conditions. Seeds are characterized by their low moisture content and significantly reduced metabolic activities. During the maturation phase, seeds accumulate storage reserves and become desiccation-tolerant and dormant. Growth is resumed after release of dormancy and the occurrence of favorable environmental conditions. Here we show that embryonic cotyledon nuclei of Arabidopsis thaliana seeds have a significantly reduced nuclear size, which is established at the beginning of seed maturation. In addition, the chromatin of embryonic cotyledon nuclei from mature seeds is highly condensed. Nuclei regain their size and chromatin condensation level during germination. The reduction in nuclear size is controlled by the seed maturation regulator ABSCISIC ACID-INSENSITIVE 3, and the increase during germination requires two predicted nuclear matrix proteins, LITTLE NUCLEI 1 and LITTLE NUCLEI 2. Our results suggest that the specific properties of nuclei in ripe seeds are an adaptation to desiccation, independent of dormancy. We conclude that the changes in nuclear size and chromatin condensation in seeds are independent, developmentally controlled processes.

  15. Effects of polysaccharides from Pholiota nameko on maturation of murine bone marrow-derived dendritic cells.

    Science.gov (United States)

    Li, Haiping; Liu, Lizeng; Tao, Yongqing; Zhao, Pei; Wang, Fengling; Huai, Lihua; Zhi, Dexian; Liu, Jiangmei; Li, Guoliang; Dang, Chunlan; Xu, Yufeng

    2014-02-01

    This paper studied some structure characters of the Pholiota nameko polysaccharides (PNPS-1), including morphology under SEM and AFM, also the effects of PNPS-1 on the maturation of bone marrow dendritic cells (BMDCs) via concrete changes both inside and outside BMDCs. These impacts on BMDCs were assessed with use of inverted phase contrast microscope for morphology, flow cytometry for key surface molecules, mixed lymphocyte reaction (MLR) for allogeneic T cells proliferation, and bio-assay and enzyme linked immunosorbent assay (ELISA) for cytokine production. We found that PNPS-1 could inhibit phenotypic maturation as evidenced by decreasing expression of CD11c, CD40, CD80, CD83, CD86, and I-A/I-E. Functional maturation inhibition was further confirmed by decreased naive T cell stimulatory activity of BMDCs. Finally, PNPS-1 also stimulated production of more cytokine IL-10 and less IL-12 and TNF-α. These data indicated that PNPS-1 could markedly inhibit the maturation of BMDCs and had potential significant down-regulation immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Naturally Engineered Maturation of Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gaetano J. Scuderi

    2017-05-01

    Full Text Available Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte

  17. Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells.

    Directory of Open Access Journals (Sweden)

    Adam G Grieve

    Full Text Available Mutations in the inositol polyphosphate 5-phosphatase OCRL1 cause Lowe Syndrome, leading to cataracts, mental retardation and renal failure. We noted that cell types affected in Lowe Syndrome are highly polarized, and therefore we studied OCRL1 in epithelial cells as they mature from isolated individual cells into polarized sheets and cysts with extensive communication between neighbouring cells. We show that a proportion of OCRL1 targets intercellular junctions at the early stages of their formation, co-localizing both with adherens junctional components and with tight junctional components. Correlating with this distribution, OCRL1 forms complexes with junctional components α-catenin and zonula occludens (ZO-1/2/3. Depletion of OCRL1 in epithelial cells growing as a sheet inhibits maturation; cells remain flat, fail to polarize apical markers and also show reduced proliferation. The effect on shape is reverted by re-expressed OCRL1 and requires the 5'-phosphatase domain, indicating that down-regulation of 5-phosphorylated inositides is necessary for epithelial development. The effect of OCRL1 in epithelial maturation is seen more strongly in 3-dimensional cultures, where epithelial cells lacking OCRL1 not only fail to form a central lumen, but also do not have the correct intracellular distribution of ZO-1, suggesting that OCRL1 functions early in the maturation of intercellular junctions when cells grow as cysts. A role of OCRL1 in junctions of polarized cells may explain the pattern of organs affected in Lowe Syndrome.

  18. Effect of gonadotropins on oocyte maturation in vitro: an animal model.

    Science.gov (United States)

    Sha, Wei; Xu, Bao-Zeng; Li, Mo; Liu, Di; Feng, Huai L; Sun, Qing-Yuan

    2010-03-15

    Analysis of the effects of human-derived gonadotropin drugs, FSH and LH (Repronex) and hCG (Novarel), on oocyte maturation, using a porcine oocyte in vitro maturation system as a culture model. Randomized research experimental study. Academic basic research laboratory. Prepubertal gilts that were slaughtered in the local slaughter house. Oocytes will be exposed to immunofluorescent staining and confocal laser scanning microscopy: Western blot analysis on cumulus-oocyte-complexes following treatment with different concentrations of the gonadotropin drugs Repronex, Novarel, and a Repronex and Novarel combination. Analysis of porcine oocyte spindle and chromosomal configuration with alpha-tubulin-fluorescein isothiocyanate antibody and propidium iodide staining. Porcine oocyte mitochondrial distribution and aggregation pattern staining was assessed with Mito Tracker Red CMXRox probe. Porcine oocyte cortical granule distribution was observed via peanut agglutinin-fluorescein isothiocyannate staining; Western blot analysis detected extra-cellular signal-regulated kinase 1/2 activation in cumulus cells. An increase of gonadotropin concentration in the culture medium resulted in an increase in the following: the percentage of oocytes reaching metaphase II, normal configuration of the spindle, normal chromosomal alignment, cortical granule migration, and mitochondrial aggregation. Levels of nuclear and cytoplasmic maturation peaked as the concentration of gonadotropins approached its threshold level. Addition of a threshold concentration of the gonadotropin drugs Repronex, Novarel, and a combination of the two can significantly improve porcine oocyte maturation in vitro. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Regulation of two loblolly pine (Pinus taeda L.) isocitrate lyase genes in megagametophytes of mature and stratified seeds and during postgerminative growth.

    Science.gov (United States)

    Mullen, R T; Gifford, D J

    1997-03-01

    Two full-length cDNAs encoding the glyoxysomal enzyme isocitrate lyase (ICL) were isolated from a lambda ZAP cDNA library prepared from megagametophyte mRNAs extracted from seeds imbibed at 30 degrees C for 8 days. The cDNAs, designated Ptbs ICL 8 and Ptbs ICL 12, have open reading frames of 1740 and 1719 bp, with deduced amino acid sequences of 580 and 573 residues, respectively. The predicted amino acid sequences of Ptbs ICL 8 and Ptbs ICL 12 exhibit a 79% identity with each other, and have a greater than 75% identity with ICLs from various angiosperm species. The C-termini of Ptbs ICL 8 and Ptbs ICL 12 terminate with the tripeptide Ser-Arg-Met and Ala-Arg-Met, respectively, both being conserved variants of the type 1 peroxisomal targeting signal. RNA blot and slot analysis revealed that Ptbs ICL 8 and Ptbs ICL 12 mRNAs were present at low levels in the megagametophyte of the mature and stratified seeds, and that the level of both transcripts increased markedly upon seed germination. Protein blot analysis indicated that the steady-state level of ICL was low in the mature and stratified seed, then increased rapidly upon seed germination, peaking at around 8-10 days after imbibition (DAI). Changes in the level of ICL activity in cell-free extracts was similar to the steady-state protein content with the exception that ICL activity was not detected in megagametophyte extracts of mature or stratified seeds. From 10-12 DAI when the megagametophyte tissue senesced, ICL activity decreased rapidly to near undetectable levels. In contrast, steady-state levels of ICL protein and mRNA remained relatively constant during megagametophyte senescence. In vivo synthesis of ICL protein was measured to shed light on these differences. ICL immunoselected from [(35)S]-methionine labelled proteins indicated that ICL was synthesized at very low levels during megagametophyte senescence. Together, the results show that loblolly pine ICL gene expression is complex. While temporal

  20. Sensitive periods in affective development: nonlinear maturation of fear learning.

    Science.gov (United States)

    Hartley, Catherine A; Lee, Francis S

    2015-01-01

    At specific maturational stages, neural circuits enter sensitive periods of heightened plasticity, during which the development of both brain and behavior are highly receptive to particular experiential information. A relatively advanced understanding of the regulatory mechanisms governing the initiation, closure, and reinstatement of sensitive period plasticity has emerged from extensive research examining the development of the visual system. In this article, we discuss a large body of work characterizing the pronounced nonlinear changes in fear learning and extinction that occur from childhood through adulthood, and their underlying neural substrates. We draw upon the model of sensitive period regulation within the visual system, and present burgeoning evidence suggesting that parallel mechanisms may regulate the qualitative changes in fear learning across development.

  1. Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.

    Science.gov (United States)

    Shukunami, Chisa; Takimoto, Aki; Nishizaki, Yuriko; Yoshimoto, Yuki; Tanaka, Seima; Miura, Shigenori; Watanabe, Hitomi; Sakuma, Tetsushi; Yamamoto, Takashi; Kondoh, Gen; Hiraki, Yuji

    2018-02-16

    Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5'-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (-1030 to -295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5'-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.

  2. Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

    Science.gov (United States)

    Lin, Zi-Li; Kim, Nam-Hyung

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. © 2015 International Federation for Cell Biology.

  3. 7 CFR 51.1904 - Maturity classification.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Maturity classification. 51.1904 Section 51.1904... STANDARDS) United States Consumer Standards for Fresh Tomatoes Size and Maturity Classification § 51.1904 Maturity classification. Tomatoes which are characteristically red when ripe, but are not overripe or soft...

  4. A genome-wide RNAi screen to dissect centriole duplication and centrosome maturation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jeroen Dobbelaere

    2008-09-01

    Full Text Available Centrosomes comprise a pair of centrioles surrounded by an amorphous pericentriolar material (PCM. Here, we have performed a microscopy-based genome-wide RNA interference (RNAi screen in Drosophila cells to identify proteins required for centriole duplication and mitotic PCM recruitment. We analysed 92% of the Drosophila genome (13,059 genes and identified 32 genes involved in centrosome function. An extensive series of secondary screens classified these genes into four categories: (1 nine are required for centriole duplication, (2 11 are required for centrosome maturation, (3 nine are required for both functions, and (4 three genes regulate centrosome separation. These 32 hits include several new centrosomal components, some of which have human homologs. In addition, we find that the individual depletion of only two proteins, Polo and Centrosomin (Cnn can completely block centrosome maturation. Cnn is phosphorylated during mitosis in a Polo-dependent manner, suggesting that the Polo-dependent phosphorylation of Cnn initiates centrosome maturation in flies.

  5. Cervical vertebral maturation as a biologic indicator of skeletal maturity.

    Science.gov (United States)

    Santiago, Rodrigo César; de Miranda Costa, Luiz Felipe; Vitral, Robert Willer Farinazzo; Fraga, Marcelo Reis; Bolognese, Ana Maria; Maia, Lucianne Cople

    2012-11-01

    To identify and review the literature regarding the reliability of cervical vertebrae maturation (CVM) staging to predict the pubertal spurt. The selection criteria included cross-sectional and longitudinal descriptive studies in humans that evaluated qualitatively or quantitatively the accuracy and reproducibility of the CVM method on lateral cephalometric radiographs, as well as the correlation with a standard method established by hand-wrist radiographs. The searches retrieved 343 unique citations. Twenty-three studies met the inclusion criteria. Six articles had moderate to high scores, while 17 of 23 had low scores. Analysis also showed a moderate to high statistically significant correlation between CVM and hand-wrist maturation methods. There was a moderate to high reproducibility of the CVM method, and only one specific study investigated the accuracy of the CVM index in detecting peak pubertal growth. This systematic review has shown that the studies on CVM method for radiographic assessment of skeletal maturation stages suffer from serious methodological failures. Better-designed studies with adequate accuracy, reproducibility, and correlation analysis, including studies with appropriate sensitivity-specificity analysis, should be performed.

  6. Correlation between chronological age, cervical vertebral maturation and Fishman's skeletal maturity indicators in southern Chinese.

    Science.gov (United States)

    Alkhal, Hessa Abdulla; Wong, Ricky W K; Rabie, A Bakr M

    2008-07-01

    To investigate the correlation between chronological age, cervical vertebral maturation (CVM), and Fishman's hand-wrist skeletal maturity indicators in southern Chinese. Four hundred contemporary hand-wrist and lateral cephalometric radiographs of southern Chinese subjects were randomly selected and analyzed. The female subjects were between 10 and 15 years of age, and the male subjects were between 12 and 17 years of age; all subjects were within the circumpubertal period. The CVM was assessed using the method developed by Baccetti and coworkers, but the hand-wrist maturation was assessed using the method developed by Fishman. These two methods and the chronological age were correlated using the Spearman rank correlation analysis. The CVM was significantly correlated with the hand-wrist skeletal age (Spearman r male = 0.9206, female = 0.9363). All patients in the cervical maturation stage (CS3) of CVM were discovered to be in the skeletal maturational indicator (SMI2 or SMI3) stages of hand-wrist maturation (HWM), which was around the peak of the growth spurt. Low correlations were found between the CVM and chronological age (male r = 0.7577; female r = 0.7877) and between the HWM and chronological age (male r = 0.7492; female r = 0.7758). CVM is a valid indicator of skeletal growth during the circumpubertal and has a high correlation with the HWM for the southern Chinese population. However, the low correlations found between the chronological age and both CVM and HWM showed that the chronological age was not suitable to measure skeletal maturity.

  7. Set-Theoretic Approach to Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan

    Despite being widely accepted and applied, maturity models in Information Systems (IS) have been criticized for the lack of theoretical grounding, methodological rigor, empirical validations, and ignorance of multiple and non-linear paths to maturity. This PhD thesis focuses on addressing...... these criticisms by incorporating recent developments in configuration theory, in particular application of set-theoretic approaches. The aim is to show the potential of employing a set-theoretic approach for maturity model research and empirically demonstrating equifinal paths to maturity. Specifically...... methodological guidelines consisting of detailed procedures to systematically apply set theoretic approaches for maturity model research and provides demonstrations of it application on three datasets. The thesis is a collection of six research papers that are written in a sequential manner. The first paper...

  8. Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

    Directory of Open Access Journals (Sweden)

    Shu-Wu Xie

    2016-05-01

    Full Text Available Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39, which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

  9. STUDY OF EMOTIONAL MATURITY OF STUDENTS FROM THE PEDAGOGICAL HIGH SCHOOL

    Directory of Open Access Journals (Sweden)

    T. L. Shabanova

    2018-01-01

    Full Text Available Introduction. The article analyzes the phenomenon of emotional maturity from the position of various psychological approaches (psychoanalytic, existential, humanistic, cognitive, cultural-historical. It is emphasized that the problem of studying emotional maturity, its structure, mechanisms, conditions of formation, especially in the context of growing young people and preparing for the implementation of specific professional activities, remains the subject of scientific discussions and is not fully understood by domestic and foreign psychologists.Materials and Methods. The results of our own research in the period 2015-2017 are described. on the sample of students of three faculties of the pedagogical university (Mininsky University (the volume of 157 people of the indicators of emotional maturity in accordance with the presented author's model, which includes the following components: emotional value orientation, cognitive reactions and emotional cognition, affective reactions, emotional self-regulation of behavior.Results. The system of mechanisms of fastening and manifestation of emotions at different levels of the personality structure characterizing the opposite variants of emotional development of students is described: crisis and mature. A significant percentage of the young people surveyed (44, 6 with a crisis type of emotional development was revealed. These subjects have significantly higher rates of personal anxiety and accompanying experiences of fear, shame and guilt, a less developed ability to emotionally cognize and control their emotions, dominate strategies to avoid difficulties and problems, as well as aggressive behavior towards others in stressful situations.Discussion and Conclusions. The obtained results testify to the need for special psychological work with students-future teachers in the framework of training. First of all, it is necessary to pay attention to the formation of work skills with their own experiences, the

  10. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. ANALISIS TINGKAT KEMATANGAN (MATURITY LEVELS UNIT LAYANAN PENGADAAN KABUPATEN BADUNG

    Directory of Open Access Journals (Sweden)

    I Gde Uma Darmapramita

    2015-07-01

    Full Text Available The implementation of government procurement of goods and service is governed by presidential regulation number 70 year of 2012.  According to that, in Badung Regency implemented centralized in Procurement Service Unit of Badung Regency. As the one of Indonesia procurement unit pilot, Procurement Service Unit of Badung Regency has given the opportunity to perform a self assessment of its  maturity levels as government unit. The objective of this research is to find factors that influence Procuremet Service Unit of Badung Regency maturity levels, and also to find out in what level is Procurement Service Unit of Badung Regency stand. Data collection for this research have done by  using questionnaire that involve 50 respondents who understand very well about the duties and function of Procurement Service Unit of Badung Regency to perform a government procurement of good and services. The data analysis have been performed by use of factor analysis and supported by SPSS program. The result shows there are 3 factors that influent the Procurement Service Unit of Badung Regency maturity levels, which are : the synergy and organization culture, resources and risk management and organization’s performance development.  Whereas the maturity levels of Procurement Service Unit of Badung Regency is stand at compliance. Based to the factors that formed, the highly commitment and strong leadership of Badung Regency leader are very decisive to push ahead the enhancement  and  the development of Procurement Service Unit of Badung Regency.  First thing can be done is to establish an independent Procurement Service Unit therewith its Procurement Unit Development road maps that can be tiered and sustainable plan, monitor and evaluate

  12. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  13. Sex Ratio And Size At First Maturity Of Blue Swimming Crab (Portunus pelagicus Salemo Island Pangkep Regency

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    Muh. Saleh Nurdin

    2016-03-01

    Full Text Available Blue swimming crab (Portunuspelagicus is aeconomical valuable fisheries importantcommodity  due to the high demand and availability jobs created for the fishermen. Due to their high demand blue swimming crab heavily exploited from Salemo Island. This study aimed at comparing the sex ratio and the size at first maturity of blue swimming crab caught in mangrove ecosystems, coral reefs, and seagrass. Sex ratio was analyzed using chi square test and the size at first maturity was analyzed using the Spearman-Karber formula. The results showed the sex ratio ofmales and femalessmall crab caught in every ecosystem is balanced. The size at first maturity of blue swimming crab caught in mangrove, seagrass and coral reefs, each to the male 81,08 mm, 102,36 mm and 102,87 mm in width and size of female 94,54 mm, 83,35 mm, 98,31 mm width. In a reference to government regulations, the blue male swimming crab caught in the coral reef and seagrass ecosystems have yet to size at first maturity is allowed to be captured. Keywords: blue swimming crab, sex ratio,size at first maturity, Salemo Island

  14. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  15. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  16. Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function.

    Science.gov (United States)

    Wang, Bin; Wang, Yujie; Frabutt, Dylan A; Zhang, Xihe; Yao, Xiaoyu; Hu, Dan; Zhang, Zhuo; Liu, Chaonan; Zheng, Shimin; Xiang, Shi-Hua; Zheng, Yong-Hui

    2017-04-07

    The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP 1 and the fusion-mediating GP 2 subunits and incorporated into virions to initiate infection. GP 1 and GP 2 form heterodimers that have 15 or two N -glycosylation sites (NGSs), respectively. Here we investigated the mechanism of how N -glycosylation contributes to GP expression, maturation, and function. As reported before, we found that, although GP 1 NGSs are not critical, the two GP 2 NGSs, Asn 563 and Asn 618 , are essential for GP function. Further analysis uncovered that Asn 563 and Asn 618 regulate GP processing, demannosylation, oligomerization, and conformation. Consequently, these two NGSs are required for GP incorporation into EBOV-like particles and HIV type 1 (HIV-1) pseudovirions and determine viral transduction efficiency. Using CRISPR/Cas9 technology, we knocked out the two classical endoplasmic reticulum chaperones calnexin (CNX) and/or calreticulin (CRT) and found that both CNX and CRT increase GP expression. Nevertheless, NGSs are not required for the GP interaction with CNX or CRT. Together, we conclude that, although Asn 563 and Asn 618 are not required for EBOV GP expression, they synergistically regulate its maturation, which determines its functionality. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Actin cytoskeleton modulates calcium signaling during maturation of starfish oocytes.

    Science.gov (United States)

    Kyozuka, Keiichiro; Chun, Jong T; Puppo, Agostina; Gragnaniello, Gianni; Garante, Ezio; Santella, Luigia

    2008-08-15

    Before successful fertilization can occur, oocytes must undergo meiotic maturation. In starfish, this can be achieved in vitro by applying 1-methyladenine (1-MA). The immediate response to 1-MA is the fast Ca2+ release in the cell cortex. Here, we show that this Ca2+ wave always initiates in the vegetal hemisphere and propagates through the cortex, which is the space immediately under the plasma membrane. We have observed that alteration of the cortical actin cytoskeleton by latrunculin-A and jasplakinolide can potently affect the Ca2+ waves triggered by 1-MA. This indicates that the cortical actin cytoskeleton modulates Ca2+ release during meiotic maturation. The Ca2+ wave was inhibited by the classical antagonists of the InsP(3)-linked Ca2+ signaling pathway, U73122 and heparin. To our surprise, however, these two inhibitors induced remarkable actin hyper-polymerization in the cell cortex, suggesting that their inhibitory effect on Ca2+ release may be attributed to the perturbation of the cortical actin cytoskeleton. In post-meiotic eggs, U73122 and jasplakinolide blocked the elevation of the vitelline layer by uncaged InsP(3), despite the massive release of Ca2+, implying that exocytosis of the cortical granules requires not only a Ca2+ rise, but also regulation of the cortical actin cytoskeleton. Our results suggest that the cortical actin cytoskeleton of starfish oocytes plays critical roles both in generating Ca2+ signals and in regulating cortical granule exocytosis.

  18. Spatial accumulation pattern of citrulline and other nutrients in immature and mature watermelon fruits.

    Science.gov (United States)

    Akashi, Kinya; Mifune, Yuki; Morita, Kaori; Ishitsuka, Souichi; Tsujimoto, Hisashi; Ishihara, Toshiyuki

    2017-01-01

    Watermelon (Citrullus lanatus L.) originates from arid regions of southern Africa, and its fruit contains a large amount of the amino acid citrulline, an efficient hydroxyl radical scavenger. Citrulline is implicated in the production of nitric oxide in human endothelium, and potential health benefits including vasodilatation and antioxidant functions have been suggested. However, citrulline metabolism in watermelon fruits is poorly understood. This study examined the accumulation pattern of citrulline and other nutrients in immature and mature watermelon fruits. In mature fruits, highest citrulline concentration was observed in the outer peel, followed by the central portion of the flesh and inner rinds, whereas the level was lower in the peripheral portion of the flesh. Citrulline content was generally low in immature fruits. Spatial and developmental patterns of citrulline accumulation were largely different from those of the antioxidant lycopene, total proteins, and soluble sugars such as glucose, fructose, and sucrose. Principal component analysis suggested a clear distinction of the central flesh and outer peels in mature fruits from other tissues in terms of the levels of major nutrients. These observations suggested that citrulline accumulation may be regulated in a distinct manner from other nutrients during watermelon fruit maturation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  19. Thinning of the lateral prefrontal cortex during adolescence predicts emotion regulation in females.

    Science.gov (United States)

    Vijayakumar, Nandita; Whittle, Sarah; Yücel, Murat; Dennison, Meg; Simmons, Julian; Allen, Nicholas B

    2014-11-01

    Adolescence is a crucial period for the development of adaptive emotion regulation strategies. Despite the fact that structural maturation of the prefrontal cortex during adolescence is often assumed to underlie the maturation of emotion regulation strategies, no longitudinal studies have directly assessed this relationship. This study examined whether use of cognitive reappraisal strategies during late adolescence was predicted by (i) absolute prefrontal cortical thickness during early adolescence and (ii) structural maturation of the prefrontal cortex between early and mid-adolescence. Ninety-two adolescents underwent baseline and follow-up magnetic resonance imaging scans when they were aged approximately 12 and 16 years, respectively. FreeSurfer software was used to obtain cortical thickness estimates for three prefrontal regions [anterior cingulate cortex; dorsolateral prefrontal cortex (dlPFC); ventrolateral prefrontal cortex (vlPFC)]. The Emotion Regulation Questionnaire was completed when adolescents were aged approximately 19 years. Results showed that greater cortical thinning of the left dlPFC and left vlPFC during adolescence was significantly associated with greater use of cognitive reappraisal in females, though no such relationship was evident in males. Furthermore, baseline left dlPFC thickness predicted cognitive reappraisal at trend level. These findings suggest that cortical maturation may play a role in the development of adaptive emotion regulation strategies during adolescence. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

    Science.gov (United States)

    Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

    2016-01-01

    Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International

  1. Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway.

    Science.gov (United States)

    Kim, Tae Sung; Shin, Yern-Hyerk; Lee, Hye-Mi; Kim, Jin Kyung; Choe, Jin Ho; Jang, Ji-Chan; Um, Soohyun; Jin, Hyo Sun; Komatsu, Masaaki; Cha, Guang-Ho; Chae, Han-Jung; Oh, Dong-Chan; Jo, Eun-Kyeong

    2017-06-13

    The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster-Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.

  2. Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

    Science.gov (United States)

    Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T.; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R.; Schenk, Mirjam; Sieling, Peter A.; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S.; Bruns, Heiko; Lewinsohn, David M.; Hollis, Bruce W.; Hewison, Martin; Adams, John S.; Steinmeyer, Andreas; Zügel, Ulrich; Cheng, Genhong; Jo, Eun-Kyeong; Bloom, Barry R.; Modlin, Robert L.

    2012-01-01

    Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection. PMID:21998409

  3. Whose Maturity is it Anyway?

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi; Mukkamala, Raghava Rao

    2017-01-01

    This paper presents results from an ongoing empirical study that seeks to understand the influence of different quantitative methods on the design and assessment of maturity models. Although there have been many academic publications on maturity models, there exists a significant lack of understa...

  4. Maturity of the PWR

    International Nuclear Information System (INIS)

    Bacher, P.; Rapin, M.; Aboudarham, L.; Bitsch, D.

    1983-03-01

    Figures illustrating the predominant position of the PWR system are presented. The question is whether on the basis of these figures the PWR can be considered to have reached maturity. The following analysis, based on the French program experience, is an attempt to pinpoint those areas in which industrial maturity of the PWR has been attained, and in which areas a certain evolution can still be expected to take place

  5. Sexual maturation and changes in water and salt transport components in the kidney and intestine of three-spined stickleback (Gasterosteus aculeatus L.).

    Science.gov (United States)

    Madsen, Steffen S; Weber, Claus; Nielsen, Andreas M; Mohiseni, Mohammad; Bosssus, Maryline C; Tipsmark, Christian K; Borg, Bertil

    2015-10-01

    Mature three-spined stickleback males use spiggin threads secreted from their kidney to glue together nest material. This requires strongly hypertrophied renal proximal tubular cells, which compromises renal osmoregulatory function during the breeding period. Experimental evidence suggests that the intestine takes over hypotonic fluid secretion at that stage but the mechanism is unexplored. To unravel the molecular mechanism we analyzed and compared transcript levels of several membrane proteins involved in water and salt transport in intestinal and renal tissues, in non-mature males (NM), mature males (MM), and mature females (MF). Aquaporin paralogs aqp1a, -3a, -8aa, -8ab, -10a, and -10b, two Na(+),K(+)-ATPase alpha-1 subunit isoforms (nka547, nka976), Na(+),K(+),2Cl(-)-, and Na(+),Cl(-)-cotransporters (nkcc1a, nkcc2, ncc), the cystic fibrosis transmembrane conductance regulator (cftr) and two claudin isoforms (cldn2, cldn15a) were expressed in the intestine and kidney in all groups. There were no differences in aqp and cldn expression between intestines of NM and MM; nkcc2 was lower and nka levels tended to be higher in intestines of MM than in NM. In the kidney, aqp1 and aqp8ab levels were lower in MM than in NM, whereas aqp3a, nkcc1a, cldn15a, and spiggin were markedly elevated. This was accompanied by marked hypertrophy of kidney tubules in MM. The data support an altered kidney function in terms of water handling in mature males, whereas there was no support for modified trans-epithelial water permeability or salt-secretory activity in the intestine of mature males. Salt-absorptive activity in the intestine may, however, be down-regulated during male maturation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Intra-follicular interactions affecting mammalian oocyte maturation

    NARCIS (Netherlands)

    van Tol, H.T.A.|info:eu-repo/dai/nl/313871817

    2009-01-01

    Nuclear oocyte maturation is defined as reinitiation and progression of the first meiotic division and subsequently formation of the methaphase II (MII) plate. Concomitantly with nuclear maturation, cytoplasmic maturation which is essential for proper fertilization and early embryo development is

  7. Growth indicators in orthodontic patients. Part 1: comparison of cervical vertebral maturation and hand-wrist skeletal maturation.

    Science.gov (United States)

    Litsas, G; Ari-Demirkaya, A

    2010-12-01

    The purpose of this study was to predict the skeletal maturation status based on the assessment of cervical vertebrae from lateral cephalometric radiographs and to compare these findings with the skeletal maturity of the same individuals judged from the hand-wrist radiographs. Lateral cephalometric and left hand-wrist radiographs of 393 Caucasian children from 8 to 18 years old were evaluated. On the hand-wrist radiographs the classification of Bjork [1972] and Grave and Brown [1976] was used to assess skeletal maturity (HWSS). Cervical vertebral maturation was also evaluated on lateral cephalometric radiographs using the improved CVMS method described by Baccetti, Franchi, and McNamara [2002]. These methods were correlated using the chi-square test. The chi-square test showed that skeletal maturational values obtained by the CVMS method were significantly correlated with the skeletal values obtained from the hand-wrist analysis for both genders (pmaturity.

  8. Circadian rhythms regulate amelogenesis.

    Science.gov (United States)

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-07-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Maturity acceleration of Italian dried sausage by Staphylococcus carnosus - Relationship between maturity and flavor compounds

    DEFF Research Database (Denmark)

    Stahnke, Louise Heller; Holck, A.; Jensen, Anni

    2002-01-01

    . Sausages with S. carnosus 833 matured more than 2 wk faster than control sausages. Maturity correlated significantly with higher amounts of branched-chain aldehydes and alcohols and both branched- and straight-chain methyl ketones-compounds arising from the breakdown of the amino acids leucine, isoleucine...

  10. A PACS maturity model: a systematic meta-analytic review on maturation and evolvability of PACS in the hospital enterprise.

    NARCIS (Netherlands)

    Wetering, R. van de; Batenburg, R.

    2009-01-01

    INTRODUCTION: With PACS and medical imaging technology maturing, the importance of organizational maturity and effective deployment of PACS in the hospital enterprise are becoming significant. OBJECTIVE: The objective of this paper is twofold. Firstly, PACS literature on maturity and evolvability in

  11. PROJECT MANAGEMENT MATURITY: AN ASSESSMENT OF MATURITY FOR DEVELOPING PILOT PLANTS

    Directory of Open Access Journals (Sweden)

    H.K. Mittermaier

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: Despite the current economic climate, the South African mining and engineering industry is experiencing a very promising future, with a large number of capital projects in the offing. It is inevitable that pilot plant development will form part of this future as a risk mitigation technique. This study found that, even though the terms ‘pilot plant’ and ‘project management maturity’ are familiar within the industry, no link between these two could be found in the literature. A number of maturity models exist; and one developed by PMSolutions was selected to perform an assessment of the current level of project management maturity within the South African mining and engineering industry pertaining to the development of pilot plants. The Delphi technique was used to determine the views of experts in the South African mining, mineral processing, petrochemical, nuclear, and mechanical sectors regarding this maturity. A significant difference was observed between the current level of maturity and the required level of maturity in all but one of the nine knowledge areas defined by the Project Management Institute. The two knowledge areas of project time and risk management showed significant differences between current and required maturity levels, and were identified as key areas for improvement.

    AFRIKAANSE OPSOMMING: Ten spyte van die huidige ekonomiese klimaat ondervind die Suid-Afrikaanse mynbou- en ingenieursbedryf ’n baie bemoedigende toekoms, met ’n groot aantal kapitaalprojekte in die vooruitsig. Ten einde risiko’s te verlaag, sal die ontwikkeling van loodsaanlegte noodwendig deel van hierdie toekoms uitmaak. Daar is gevind dat, alhoewel die terme ‘loodsaanleg’ en ‘projekbestuur volwassenheid’ in die nywerheid bekend is, geen skakeling van hierdie twee terme in die literatuur opgespoor kon word nie. ’n Aantal volwassenheid modelle bestaan; en een wat deur PMSolutions ontwikkel is, is gekies om

  12. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    Science.gov (United States)

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  13. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  14. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: Cross talk between MAPK signalling pathways

    International Nuclear Information System (INIS)

    Trompezinski, Sandra; Migdal, Camille; Tailhardat, Magalie; Le Varlet, Beatrice; Courtellemont, Pascal; Haftek, Marek; Serres, Mireille

    2008-01-01

    Dendritic cells (DCs), efficient-antigen presenting cells play an important role in initiating and regulating immune responses. DC maturation following exposure to nickel or DNCB induced an up-regulation of phenotypic markers and inflammatory cytokine secretion. Early intracellular mechanisms involved in DC maturation required to be precise. To address this purpose, DCs derived from human monocytes were treated with sensitizers (nickel, DNCB or thimerosal) in comparison with an irritant (SDS). Our data confirming the up-regulation of CD86, CD54 and cytokine secretion (IL-8 and TNFα) induced by sensitizers but not by SDS, signalling transduction involved in DC maturation was investigated using these chemicals. Kinase activity measurement was assessed using two new sensitive procedures (Face TM and CBA) requiring few cells. SDS did not induce changes in signalling pathways whereas NiSO 4 , DNCB and thimerosal markedly activated p38 MAPK and JNK, in contrast Erk1/2 phosphorylation was completely inhibited by DNCB or thimerosal and only activated by nickel. A pre-treatment with p38 MAPK inhibitor (SB203580) suppressed Erk1/2 inhibition induced by DNCB or thimerosal demonstrating a direct interaction between p38 MAPK and Erk1/2. A pre-treatment with an antioxidant, N-acetyl-L-cysteine (NAC) markedly reduced Erk1/2 inhibition and p38 MAPK phosphorylation induced by DNCB and thimerosal, suggesting a direct activation of p38 MAPK via an oxidative stress and a regulation of MAPK signalling pathways depending on chemicals. Because of a high sensitivity of kinase activity measurements, these procedures will be suitable for weak or moderate sensitizer screening

  15. Assessment of skeletal maturation using mandibular second molar maturation stages.

    Science.gov (United States)

    Goyal, S; Goyal, S; Gugnani, N

    2014-01-01

    To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.

  16. A Set Theoretical Approach to Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester; Vatrapu, Ravi; Andersen, Kim Normann

    2016-01-01

    characterized by equifinality, multiple conjunctural causation, and case diversity. We prescribe methodological guidelines consisting of a six-step procedure to systematically apply set theoretic methods to conceptualize, develop, and empirically derive maturity models and provide a demonstration......Maturity Model research in IS has been criticized for the lack of theoretical grounding, methodological rigor, empirical validations, and ignorance of multiple and non-linear paths to maturity. To address these criticisms, this paper proposes a novel set-theoretical approach to maturity models...

  17. RNAi Screen in Drosophila melanogastor Identifies Regulators of Steroidogenesis and Developmental Maturation

    DEFF Research Database (Denmark)

    Danielsen, Erik Thomas

    and duration required for juvenile-adult transition. This PhD project demonstrates the power of Drosophila genetics by taking an in vivo genome-wide RNAi screening approach to uncover genes required for the function of steroid producing tissue and developmental maturation. In total, 1909 genes were found...... to be required for the prothoracic gland function and affected the developmental timing for the juvenile-adult transition. Among the screen hits, we focused on an uncharacterized gene, sit (CG5278), which is highly expressed in the gland and is required for ecdysone production. Sit is a homolog of mammalian very...... flux of cholesterol uptake in the gland cells and affected the endosomal trafficking. Therefore this gene was suggested to be named stuck in traffic (sit). Sit’s role in cholesterol uptake was also supported by the observation that the developmental delayed phenotype from loss of sit expression...

  18. A maturity model for blockchain adoption

    OpenAIRE

    Wang, Huaiqing; Chen, Kun; Xu, Dongming

    2016-01-01

    Background: The rapid development of the blockchain technology and its various applications has rendered it important to understand the guidelines for adopting it. Methods: The comparative analysis method is used to analyze different dimensions of the maturity model, which is mainly based on the commonly used capability maturity model. Results: The blockchain maturity model and its adoption process have been discussed and presented. Conclusions: This study serves as a guide to institutions to...

  19. Rac1 acts in conjunction with Nedd4 and dishevelled-1 to promote maturation of cell-cell contacts

    NARCIS (Netherlands)

    M. Nethe (Micha); B.J. de Kreuk (Bart-Jan); D.V.F. Tauriello (Daniele); E.C. Anthony (Eloise); B. Snoek (Barbara); T. Stumpel (Thomas); M. Salinas; K. Maurice (Karelle); D. Geerts (Dirk); A.M. Deelder (André); P. Hensbergen (Paul); P.L. Hordijk (Peter )

    2012-01-01

    textabstractThe Rho-GTPase Rac1 promotes actin polymerization and membrane protrusion that mediate initial contact and subsequent maturation of cell-cell junctions. Here we report that Rac1 associates with the ubiquitin-protein ligase neural precursor cell expressed developmentally down-regulated 4

  20. Relation between extent of myostatin depletion and muscle growth in mature mice

    OpenAIRE

    Welle, Stephen; Burgess, Kerri; Thornton, Charles A.; Tawil, Rabi

    2009-01-01

    Myostatin is a negative regulator of muscle growth and fiber size. Changes in myostatin expression might contribute to changes in muscle mass associated with various conditions, and reducing the amount of active myostatin is a potential strategy for preventing or reversing muscle atrophy. The present study was done to determine the extent to which myostatin levels must decline to induce growth of mature muscles. Myostatin expression was reduced by activating Cre recombinase in adult mice with...

  1. Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells.

    Science.gov (United States)

    Xu, Cong; Wang, Li; Yu, Yue; Yin, Fangchao; Zhang, Xiaoqing; Jiang, Lei; Qin, Jianhua

    2017-08-22

    Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function. The calcium imaging of hiPSC-CMs demonstrated a more mature Ca 2+ spark pattern as well. Furthermore, the expression of sarcomere genes (TNNI3, MYH6 and MYH7), potassium channel genes (KCNE1 and KCNH2), and calcium channel genes (RYR2) was significantly up-regulated on the substrate with an onion epithelium-like structure instead of the surface without the structure, indicating a more matured status of cardiomyocytes induced by this structure. It appears that the biomimetic micropatterned structure, analogous to in vivo cellular organization, is an important factor that might promote the maturation of hiPSC-CMs, providing new biological insights to guide hiPSC-CM maturation by biophysical factors. The established approach may offer an effective in vitro model for investigating cardiomyocyte differentiation, maturation and tissue engineering applications.

  2. Changes in gene expression associated with reproductive maturation in wild female baboons.

    Science.gov (United States)

    Babbitt, Courtney C; Tung, Jenny; Wray, Gregory A; Alberts, Susan C

    2012-01-01

    Changes in gene expression during development play an important role in shaping morphological and behavioral differences, including between humans and nonhuman primates. Although many of the most striking developmental changes occur during early development, reproductive maturation represents another critical window in primate life history. However, this process is difficult to study at the molecular level in natural primate populations. Here, we took advantage of ovarian samples made available through an unusual episode of human-wildlife conflict to identify genes that are important in this process. Specifically, we used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in the ovarian tissue of juvenile and adult female baboons from Amboseli National Park, Kenya. We combined this information with prior evidence of selection occurring on two primate lineages (human and chimpanzee). We found that in cases in which genes were both differentially expressed over the course of ovarian maturation and also linked to lineage-specific selection this selective signature was much more likely to occur in regulatory regions than in coding regions. These results suggest that adaptive change in the development of the primate ovary may be largely driven at the mechanistic level by selection on gene regulation, potentially in relationship to the physiology or timing of female reproductive maturation.

  3. Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

    Directory of Open Access Journals (Sweden)

    Jie Dong

    Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

  4. Mature students' perspectives of studying radiography

    International Nuclear Information System (INIS)

    Williams, M.; Decker, S.

    2009-01-01

    The study set out to explore the experiences of all final year mature students on a diagnostic radiography course, in one United Kingdom University. The aims were to identify any difficulties they may have had and to make recommendations to improve mature students' learning experiences with the hope of lowering attrition rates in this group. A qualitative study involving one-to-one audio recorded interviews was utilised. Analysis of the transcripts of interviews suggested that the group believed that their maturity and previous experiences helped them in the clinical environment and put them in a good position, when asked, to counsel younger students. However for some of the mature students these experiential skills did not extend fully into seeking appropriate support for themselves. The mature students were found to be highly motivated but there was a conflict between balancing clinical and academic aspects of studying as well as balancing studying with home life. The group was found to be unprepared for the volume of academic work and its detrimental effect on family life as they sacrificed other aspects of their lives in order to complete the course. It is recommended that forewarning and forearming prospective mature students be considered by radiography education providers. Setting up and utilising an on-line forum providing a 24/7 peer support environment would aid in coping with academic, clinical or personal problems

  5. An AICD-based functional screen to identify APP metabolism regulators

    Directory of Open Access Journals (Sweden)

    Lee Jeremy C

    2007-08-01

    Full Text Available Abstract Background A central event in Alzheimer's disease (AD is the regulated intramembraneous proteolysis of the β-amyloid precursor protein (APP, to generate the β-amyloid (Aβ peptide and the APP intracellular domain (AICD. Aβ is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered. Results To validate this experimental approach we modulated α-, β-, and γ-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis. Conclusion Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y.

  6. Induction of ovarian maturation in Penaeus monodon by molecular signal interventional approach.

    Science.gov (United States)

    Devaraj, Halagowder; Saravanakumar, Marimuthu; Thiyagu, Mani

    2012-11-01

    Vitellogenin (VTG) synthesis in the hepatopancreas and ovary is negatively regulated by vitellogenesis-inhibiting hormone (VIH) produced in the neurosecretory cell of X-organ/sinus gland complex of the eyestalks of penaeid shrimp. Eyestalk ablation is used commercially to induce ovarian maturation in shrimps which leads to an eventual loss of the spawner. The aim of the present study was to understand the molecular mechanism of VIH regulation in ovarian development and its inhibition of VTG gene expression by using a MEK-specific inhibitor (U0126). The real-time quantitative PCR results showed VTG mRNA level was progressively increased in the ovary and hepatopancreas of unilateral eyestalk-ablated and inhibitor-treated shrimps. Western blot analysis also showed that phosphoMEK was detected only in the unilateral eyestalk-ablated and control shrimp, whereas phospho-MEK was not detected in inhibitor-treated shrimp. DAX-1, SF-1, and StAR expression correlated with changes in VIH mRNA and altered phospho-ERK levels. This is consistent with the hypothesis that suppression of DAX-1 results in SF-1-mediated StAR protein upregulation of estradiol that is implicated in vitellogenesis. This is the first report that demonstrates the molecular mechanism of VIH suppression via MEK pathway to induce ovarian maturation in female Penaeus monodon by molecular signal intervention, a less-invasive method than traditional eyestalk ablation. Copyright © 2012 Wiley Periodicals, Inc.

  7. From maturity to value-added innovation: lessons from the pharmaceutical and agro-biotechnology industries.

    Science.gov (United States)

    Mittra, James; Tait, Joyce; Wield, David

    2011-03-01

    The pharmaceutical and agro-biotechnology industries have been confronted by dwindling product pipelines and rapid developments in life sciences, thus demanding a strategic rethink of conventional research and development. Despite offering both industries a solution to the pipeline problem, the life sciences have also brought complex regulatory challenges for firms. In this paper, we comment on the response of these industries to the life science trajectory, in the context of maturing conventional small-molecule product pipelines and routes to market. The challenges of managing transition from maturity to new high-value-added innovation models are addressed. Furthermore, we argue that regulation plays a crucial role in shaping the innovation systems of both industries, and as such, we suggest potentially useful changes to the current regulatory system. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Relationship between cervical vertebral maturation and mandibular growth.

    Science.gov (United States)

    Ball, Gina; Woodside, Donald; Tompson, Bryan; Hunter, W Stuart; Posluns, James

    2011-05-01

    The cervical vertebrae have been proposed as a method of determining biologic maturity. The purposes of this study were to establish a pattern of mandibular growth and to relate this pattern to the stages of cervical vertebral maturation. Cephalometric radiographs, taken annually from ages 9 to 18 years, were evaluated for 90 boys from the Burlington Growth Center, Toronto, Ontario, Canada. Mandibular lengths were measured from articulare to gnathion, and incremental growth was determined. Cervical vertebral maturation stages were assessed by using a 6-stage method. Advanced, average, and delayed maturation groups were established. The prepubertal mandibular growth minimum velocity occurred during cervical stages 1 through 4 (P = 0.7327). Peak mandibular growth velocity occurred most frequently during stage 4 in all 3 maturation groups, with a statistical difference in the average and delayed groups (P cervical stages 1 through 6 does not occur annually; time spent in each stage varies depending on the stage and the maturation group. Cervical vertebral maturation stages cannot accurately identify the mandibular prepubertal growth minimum and therefore cannot predict the onset of the peak in mandibular growth. The cervical vertebral maturation stages should be used with other methods of biologic maturity assessment when considering both dentofacial orthopedic treatment and orthognathic surgery. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. Effects of Crocin Supplementation during In Vitro Maturation of Mouse Oocytes on Glutathione Synthesis and Cytoplasmic Maturation

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    Elham Mokhber Maleki

    2016-05-01

    Full Text Available Background: Crocin is an active ingredient of saffron (Crocus sativus L. and its antioxidant properties have been previously investigated. This carotenoid scavenges free radicals and stimulates glutathione (GSH synthesis; consequently, it may protect cells against oxidative stress. The aim of this research is to protect oocytes from oxidative stress by the addition of a natural source antioxidant. Materials and Methods: In the present in vitro experimental study, we collected cumulus oocyte complexes (COCs from mouse ovaries of euthanized, 6-8 week-old female Naval Medical Research Institute (NMRI mice. Oocytes were subjected to in vitro maturation (IVM in the presence of either crocin (5 or 10 μg/ml, 5 mM buthionine-[S-R]- sulfoximine (BSO, or the combination of crocin plus BSO. Oocytes that matured in vitro in a medium without crocin or BSO supplements were considered as controls. Following 16-18 hours of IVM, matured oocytes (n=631 were fertilized by capacitated sperm from NMRI male mice, and cultured in vitro for up to 96 hours to assess preimplantation embryonic development. The levels of GSH in metaphase II (MII oocytes after IVM (n=240 were also assessed by the 5, 5-dithio-bis (2-nitrobenzoic acid (DTNB-GSH reductase recycling assay. Results: Supplementation of IVM media with 10 μg/ml crocin significantly (P<0.05 increased nuclear maturation, preimplantation development and GSH concentrations compared with the control group. Maturation of oocytes in IVM medium supplemented with BSO alone or the combination of 5 μg/ml crocin and BSO drastically decreased GSH concentrations and subsequently resulted in low rates of maturation, fertilization and blastocyst development. However, the combination of 10 μg/ml crocin with 5 mM BSO increased the level of nuclear maturation which was comparable to the control group. Conclusion: Supplementation of IVM media with crocin can improve nuclear maturation rates and subsequent developmental potential

  10. TGF-β1 regulation of estrogen production in mature rat Leydig cells.

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    Man-Li Liu

    Full Text Available BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1 is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2 synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP, respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

  11. Effect of Maize Hybrid Maturity and Grain Hardness on Fumonisin and Zearalenone Contamination

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    Amedeo Reyneri

    2011-02-01

    Full Text Available The level of resistance in commercial hybrids for Fusarium ear rot is still not in general adequate to prevent unacceptable toxin concentrations in field. The purpose of this experiment was to verify the behaviour of commercial dent maize hybrids for fumonisin and zearalenone contamination and to identify the variety traits that influence the production of these toxins. Field experiments were carried out in 2000, 2001 and 2002 to evaluate the effect of maize hybrid maturity and endosperm hardness on European Corn Borer (ECB incidence, fungal ear rot incidence and severity and on fumonisin B1 and zearalenone contents. Nineteen yellow soft commercial hybrids, from the 500, 600 and 700 FAO maturity groups, were compared in 4 sites in NW Italy. Hybrid were grouped in 3 endosperm hardness categories (hard, intermediate, soft in function of Hard/Soft (H/S endosperm ratio. No effect due to endosperm hardness or hybrid maturity on the ECB infestation or fungal ear rot incidence and severity was observed. Grain hardness significant influenced fumonisin B1 content: hard endosperm hybrids showed 50% lower contamination than soft hybrids. The presence of fumonisin B1 in the grain of different maturity hybrids only resulted to be significantly different in 2001 experiment, with a mean concentration 2 times higher in the later hybrids (FAO rating 700 compared to the medium and medium-late hybrids. The zearalenone content never resulted to be significantly different in function of the endosperm hardness, while, late maturing hybrids, in which grain moisture content decreases slowly below 30%, are more susceptible to zearalenone contamination. This research has highlighted the presence of variety traits that can influence mycotoxin contamination. An accurate choice of hybrid, considering the territorial and cultivation context, could contribute to achieve products, that contain mycotoxins, which do not exceed the maximum international and UE regulation levels.

  12. 7 CFR 1421.101 - Maturity dates.

    Science.gov (United States)

    2010-01-01

    ... filed and disbursed except, for transferred marketing assistance loan collateral. The maturity date for transferred marketing assistance loan collateral will be the maturity date applicable to the original loan... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS GRAINS AND SIMILARLY HANDLED COMMODITIES-MARKETING...

  13. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  14. A Systematic Literature Review of Agile Maturity Model Research

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    Vaughan Henriques

    2017-02-01

    Full Text Available Background/Aim/Purpose: A commonly implemented software process improvement framework is the capability maturity model integrated (CMMI. Existing literature indicates higher levels of CMMI maturity could result in a loss of agility due to its organizational focus. To maintain agility, research has focussed attention on agile maturity models. The objective of this paper is to find the common research themes and conclusions in agile maturity model research. Methodology: This research adopts a systematic approach to agile maturity model research, using Google Scholar, Science Direct, and IEEE Xplore as sources. In total 531 articles were initially found matching the search criteria, which was filtered to 39 articles by applying specific exclusion criteria. Contribution:: The article highlights the trends in agile maturity model research, specifically bringing to light the lack of research providing validation of such models. Findings: Two major themes emerge, being the coexistence of agile and CMMI and the development of agile principle based maturity models. The research trend indicates an increase in agile maturity model articles, particularly in the latter half of the last decade, with concentrations of research coinciding with version updates of CMMI. While there is general consensus around higher CMMI maturity levels being incompatible with true agility, there is evidence of the two coexisting when agile is introduced into already highly matured environments. Future Research:\tFuture research direction for this topic should include how to attain higher levels of CMMI maturity using only agile methods, how governance is addressed in agile environments, and whether existing agile maturity models relate to improved project success.

  15. Customer-Provider Strategic Alignment: A Maturity Model

    Science.gov (United States)

    Luftman, Jerry; Brown, Carol V.; Balaji, S.

    This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

  16. Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

    2009-01-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

  17. A correlative study of dental age and skeletal maturation.

    Science.gov (United States)

    Sachan, Kiran; Sharma, Vijay Prakash; Tandon, Pradeep

    2011-01-01

    Skeletal age had been assessed by comparison between maturation of hand-wrist with stages of cervical vertebrae or canine calcification stages in past and this had been closely related to craniofacial growth. The importance of pubertal growth spurt in various types of orthodontic therapies is already established. Hence, this study was aimed to evaluate the relationship of skeletal maturity by hand-wrist with cervical vertebral maturation indicators and canine calcification stages. The study consisted of randomly selected 90 children from Lucknow population with 45 males (age range 10-13 years) and 45 females (age range 9-12 years). Lateral Cephalogram, hand-wrist x-ray, and periapical x-rays of maxillary and mandibular right canines were taken. Mean, standard deviation was calculated of different groups. Correlation was made among cervical vertebral maturation, hand wrist maturation, and canine calcification stages at various age groups. There was strong correlation between skeletal maturation indicator and cervical vertebral maturation indicator for both male (0.849) and female (0.932), whereas correlation between skeletal maturation indicator and canine calcification was good for both male and female (0.635, 0.891). It was concluded that cervical vertebral maturation indicator and canine calcification stages can also be used for assessing skeletal maturity.

  18. Maturation of sugar maple seed

    Science.gov (United States)

    Clayton M., Jr. Carl; Albert G., Jr. Snow; Albert G. Snow

    1971-01-01

    The seeds of a sugar maple tree (Acer saccharum Marsh.) do not mature at the same time every year. And different trees mature their seeds at different times. So time of year is not a reliable measure of when seeds are ripe. Better criteria are needed. In recent studies we have found that moisture content and color are the best criteria for judging when sugar maple...

  19. Assessing organisational governance maturity: A retail industry case study

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    Hendrik Marius Wessels

    2016-05-01

    Full Text Available For any business to operate effectively, a governance framework that operates at the relevant maturity level is required. An organisational governance maturity framework is a tool that leadership can use to determine governance maturity. This study aims to determine whether the organisational governance maturity framework (developed by Wilkinson can be applied to the selected retail industry organisation to assess the maturity of the organisation’s governance, limited to the ‘leadership’ attribute. Firstly, a high-level literature review on ethical leadership, ethical decision-making, ethical foundation and culture (‘tone at the top’, and organisational governance and maturity was conducted. Secondly, a Johannesburg Stock Exchange (JSE listed South African-based company was selected for the empirical part of the study using a single case study research design. The empirical results confirmed that the organisational governance maturity framework can be used to determine the maturity level of organisational governance for the selected attribute of ‘leadership’

  20. Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.

    Science.gov (United States)

    Paco, Sonia; Hummel, Manuela; Plá, Virginia; Sumoy, Lauro; Aguado, Fernando

    2016-04-23

    cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.

  1. Physical Activity-Related Injury Profile in Children and Adolescents According to Their Age, Maturation, and Level of Sports Participation.

    Science.gov (United States)

    Costa E Silva, Lara; Fragoso, Maria Isabel; Teles, Júlia

    Physical activity (PA) is beneficial, enhancing healthy development. However, one-third of school-age children practicing sports regularly suffer from an injury. These injuries are associated with sex, chronological age, and PA level. To identify the importance of age, PA level, and maturity as predictors of injury in Portuguese youth. Descriptive epidemiological study. Level 3. Information about injury and PA level was assessed via 2 questionnaires (LESADO RAPIL II) from 647 subjects aged 10 to 17 years. Maturity offset according to Mirwald (time before or after peak height velocity) and Tanner-Whitehouse III bone age estimates were used to evaluate maturation. Binary logistic regression and gamma regression were used to determine significant predictors of injury and injury rate. Injury occurrence was higher for both sexes in recreational, school, and federated athletes (athletes engaged in sports that are regulated by their respective federations, with formal competition). These injuries also increased with age in boys and in the higher maturity offset group in girls. Injury rate was higher for both sexes in the no sports participation group. Early-maturing girls, with higher bone age and lower maturity offset, showed higher injury rate. Injuries in Portuguese youth were related to PA level, age, and biological maturation. Recreational, school, and federated athletes had more injury ocurrences while subjects with no sports participation had higher injury risk. Older subjects had more injuries. Early-maturing girls that had just passed peak height velocity may be particularly vulnerable to risk of sports injury because of the growing process. Increased knowledge about injury with specific PA exposure data is important to an overall risk management strategy. This study has deepened the association between injury and biological maturation variables.

  2. Melanogenesis in dermal melanocytes of Japanese Silky chicken embryos.

    Science.gov (United States)

    Ortolani-Machado, C F; Freitas, P F; Faraco, C D

    2009-08-01

    The Japanese Silky chicken (SK) shows dermal and visceral hyperpigmentation. This study characterizes ultrastructurally the melanin granules developing in dermal melanocytes of the dorsal skin of SK, in an attempt to better understand the processes of melanogenesis in these permanently ectopic cells. The steps of melanogenesis are similar to those described for epidermal melanocytes, with melanosomes going from stage I to IV but, in SK, the maturation occurs in the cell body, as well as in the cytoplasmic processes. At stage III, the deposition of melanin is cumulative and can aggregate in rounded structures, which combine to turn into the mature granule. The final destiny of mature melanosomes is still unclear, although it was observed that dermal macrophages can accumulate melanin granules in their phagosomes. Even with the close proximity between melanocytes and other dermal cells, the transference of melanosomes was not observed. Our findings indicate that melanogenesis in dermal melanocytes in SK has the same morphological characteristics found in epidermal melanocytes, but the functional aspect still remains to be elucidated.

  3. α-Naphthoflavone Increases Lipid Accumulation in Mature Adipocytes and Enhances Adipocyte-Stimulated Endothelial Tube Formation

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    Mei-Lin Wang

    2015-04-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-activated factor that regulates biological effects associated with obesity. The AhR agonists, such as environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD and β-naphthoflavone (BNF, inhibit preadipocyte differentiation and interfere with the functions of adipose tissue, whereas the antagonist may have opposite or protective effects in obesity. This study investigated the effects of α-naphthoflavone (α-NF, an AhR antagonist, on adipogenesis- and angiogenesis-associated factors in mature adipocytes and on cross-talk of mature adipocytes with endothelial cells (ECs. Besides, the roles of the AhR on lipid accumulation and on secretion of vascular endothelial growth factor were also determined by introducing siRNA of AhR. Differentiated 3T3-L1 cells were treated with α-naphthoflavone (α-NF (1–5 μM for 16 h. Lipid accumulation and the expressions of AhR-associated factors in the cells were determined. The interaction between adipocytes and ECs was investigated by cultivating ECs with conditioned medium (CM from α-NF-treated mature adipocytes, followed by the determination of endothelial tube formation. The results showed that α-NF significantly increased triglyceride (TG accumulation in mature adipocytes, which was associated with increased expression of hormone-sensitive lipase (HSL, estrogen receptor (ER, as well as decreased expression of AhR, AhR nuclear translocator (ARNT, cytochrome P4501B1 (CYP1B1, and nuclear factor erythroid-2-related factor (NRF-2 proteins. In addition, CM stimulated formation of tube-like structures in ECs, and α-NF further enhanced such stimulation in association with modulated the secretions of various angiogenic mediators by mature adipocytes. Similarly, increased TG accumulation and vascular endothelial growth factor (VEGF secretion were observed in AhR-knockout cells. In conclusion, α-NF increased TG accumulation in mature adipocytes and

  4. Potential targets of transforming growth factor-beta1 during inhibition of oocyte maturation in zebrafish

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    Clelland Eric

    2005-09-01

    Full Text Available Abstract Background TGF-beta is a multifunctional growth factor involved in regulating a variety of cellular activities. Unlike mammals, the function of TGF-beta in the reproduction of lower vertebrates, such as fish, is not clear. Recently, we showed that TGF-beta1 inhibits gonadotropin- and 17alpha, 20beta-dihydroxyprogesterone (DHP-induced maturation in zebrafish. The aim of the present study was to investigate the mechanisms underlying this action. Method To determine if the effect of TGF-beta1 on oocyte maturation involves transcription and/or translation, ovarian follicles were pre-treated with actinomycin D, a blocker of transcription, and cyclohexamide, an inhibitor of translation, and incubated with hCG or DHP, either alone or in combination with TGF-beta1 and oocyte maturation scored. To determine the effect of TGF-beta1 on mRNA levels of several key effectors of oocyte maturation, three sets of experiments were performed. First, follicles were treated with control medium or TGF-beta1 for 2, 6, 12, and 24 h. Second, follicles were treated with different concentrations of TGF-beta1 (0 to 10 ng/ml for 18 h. Third, follicles were incubated with hCG in the absence or presence of TGF-beta1 for 18 h. At the end of each experiment, total RNA was extracted and reverse transcribed. PCR using primers specific for 20beta-hydroxysteroid dehydrogenase (20beta-HSD which is involved in DHP production, follicle stimulating hormone receptor (FSHR, luteinizing hormone receptor (LHR, the two forms of membrane progestin receptor: mPR-alpha and mPR-beta, as well as GAPDH (control, were performed. Results Treatment with actinomycin D, a blocker of transcription, reduced the inhibitory effect of TGF-beta1 on DHP-induced oocyte maturation, indicating that the inhibitory action of TGF-beta1 is in part due to regulation of gene transcription. Treatment with TGF-beta1 caused a dose and time-dependent decrease in mRNA levels of 20beta-HSD, LHR and mPR-beta in

  5. Towards a Sustainable Design for Maturity Measurement Marketplace

    DEFF Research Database (Denmark)

    Lasrado, Lester; Vatrapu, Ravi; Kærsgaard, Henrik Bjerre

    2016-01-01

    In this research-in-progress paper, we propose a solution in form of an IT artefact to address both theoretical and practical challenges faced by maturity model designers. We identify and list out the existing challenges & criticisms of maturity models research through an extensive literature...... review, followed by semi-structured interviews with four maturity model designers. We also explore different motivations of building a maturity model, and using them further scope the boundaries of our solution....

  6. Game Maturity Model for Health Care.

    Science.gov (United States)

    de Boer, Jan C; Adriani, Paul; van Houwelingen, Jan Willem; Geerts, A

    2016-04-01

    This article introduces the Game Maturity Model for the healthcare industry as an extension to the general Game Maturity Model and describes the usage by two case studies of applied health games. The Game Maturity Model for healthcare provides a practical and value-adding method to assess existing games and to determine strategic considerations for application of applied health games. Our forecast is that within 5 years the use and development of applied games will have a role in our daily lives and the way we organize health care that will be similar to the role social media has today.

  7. Significant Down-Regulation of “Biological Adhesion” Genes in Porcine Oocytes after IVM

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    Joanna Budna

    2017-12-01

    Full Text Available Proper maturation of the mammalian oocyte is a compound processes determining successful monospermic fertilization, however the number of fully mature porcine oocytes is still unsatisfactory. Since oocytes’ maturation and fertilization involve cellular adhesion and membranous contact, the aim was to investigate cell adhesion ontology group in porcine oocytes. The oocytes were collected from ovaries of 45 pubertal crossbred Landrace gilts and subjected to two BCB tests. After the first test, only granulosa cell-free BCB+ oocytes were directly exposed to microarray assays and RT-qPCR (“before IVM” group, or first in vitro matured and then if classified as BCB+ passed to molecular analyses (“after IVM” group. As a result, we have discovered substantial down-regulation of genes involved in adhesion processes, such as: organization of actin cytoskeleton, migration, proliferation, differentiation, apoptosis, survival or angiogenesis in porcine oocytes after IVM, compared to oocytes analyzed before IVM. In conclusion, we found that biological adhesion may be recognized as the process involved in porcine oocytes’ successful IVM. Down-regulation of genes included in this ontology group in immature oocytes after IVM points to their unique function in oocyte’s achievement of fully mature stages. Thus, results indicated new molecular markers involved in porcine oocyte IVM, displaying essential roles in biological adhesion processes.

  8. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

  9. Epithelial–stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-01-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj—a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. Subject Categories Development & Differentiation; Immunology; Signal Transduction PMID:25378482

  10. Vegetative propagation of mature and juvenile northern red oak

    Science.gov (United States)

    James J. Zaczek; K. C. Steiner; C. W., Jr. Heuser

    1993-01-01

    Rooting trials were established to evaluate rooting success of cuttings from mature and juvenile, grafted and ungrafted northern red oak (NRO). Buds from 4 mature NRO ortets and juvenile seedlings were grafted onto juvenile and mature rootstock. Cuttings were collected from the grafts and from juvenile and mature shoots developed in situ and...

  11. Decision-Making Style and Vocational Maturity.

    Science.gov (United States)

    Phillips, Susan D.; Strohmer, Douglas C.

    1982-01-01

    Examined the relationship between decision-making style, scholastic achievement, and vocational maturity for college students (N=64). Results did not support the hypothesized relationship between rationality and attitudinal and cognitive maturity. Scholastic achievement and lack of dependent decision style were found to be moderately predictive of…

  12. Color back projection for fruit maturity evaluation

    Science.gov (United States)

    Zhang, Dong; Lee, Dah-Jye; Desai, Alok

    2013-12-01

    In general, fruits and vegetables such as tomatoes and dates are harvested before they fully ripen. After harvesting, they continue to ripen and their color changes. Color is a good indicator of fruit maturity. For example, tomatoes change color from dark green to light green and then pink, light red, and dark red. Assessing tomato maturity helps maximize its shelf life. Color is used to determine the length of time the tomatoes can be transported. Medjool dates change color from green to yellow, and the orange, light red and dark red. Assessing date maturity helps determine the length of drying process to help ripen the dates. Color evaluation is an important step in the processing and inventory control of fruits and vegetables that directly affects profitability. This paper presents an efficient color back projection and image processing technique that is designed specifically for real-time maturity evaluation of fruits. This color processing method requires very simple training procedure to obtain the frequencies of colors that appear in each maturity stage. This color statistics is used to back project colors to predefined color indexes. Fruit maturity is then evaluated by analyzing the reprojected color indexes. This method has been implemented and used for commercial production.

  13. Long Maturity Forward Rates

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    2001-01-01

    The paper aims to improve the knowledge of the empirical properties of the long maturity region of the forward rate curve. Firstly, the theoretical negative correlation between the slope at the long end of the forward rate curve and the term structure variance is recovered empirically and found...... to be statistically significant. Secondly, the expectations hypothesis is analyzed for the long maturity region of the forward rate curve using "forward rate" regressions. The expectations hypothesis is numerically close to being accepted but is statistically rejected. The findings provide mixed support...... for the affine term structure model....

  14. TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway

    Science.gov (United States)

    Falace, Antonio; Buhler, Emmanuelle; Fadda, Manuela; Watrin, Françoise; Lippiello, Pellegrino; Pallesi-Pocachard, Emilie; Baldelli, Pietro; Benfenati, Fabio; Zara, Federico; Represa, Alfonso; Fassio, Anna; Cardoso, Carlos

    2014-01-01

    Alterations in the formation of brain networks are associated with several neurodevelopmental disorders. Mutations in TBC1 domain family member 24 (TBC1D24) are responsible for syndromes that combine cortical malformations, intellectual disability, and epilepsy, but the function of TBC1D24 in the brain remains unknown. We report here that in utero TBC1D24 knockdown in the rat developing neocortex affects the multipolar-bipolar transition of neurons leading to delayed radial migration. Furthermore, we find that TBC1D24-knockdown neurons display an abnormal maturation and retain immature morphofunctional properties. TBC1D24 interacts with ADP ribosylation factor (ARF)6, a small GTPase crucial for membrane trafficking. We show that in vivo, overexpression of the dominant-negative form of ARF6 rescues the neuronal migration and dendritic outgrowth defects induced by TBC1D24 knockdown, suggesting that TBC1D24 prevents ARF6 activation. Overall, our findings demonstrate an essential role of TBC1D24 in neuronal migration and maturation and highlight the physiological relevance of the ARF6-dependent membrane-trafficking pathway in brain development. PMID:24469796

  15. Public Sector IS Maturity Models

    DEFF Research Database (Denmark)

    Zinner Henriksen, Helle; Andersen, Kim Normann; Medaglia, Rony

    2011-01-01

    Online applications and processing of tax forms, driver licenses, and construction permits are examples of where policy attention and research have been united in efforts aiming to categorize the maturity level of e-services. Less attention has been attributed to policy areas with continuous online...... citizenpublic interaction, such as in public education. In this paper we use a revised version of the Public Sector Process Rebuilding (PPR) maturity model for mapping 200 websites of public primary schools in Denmark. Findings reveal a much less favorable picture of the digitization of the Danish public sector...... compared to the high ranking it has received in the international benchmark studies. This paper aims at closing the gap between the predominant scope of maturity models and the frequency of citizen-public sector interaction, and calls for increased attention to the activities of government where the scale...

  16. Service Quality and Process Maturity Assessment

    Directory of Open Access Journals (Sweden)

    Serek Radomir

    2013-12-01

    Full Text Available This article deals with service quality and the methods for its measurement and improvements to reach the so called service excellence. Besides older methods such as SERVQUAL and SERPERF, there are also shortly described capability maturity models based on which the own methodology is developed and used for process maturity assessment in organizations providing technical services. This method is equally described and accompanied by examples on pictures. The verification of method functionality is explored on finding a correlation between service employee satisfaction and average process maturity in a service organization. The results seem to be quite promising and open an arena for further studies.

  17. A regulatory network-based approach dissects late maturation processes related to the acquisition of desiccation tolerance and longevity of Medicago truncatula seeds.

    Science.gov (United States)

    Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K; Buitink, Julia

    2013-10-01

    In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states.

  18. Genotype x environmental interaction for mature size and rate of maturing for Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte infected fescue.

    Science.gov (United States)

    Sandelin, B A; Brown, A H; Brown, M A; Johnson, Z B; Kellogg, D W; Stelzleni, A M

    2002-12-01

    Mature weight and rate of maturing were estimated in 177 Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte-infected tall fescue over a 4-yr period to evaluate genotype x environment interactions. Data were collected every 28 d until cows were approximately 18 mo of age and then at prebreeding, postcalving, and weaning of calf. All cows with weight data to at least 42 mo of age were included in the analysis. Mature weight and rate of maturing were estimated using the three-parameter growth curve model described by Brody (1945). Data were pooled over year and analyzed by the general linear model procedure of SAS. Included in the models for mature weight and rate of maturing were the independent variables of genotype, environment, and genotype x environment interaction. There was a genotype x environment interaction (P < 0.01) for mature body weight (BW) but not for rate of maturing. Angus cows grazing fescue pastures had greater (P < 0.01) mean mature BW than Angus x Brahman cows grazing bermudagrass (611 +/- 17 vs 546 +/- 16 kg). Angus x Brahman cows grazing bermudagrass had lower (P < 0.05) mean mature BW than Brahman x Angus cows grazing bermudagrass or endophyte-infected fescue and Brahman cows grazing bermudagrass (546 +/- 16 vs 624 +/- 19, 614 +/- 22 and 598 +/- 20 kg, respectively). Brahman cows grazing endophyte-infected fescue had smaller (P < 0.05) mean mature BW than all genotype x forage combinations except for Angus x Brahman cows grazing bermudagrass. Angus cows had a smaller (P < 0.05) mean rate of maturing than Angus x Brahman and Brahman x Angus cows (0.039 +/- 0.002 vs 0.054 +/- 0.002 and 0.049 +/- 0.002%/mo, respectively), respectively, and Angus x Brahman cows had a larger (P < 0.05) mean rate of maturing than Brahman x Angus and Brahman cows (0.054 +/- 0.002 vs 0.049 +/- 0.002 and 0.041 +/- 0.002 %/mo, respectively). There was a direct breed x forage interaction (P < 0.05) for mature BW. These data suggest that the

  19. Induction and inhibition of oocyte maturation by EDCs in zebrafish

    Directory of Open Access Journals (Sweden)

    Tokumoto Mika

    2005-12-01

    Full Text Available Abstract Background Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH, which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC, diethylstilbestrol (DES, a nonsteroidal estrogen. Methods In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation. Results Among agents tested, tamoxifen (TAM and its metabolite 4-hydroxytamoxifen (4-OHT showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent. Conclusion These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.

  20. On the occurrence of nuclei in mature sieve elements.

    Science.gov (United States)

    Event, R F; Davis, J D; Tucker, C M; Alfieri, F J

    1970-12-01

    The secondary phloem of 3 species of the Taxodiaceae and 13 species of woody dicotyledons was examined for the occurrence of nuclei in mature sieve elements. Nuclei were found in all mature sieve cells of Metasequoia glyptostroboides, Sequoia sempervirens and Taxodium distichum, and in some mature sieve-tube members in 12 of the 13 species of woody dicotyledons. Except for nuclei of sieve cells undergoing cessation of function, the nuclei in mature sieve cells of M. glyptostroboides, S. sempervirens and T. distichum were normal in appearance. The occurrence and morphology of nuclei in mature sieve-tube members of the woody dicotyledons were quite variable. Only 3 species, Robinia pseudoacacia, Ulmus americana and Vitis riparia, contained some mature sieve elements with apparently normal nuclei.

  1. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    Science.gov (United States)

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. A model-independent view of the mature organization

    Energy Technology Data Exchange (ETDEWEB)

    Hanna, M.; Langston, D.

    1996-12-31

    Over the last 10 years, industry has been dealing with the issues of process and organizational maturity. This focus on process is driven by the success that manufacturing organizations have had implementing the management principles of W. Edwards Deming and Joseph M. Juran. The organizational-maturity focus is driven by organizations striving to be ISO 9000 compliant or to achieve a specific level on one of the maturity models. Unfortunately, each of the models takes a specific view into what is a very broad arena. That is to say, each model addresses only a specific subset of the characteristics of maturity. This paper attempts to extend beyond these specific views to answer the general question, What is a mature organization and its relationship to Quantitative management and statistical process control?

  3. Analysis of business process maturity and organisational performance relations

    Directory of Open Access Journals (Sweden)

    Kalinowski T. Bartosz

    2016-12-01

    Full Text Available The paper aims to present results of the study on business process maturity in relation to organisational performance. A two-phase methodology, based on literature review and survey was used. The literature is a source of knowledge about business process maturity and organisational performance, whereas the research on process maturity vs organisational performance in Polish Enterprises provides findings based on 84 surveyed companies. The main areas of the research covered: identification and analysis of maturity related variables and identification of organisational performance perspectives and its relation to process maturity. The study shows that there is a significant positive relation between process maturity and organisational performance. Although there are research on such relation available, they are scarce and have some significant limitations in terms of research sample or the scope of maturity or organisational performance covered. This publication is part of a project funded by the National Science Centre awarded by decision number DEC-2011/01/D/HS4/04070.

  4. Maturation arrest of human oocytes at germinal vesicle stage

    Directory of Open Access Journals (Sweden)

    Zhi Qin Chen

    2010-01-01

    Full Text Available Maturation arrest of human oocytes may occur at various stages of the cell cycle. A total failure of human oocytes to complete meiosis is rarely observed during assisted conception cycles. We describe here a case of infertile couples for whom all oocytes repeatedly failed to mature at germinal vesicle (GV stage during in vitro fertilization/Intra cytoplasmic sperm injection (IVF/ICSI. The patient underwent controlled ovarian stimulation followed by oocyte retrieval and IVF/ICSI. The oocytes were stripped off cumulus cells prior to the ICSI procedure and their maturity status was defined. The oocyte maturation was repeatedly arrested at the GV. Oocyte maturation arrest may be the cause of infertility in this couple. The recognition of oocyte maturation arrest as a specific medical condition may contribute to the characterization of the currently known as "oocyte factor." The cellular and genetic mechanisms causing oocyte maturation arrest should be the subject for further investigation.

  5. Breeding of cocksfoot cultivars with different maturity

    Directory of Open Access Journals (Sweden)

    Babić Snežana

    2017-01-01

    Full Text Available One of the most important criteria in breeding process of perennial grasses is maturity. Cultivars with different maturity play a very important role in utilization of perennial grasses, by providing the ability to create a mixture of different aspects utilization and time. The first grass species in Serbia whose breeding program involved this criterion was cocksfoot (Dactylis glomerata L.. In general cocksfoot is early to medium-early in maturity in comparison with other grasses and legumes, and that is mayor problem since in the optimum phase for cutting, cocksfoot is often earlier then other species in mixtures. As a result of this work, in the previous period, two cultivars of different maturity were released, Kruševačka 24 (K-24 and Kruševačka 25 (K-25. K-24 is medium and K-25 is late in maturity. New material is adapted to local agro-ecological conditions and productive in the same time. In breeding process of both cultivars initial material originated from autochthonous populations collected in eastern and central Serbia. Material from the wild flora is selected based on medium and late maturity which is already adapted and has good productivity. We applied the standard method of phenotypic recurrent selection with the creation of synthetic varieties by polycross.

  6. The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice

    Science.gov (United States)

    Holmes, Greg; Bromage, Timothy G.; Basilico, Claudio

    2011-01-01

    We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1α1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo. PMID:21703370

  7. Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells

    Science.gov (United States)

    Patzelt, Thomas; Keppler, Selina J.; Gorka, Oliver; Thoene, Silvia; Wartewig, Tim; Reth, Michael; Förster, Irmgard; Lang, Roland; Buchner, Maike; Ruland, Jürgen

    2018-01-01

    The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1. Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma. PMID:29507226

  8. Determinants of relative skeletal maturity in South African children.

    Science.gov (United States)

    Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

    2012-01-01

    The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

    DEFF Research Database (Denmark)

    Martinat, Cecile; Bacci, Jean-Jacques; Leete, Thomas

    2006-01-01

    's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1......Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson......, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation...

  10. A comparison of skeletal maturation in patients with tooth agenesis and unaffected controls assessed by the cervical vertebral maturation (CVM) index.

    Science.gov (United States)

    Casey, Christine; Gill, Daljit S; Jones, Steven P

    2013-12-01

    The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation. A retrospective cross-sectional study. Eastman Dental Hospital, London, UK. A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital. There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis. The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

  11. The Rho-GTPase effector ROCK regulates meiotic maturation of the bovine oocyte via myosin light chain phosphorylation and cofilin phosphorylation.

    Science.gov (United States)

    Lee, So-Rim; Xu, Yong-Nan; Jo, Yu-Jin; Namgoong, Suk; Kim, Nam-Hyung

    2015-11-01

    Oocyte meiosis involves a unique asymmetric division involving spindle movement from the central cytoplasm to the cortex, followed by polar body extrusion. ROCK is a Rho-GTPase effector involved in various cellular functions in somatic cells as well as oocyte meiosis. ROCK was previously shown to promote actin organization by phosphorylating several downstream targets, including LIM domain kinase (LIMK), phosphorylated cofilin (p-cofilin), and myosin light chain (MLC). In this study, we investigated the roles of ROCK and MLC during bovine oocyte meiosis. We found that ROCK was localized around the nucleus at the oocyte's germinal-vesicle (GV) stage, but spreads to the rest of the cytoplasm in later developmental stages. On the other hand, phosphorylated MLC (p-MLC) localized at the cortex, and its abundance decreased by the metaphase-II stage. Disrupting ROCK activity, via RNAi or the chemical inhibitor Y-27632, blocked both cell cycle progression and polar body extrusion. ROCK inhibition also resulted in decreased cortical actin, p-cofilin, and p-MLC levels. Similar to the phenotype associated with inhibition of ROCK activity, inhibition of MLC kinase by the chemical inhibitor ML-7 caused defects in polar body extrusion. Collectively, our results suggest that the ROCK/MLC/actomyosin as well as ROCK/LIMK/cofilin pathways regulate meiotic spindle migration and cytokinesis during bovine oocyte maturation. © 2015 Wiley Periodicals, Inc.

  12. Maturity of hospital information systems: Most important influencing factors.

    Science.gov (United States)

    Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

    2017-07-01

    Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

  13. Mall shopping preferences and patronage of mature shoppers

    Directory of Open Access Journals (Sweden)

    Gabriel G. Rousseau

    2014-04-01

    Research purpose: The purpose of this study was to investigate the buying behaviour of mature consumers (older than 55 in Port Elizabeth shopping malls. Motivation for the study: The perception of mature shoppers as old people with limited financial resources is untrue. This study investigates the behaviours of mature shoppers. Research design, approach and method: A model guided the investigation. The authors facilitated four focus groups to gain insight into mature consumers’ buying behaviours. A field survey followed with a sample of mall shoppers (n = 680. The authors performed content analysis of the focus group material and used SPSS and AMOS programs to analyse the data quantitatively. Main findings: Focus group interviews revealed specific buying behaviours of mature shoppers. The survey showed significant relationships between various determinants that influence respondents’ buying behaviours with adequate model fit indices. These results confirmed the convergent and discriminant validity of the model that comprises mall shopping anticipation, experience and patronage. Practical/managerial implications: Mature shoppers’ expectations exceeded their experiences, suggesting dissatisfaction with some aspects of their experiences. Retailers and shopping mall managers need to redesign malls if they wish to cater for the segment of ageing shoppers and their spending power. Contribution/value-add: The study contributes to the research available in South Africa on service at shopping malls that cater for mature consumers.

  14. Physical activity and biological maturation: a systematic review

    Directory of Open Access Journals (Sweden)

    Eliane Denise Araújo Bacil

    2015-03-01

    Full Text Available OBJECTIVE: To analyze the association between physical activity (PA and biological maturation in children and adolescents. DATA SOURCE: We performed a systematic review in April 2013 in the electronic databases of PubMed/MEDLINE, SportDiscus, Web of Science and LILACS without time restrictions. A total of 628 potentially relevant articles were identified and 10 met the inclusion criteria for this review: cross-sectional or longitudinal studies, published in Portuguese, English or Spanish, with schoolchildren aged 9-15 years old of both genders. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an inverse association between PA and biological maturation. PA decreases with increased biological and chronological age in both genders. Boys tend to be more physically active than girls; however, when controlling for biological age, the gender differences disappear. The association between PA and timing of maturation varies between the genders. Variation in the timing of biological maturation affects the tracking of PA in early adolescent girls. This review suggests that mediators (BMI, depression, low self-esteem, and concerns about body weight can explain the association between PA and biological maturation. CONCLUSIONS: There is an association between PA and biological maturation. PA decreases with increasing biological age with no differences between genders. As for the timing of biological maturation, this association varies between genders.

  15. Age of biological maturity of Malaysian girls by ethnicity.

    Science.gov (United States)

    Noor Laily Abu Bakar; Prasanta K Majumdar; Tan Boon Ann

    1983-01-01

    This study estimates the age of biological maturity, defined as the end of adolescent sterility, of Malaysian girls by employing an indiredt methodology. Biological maturity usually occurs about 3 years after puberty. Adolescent subfecundity is due to anovulatory cycles or to short luteal phases among menarchial girls. In this study, age at biological maturity is estimated by considering retrospective fertility and family survey data on marriage, 1st birt, and contraceptive use. The waiting time for the biologically mature females to conceive is 3.0 months; 3.2 months among the Malays, 2.7 months among the Chinese, and 2.8 months among the Indians. The maximum age of attaining biological maturity is 20 for all ethnic groups except Indians (19 years). The maximum age is estimated by considering females whose 1st pregnancy ended in a live birth and who have been living most of the time with their husbands since marriage, with no contraceptive usage. The expected age of biological maturity at birth is 15.6 years; 15.3 years for the Malays, 15.4 years for the Chinese, and 14.8 years for the Indians. The means age of attaining biological maturity coincides with the expected age of attaining biological maturity at birth.

  16. Effects of posttreatment skeletal maturity measured with the cervical vertebral maturation method on incisor alignment relapse.

    Science.gov (United States)

    Fudalej, Piotr; Rothe, Laura E; Bollen, Anne-Marie

    2008-08-01

    Our aim was to test the hypothesis that relapse of incisor alignment is associated with skeletal maturity at the end of treatment, as assessed with the cervical vertebral maturation (CVM) method. This was a case-control study with information from the postretention database at the University of Washington. Mandibular incisor irregularity (II) at least 10 years out of retention (T3) was used to define the subjects (II >6 mm, relapse group) and the controls (II 0.05). Pretreatment II and postretention time were found to be correlated with long-term incisor stability (P = 0.007 and 0.034, respectively). Sex was not related to relapse (P = 0.33). Maturity of craniofacial structures at the end of treatment evaluated with the CVM method is not associated with long-term stability of incisor alignment.

  17. Maturity Model for Advancing Smart Grid Interoperability

    Energy Technology Data Exchange (ETDEWEB)

    Knight, Mark; Widergren, Steven E.; Mater, J.; Montgomery, Austin

    2013-10-28

    Abstract—Interoperability is about the properties of devices and systems to connect and work properly. Advancing interoperability eases integration and maintenance of the resulting interconnection. This leads to faster integration, lower labor and component costs, predictability of projects and the resulting performance, and evolutionary paths for upgrade. When specifications are shared and standardized, competition and novel solutions can bring new value streams to the community of stakeholders involved. Advancing interoperability involves reaching agreement for how things join at their interfaces. The quality of the agreements and the alignment of parties involved in the agreement present challenges that are best met with process improvement techniques. The GridWise® Architecture Council (GWAC) sponsored by the United States Department of Energy is supporting an effort to use concepts from capability maturity models used in the software industry to advance interoperability of smart grid technology. An interoperability maturity model has been drafted and experience is being gained through trials on various types of projects and community efforts. This paper describes the value and objectives of maturity models, the nature of the interoperability maturity model and how it compares with other maturity models, and experiences gained with its use.

  18. Maturity grids as tools for change management

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2011-01-01

    A maturity grid is a change management tool. Levels of maturity are assigned against aspects of an area under study, thus creating a grid. Text descriptions at the resulting intersections describe the typical behaviour exhibited by a firm for each area under study and from the basis...... for the assessment scale. It is a flexible assessment technique that is used by practitioners in industry, consultants and researchers in academia for diagnostic, reflective and improvement purposes. A large number of maturity grids have been proposed to assess a range of capabilities including quality management...

  19. Genetic transformation of mature citrus plants.

    Science.gov (United States)

    Cervera, Magdalena; Juárez, José; Navarro, Luis; Peña, Leandro

    2005-01-01

    Most woody fruit species have long juvenile periods that drastically prolong the time required to analyze mature traits. Evaluation of characteristics related to fruits is a requisite to release any new variety into the market. Because of a decline in regenerative and transformation potential, genetic transformation procedures usually employ juvenile material as the source of plant tissue, therefore resulting in the production of juvenile plants. Direct transformation of mature material could ensure the production of adult transgenic plants, bypassing in this way the juvenile phase. Invigoration of the source adult material, establishment of adequate transformation and regeneration conditions, and acceleration of plant development through grafting allowed us to produce transgenic mature sweet orange trees flowering and bearing fruits in a short time period.

  20. Interest rate models for pension and insurance regulation

    NARCIS (Netherlands)

    Broeders, Dirk; de Jong, Frank; Schotman, Peter

    2016-01-01

    Liabilities of pension funds and life insurers typically have very long times to maturity. The valuation of such liabilities introduces particular challenges as it relies on long term interest rates. As the market for long term interest rates is less liquid, financial institutions and the regulator

  1. Interest Rate Models for Pension and Insurance Regulation

    NARCIS (Netherlands)

    Broeders, D.W.G.A.; de Jong, Frank; Schotman, Peter

    Liabilities of pension funds and life insurers typically have very long times to maturity. The valuation of such liabilities introduces particular challenges as it relies on long term interest rates. As the market for long term interest rates is less liquid, financial institutions and the regulator

  2. Skeletal maturity assessment using mandibular canine calcification stages

    Directory of Open Access Journals (Sweden)

    Vildana Džemidžić

    2016-11-01

    Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

  3. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.

    Science.gov (United States)

    Annis, Ryan P; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X; Hammond, Scott M; Deshmukh, Mohanish

    2016-12-01

    Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival. © 2016 Federation of European Biochemical Societies.

  4. Maturity Models in Supply Chain Sustainability: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Elisabete Correia

    2017-01-01

    Full Text Available A systematic literature review of supply chain maturity models with sustainability concerns is presented. The objective is to give insights into methodological issues related to maturity models, namely the research objectives; the research methods used to develop, validate and test them; the scope; and the main characteristics associated with their design. The literature review was performed based on journal articles and conference papers from 2000 to 2015 using the SCOPUS, Emerald Insight, EBSCO and Web of Science databases. Most of the analysed papers have as main objective the development of maturity models and their validation. The case study is the methodology that is most widely used by researchers to develop and validate maturity models. From the sustainability perspective, the scope of the analysed maturity models is the Triple Bottom Line (TBL and environmental dimension, focusing on a specific process (eco-design and new product development and without a broad SC perspective. The dominant characteristics associated with the design of the maturity models are the maturity grids and a continuous representation. In addition, results do not allow identifying a trend for a specific number of maturity levels. The comprehensive review, analysis, and synthesis of the maturity model literature represent an important contribution to the organization of this research area, making possible to clarify some confusion that exists about concepts, approaches and components of maturity models in sustainability. Various aspects associated with the maturity models (i.e., research objectives, research methods, scope and characteristics of the design of models are explored to contribute to the evolution and significance of this multidimensional area.

  5. Cervical vertebral and dental maturity in Turkish subjects.

    Science.gov (United States)

    Başaran, Güvenç; Ozer, Törün; Hamamci, Nihal

    2007-04-01

    The aim of this study was to investigate the relationships between the stages of calcification of teeth and the cervical vertebral maturity stages in Turkish subjects. A retrospective cross-sectional study was designed. The final study population consisted of 590 Turkish subjects. Statistical analysis of the data was performed with computer software. Spearman rank order correlation coefficients were used to assess the relationship between cervical vertebral and dental maturation. For a better understanding of the relationship between cervical vertebral maturation indexes and dental age, percentage distributions of the studied teeth were also calculated. Strict correlations were found between dental and cervical vertebral maturation of Turkish subjects. For males, the sequence from lowest to the highest was third molar, central incisor, canine, first premolar, second premolar, first molar, and second molar. For females, the sequence from lowest to the highest was third molar, canine, second premolar, first premolar, central incisor, first molar, and second molar. Dental maturation stages can be used as a reliable indicator of facial growth.

  6. Neurokinin B is critical for normal timing of sexual maturation but dispensable for adult reproductive function in female mice.

    Science.gov (United States)

    True, Cadence; Nasrin Alam, Sayeda; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B

    2015-04-01

    Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2-/- mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2-/- females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2-/- females were fertile, although they produced fewer pups per litter. Thus, female Tac2-/- mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors.

  7. Moral Complexity: The Fatal Attraction of Truthiness and the Importance of Mature Moral Functioning.

    Science.gov (United States)

    Narvaez, Darcia

    2010-03-01

    Recently, intuitionist theories have been effective in capturing the academic discourse about morality. Intuitionist theories, like rationalist theories, offer important but only partial understanding of moral functioning. Both can be fallacious and succumb to truthiness: the attachment to one's opinions because they "feel right," potentially leading to harmful action or inaction. Both intuition and reasoning are involved in deliberation and expertise. Both are malleable from environmental and educational influence, making questions of normativity-which intuitions and reasoning skills to foster-of utmost importance. Good intuition and reasoning inform mature moral functioning, which needs to include capacities that promote sustainable human well-being. Individual capacities for habituated empathic concern and moral metacognition-moral locus of control, moral self-regulation, and moral self-reflection-comprise mature moral functioning, which also requires collective capacities for moral dialogue and moral institutions. These capacities underlie moral innovation and are necessary for solving the complex challenges humanity faces. © The Author(s) 2010.

  8. Regulation of stem-cell mediated host immunity by the sphingolipid ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Regulation of stem-cell mediated host immunity by the sphingolipid pathway ... in the generation of mature immune cells and the functioning of the surrounding ... methods with human cells and genetically engineered mice to examine how the ...

  9. MD3M: The Master Data Management Maturity Model

    NARCIS (Netherlands)

    Spruit, Marco|info:eu-repo/dai/nl/297391879; Pietzka, Katharina

    2015-01-01

    This research aims to assess the master data maturity of an organization. It is based on thorough literature study to derive the main concepts and best practices in master data maturity assessment. A maturity matrix relating 13 focus areas and 65 capabilities was designed and validated. Furthermore,

  10. Assessing the Harvest Maturity of Brazilian Mangoes

    NARCIS (Netherlands)

    Pereira, T.; Tijskens, L.M.M.; Vanoli, M.; Rizzolo, A.; Eccher Zerbini, P.C.; Torricelli, A.; Filgueiras, H.; Spinelli, L.

    2010-01-01

    No clear criterion exists to determine the optimum time to harvest mango. Some empirical relations are used to assess maturity, such as shoulder development. Moreover, as a result of the typical growing conditions in tropical climates, a huge variation in maturity and ripeness exists, seriously

  11. Proteolytic Cleavage of ProBDNF into Mature BDNF in the Basolateral Amygdala Is Necessary for Defeat-Induced Social Avoidance

    Science.gov (United States)

    Dulka, Brooke N.; Ford, Ellen C.; Lee, Melissa A.; Donnell, Nathaniel J.; Goode, Travis D.; Prosser, Rebecca; Cooper, Matthew A.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in…

  12. Maturation of human oocytes in vitro

    Directory of Open Access Journals (Sweden)

    Mojca Čižek-Sajko

    2007-01-01

    Full Text Available Background: Immature oocyte retrieval followed by in vitro maturation is a promising infertility treatment option. In patients with morphologically normal ovaries and regular menstrual cycles and in patients with polycystic ovary syndrome (PCOS we attempted to assess the success of oocyte in vitro maturation in in vitro fertilization (IVF procedures.Methods: Retrospectively we analyzed 87 IVF procedures with in vitro maturation of oocytes carried out in 73 infertile couples treated at the Maribor Teaching Hospital. We compared the success following three different hormone priming protocols: regular cycling patients with normal ovaries and without hormone priming (Group A, n = 27; patients with PCOS and hormone priming with follitropin (follicle stimulating hormone, FSH (Group B, n = 22; patients with PCOS and hormone priming with human chorionic gonadotrophin (hCG (Group C, n = 38. Success of the procedure was evaluated on the basis of the ability of oocytes to mature, fertilize and develop into embryos, and on the basis of the quality of embryos and their ability to implant in the uterus.Results: In regular cycling patients with normal ovaries (n = 27 we obtained a significantly lower number of immature oocytes (3.2 ± 2.5 compared with patients with PCOS and FSH priming (11.7 ± 7.2 or those with PCOS and hCG priming (10.4 ± 7.2. The oocyte maturation rate, the fertilization rate and the embryo cleavage rate were as follows: in Group A 57.7 %, 63.2 % and 91.7 %, in Group B 57.6 %, 66.2 % and 90.0 %, and in Group C 58.0 %, 66.2 % and 91.0 % (the differences between groups were not statistically significant. Six pregnancies were recorded only in patients with PCOS. The pregnancy rate per embryo transfer was 1/20 (5.0 % in patients with FSH priming, and 5/33 (15.2 % in patients with hCG priming.Conclusions: Oocyte in vitro maturation is successful in patients with normal ovaries and regular menstrual cycle as well as in those with polycystic

  13. Determinants of loan maturity in small business lending

    Directory of Open Access Journals (Sweden)

    Ashiqur Rahman

    2017-06-01

    Full Text Available This paper investigates the determinants of loan maturity of small and medium enterprises (SMEs in the context of Visegrad countries: Czech Republic, Slovak Republic, Poland, and Hungary. The data of instead of for this paper was obtained from the Business Environment and Enterprise Performance Survey (BEEPS, which is a joint project of the European Bank for Reconstruction and Development and the World Bank. By using a binary logistic model, we have found that loan maturity is shorter for older and mature firms, firms owned by female and firms experiencing a shortage of liquidity. At the same time, we have also found that firms having concentrated ownership structure and more tangible assets can borrow for a longer period. In addition to that, we have found evidence that loan maturity is longer for the firms located closer to a bank branch. We also provide empirical support for the assumption that bank low competition is associated with longer maturity. From the obtained results, we may recommend SMEs to borrow from banks that are within their vicinity since this may increase the maturity of loans. Policy makers are recommended to implement policies so that to alleviate gender-related discrimination and take initiatives to moderate the level of competition at this market.

  14. Comparative transcriptome analyses of a late-maturing mandarin mutant and its original cultivar reveals gene expression profiling associated with citrus fruit maturation

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2017-05-01

    Full Text Available Characteristics of late maturity in fruit are good agronomic traits for extending the harvest period and marketing time. However, underlying molecular basis of the late-maturing mechanism in fruit is largely unknown. In this study, RNA sequencing (RNA-Seq technology was used to identify differentially expressed genes (DEGs related to late-maturing characteristics from a late-maturing mutant ‘Huawan Wuzishatangju’ (HWWZSTJ (Citrus reticulata Blanco and its original line ‘Wuzishatangju’ (WZSTJ. A total of approximately 17.0 Gb and 84.2 M paried-end reads were obtained. DEGs were significantly enriched in the pathway of photosynthesis, phenylpropanoid biosynthesis, carotenoid biosynthesis, chlorophyll and abscisic acid (ABA metabolism. Thirteen candidate transcripts related to chlorophyll metabolism, carotenoid biosynthesis and ABA metabolism were analyzed using real-time quantitative PCR (qPCR at all fruit maturing stages of HWWZSTJ and WZSTJ. Chlorophyllase (CLH and divinyl reductase (DVR from chlorophyll metabolism, phytoene synthase (PSY and capsanthin/capsorubin synthase (CCS from carotenoid biosynthesis, and abscisic acid 8′-hydroxylase (AB1 and 9-cis-epoxycarotenoid dioxygenase (NCED1 from ABA metabolism were cloned and analyzed. The expression pattern of NCED1 indicated its role in the late-maturing characteristics of HWWZSTJ. There were 270 consecutive bases missing in HWWZSTJ in comparison with full-length sequences of NCED1 cDNA from WZSTJ. Those results suggested that NCED1 might play an important role in the late maturity of HWWZSTJ. This study provides new information on complex process that results in the late maturity of Citrus fruit at the transcriptional level.

  15. Maturity In The Petrochemical Industry Features, Motives And Combating

    International Nuclear Information System (INIS)

    Farag, H.; El Messirie, A.

    2004-01-01

    Petrochemicals give the highest value from crude oil and natural gas but suffers from maturity like any other business. Petrochemicals companies are promoting their business in the direction from oil and gas commodities. Specialities and life science. Reasons of maturity are expired patents, low demand, over capacity, intense competition. Actions to combat maturity are to restructure capacity achieving mega sizes, do downstream, and restructuring business practices. Strategies followed by some companies to combat maturity include exit, focus on core business and exploit a competitive advantage

  16. Patterns of pulmonary maturation in normal and abnormal pregnancy.

    Science.gov (United States)

    Goldkrand, J W; Slattery, D S

    1979-03-01

    Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

  17. early maturing mutants in Indica rice and their traits

    International Nuclear Information System (INIS)

    Chen Xiulan; He Zhentian; Han Yuepeng; Liu Xueyu; Yang Hefeng; Xu Chenwu; Gu Shiliang

    1998-01-01

    The correlation and genetic parameters of eleven agronomic characters of 50 early mature lines induced from late mature cultivar, IR 1529-68-3-2 were studied by morphological classification and correlation and regression analysis. The results showed that: 1. The early mutants could be divided into two ecotype: early mature type and medium mature type of mid-maturity rice. 2. The 1000-grain weight of early mutants negatively correlated with the length of growing period. 3. According to direct path coefficients, the relation with heading period of early mutants was in order of 1000-grain-weight>plant height>seed sterility. 4.The higher heritability in broad sense were found in plant height, 1000 grain weight and heading period of the early mutants

  18. CsSCL1 is differentially regulated upon maturation in chestnut microshoots and is specifically expressed in rooting-competent cells.

    Science.gov (United States)

    Vielba, Jesús M; Díaz-Sala, Carmen; Ferro, Enrique; Rico, Saleta; Lamprecht, María; Abarca, Dolores; Ballester, Antonio; Sánchez, Conchi

    2011-10-01

    The Castanea sativa SCL1 gene (CsSCL1) has previously been shown to be induced by auxin during adventitious root (AR) formation in rooting-competent microshoots. However, its expression has not previously been analyzed in rooting-incompetent shoots. This study focuses on the regulation of CsSCL1 during maturation and the role of the gene in the formation of AR. The expression of CsSCL1 in rooting-incompetent microshoots and other tissues was investigated by quantitative reverse transcriptase--polymerase chain reaction. The analysis was complemented by in situ hybridization of the basal segments of rooting-competent and --incompetent microshoots during AR induction, as well as in AR and lateral roots. It was found that CsSCL1 is upregulated by auxin in a cell-type- and phase-dependent manner during the induction of AR. In root-forming shoots, CsSCL1 mRNA was specifically located in the cambial zone and derivative cells, which are rooting-competent cells, whereas in rooting-incompetent shoots the hybridization signal was more diffuse and evenly distributed through the phloem and parenchyma. CsSCL1 expression was also detected in lateral roots and axillary buds. The different CsSCL1 expression patterns in rooting-competent and -incompetent microshoots, together with the specific location of transcripts in cell types involved in root meristem initiation and in the root primordia of AR and lateral roots, indicate an important role for the gene in determining whether certain cells will enter the root differentiation pathway and its involvement in meristem maintenance.

  19. Digital Maturity of the Firm's Business Model

    DEFF Research Database (Denmark)

    Groskovs, Sergejs; Vemula, Sreekanth

    We propose a digital maturity assessment model as an instrument for researchers and a strategic tool for managers. Existing literature lacks a conceptually clear way to measure the construct of digital maturity at the level of the firms business model. Our proposed instrument thus opens avenues f...

  20. JUNGBRUNNEN1, a Reactive Oxygen Species–Responsive NAC Transcription Factor, Regulates Longevity in Arabidopsis

    NARCIS (Netherlands)

    Wu, A.; Devi Allu, A.; Garapati, P.; Siddiqui, H.; Dortay, H.; Zanor, M.I.; Amparo Asensi-Fabado, M.; Munne´ -Bosch, S.; Antonio, C.; Tohge, T.; Fernie, A.R.; Kaufmann, K.; Xue, G.P.; Mueller-Roeber, B.; Balazadeh, S.

    2012-01-01

    The transition from juvenility through maturation to senescence is a complex process that involves the regulation of longevity. Here, we identify JUNGBRUNNEN1 (JUB1), a hydrogen peroxide (H2O2)-induced NAC transcription factor, as a central longevity regulator in Arabidopsis thaliana. JUB1

  1. Chromatin maturation depends on continued DNA-replication

    International Nuclear Information System (INIS)

    Schlaeger, E.J.; Puelm, W.; Knippers, R.

    1983-01-01

    The structure of [ 3 H]thymidine pulse-labeled chromatin in lymphocytes differs from that of non-replicating chromatin by several operational criteria which are related to the higher nuclease sensitivity of replicating chromatin. These structural features of replicating chromatin rapidly disappear when the [ 3 H]thymidine pulse is followed by a chase in the presence of an excess of non-radioactive thymidine. However, when the rate of DNA replication is reduced, as in cycloheximide-treated lymphocytes, chromatin maturation is retarded. No chromatin maturation is observed when nuclei from pulse-labeled lymphocytes are incubated in vitro in the absence of DNA precursors. In contrast, when these nuclei are incubated under conditions known to be optimal for DNA replication, the structure of replicating chromatin is efficiently converted to that of 'mature', non-replicating chromatin. The authors conclude that the properties of nascent DNA and/or the distance from the replication fork are important factors in chromatin maturation. (Auth.)

  2. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity

    Science.gov (United States)

    Al-Wandawi, H. K.; Abdul-Rahman, M. H.; Al-Shaickley, K. A.

    Tomatoes (Lycopersicon esculentum L.,var.Monte carlo) have been Y-irradiated (100-400Krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100,200 and 300 krad at mature-green, 48 hour after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples . on the other hand, radiation had no significant effect on PH, titrable acidity and °Brix of tomatoes.

  3. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity

    International Nuclear Information System (INIS)

    Al-Wandawi, H.K.; Abdul-Rahman, M.H.; Al-Shaickley, K.A.

    1983-01-01

    Tomatoes (Lycopersicon esculentum L., var. Monte Carlo) have been γ-irradiated (100 to 400 krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100, 200 and 300 krad at mature-green, 48 hours after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples. On the other hand, radiation had no significant effect on PH, titrable acidity and deg Brix of tomatoes. (author)

  4. Association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity.

    Science.gov (United States)

    Mahmood, Hafiz Taha; Shaikh, Attiya; Fida, Mubassar

    2016-10-01

    Various methods have been proposed to evaluate a patient's developmental status. However, most of them lacked precision and failed to give a reliable estimate of skeletal maturity. The aims of this study were to evaluate the association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity and to determine its validity in assessing the different stages of the adolescent growth spurt. A cross-sectional study was performed on the pretreatment lateral cephalograms of 252 subjects aged 8 to 21 years. The sample was divided into 6 groups based on the cervical vertebral maturation stages. The frontal sinus index was calculated by dividing the frontal sinus height and width, and the cervical stages were evaluated on the same radiograph. The Kruskal-Wallis test was applied to compare frontal sinus index values at different cervical stages, and the post hoc Dunnett T3 test was applied to compare frontal sinus index values between adjacent cervical stages for each sex. The Kendall tau-b values were computed to assess the correlation between the cervical stages and the sinus index. A P value of ≤0.05 was considered statistically significant. The height and width of the frontal sinus were significantly larger in the male subjects than in the females. A significant association was found between the frontal sinus height and width and cervical stages (P ≤0.001) in both sexes. However, the changes in the frontal sinus index across the different cervical stages were found to be significant (P ≤0.001) in male subjects only. Similarly, a weak negative correlation was found between the sinus index and the cervical stages in male subjects (tau-b = -0.271; P cervical stages. The frontal sinus index cannot be used to identify the prepubertal, pubertal, and postpubertal stages of the adolescent growth spurt. Therefore, it cannot be used as a reliable maturity indicator. Copyright © 2016 American Association of

  5. A maturity model for industrial supply chains

    NARCIS (Netherlands)

    Hameri, A.P.; McKay, K.N.; Wiers, V.C.S.

    2013-01-01

    This article takes an evolutionary view of supply chains to suggest a series of distinct, contextual phases for supply chain execution and what maturity might mean at each phase. For example, what is best practice in a mature industry might not be best practice in a pioneering situation.Three

  6. Moving towards maturity in business model definitions

    DEFF Research Database (Denmark)

    Nielsen, Christian; Lund, Morten; Bukh, Per Nikolaj

    2014-01-01

    The field of business models has, as is the case with all emerging fields of practice, slowly matured through the development of frameworks, models, concepts and ideas over the last 15 years. New concepts, theories and models typically transcend a series of maturity phases. For the concept of Bus...

  7. Changes in photosynthetic performance and antioxidative strategies during maturation of Norway maple (Acer platanoides L.) leaves.

    Science.gov (United States)

    Lepeduš, Hrvoje; Gaća, Vlatka; Viljevac, Marija; Kovač, Spomenka; Fulgosi, Hrvoje; Simić, Domagoj; Jurković, Vlatka; Cesar, Vera

    2011-04-01

    Different structural and functional changes take place during leaf development. Since some of them are highly connected to oxidative metabolism, regulation of reactive oxygen species (ROS) abundance is required. Most of the reactive oxygen species ROS in plant cells are produced in chloroplasts as a result of highly energetic reactions of photosynthesis. The aim of our study was to examine the changes in concentration of oxidative stress parameters (TBARS - thiobarbituric acid-reacting substances and protein carbonyls) as well as antioxidative strategies during development of maple (Acer platanoides L.) leaves in the light of their enhanced photosynthetic performance. We reveal that biogenesis of the photosynthetic apparatus during maple leaf maturation corresponded with oxidative damage of lipids, but not proteins. In addition, antioxidative responses in young leaves differed from that in older leaves. Young leaves had high values of non-photochemical quenching (NPQ) and catalase (CAT, EC 1.11.1.6) activity which declined during the maturation process. Developing leaves were characterized by an increase in TBARS level, the content of non-enzymatic antioxidants as well as ascorbate peroxidase activity (APX, EC 1.11.1.11), while the content of protein carbonyls decreased with leaf maturation. Fully developed leaves had the highest lipid peroxidation level accompanied by a maximum in ascorbic acid content and superoxide dismutase activity (SOD, EC1.15.1.1). These observations imply completely different antioxidative strategies during leaf maturation enabling them to perform their basic function. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Insulin-like growth factor I: a biologic maturation indicator.

    Science.gov (United States)

    Ishaq, Ramy Abdul Rahman; Soliman, Sanaa Abou Zeid; Foda, Manal Yehya; Fayed, Mona Mohamed Salah

    2012-11-01

    Determination of the maturation level and the subsequent evaluation of growth potential during preadolescence and adolescence are important for optimal orthodontic treatment planning and timing. This study was undertaken to evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as a maturation indicator by correlating it to the cervical vertebral maturation index. The study was conducted with 120 subjects, equally divided into 60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral cephalometric radiograph and a blood sample were taken from each subject. For each subject, cervical vertebral maturation and IGF-I serum level were assessed. Mean values of IGF-I in each stage of cervical vertebral maturation were calculated, and the means in each stage were statistically compared with those of the other stages. The IGF-I mean value at each cervical vertebral maturation stage was statistically different from the mean values at the other stages. The highest mean values were observed in stage 4, followed by stage 5 in males and stage 3 in females. IGF-I serum level is a reliable maturation indicator that could be applied in orthodontic diagnosis. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. Antibody Affinity Maturation in Fishes—Our Current Understanding

    Directory of Open Access Journals (Sweden)

    Brad G. Magor

    2015-07-01

    Full Text Available It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig mutator enzyme activation-induced cytidine deaminase (AID. We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes.

  10. Characterisation and changes in the antioxidant system of chloroplasts and chromoplasts isolated from green and mature pepper fruits.

    Science.gov (United States)

    Martí, M C; Camejo, D; Olmos, E; Sandalio, L M; Fernández-García, N; Jiménez, A; Sevilla, F

    2009-07-01

    Purification and characterisation of pepper (Capsicum annuum L) chloroplasts and chromoplasts isolated from commercial green, red and yellow mature fruits were undertaken. Induction of the synthesis of several antioxidants in organelles isolated from mature fruits was found. The ultrastructure of organelles and the presence and activity of SOD isozymes and enzymes involved in the ASC-GSH cycle, together with the non-enzymatic antioxidant content and some oxidative parameters, were analysed. It was found that lipids, rather than proteins, seem to be a target for oxidation in the chromoplasts. The ascorbate and glutathione contents were elicited during differentiation of chloroplasts into chromoplasts in both red and yellow fruits. The activity of SOD and of components of the ASC-GSH cycle was up-regulated, suggesting that these enzymes may play a role in the protection of plastids and could act as modulators of signal molecules such as O(2) ( -) and H(2)O(2) during fruit maturation. The presence of an Mn-SOD in chromoplasts isolated from yellow pepper fruits was also investigated in terms of structural and antioxidant differences between the two cultivars.

  11. Salt, chloride, bleach, and innate host defense

    Science.gov (United States)

    Wang, Guoshun; Nauseef, William M.

    2015-01-01

    Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979

  12. Salt, chloride, bleach, and innate host defense.

    Science.gov (United States)

    Wang, Guoshun; Nauseef, William M

    2015-08-01

    Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.

  13. A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation.

    Science.gov (United States)

    Saugstad, L F

    1999-10-19

    The planum temporale (PT) bias, PT leftward, PT symmetry, and PT rightward reversal and sidedness preference, consistent right-handedness, ambilaterality, and consistent left-handedness are placed on a continuum mirroring the normal variation in rate of brain maturation. Maturational rate declines as we pass from PT leftward bias and consistent right-handedness to PT reversal and consistent left-handedness. Concomitantly, we expect an increased prevalence of males due to their pubertal age being about 2 years later than that of females, and a shift in cognitive profile from higher verbal scores than performance scores on the WAIS to higher performance than verbal scores. Three disorders fulfilling the criteria of late CNS maturation apart from the corresponding cognitive profile were studied: infantile autism (IA), schizophrenia (S), and developmental dyslexia (DD). These disorders have in common deficits in cognition, perception, and somatomotor function. The deficits range from an arrest in brain development (which is evident in infancy superimposed on late maturation in IA) to overall delayed brain and somatic development in S (culminating in postpubertal psychotic episodes and persistent and generalized residual deficits). Finally, reading inability, problems in perception (vision and hearing) and in motor coordination, particularly between the two hemispheres, characterize DD. Enhancing brain maturation and the prevalence of 'normal' cerebral asymmetry--laterality is preferable if we want to reduce the risk of developing the above-mentioned disorders. It is suggested that in the past environmental challenges have favored early maturation, with its abundant neuronal population, arborization and excessive density of synapses and cerebral excitability which has powered evolution through the mechanism of natural selection. Early maturation is obtainable through optimal nutrition, including a satisfactory amount of marine fat (PUFA), before and during pregnancy and

  14. Grammar Maturity Model

    NARCIS (Netherlands)

    Zaytsev, V.; Pierantonio, A.; Schätz, B.; Tamzalit, D.

    2014-01-01

    The evolution of a software language (whether modelled by a grammar or a schema or a metamodel) is not limited to development of new versions and dialects. An important dimension of a software language evolution is maturing in the sense of improving the quality of its definition. In this paper, we

  15. Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan

    2008-01-01

    The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1...... polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC......-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza...

  16. Developmental programming of long non-coding RNAs during postnatal liver maturation in mice.

    Directory of Open Access Journals (Sweden)

    Lai Peng

    Full Text Available The liver is a vital organ with critical functions in metabolism, protein synthesis, and immune defense. Most of the liver functions are not mature at birth and many changes happen during postnatal liver development. However, it is unclear what changes occur in liver after birth, at what developmental stages they occur, and how the developmental processes are regulated. Long non-coding RNAs (lncRNAs are involved in organ development and cell differentiation. Here, we analyzed the transcriptome of lncRNAs in mouse liver from perinatal (day -2 to adult (day 60 by RNA-Sequencing, with an attempt to understand the role of lncRNAs in liver maturation. We found around 15,000 genes expressed, including about 2,000 lncRNAs. Most lncRNAs were expressed at a lower level than coding RNAs. Both coding RNAs and lncRNAs displayed three major ontogenic patterns: enriched at neonatal, adolescent, or adult stages. Neighboring coding and non-coding RNAs showed the trend to exhibit highly correlated ontogenic expression patterns. Gene ontology (GO analysis revealed that some lncRNAs enriched at neonatal ages have their neighbor protein coding genes also enriched at neonatal ages and associated with cell proliferation, immune activation related processes, tissue organization pathways, and hematopoiesis; other lncRNAs enriched at adolescent ages have their neighbor protein coding genes associated with different metabolic processes. These data reveal significant functional transition during postnatal liver development and imply the potential importance of lncRNAs in liver maturation.

  17. Tomato seeds maturity detection system based on chlorophyll fluorescence

    Science.gov (United States)

    Li, Cuiling; Wang, Xiu; Meng, Zhijun

    2016-10-01

    Chlorophyll fluorescence intensity can be used as seed maturity and quality evaluation indicator. Chlorophyll fluorescence intensity of seed coats is tested to judge the level of chlorophyll content in seeds, and further to judge the maturity and quality of seeds. This research developed a detection system of tomato seeds maturity based on chlorophyll fluorescence spectrum technology, the system included an excitation light source unit, a fluorescent signal acquisition unit and a data processing unit. The excitation light source unit consisted of two high power LEDs, two radiators and two constant current power supplies, and it was designed to excite chlorophyll fluorescence of tomato seeds. The fluorescent signal acquisition unit was made up of a fluorescence spectrometer, an optical fiber, an optical fiber scaffolds and a narrowband filter. The data processing unit mainly included a computer. Tomato fruits of green ripe stage, discoloration stage, firm ripe stage and full ripe stage were harvested, and their seeds were collected directly. In this research, the developed tomato seeds maturity testing system was used to collect fluorescence spectrums of tomato seeds of different maturities. Principal component analysis (PCA) method was utilized to reduce the dimension of spectral data and extract principal components, and PCA was combined with linear discriminant analysis (LDA) to establish discriminant model of tomato seeds maturity, the discriminant accuracy was greater than 90%. Research results show that using chlorophyll fluorescence spectrum technology is feasible for seeds maturity detection, and the developed tomato seeds maturity testing system has high detection accuracy.

  18. Guidelines for assessing the knowledge management maturity of organizations

    Directory of Open Access Journals (Sweden)

    C. J. Kruger

    2007-11-01

    Full Text Available In a recent article Kruger and Snyman hypothesized that progressions in knowledge management maturity (from a strategic perspective are directly related to an increased ability to speed up the strategic cycle of imitation, consolidation and innovation. The arguments proposed, however, neglected to supply the reader with a practical toolkit or even a roadmap (a time-related matrix, or questionnaire to successfully measure succession in knowledge management maturity. This article builds on the previous one and proposes a questionnaire consisting of six sections, containing 101 descriptive questions, to enable organizations to test and assess their knowledge management maturity empirically. The development of an instrument to measure knowledge management maturity required adhering to a research design that combined theoretical propositions with practical experimentation. As a point of departure, a knowledge management maturity matrix consisting of seven maturity levels was formulated. All questions contained within the matrix were benchmarked against a survey questionnaire developed by the public management service of the OECD (PUMA and were also pre-tested and validated. This process of refinement led to the formulation of the Knowledge Management Maturity Questionnaire. To avoid any taint of this research being based only on theoretical propositions, the questionnaire was tested by 178 master students of the University of Pretoria, South Africa, in nine different industries. The proposed questionnaire provides a bridge between theoretical propositions and practical usability, not only enabling knowledge management practitioners to assess the level of knowledge management maturity reached successfully but, more importantly, also serving as a guideline to institutionalize further and future knowledge management endeavours.

  19. cAMP and EPAC are key players in the regulation of the signal transduction pathway involved in the α-hemolysin autophagic response.

    Directory of Open Access Journals (Sweden)

    María Belén Mestre

    Full Text Available Staphylococcus aureus is a microorganism that causes serious diseases in the human being. This microorganism is able to escape the phagolysosomal pathway, increasing intracellular bacterial survival and killing the eukaryotic host cell to spread the infection. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. We have shown that the pore-forming toxin α-hemolysin (Hla is the S. aureus-secreted factor responsible for the activation of the autophagic pathway and that this response occurs through a PI3K/Beclin1-independent form. In the present report we demonstrate that cAMP has a key role in the regulation of this autophagic response. Our results indicate that cAMP is able to inhibit the autophagy induced by Hla and that PKA, the classical cAMP effector, does not participate in this regulation. We present evidence that EPAC and Rap2b, through calpain activation, are the proteins involved in the regulation of Hla-induced autophagy. Similar results were obtained in cells infected with different S. aureus strains. Interestingly, in this report we show, for the first time to our knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing phagosome. We believe that our findings have important implications in understanding innate immune processes involved in intracellular pathogen invasion of the host cell.

  20. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    Science.gov (United States)

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Impact of in vitro treatments of physiological levels of estradiol and progesterone observed in pregnancy on bovine monocyte-derived dendritic cell differentiation and maturation

    NARCIS (Netherlands)

    Pomeroy, Brianna; Klaessig, Suzanne; Schukken, Ynte

    2016-01-01

    The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and

  2. Sequential Analysis of Global Gene Expression Profiles in Immature and In vitro Matured Bovine Oocytes: Potential Molecular Markers of Oocyte Maturation

    LENUS (Irish Health Repository)

    Mamo, Solomon

    2011-03-16

    Abstract Background Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results 8489 transcripts were detected across the two oocyte groups, of which ~25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of α-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource

  3. Cone and Seed Maturation of Southern Pines

    Science.gov (United States)

    James P. Barnett

    1976-01-01

    If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

  4. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

    Science.gov (United States)

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-04-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. © The Author 2016. Published by

  5. Self trust, a major challenge for nuclear regulators

    Energy Technology Data Exchange (ETDEWEB)

    Eibenschutz, J. [National Nuclear Safety and Safeguards Commission (CNSN), Mexico City (Mexico)

    2014-07-01

    Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

  6. Self trust, a major challenge for nuclear regulators

    International Nuclear Information System (INIS)

    Eibenschutz, J.

    2014-01-01

    Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

  7. Virtual Reality Game Education to Learn Traffic Regulation

    OpenAIRE

    Andru Deva Lukito

    2017-01-01

    Abstract – Traffic accident has become number 3 of children death cause in the world according to WHO[1]. Traffic accident that involve children often caused by their own by breaking the law or regulation. Therefor education about traffic regulation and law including traffic sign and its meaning must be given to children early. Because education means process to change a person or a group attitude and behavior in order to make them mature through teaching and training [2]. One of them that ca...

  8. Analyzing Project Management Maturity Level in Indonesia

    Directory of Open Access Journals (Sweden)

    Eliot Simangunsong

    2013-04-01

    Full Text Available Project management has been generally known and increasingly used by many organizations to gain competitive advantage. In this context, many studies have proposed maturity models to evaluate how project management knowledge has been deployed effectively and efficiently in or- ganization. As a developing country, Indonesia needs many development projects managed by government and private companies in different industries. Here, a study to assess project manage- ment maturity level in Indonesian businesses may bring insight about current business practices, which is important to speed up country development and business sustainability. Adapting the Project Management Maturity Model (ProMMM, a survey instrument has been developed and ap- plied to professionals from Jakarta and surrounding area. The result of analysis shows that con- struction and primary industry have a higher maturity level compare to manufacturing and servic- es. It is to be noted, however, that the level of project management understanding is low across in- dustries. This indicates that more quality project management training or certification is required to improve overall project management knowledge in Indonesia.

  9. Mature teratoma of the posterior mediastinum

    International Nuclear Information System (INIS)

    Kurosaki, Y.; Tanaka, Y.O.; Itai, Y.

    1998-01-01

    The vast majority of germ cell tumors in the thorax arise at or near the thymus. We report a case of a 41-year-old man with mature teratoma of the posterior mediastinum. He was asymptomatic and was incidentally found to have a posterior mediastinal mass. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification. The differential diagnosis included neurogenic tumors, liposarcoma, and extramedullary hematopoiesis. (orig.)

  10. Mature Oocyte Cryopreservation for Fertility Preservation.

    Science.gov (United States)

    Liang, Tina; Motan, Tarek

    2016-01-01

    In recent decades, advances in cancer treatment have led to a dramatic improvement in long term survival. This has led to an increasing focus on quality of life after surviving cancer treatment, with fertility being an important aspect. Given the known reproductive risks of cancer therapies, there has been a growing interest in the field of fertility preservation (also referred to as oncofertility). Mature oocyte cryopreservation is no longer considered experimental and has become a realistic option for reproductive aged women prior to undergoing cancer treatment. Additionally, as cryopreservation techniques improve, mature oocyte cryopreservation is increasing being marketed to healthy women without cancer wishing to delay child bearing, also termed "social egg freezing". This chapter provides a review of the current technology, use, and outcomes of mature oocyte cryopreservation. It also outlines the ethical debate surrounding social egg freezing and directions for future research in female fertility preservation.

  11. POSTTREATMENT NEUROBLASTOMA MATURATION TO GANGLIONIC CELL TUMOR

    Directory of Open Access Journals (Sweden)

    M. V. Ryzhova

    2012-01-01

    Full Text Available Tumor cells can differentiate into more mature forms in undifferentiated or poorly differentiated tumors, such as medulloblastomas with increased nodularity, as well as neuroblastomas. The authors describe 2 cases of neuroblastoma maturation into ganglioneuroblastoma 5 months after chemotherapy in a 2-year-old girl and 3 years after radiotherapy in a 16-year-old girl.

  12. Information system maturity and the hospitality enterprise performance

    Directory of Open Access Journals (Sweden)

    Daniela Garbin Pranicevic

    2015-01-01

    Full Text Available The purpose of this paper is to empirically evaluate the relationship between the maturity of hotels’ information systems and their performance. This study uses customized models of information system (IS maturity and hotel performance measurement. Since we wanted to include the intangible aspects of performance, we opted for an adapted application of the Balanced Scorecard model. In the empirical part of the paper, fundamental constructs of the model are verified, while the individual items are further evaluated by employing discriminant analysis to distinguish hotels with relatively low and high performance levels. The findings demonstrate the existence of a significant and positive relationship between IS maturity and two dimensions of performance in the hospitality industry – process quality and guest relationships. The level of employee development and financial performance do not seem to be related to IS maturity. Although representative, the sample is relatively small, and the primary data were collected in a single country. The paper provides a framework of IS maturity items in the hospitality industry which seem to contribute to hotels’ business performances. As such, it can serve as a practical framework relevant for IT management in tourism and hospitality. The paper addresses a topic already discussed in a range of industries, although it does not seem to have been empirically evaluated by many studies of the tourism and hospitality industry. In addition, a new theoretical model of IT maturity in tourism and hospitality is proposed.

  13. Melatonin-induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence.

    Science.gov (United States)

    He, Bin; Yin, Chao; Gong, Yabin; Liu, Jie; Guo, Huiduo; Zhao, Ruqian

    2018-01-01

    Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin-treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence. © 2017 Wiley Periodicals, Inc.

  14. CT findings of overian teratomas : mature versus immature

    International Nuclear Information System (INIS)

    Kim, Jong Chul; Kim, Young Wol

    1996-01-01

    To differentiate mature and immature ovarian teratomas, using CT findings. The CT findings of ten mature ovarian teratomas (in one patient, bilateral) and ten which were immature were compared, using statistical analysis. Images were evaluated for size, margins, architecture, contents (mural nodules, fat, calcification), septa, local invasion and distant metastasis. These findings were compared with pathologic findings. Of the ten mature tumors, nine were well defined and predominantly cystic in internal architecture, and one was mixed. Mural nodules were found in six tumor, fat in all, distinct calcification in seven, and regular septa in three lesions. Of the ten immature humors, eight had irregular margins. Seven were predominantly solid in internal architecture and irregularly enhanced, two were mixed, and one was mainly cystic. Fat was detected in five lesions, indistinct scattered calcification in six, irregular septa in three, and local invasion of distant metastasis in four patients. Compared with mature ovarian teratomas, those that are immature tend to show CT findings of marginal irregularity, solid mass with irregular enhacement, scattered indistinct calcifications, septal irregularity, local invasion or distant metastasis. Our experience suggests that these findings may be helpful in differentiation of mature and immature ovarian teratomas

  15. The RNA-binding protein, ZFP36L2, influences ovulation and oocyte maturation.

    Directory of Open Access Journals (Sweden)

    Christopher B Ball

    Full Text Available ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004, suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3'UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.

  16. Indeks Penilaian Kematangan (Maturity Manajemen Keamanan Layanan TI

    Directory of Open Access Journals (Sweden)

    Farroh Sakinah

    2014-09-01

    Full Text Available Pemanfaatan Teknologi Informasi (TI dalam mendukung terselenggaranya pelayanan yang optimal menjadi kebutuhan utama organisasi saat ini. Jaminan pengelolaan layanan dan keamanan yang baik menjadi salah satu tolok ukurnya. Pengimplementasian sebuah standar menjadi salah satu solusinya meskipun penggunaan satu buah standar dirasa belum maksimal melihat cakupan yang disediakan kurang luas sehingga diadakannya upaya penggabungan beberapa standar dengan harapan standar-standar tersebut dapat saling melengkapi. Pengimplementasian beberapa standar ini dapat dimonitoring tingkat kematangannya (maturity dengan menggunakan alat ukur penilaian kematangan (maturity. Alat ukur kematangan (maturity manajemen keamanan layanan ini merupakan gabungan pemetaan dari control objective IT Governance COBIT 4.1 yang dipenuhi kebutuhan manajemen layanannya sesuai dengan Service Management di dalam ITIL v3 (Information Technology Infrastructure Library. Selanjutnya kebutuhan manajemen layanan ini diukur dengan maturity level COBIT 4.1 dan disesuaikan dengan framework ISO 27000 untuk memaksimalkan manajemen keamanan informasi.

  17. mTORC1 directly phosphorylates and regulates human MAF1.

    OpenAIRE

    Michels Annemieke A; Robitaille Aaron M; Buczynski-Ruchonnet Diane; Hodroj Wassim; Reina Jaime H; Hall Michael N; Hernandez Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the p...

  18. Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing.

    Science.gov (United States)

    Clancy, Danielle M; Sullivan, Graeme P; Moran, Hannah B T; Henry, Conor M; Reeves, Emer P; McElvaney, Noel G; Lavelle, Ed C; Martin, Seamus J

    2018-03-13

    Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation. Here, we show that proteases liberated from activated neutrophils can positively or negatively regulate the activity of six IL-1 family cytokines (IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ) with exquisite sensitivity. In contrast, extracellular neutrophil proteases displayed very poor bactericidal activity, exhibiting 100-fold greater potency toward cytokine processing than bacterial killing. Thus, in addition to their classical role as phagocytes, neutrophils play an important immunoregulatory role through deployment of their granule proteases into the extracellular space to process multiple IL-1 family cytokines. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Methodology for Diagnostics of the Company Management and Technological Maturity

    Directory of Open Access Journals (Sweden)

    Olena Martynyuk

    2017-12-01

    Full Text Available Approaches to the measurement and assessment of the company technological maturity level and management maturity apart, formulated in scientific researches and practical recommendations, significantly differ according to their purpose, content and depth of the factors analysis. Studies of the company technological maturity and possibility for implementing business processes and certain IT technologies have become more advanced in some degree. The general idea of forming a model of diagnostics of the management and technological maturity is based on the determination of prevailing company system influence components. Management techniques are a nucleus of the model, and the innovation level of management techniques is an energy impulse inciting to development. Basing on the analysis performed, the author created a concept of levels of the company management and technological maturity considering the main parameters of the company management and technological maturity. A composite algorithm was proposed for determining the level of managerial technological maturity (LMTM, end exposition of a complex of management techniques to ensure the company dynamic progress based on determining a level of the management and technological maturity. The advantages and disadvantages are determined by the methodology. The performed approbation has confirmed the approach validity and its usefulness. The approbation shows the reliability and unambiguity of interpreting results. To use it for bigger enterprises and corporations, it is not even necessary to change identification parameters.

  20. Mature teratoma of the posterior mediastinum

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Y.; Tanaka, Y.O.; Itai, Y. [Department of Radiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305 (Japan)

    1998-02-01

    The vast majority of germ cell tumors in the thorax arise at or near the thymus. We report a case of a 41-year-old man with mature teratoma of the posterior mediastinum. He was asymptomatic and was incidentally found to have a posterior mediastinal mass. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification. The differential diagnosis included neurogenic tumors, liposarcoma, and extramedullary hematopoiesis. (orig.) With 2 figs., 18 refs.

  1. Impact of in vitro treatments of physiological levels of estradiol and progesterone observed in pregnancy on bovine monocyte-derived dendritic cell differentiation and maturation

    NARCIS (Netherlands)

    Pomeroy, Brianna; Klaessig, Suzanne; Schukken, Ynte

    2016-01-01

    The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and

  2. ASSOCIATION BETWEEN DENTAL AND SKELETAL MATURATION STAGES IN CROATIAN SUBJECTS.

    Science.gov (United States)

    Srkoc, Tamara; Mestrović, Senka; Anić-Milosević, Sandra; Slaj, Mladen

    2015-12-01

    This study investigated the relationships between the stages of calcification of teeth and cervical vertebral maturation. The sample consisted of 295 subjects (129 male and 166 female), mean age 13.36 ± 2.65 (range 7-18) years. Dental age was evaluated from panoramic radiographs according to the method of Demirjian. Cervical vertebral maturation was determined on lateral cephalometric radiographs using cervical vertebrae maturation stages (CVS). For assessing the relationship between cervical vertebral and dental maturation, percentage distributions of the stages of calcification for each studied tooth were calculated. Only in the first CVS stage, boys and girls were of the same age. In all other stages (CVS 2-CVS 6) girls were by 0.98 (range 0.23-1.86) younger than boys. Gender differences in the mineralization pattern were also observed. It was found that dental maturation was finished earlier in female subjects. The highest correlation coefficient between dental and skeletal maturity was found for second premolars. Mineralization pattern of second premolars could be considered as a guideline for prediction of the pubertal growth spurt. Dental maturation stages might be clinically useful as a reliable indicator of facial growth.

  3. Radium retention in mature beagles injected at 5 years of age

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Bruenger, F.W.; Jones, C.W.; Taylor, G.N.; Mays, C.W.

    1982-01-01

    Retention of 226 Ra was substantially lower in mature beagles injected at 5 years of age compared to corresponding values for 1 1/2-year-old young adult beagles. As with young adults, average retention in mature dogs given about 10 μCi/kg exceeded that of mature dogs given 4 μCi/kg or less. Measured 222 Rn/ 226 Ra ratios in bone were similar in mature and young adults. About 66% of the injected radium was excreted by mature dogs during the first 3 weeks, about 2/3 of the total excretion appearing in the feces. Distribution of 226 Ra within the skeleton was similar in mature and young adult beagles

  4. MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection.

    Science.gov (United States)

    Kim, Jin Kyung; Yuk, Jae-Min; Kim, Soo Yeon; Kim, Tae Sung; Jin, Hyo Sun; Yang, Chul-Su; Jo, Eun-Kyeong

    2015-06-01

    MicroRNAs (miRNAs) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis. Although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of miRNAs and whether they specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that M. tuberculosis infection of macrophages leads to increased expression of miRNA-125a-3p (miR-125a), which targets UV radiation resistance-associated gene (UVRAG), to inhibit autophagy activation and antimicrobial responses to M. tuberculosis. Forced expression of miR-125a significantly blocked M. tuberculosis-induced activation of autophagy and phagosomal maturation in macrophages, and inhibitors of miR-125a counteracted these effects. Both TLR2 and MyD88 were required for biogenesis of miR-125a during M. tuberculosis infection. Notably, activation of the AMP-activated protein kinase significantly inhibited the expression of miR-125a in M. tuberculosis-infected macrophages. Moreover, either overexpression of miR-125a or silencing of UVRAG significantly attenuated the antimicrobial effects of macrophages against M. tuberculosis. Taken together, these data indicate that miR-125a regulates the innate host defense by inhibiting the activation of autophagy and antimicrobial effects against M. tuberculosis through targeting UVRAG. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. Radiation induced early maturing mutants in barley

    International Nuclear Information System (INIS)

    Kumar, R.; Chauhan, S.V.S.; Sharma, R.P.

    1978-01-01

    In M 2 generation, two early maturing plants were screened from a single spike progeny of a plant obtained from 20 kR of gamma-ray irradiation of a six-rowed barley (Hordeum vulgare L. var. Jyoti). Their true breeding nature was confirmed in M 3 generation. These mutants flower and mature 38 and 22 days earlier than those of control. (auth.)

  6. In vitro maturation of human oocytes for assisted reproduction.

    Science.gov (United States)

    Jurema, Marcus W; Nogueira, Daniela

    2006-11-01

    To describe and evaluate the current practice of in vitro maturation of oocytes for assisted reproduction. Review of the available and relevant literature regarding in vitro maturation of oocytes. In vitro maturation of human oocytes retrieved from antral ovarian follicles is an emerging procedure quickly being incorporated into the realm of assisted reproductive technologies. This new technology has several potential advantages over traditional controlled ovarian hyperstimulation for IVF, such as reduction of costs by minimizing gonadotropin and GnRH analogue use, elimination of ovarian hyperstimulation syndrome, and simplicity of protocol. In vitro maturation of oocytes for assisted reproduction in human beings still is undergoing refinement but currently is providing efficacy and safety outcome comparable to that of traditional IVF in recent selected studies. Implementing in vitro maturation into an established IVF practice is feasible and requires only a few simple adjustments. Crucial to the advancement and optimization of the technology is a better understanding of how to maximize immature oocyte developmental competence and endometrial receptivity.

  7. A Comparison of Skeletal Maturation assessed from MP3 and Its Correlation with Dental Maturation

    Directory of Open Access Journals (Sweden)

    Vishnu Vardhan Reddy

    2014-01-01

    Full Text Available To compare the various ossification stages of middle phalanges of third finger (MP3 and developmental stages of 2nd mandibular molar during the entire process of pubertal growth spurt. Evaluate the feasibility of recording MP3 stages using standard dental X-ray film. The mandibular 2nd molar exhibited highly significant correlation for both the males and females. This study showed a good correlation between the MP3 and dental maturity indicators. Therefore, 2nd molar tooth could be used as maturity indicator for the entire period of pubertal growth spurt. It can be used as an adjunct to the hand and wrist radiograph.

  8. Toward the Decision Tree for Inferring Requirements Maturation Types

    Science.gov (United States)

    Nakatani, Takako; Kondo, Narihito; Shirogane, Junko; Kaiya, Haruhiko; Hori, Shozo; Katamine, Keiichi

    Requirements are elicited step by step during the requirements engineering (RE) process. However, some types of requirements are elicited completely after the scheduled requirements elicitation process is finished. Such a situation is regarded as problematic situation. In our study, the difficulties of eliciting various kinds of requirements is observed by components. We refer to the components as observation targets (OTs) and introduce the word “Requirements maturation.” It means when and how requirements are elicited completely in the project. The requirements maturation is discussed on physical and logical OTs. OTs Viewed from a logical viewpoint are called logical OTs, e.g. quality requirements. The requirements of physical OTs, e.g., modules, components, subsystems, etc., includes functional and non-functional requirements. They are influenced by their requesters' environmental changes, as well as developers' technical changes. In order to infer the requirements maturation period of each OT, we need to know how much these factors influence the OTs' requirements maturation. According to the observation of actual past projects, we defined the PRINCE (Pre Requirements Intelligence Net Consideration and Evaluation) model. It aims to guide developers in their observation of the requirements maturation of OTs. We quantitatively analyzed the actual cases with their requirements elicitation process and extracted essential factors that influence the requirements maturation. The results of interviews of project managers are analyzed by WEKA, a data mining system, from which the decision tree was derived. This paper introduces the PRINCE model and the category of logical OTs to be observed. The decision tree that helps developers infer the maturation type of an OT is also described. We evaluate the tree through real projects and discuss its ability to infer the requirements maturation types.

  9. The maturation and germination of Phytophthora ramorum Chlamydospores

    Science.gov (United States)

    Aaron L. Smith; Everett M. Hansen

    2008-01-01

    Chlamydospores are a distinctive feature of Phytophthora ramorum. They are formed quickly in agar, and within colonized leaves. We followed their development and maturation in vitro and in vivo, and studied conditions affecting their germination. Cell walls of mature P. ramorum chlamydospores...

  10. Study of Kerogen Maturity using Transmission Fourier Transform Infrared Spectroscopy (FTIR)

    Science.gov (United States)

    Dang, S. T.

    2014-12-01

    Maturity of kerogen in shale governs the productivity and generation hydrocarbon type. There are generally two accepted methods to measure kerogen maturity; one is the measurement of vitrinite reflectance, %Ro, and another is the measurement of Tmax through pyrolysis. However, each of these techniques has its own limits; vitrinite reflectance measurement cannot be applied to marine shale and pre-Silurian shales, which lack plant materials. Furthermore, %Ro, requires the isolation and identification of vitrinite macerals and statistical measurements of at least 50 macerals. Tmax measurement is questionable for mature and post-mature samples. In addition, there are questions involving the effects of solvents on Tmax determinations. Fourier Transmission Infrared Spectroscopy, FTIR, can be applied for both qualitative and quantitative assessment on organics maturity in shale. The technique does not require separating organic matter or identifying macerals. A CH2/CH3 index, RCH, calculated from FTIR spectra is more objective than other measurements. The index increases with maturity (both natural maturation and synthetic maturation through hydrous and dry pyrolysis). The new maturity index RCH can be calibrated to vitrinite reflectance which allows the definition of the following values for levels of maturity: 1) immature—RCH > 1.6±0.2; 2) oil window-- 1.6±0.2 1.3±0.3; 3) wet gas window--1.3±0.3 1.13±0.05; and 4) dry gas window RCH < 1.13±0.05.

  11. Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kurt F. Hauser

    2018-01-01

    Full Text Available The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

  12. Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System.

    Science.gov (United States)

    Hauser, Kurt F; Knapp, Pamela E

    2017-01-01

    The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS) regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance) during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

  13. Detection of optimum maturity of maize using image processing and ...

    African Journals Online (AJOL)

    A CCD camera for image acquisition of the different green colorations of the maize leaves at maturity was used. Different color features were extracted from the image processing system (MATLAB) and used as inputs to the artificial neural network that classify different levels of maturity. Keywords: Maize, Maturity, CCD ...

  14. Correlation between cervical vertebral and dental maturity in Iranian subjects.

    Science.gov (United States)

    Heravi, Farzin; Imanimoghaddam, Mahrokh; Rahimi, Hoda

    2011-12-01

    Determination of the skeletal maturation is extremely important in clinical orthodontics. Cervical vertebral maturation is an effective diagnostic tool for determining the adolescent growth spurt. The aim of this study was to investigate the correlation between the stages of calcification of teeth and the cervical vertebral maturity stages.

  15. Plant-specific volatile organic compound emission rates from young and mature leaves of Mediterranean vegetation

    Science.gov (United States)

    Bracho-Nunez, Araceli; Welter, Saskia; Staudt, Michael; Kesselmeier, Jürgen

    2011-08-01

    The seasonality of vegetation, i.e., developmental stages and phenological processes, affects the emission of volatile organic compounds (VOCs). Despite the potential significance, the contributions of seasonality to VOC emission quality and quantity are not well understood and are therefore often ignored in emission simulations. We investigated the VOC emission patterns of young and mature leaves of several Mediterranean plant species in relation to their physiological and developmental changes during the growing period and estimated Es. Foliar emissions of isoprenoids and oxygenated VOCs like methanol and acetone were measured online by means of a proton transfer reaction mass spectrometer (PTR-MS) and offline with gas chromatography coupled with a mass spectrometer and flame ionization detector. The results suggest that VOC emission is a developmentally regulated process and that quantitative and qualitative variability is plant species specific. Leaf ontogeny clearly influenced both the VOC Es and the relative importance of different VOCs. Methanol was the major compound contributing to the sum of target VOC emissions in young leaves (11.8 ± 10.4 μg g-1 h-1), while its contribution was minor in mature leaves (4.1 ± 4.1 μg g-1 h-1). Several plant species showed a decrease or complete subsidence of monoterpene, sesquiterpene, and acetone emissions upon maturity, perhaps indicating a potential response to the higher defense demands of young emerging leaves.

  16. Quercetin Efficacy on in vitro Maturation of Porcine Oocytes

    Directory of Open Access Journals (Sweden)

    Delia Orlovschi

    2014-05-01

    Full Text Available The present study proposed to examine the effects of a polyphenol (quercetin on in vitro maturated parameters. Quercetin it has been extensively studied by researchers on animals over the 35 years. It is a plant derived flavonoid from fruits and vegetables that has antioxidant action as a free radical scavenger. Immature porcine oocytes were untreated and treated with 5, 15, 25, 35 µg/ml quercetin during in vitro maturation. After then the mature oocytes were fertilized. It was observed that cumulus cell expansion of COCs cultured in maturation media supplemented with 5 µg/ml quercetin in grad 3 could be very significantly increased (p<0.001. In grad 4 could be significantly between different levels of quercetin (5 vs. 25, 5 vs. 35, p<0.001. The rates of embryos cultured in medium supplemented with different levels of quercetin did not presented significantly statistically different. The presence of 25 µg/ml quercetin in the maturation medium increased the percentage of embryos in the morula stage compared with the control. In the morula stage all the concentrations of quercetin resulted percentages increased to control. This results shows that quercetin added during in vitro maturation has a positive effect on future embryos development.

  17. Effect of melatonin on maturation capacity and fertilization of Nili ...

    African Journals Online (AJOL)

    This study evaluated the effect of melatonin supplementation of in vitro maturation media on in vitro maturation (IVM) and in vitro fertilization (IVF) rate of buffalo oocytes. Cumulus oocytes complexes (COCs) were aspirated from follicles of 2-8 mm diameter. In experiment I, COCs were matured in IVM medium supplemented ...

  18. As Technologies for Nucleotide Therapeutics Mature, Products Emerge.

    Science.gov (United States)

    Beierlein, Jennifer M; McNamee, Laura M; Ledley, Fred D

    2017-12-15

    The long path from initial research on oligonucleotide therapies to approval of antisense products is not unfamiliar. This lag resembles those encountered with monoclonal antibodies, gene therapies, and many biological targets and is consistent with studies of innovation showing that technology maturation is a critical determinant of product success. We previously described an analytical model for the maturation of biomedical research, demonstrating that the efficiency of targeted and biological development is connected to metrics of technology growth. The present work applies this model to characterize the advance of oligonucleotide therapeutics. We show that recent oligonucleotide product approvals incorporate technologies and targets that are past the established point of technology growth, as do most of the oligonucleotide products currently in phase 3. Less mature oligonucleotide technologies, such as miRNAs and some novel gene targets, have not passed the established point and have not yielded products. This analysis shows that oligonucleotide product development has followed largely predictable patterns of innovation. While technology maturation alone does not ensure success, these data show that many oligonucleotide technologies are sufficiently mature to be considered part of the arsenal for therapeutic development. These results demonstrate the importance of technology assessment in strategic management of biomedical technologies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation.

    Directory of Open Access Journals (Sweden)

    B Frank Eames

    2011-08-01

    Full Text Available Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG-rich matrix, then undergo a developmental transition, termed "maturation," when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regulate interactions between chondrocytes and perichondrium, using zebrafish mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which ultimately dictates the timing of perichondral bone development. In a mutagenesis screen, we isolated a class of mutants with decreased cartilage matrix and increased perichondral bone. Positional cloning identified lesions in two genes, fam20b and xylosyltransferase1 (xylt1, both of which encode PG synthesis enzymes. Mutants failed to produce wild-type levels of chondroitin sulfate PGs, which are normally abundant in cartilage matrix, and initiated perichondral bone formation earlier than their wild-type siblings. Primary chondrocyte defects might induce the bone phenotype secondarily, because mutant chondrocytes precociously initiated maturation, showing increased and early expression of such markers as runx2b, collagen type 10a1, and ihh co-orthologs, and ihha mutation suppressed early perichondral bone in PG mutants. Ultrastructural analyses demonstrated aberrant matrix organization and also early cellular features of chondrocyte hypertrophy in mutants. Refining previous in vitro reports, which demonstrated that fam20b and xylt1 were involved in PG synthesis, our in vivo analyses reveal that these genes function in cartilage matrix production and ultimately regulate the timing of skeletal development.

  20. Relationship between Problem-Solving Ability and Career Maturity ...

    African Journals Online (AJOL)

    This study investigated the relationship between problem-solving ability and career maturity of secondary school students in Ibadan, Oyo State, Nigeria. 230 final year secondary school students completed self-report measures of problem solving and career maturity. Multiple regression analysis was used to analyse the data ...

  1. Mature age job seekers : The role of proactivity

    NARCIS (Netherlands)

    Zacher, Hannes; Bock, Angelika

    2014-01-01

    Purpose - In the context of demographic and economic changes, helping mature age job seekers find employment is imperative. The purpose of this paper is to examine mature age job seekers' proactive personality as a moderator of the relationship between age and job search intensity; and to examine

  2. Use of homologous and heterologous gene expression profiling tools to characterize transcription dynamics during apple fruit maturation and ripening

    Directory of Open Access Journals (Sweden)

    Sansavini Silviero

    2010-10-01

    Full Text Available Abstract Background Fruit development, maturation and ripening consists of a complex series of biochemical and physiological changes that in climacteric fruits, including apple and tomato, are coordinated by the gaseous hormone ethylene. These changes lead to final fruit quality and understanding of the functional machinery underlying these processes is of both biological and practical importance. To date many reports have been made on the analysis of gene expression in apple. In this study we focused our investigation on the role of ethylene during apple maturation, specifically comparing transcriptomics of normal ripening with changes resulting from application of the hormone receptor competitor 1-Methylcyclopropene. Results To gain insight into the molecular process regulating ripening in apple, and to compare to tomato (model species for ripening studies, we utilized both homologous and heterologous (tomato microarray to profile transcriptome dynamics of genes involved in fruit development and ripening, emphasizing those which are ethylene regulated. The use of both types of microarrays facilitated transcriptome comparison between apple and tomato (for the later using data previously published and available at the TED: tomato expression database and highlighted genes conserved during ripening of both species, which in turn represent a foundation for further comparative genomic studies. The cross-species analysis had the secondary aim of examining the efficiency of heterologous (specifically tomato microarray hybridization for candidate gene identification as related to the ripening process. The resulting transcriptomics data revealed coordinated gene expression during fruit ripening of a subset of ripening-related and ethylene responsive genes, further facilitating the analysis of ethylene response during fruit maturation and ripening. Conclusion Our combined strategy based on microarray hybridization enabled transcriptome characterization

  3. Use of homologous and heterologous gene expression profiling tools to characterize transcription dynamics during apple fruit maturation and ripening.

    Science.gov (United States)

    Costa, Fabrizio; Alba, Rob; Schouten, Henk; Soglio, Valeria; Gianfranceschi, Luca; Serra, Sara; Musacchi, Stefano; Sansavini, Silviero; Costa, Guglielmo; Fei, Zhangjun; Giovannoni, James

    2010-10-25

    Fruit development, maturation and ripening consists of a complex series of biochemical and physiological changes that in climacteric fruits, including apple and tomato, are coordinated by the gaseous hormone ethylene. These changes lead to final fruit quality and understanding of the functional machinery underlying these processes is of both biological and practical importance. To date many reports have been made on the analysis of gene expression in apple. In this study we focused our investigation on the role of ethylene during apple maturation, specifically comparing transcriptomics of normal ripening with changes resulting from application of the hormone receptor competitor 1-methylcyclopropene. To gain insight into the molecular process regulating ripening in apple, and to compare to tomato (model species for ripening studies), we utilized both homologous and heterologous (tomato) microarray to profile transcriptome dynamics of genes involved in fruit development and ripening, emphasizing those which are ethylene regulated.The use of both types of microarrays facilitated transcriptome comparison between apple and tomato (for the later using data previously published and available at the TED: tomato expression database) and highlighted genes conserved during ripening of both species, which in turn represent a foundation for further comparative genomic studies. The cross-species analysis had the secondary aim of examining the efficiency of heterologous (specifically tomato) microarray hybridization for candidate gene identification as related to the ripening process. The resulting transcriptomics data revealed coordinated gene expression during fruit ripening of a subset of ripening-related and ethylene responsive genes, further facilitating the analysis of ethylene response during fruit maturation and ripening. Our combined strategy based on microarray hybridization enabled transcriptome characterization during normal climacteric apple ripening, as well as

  4. [Maturation diagnosis in full term hypotrophic fetuses].

    Science.gov (United States)

    Scharnke, H D; Gartzke, J; Fleischer, G; Isbruch, E

    1977-01-01

    Foam-Test by Clements is a valuable method for determining the foetus maturity of lungs. We introduce this test along with other parameters for the maturity-diagnosis since one year. In 15% result, the Foam-Test was not applicable because of blood, or meconic amniotic fluid, other wise wrong negative and in 0% wrong positive results. By unmatured child, there was doubtable results with Foam-Test. Since it is important to determine the early delivery of unmatured children, particularly the case of foetus maturity of lungs must be exact, we therefore decided to use the Lecithin/Sphingomyelinquotients in some cases. The results of Lecithin/Sphingomyelinquotient in unmatured children are almost with the approximated date under two. From this, one must deduce from these children, that the intrauterine unmatured lungs lately took place.

  5. Connective tissue fibroblasts and Tcf4 regulate myogenesis

    Science.gov (United States)

    Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

    2011-01-01

    Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

  6. Tip cells: master regulators of tubulogenesis?

    Science.gov (United States)

    Weavers, Helen; Skaer, Helen

    2014-07-01

    The normal development of an organ depends on the coordinated regulation of multiple cell activities. Focusing on tubulogenesis, we review the role of specialised cells or groups of cells that are selected from within tissue primordia and differentiate at the outgrowing tips or leading edge of developing tubules. Tip or leading cells develop distinctive patterns of gene expression that enable them to act both as sensors and transmitters of intercellular signalling. This enables them to explore the environment, respond to both tissue intrinsic signals and extrinsic cues from surrounding tissues and to regulate the behaviour of their neighbours, including the setting of cell fate, patterning cell division, inducing polarity and promoting cell movement and cell rearrangements by neighbour exchange. Tip cells are also able to transmit mechanical tension to promote tissue remodelling and, by interacting with the extracellular matrix, they can dictate migratory pathways and organ shape. Where separate tubular structures fuse to form networks, as in the airways of insects or the vascular system of vertebrates, specialised fusion tip cells act to interconnect disparate elements of the developing network. Finally, we consider their importance in the maturation of mature physiological function and in the development of disease. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke

    understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...

  8. Towards a Maturity Modeling Approach for the Implementation of Industrial Internet

    DEFF Research Database (Denmark)

    Menon, Karan; Kärkkäinen, Hannu; Lasrado, Lester Allan

    2016-01-01

    guidelines for industrial internet maturity model for mass production manufacturing industries which use heavy equipment. The detailed research design presented here uses ADR methodology to enable the construction of the ensemble artefact. The industrial internet maturity model will be tested, developed......This Research-in-Progress paper facilitates the design and provides guidelines for the development of a maturity model to achieve a coordinated, systematic and stepwise adoption of industrial internet, thus enabling the industrial internet to be used to its full potential in manufacturing...... enterprises. Using analogous maturity models from the fields of supply chain management and product lifecycle maturity among others, this paper explains why a maturity model approach would facilitate the step-by-step implementation of industrial internet. The paper goes on to provide systematic design...

  9. Trade-Offs of Flowering and Maturity Synchronisation for Pineapple Quality.

    Directory of Open Access Journals (Sweden)

    V Nicodème Fassinou Hotegni

    Full Text Available In the pineapple sector of Benin, poor fruit quality prevents pineapple producers to enter the European market. We investigated effects of common cultural practices, flowering and maturity synchronisation, (1 to quantify the trade-offs of flowering and maturity synchronisation for pineapple quality and the proportion of fruits exportable to European markets, and (2 to determine the effect of harvesting practice on quality attributes. Four on-farm experiments were conducted during three years using cultivars Sugarloaf and Smooth Cayenne. A split-split plot design was used in each experiment, with flowering induction practice as main factor (artificial or natural flowering induction, maturity induction practice as split factor (artificial or natural maturity induction and harvesting practice as the split-split factor (farmers' harvest practice or individual fruit harvesting at optimum maturity. Artificial flowering induction gave fruits with lower infructescence weight, higher ratio crown: infructescence length, and a lower proportion of fruits exportable to European markets than natural flowering induction. The costs of the improvements by natural flowering induction were huge: the longer durations from planting to flowering induction and harvesting, the higher number of harvestings of the fruits increasing the labour cost and the lower proportion of plants producing fruits compared with crops from artificially flowering-induced plants. Artificial maturity induction decreased the total soluble solids concentration in the fruits compared with natural maturity induction thus decreasing the proportion of fruits exportable to European markets, at a benefit of only a slightly shorter time from flowering induction to harvesting. Harvesting individual fruits at optimum maturity gave fruits with higher total soluble solids in naturally maturity induced fruits compared with the farmers' harvest practice. Given the huge costs of natural flowering induction

  10. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Wandawi, H.K.; Abdul-Rahman, M.H.; Al-Shaickley, K.A. (Iraq Atomic Energy Commission, Baghdad. Nuclear Research Inst.)

    1983-01-01

    Tomatoes (Lycopersicon esculentum L., var. Monte Carlo) have been ..gamma..-irradiated (100 to 400 krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100, 200 and 300 krad at mature-green, 48 hours after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples. On the other hand, radiation had no significant effect on PH, titrable acidity and deg Brix of tomatoes.

  11. Evaluating the Organizational Interoperability Maturity Level in ICT Research Center

    Directory of Open Access Journals (Sweden)

    Manijeh Haghighinasab

    2011-03-01

    Full Text Available Interoperability refers to the ability to provide services and to accept services from other systems or devices. Collaborative enterprises face additional challenges to interoperate seamlessly within a networked organization. The major task here is to assess the maturity level of interoperating organizations. For this purpose the maturity models for enterprise were reviewed based on vendors’ reliability and advantages versus disadvantages. Interoperability maturity model was deduced from ATHENA project as European Integrated Project in 2005, this model named as EIMM was examined in Iran information and Communication Institute as a leading Telecommunication organization. 115 questionnaires were distributed between staff of 4 departments: Information Technology, Communication Technology, Security and Strategic studies regarding six areas of concern: Enterprise Modeling, Business Strategy Process, Organization and Competences, Products and Services, Systems and Technology, Legal Environment, Security and Trust at five maturity levels: Performed, Modeled , Integrated, Interoperable and Optimizing maturity. The findings showed different levels of maturity in this Institute. To achieve Interoperability level, appropriate practices are proposed for promotion to the higher levels.

  12. Maturing interorganisational information systems

    NARCIS (Netherlands)

    Plomp, M.G.A.|info:eu-repo/dai/nl/313946809

    2012-01-01

    This thesis consists of nine chapters, divided over five parts. PART I is an introduction and the last part contains the conclusions. The remaining, intermediate parts are: PART II: Developing a maturity model for chain digitisation. This part contains two related studies concerning the development

  13. Non-Destructive Technique for Determining Mango Maturity

    OpenAIRE

    Salengke; Mursalim

    2013-01-01

    Mango (Mangifera indica L.) is an important tropical fruit that has great potential in international markets. Currently, major markets for mango include North America, Europe, and Japan. The acceptance of exported mango in destination countries depends largely on eating quality, which is affected by maturity at harvest. Mango maturity can be judged visually, based on skin color, or determined chemically based on soluble solids content, acid content, and solids:acid ratio....

  14. EMOTIONAL MATURITY OF PERSONALITY: THE PRACTICAL PROBLEM OF PSYCHOLOGICAL DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    O. I. Afonina

    2013-03-01

    Full Text Available In the dif?cult conditions of the contemporary society which are far from being favorable to maintain one’s emotional and physical health the problem of development and achievement of emotional maturity as a factor of the well-being is getting more signi?cant. Based on the theoretical concepts of different scientists who de?ned the construct of emotional maturity three groups of psychological methods for assessing emotional maturity are analyzed. The ?rst group includes the methods that are used to assess emotional maturity explicitly and have a theoretical or empirical veri?cation. The second group includes the methods that are intended to assess emotional maturity as a separate scale complimented by other scales, related to evaluating other aspects of emotionality in  the  structure  of  the  personality.  The  third  group  includes  the  methods  in  which  emotional maturity is mentioned in the description of other psychic phenomena, or in the interpretation of certain factors (scales. Psychodiagnostic methods studying different parameters depending on the theoretical concepts of the authors about the structure and content of the emotional maturity of the personality make references to concepts of emotional development, consciousness, cognitive and volitional capacities of the personality and the coping strategies the individual prefer to use. The problem of developing valid and reliable psychodiagnostic methods of studying emotional maturity of the adult personality as a holistic phenomenon still awaits attention and retains its signi?cance.

  15. Correlation between dental and cervical vertebral maturation in Iranian females.

    Science.gov (United States)

    Valizadeh, Solmaz; Eil, Nakissa; Ehsani, Sara; Bakhshandeh, Hooman

    2012-12-01

    Considerable variations in the development stage among patients of the same chronological age have led to introduce the concept of the developmental age based on the maturation of different organs such as cervical vertebrae or teeth. The purpose of this study was to investigate the correlation between the stages of tooth calcification and the cervical vertebral maturation in Iranian females. Four hundred females (age range, 8 to 14 years) participated in the study. To determine the dental maturational stage, calcification of the mandibular teeth except for third molars were rated according to the method suggested by Demirjian et al. To evaluate the stage of skeletal maturation, cervical vertebral morphologic changes were assessed on lateral cephalometric radiographs according to the method explained by Baccetti et al. Correlations between bone maturation and teeth calcification were showed by Spearman's correlation and Kendall's tau-b coefficients. The relevant associations were investigated by ordinal logistic regression models. Correlations between the two stages were observed in the first and second premolars, canine and central incisors. All these correlations were significant. The association between cervical vertebral maturation and tooth calcification was greatest in the lateral incisor (odds ratio (OR) = 11, 95% confidence interval (CI): 6.6-18.3). However, considering the 95% CI for OR, no significant difference was detected among the second molar, first molar and lateral incisor. The relationship between calcification of teeth and maturation of cervical bones was significant. Bone maturation can be predicted by using teeth calcification stages, especially in the second molar, first molar and lateral incisor.

  16. Localization of CORO1A in the Macrophages Containing Mycobacterium leprae

    International Nuclear Information System (INIS)

    Suzuki, Koichi; Takeshita, Fumihiko; Nakata, Noboru; Ishii, Norihisa; Makino, Masahiko

    2006-01-01

    Mycobacteria have acquired an intracellular lifestyle within the macrophage, which is best exemplified by the enlarged infected histiocytes seen in lepromatous leprosy. To survive within the cell, mycobacteria must escape intracellular bactericidal mechanisms. In a study of Mycobacterium bovis Bacille Calmette-Guérin (M. bovis BCG) infection, it was shown that the host protein, CORO1A, also known as tryptophan aspartate-containing coat protein (TACO), accumulates on the phagosomal membrane, resulting in inhibition of phagosome-lysosome fusion, and thus augmenting intracellular survival. In this study, we show that CORO1A strongly localizes on the membrane of phagosomes that contain Mycobacterium leprae (M. leprae), where Toll-like receptor 2 was also visualized by immunostaining. When cultured macrophages were infected with M. leprae, CORO1A recruitment from the plasma membrane to the phagosomal membrane was observed. Moderate to strong CORO1A retention was observed in late lesions that contained foamy histiocytes, in which M. leprae were difficult to detect by acid-fast staining. These results suggest that components accumulating within the phagosome rather than viable bacilli are responsible for the retention of CORO1A, and that there is also a bactericidal mechanism in the macrophage that might counter the effects of CORO1A

  17. Predicting technology operational availability using technical maturity assessment

    International Nuclear Information System (INIS)

    Kenley, C.R.; Creque, T.R.

    1998-01-01

    A technical maturity assessment method was performed by systems engineers in collaboration with an advisory panel composed of team members from different Department of Energy sites and from different engineering and science disciplines. Various stabilization technologies were assessed annually as to their relative maturity and availability for use in stabilizing nuclear materials. After three years of assessments, several of the technologies are now components of operational systems. A regression analysis of the historical assessments was performed, and it was concluded that the numerical technical maturity score produced by a team of experts can provide a powerful predictor of the time remaining until the operational application of technologies

  18. Non-matured arteriovenous fistulae for haemodialysis: diagnosis, endovascular and surgical treatment

    Directory of Open Access Journals (Sweden)

    Marko Malovrh

    2010-04-01

    Full Text Available Non-maturation is a feature of autologous vascular access. The autologous arteriovenous fistula needs time to mature and for the vein to enlarge to a size where it can be needled for dialysis. A fistula that fails early is one that either never develops adequately to support dialysis or fails within the first three months of its use. Two variables are required for fistula maturation. Firstly, the fistula should have adequate blood flow to support dialysis and secondly, it should have enough size to allow for successful repetitive cannulation. Three main reasons for maturation failure are: arterial and venous problems and the presence of accessory veins. Early diagnostics and intervention for fistula maturation minimizes catheter use and its associated complications. The identification of immature fistulae is relatively simple. Physical examination has been highlighted to be a valuable tool in assessing fistula. Any fistula that fails to mature adequately and demonstrates abnormal physical findings should be studied aggressively. Ultrasonography can successfully identify candidates who fail to meet the recently developed criteria for immature fistulae. In recent years, digital subtraction angiography and contrast-enhanced magnetic resonance angiography has been introduced for assessment of dysfunctional haemodialysis conduits, including immature fistulae. A great majority of non-matured fistulae can be successfully salvaged using percutaneous techniques. In addition to endovascular techniques, surgical intervention can also be an option. This paper reviews the process of fistula maturation and presents information regarding how to obtain a mature fistula.

  19. Revaluation of maturity and stability indices for compost ...

    African Journals Online (AJOL)

    BOD/COD ratio of compost was studied in conjunction with C/N ratio as commonly maturity index. Carbonaceous materials as well as nitrogenous materials declined in open-air conditions during 20 weeks. C/N ratio was correlated with BOD/COD, a couple parameters to qualify the compost was mature and stable.

  20. Self-Esteem and Emotional Maturity in College Students.

    Science.gov (United States)

    Leung, Jupian J.; Sand, Margaret C.

    1981-01-01

    Determined if self-esteem is related to emotional maturity. Scores from 200 male and female college students on Coopersmith's Self-Esteem Inventory and on the Washburne Social-Adjustment Inventory were correlated. Students high in self-esteem were found to be more emotionally mature than students low in self-esteem. (Author)

  1. Variations in DNA methylation, acetylated histone H4, and methylated histone H3 during Pinus radiata needle maturation in relation to the loss of in vitro organogenic capability.

    Science.gov (United States)

    Valledor, Luis; Meijón, Mónica; Hasbún, Rodrigo; Jesús Cañal, Maria; Rodríguez, Roberto

    2010-03-15

    Needle differentiation is a very complex process associated with the formation of a mature photosynthetic organ. From meristem differentiation to leaf maturation, gene control must play an important role switching required genes on and off to define tissue functions, with the epigenetic code being one of the main regulation mechanisms. In this work, we examined the connections between the variation in the levels of some epigenetic players (DNA methylation, acetylated histone H4 and histone H3 methylation at Lys 4 and Lys 9) at work during needle maturation. Our results indicate that needle maturation, which is associated with a decrease in organogenic capability, is related to an increase in heterochromatin-related epigenetic markers (high DNA methylation and low acetylated histone H4 levels, and the presence of histone H3 methylated at lys 9). Immunohistochemical analyses also showed that the DNA methylation of palisade parenchyma cell layers during the transition from immature to mature scions is associated with the loss of the capacity to induce adventitious organs. Copyright 2009 Elsevier GmbH. All rights reserved.

  2. Mature consumers’ relationship with their perfume

    Directory of Open Access Journals (Sweden)

    Lindsey DRYLIE-CAREY

    2018-01-01

    Full Text Available Glamorous and stylish, perfume is an evocative product that provokes a stimulus of the senses. It is suggested that the basis for consumer choice for this product should be based on olfactory preference, however the process related decision-making has been shown to be more complex. The mature consumer purchase decision making in this product category is often associated with long standing, established, luxury fragrance brands. In addition, at the frontline of the perfume sales process are fragrance consultants, who possess invaluable information on consumer involvement with perfume products and brands. Hence, this paper investigates CBR (consumer brand relationship and the subsequent perfume purchase behaviour of mature female consumers from a dual (industry and consumer perspective. Results indicate that important perceptual differences related to brand relationships with perfume exist between fragrance consultants and experts on one hand and consumers on the other. This research promotes a deeper understanding of current consumer approach and issues surrounding female mature purchasing behaviour for this unique category of product, and complements the growing body of literature related to luxury brands.

  3. Towards an energy management maturity model

    International Nuclear Information System (INIS)

    Antunes, Pedro; Carreira, Paulo; Mira da Silva, Miguel

    2014-01-01

    Energy management is becoming a priority as organizations strive to reduce energy costs, conform to regulatory requirements, and improve their corporate image. Despite the upsurge of interest in energy management standards, a gap persists between energy management literature and current implementation practices. This gap can be traced to the lack of an incremental improvement roadmap. In this paper we propose an Energy Management Maturity Model that can be used to guide organizations in their energy management implementation efforts to incrementally achieve compliance with energy management standards such as ISO 50001. The proposed maturity model is inspired on the Plan-Do-Check-Act cycle approach for continual improvement, and covers well-understood fundamental energy management activities common across energy management texts. The completeness of our proposal is then evaluated by establishing an ontology mapping against ISO 50001. - Highlights: • Real-world energy management activities are not aligned with the literature. • An Energy Management Maturity Model is proposed to overcome this alignment gap. • The completeness and relevance of proposed model are validated

  4. Role of WNT signaling in epididymal sperm maturation.

    Science.gov (United States)

    Cheng, Jin-Mei; Tang, Ji-Xin; Li, Jian; Wang, Yu-Qian; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun

    2018-02-01

    Spermatozoa maturation, a process required for spermatozoa to acquire progressive motility and the ability to fertilize ova, primarily occurs in the caput and corpus of the epididymis. Despite considerable efforts, the factor(s) promoting epididymal sperm maturation remains unclear. Recently, WNT signaling has been implicated in epididymal sperm maturation. To further investigate WNT signaling function in epididymal sperm maturation, we generated Wntless conditional knockout mice (Wls cKO), Wls flox/flox ; Lcn5-Cre. In these mice, WNTLESS (WLS), a conserved membrane protein required for all WNT protein secretion, was specifically disrupted in the principal cells of the caput epididymidis. Immunoblot analysis showed that WLS was significantly reduced in the caput epididymidis of Wls cKO mice. In the caput epididymidis of Wls cKO mice, WNT 10A and WNT 2b, which are typically secreted by the principal cells of the caput epididymis, were not secreted. Interestingly, sperm motility analysis showed that the WLS deficiency in the caput epididymidis had no effect on sperm motility. Moreover, fertility tests showed that Wls cKO male mice had normal fertility. These results indicate that the disruption of WLS in principal cells of the caput epididymidis inhibits WNT protein secretion but has no effect on sperm motility and male fertility, suggesting that WNT signaling in the caput epididymidis may be dispensable for epididymal sperm maturation in mice.

  5. Maturation evolution of chardonnay grape for juice preparation

    Directory of Open Access Journals (Sweden)

    Bender Angelica

    2016-01-01

    Full Text Available This study aims to evaluate the evolution of the maturation of the “Chardonnay” grape variety for the preparation of juices and its adequacy to the current legislation. Grapes from the 2015 harvest from São Lourenço do Sul-RS were used. The experimental design was completely randomized in a factorial design, with the treatment factor being the maturation stages. The physicochemical analysis of titratable acidity, soluble solids, relative density, total sugar, alcohol content, volatile acidity and SS/TA ratio were carried out in EPAGRI – Agricultural Research and Rural Extension Company of Santa Catarina, in the Videira Experimental Station (Videira SC/Brazil. Statistical analysis of the maturation stages was given by linear regression models. When comparing the maturation points of 17∘Brix and 19∘Brix to 15∘Brix, volatile acidity and alcohol content did not fit to the model, while the other tested variables fit properly. Elaborated juices had a decrease in titratable acidity and percentage increments for soluble solids, SS/TA ratio and total sugars for the harvest points at 17 and 19∘Brix. For 15∘Brix and 17∘Brix, nonconformity was observed with the identity and quality standards in relation to soluble solids and SS/TA ratio and relative density. At maturation point 19∘Brix all variables were found to be consistent.

  6. Effect of Leptin on In Vitro Nuclear Maturation and Apoptosis of Buffalo (Bubalus bubalis Oocyte

    Directory of Open Access Journals (Sweden)

    Amir Khaki

    2014-03-01

    Full Text Available Background: Leptin, as a 16 kDa adipokine, is a pleiotropic cytokine-like hormone that primarily secreted from adipose tissue. It also involves in the regulation of energy homeostasis, neuroendocrine function, immunity, lipid and glucose homeostasis, fatty acid oxidation, angiogenesis, puberty and reproduction. The aim of this study was to investigate the effects of in vitro addition of leptin to in vitro maturation (IVM medium on buffalo oocyte maturation and apoptosis. Materials and Methods: In this experimental study, Ovaries from apparently normal reproductive organs of slaughtered adult buffaloes (Bubalus bubalis with unknown breeding history were collected from Urmia Abattoir, Urmia, Iran, and were transported immediately to the laboratory in a thermos flask containing sterile normal saline with added antibiotics. Oocytes were aspirated from 2-8 mm visible follicles of the ovaries using an 18-G needle attached to a 10 ml syringe. IVM medium included tissue culture medium-199 (TCM-199, 10% fetal bovine serum (FBS, 22 μg/ml sodium pyruvate, 0.5 IU/ml ovine follicle-stimulating hormone (oFSH, 0.5 IU/ml ovine luteinizing hormone (oLH, 1 μg/ml oestradiol, 50 μg/ml gentamycin, and leptin [0 (control, 10, 50, and 100 ng/ml]. The good quality buffalo oocytes (batches of 10 oocytes were placed in a culture plate containing six 50 μl droplets of maturation medium, covered with sterilized mineral oil, and then incubated at 38.5˚C with 5% CO2 in air for 24 hours. The maturation of oocytes was evaluated under a stereomicroscope by detecting the first polar body extrusion of oocytes. FITC-Annexin V - propidium iodide (PI staining method was used to detect oocyte apoptosis. Results: From a total of 115 collected ovaries, 1100 oocytes were recovered among which 283 oocyte were suitable for IVM. In the groups of leptin treated with 0 (control, 10, 50 and 100 ng/ml, the percentage of oocytes maturation was 74.65, 83.81, 77.85, and 75.40%, while the

  7. The conserved splicing factor SUA controls alternative splicing of the developmental regulator ABI3 in Arabidopsis.

    NARCIS (Netherlands)

    Sugliani, M.; Brambilla, V.; Clerkx, E.J.M.; Koornneef, M.; Soppe, W.J.J.

    2010-01-01

    ABSCISIC ACID INSENSITIVE3 (ABI3) is a major regulator of seed maturation in Arabidopsis thaliana. We detected two ABI3 transcripts, ABI3- and ABI3-ß, which encode full-length and truncated proteins, respectively. Alternative splicing of ABI3 is developmentally regulated, and the ABI3-ß transcript

  8. The effect of plant growth regulators on optimization of tissue culture ...

    African Journals Online (AJOL)

    Mature seeds of four upland rice cultivars namely Kusan, Lamsan, Selasi and Siam were assessed for callus induction and plant regeneration on different concentrations and combinations of plant growth regulators, incorporated into MS (Murashige and Skoog) basal medium. Callus induction frequency was significantly ...

  9. Epidermal cell-shape regulation and subpopulation kinetics during butyrate-induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy.

    Science.gov (United States)

    Staiano-Coico, L; Steinberg, M; Higgins, P J

    1990-10-15

    Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB-induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation.

  10. Best practices show the way to information security maturity

    CSIR Research Space (South Africa)

    Lessing, MM

    2008-09-01

    Full Text Available A Security Maturity Model (SMM) provides an organisation with a distinct Information Security framework. Organisations that conform to these models are likely to pursue satisfactory Information Security. Additionally, the use of Security Maturity...

  11. Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival

    Science.gov (United States)

    Kozlowski, Elyse; Matsuura, Kori Y.; Ferrari, Joseph D.; Morris, Samantha A.; Powers, John T.; Daley, George Q.; Quinton, Lee J.; Mizgerd, Joseph P.

    2012-01-01

    The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3′ terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression. PMID:23209448

  12. Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival.

    Directory of Open Access Journals (Sweden)

    Matthew R Jones

    Full Text Available The Zcchc11 enzyme is implicated in microRNA (miRNA regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3' terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression.

  13. Amniocentesis for fetal lung maturity: will it become obsolete?

    Science.gov (United States)

    Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

    2013-01-01

    AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

  14. Methylation changes associated with early maturation stages in the Atlantic salmon

    Directory of Open Access Journals (Sweden)

    Pérez-Figueroa Andrés

    2011-10-01

    Full Text Available Abstract Background Early maturation in the Atlantic salmon is an interesting subject for numerous research lines. Prior to sea migration, parr can reach sexual maturation and successfully fertilize adult female eggs during the reproductive season. These individuals are known as precocious parr, mature parr or "sneakers". Reasons for early maturation are unknown and this transitory stage is usually considered to be a threshold trait. Here, we compare methylation patterns between mature and immature salmon parr from two different rivers in order to infer if such methylation differences may be related to their maturation condition. First we analyzed genetic differences between rivers by means of AFLPs. Then, we compared the DNA methylation differences between mature and immature parrs, using a Methylation-Sensitive Amplified Polymorphism (MSAP, which is a modification of the AFLPs method by making use of the differential sensitivity of a pair of restriction enzymes isoschizomeres to cytosine methylation. The tissues essayed included brain, liver and gonads. Results AFLPs statistical analysis showed that there was no significant differentiation between rivers or a significant differentiation between maturation states in each river. MSAP statistical analysis showed that among the three tissues sampled, the gonads had the highest number of significant single-locus variation among populations with 74 loci followed by brain with 70 and finally liver with only 12. Principal components analysis (PCA of the MSAP profiles revealed different profiles among different tissues (liver, brain and testis clearly separating maturation states in the testis tissue when compared to the liver. Conclusions Our results reveal that genetically-similar mature and immature salmon parr present high levels of DNA methylation variation in two of the three analyzed tissues. We hypothesize that early maturation may be mostly mediated by epigenetic processes rather than by

  15. Assessing Organizational Capabilities: Reviewing and Guiding the Development of Maturity Grids

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2012-01-01

    Managing and improving organizational capabilities is a significant and complex issue for many companies. To support management and enable improvement, performance assessments are commonly used. One way of assessing organizational capabilities is by means of maturity grids. Whilst maturity grids...... than twenty maturity grids places particular emphasis on embedded assumptions about organizational change in the formulation of the maturity ratings. The suggested roadmap encompasses four phases: planning, development, evaluation and maintenance. Each phase discusses a number of decision points...

  16. Correlation Between Dental and Cervical Vertebral Maturation in Iranian Females

    Science.gov (United States)

    Valizadeh, Solmaz; Eil, Nakissa; Ehsani, Sara; Bakhshandeh, Hooman

    2012-01-01

    Background Considerable variations in the development stage among patients of the same chronological age have led to introduce the concept of the developmental age based on the maturation of different organs such as cervical vertebrae or teeth. Objectives The purpose of this study was to investigate the correlation between the stages of tooth calcification and the cervical vertebral maturation in Iranian females. Patients and Methods Four hundred females (age range, 8 to 14 years) participated in the study. To determine the dental maturational stage, calcification of the mandibular teeth except for third molars were rated according to the method suggested by Demirjian et al. To evaluate the stage of skeletal maturation, cervical vertebral morphologic changes were assessed on lateral cephalometric radiographs according to the method explained by Baccetti et al. Correlations between bone maturation and teeth calcification were showed by Spearman's correlation and Kendall’s tau-b coefficients. The relevant associations were investigated by ordinal logistic regression models. Results Correlations between the two stages were observed in the first and second premolars, canine and central incisors. All these correlations were significant. The association between cervical vertebral maturation and tooth calcification was greatest in the lateral incisor (odds ratio (OR) = 11, 95% confidence interval (CI): 6.6-18.3). However, considering the 95% CI for OR, no significant difference was detected among the second molar, first molar and lateral incisor. Conclusion The relationship between calcification of teeth and maturation of cervical bones was significant. Bone maturation can be predicted by using teeth calcification stages, especially in the second molar, first molar and lateral incisor. PMID:23599706

  17. Changes in polyphenolics during maturation of Java plum (Syzygium cumini Lam.).

    Science.gov (United States)

    Lestario, Lydia Ninan; Howard, Luke R; Brownmiller, Cindi; Stebbins, Nathan B; Liyanage, Rohana; Lay, Jackson O

    2017-10-01

    Java plum (Syzygium cumini Lam.) is a rich source of polyphenolics with many purported health benefits, but the effect of maturation on polyphenolic content is unknown. Freeze-dried samples of Java plum from seven different maturity stages were analyzed for anthocyanin, flavonol, flavanonol and hydrolysable tannin composition by HPLC. Anthocyanins were first detected at the green-pink stage of maturity and increased throughout maturation with the largest increase occurring from the dark purple to black stages of maturation. Levels of gallotannins, ellagitannins, flavonols, gallic acid and ellagic acid were highest at early stages of maturation and decreased as the fruit ripened. For production of antioxidant-rich nutraceutical ingredients, fruit should be harvested immature to obtain extracts rich in hydrolysable tannins and flavonols. The exceptional anthocyanin content of black fruit may prove useful as a source of a natural colorant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. SOUL System Maturation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Busek Co. Inc. proposes to advance the maturity of an innovative Spacecraft on Umbilical Line (SOUL) System suitable for a wide variety of applications of interest...

  19. SOUL System Maturation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Busek Co. Inc. proposes to advance the maturity of an innovative Spacecraft on Umbilical Line (SOUL) System suitable for a wide variety of applications of interest...

  20. The Self--The Global Factor of Emotional Maturity.

    Science.gov (United States)

    Landau, Erika

    1998-01-01

    The relationship between emotional maturity and the developing self in the gifted individual is examined. Emotional maturity is seen to involve the integration of intrapersonal and interpersonal aspects of the personality. The developing self is thought to be more than the sum of its components and becomes a global factor in the development of a…

  1. Seed maturation associated transcriptional programs and regulatory networks underlying genotypic difference in seed dormancy and size/weight in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Yamasaki, Yuji; Gao, Feng; Jordan, Mark C; Ayele, Belay T

    2017-09-16

    Maturation forms one of the critical seed developmental phases and it is characterized mainly by programmed cell death, dormancy and desiccation, however, the transcriptional programs and regulatory networks underlying acquisition of dormancy and deposition of storage reserves during the maturation phase of seed development are poorly understood in wheat. The present study performed comparative spatiotemporal transcriptomic analysis of seed maturation in two wheat genotypes with contrasting seed weight/size and dormancy phenotype. The embryo and endosperm tissues of maturing seeds appeared to exhibit genotype-specific temporal shifts in gene expression profile that might contribute to the seed phenotypic variations. Functional annotations of gene clusters suggest that the two tissues exhibit distinct but genotypically overlapping molecular functions. Motif enrichment predicts genotypically distinct abscisic acid (ABA) and gibberellin (GA) regulated transcriptional networks contribute to the contrasting seed weight/size and dormancy phenotypes between the two genotypes. While other ABA responsive element (ABRE) motifs are enriched in both genotypes, the prevalence of G-box-like motif specifically in tissues of the dormant genotype suggests distinct ABA mediated transcriptional mechanisms control the establishment of dormancy during seed maturation. In agreement with this, the bZIP transcription factors that co-express with ABRE enriched embryonic genes differ with genotype. The enrichment of SITEIIATCYTC motif specifically in embryo clusters of maturing seeds irrespective of genotype predicts a tissue specific role for the respective TCP transcription factors with no or minimal contribution to the variations in seed dormancy. The results of this study advance our understanding of the seed maturation associated molecular mechanisms underlying variation in dormancy and weight/size in wheat seeds, which is a critical step towards the designing of molecular strategies

  2. Melatonin accelerates maturation inducing hormone (MIH): induced oocyte maturation in carps.

    Science.gov (United States)

    Chattoraj, Asamanja; Bhattacharyya, Sharmistha; Basu, Dipanjan; Bhattacharya, Shelley; Bhattacharya, Samir; Maitra, Saumen Kumar

    2005-02-01

    The present communication is an attempt to demonstrate the influence of melatonin on the action of maturation inducing hormone (MIH) on the maturation of oocytes in carps. The oocytes from gravid female major carp Labeo rohita were isolated and incubated separately in Medium 199 containing (a) only MIH (1 microg/ml), (b) only melatonin (at concentrations of 50, 100 or 500 pg/ml), and (c) both melatonin and MIH, but at different time intervals. In the latter group, melatonin was added to the incubating medium either (i) 4 h before addition of MIH, (ii) 2 h before addition of MIH, (iii) co-administered with MIH (0 h interval) or (iv) 2 h after addition of MIH. In each case, oocytes were further incubated for 4, 8, 12 or 16 h post- administration of MIH, and the effects of treatment on oocyte maturation were evaluated by considering the rate (%) of germinal vesicle breakdown (GVBD). Incubation of oocytes in a medium containing only melatonin did not result in GVBD of any oocyte. Nearly all the oocytes underwent GVBD when incubated with MIH for 16 h. Administration of melatonin along with MIH (at 0 h interval) or 2 h after addition of MIH did not result in any significant change in the rate of GVBD compared to that in a medium containing only MIH. However, it was quite interesting to observe that incubation of oocytes with melatonin especially 4 h prior to addition of MIH in the medium, led to an accelerated rate of GVBD in the oocytes. Experiments with the oocytes of another major carp Cyprinus carpio following an identical schedule depicted similar results except a difference in the optimum melatonin dose. In L. rohita, 50 pg/ml melatonin had maximum acceleratory effect on MIH-induced GVBD of oocytes, while it was 100 pg/ml in C. carpio. Further study revealed that pre-incubation with melatonin accelerates the action of MIH on the formation of a complex of two proteins (MPF), a regulatory component called cyclin B and the catalytic component protein kinase known as

  3. Altruism and mature care: some rival moral considerations in care ethics.

    Science.gov (United States)

    Hem, Marit Helene; Halvorsen, Kristin; Nortvedt, Per

    2014-11-01

    We discuss Carol Gilligan's original concept of mature care in the light of the altruistic approach to caring and good clinical judgment. In particular, we highlight how the concept of mature care can capture important challenges in today's nursing. Further, we illuminate how mature care might differ normatively from an altruistic approach to caring and the traditional prudential virtues in nursing. We also discuss similarities between mature care and virtue ethics. For nursing and nurses' identity, in today's health care system that is increasingly pressured to 'produce' health, we believe it is important to both developing further theories on mature care and having normative discussions about care. © The Author(s) 2014.

  4. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

    Science.gov (United States)

    Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

    2013-01-01

    Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

  5. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  6. Autophagy in C. elegans development.

    Science.gov (United States)

    Palmisano, Nicholas J; Meléndez, Alicia

    2018-04-27

    Autophagy involves the sequestration of cytoplasmic contents in a double-membrane structure referred to as the autophagosome and the degradation of its contents upon delivery to lysosomes. Autophagy activity has a role in multiple biological processes during the development of the nematode Caenorhabditis elegans. Basal levels of autophagy are required to remove aggregate prone proteins, paternal mitochondria, and spermatid-specific membranous organelles. During larval development, autophagy is required for the remodeling that occurs during dauer development, and autophagy can selectively degrade components of the miRNA-induced silencing complex, and modulate miRNA-mediated silencing. Basal levels of autophagy are important in synapse formation and in the germ line, to promote the proliferation of proliferating stem cells. Autophagy activity is also required for the efficient removal of apoptotic cell corpses by promoting phagosome maturation. Finally, autophagy is also involved in lipid homeostasis and in the aging process. In this review, we first describe the molecular complexes involved in the process of autophagy, its regulation, and mechanisms for cargo recognition. In the second section, we discuss the developmental contexts where autophagy has been shown to be important. Studies in C. elegans provide valuable insights into the physiological relevance of this process during metazoan development. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Primordial Pb, radiogenic Pb and lunar soil maturity

    International Nuclear Information System (INIS)

    Reed, G.W. Jr.; Jovanovic, S.

    1978-01-01

    The soil maturity index I/sub s//FeO does not apply to either 204 Pb/sub r/ or C/sub hyd/; both are directly correlated with the submicron Fe 0 (I/sub s/) content. They act as an index of soil maturity which is independent of soil composition. In contrast to primordial Pb, radiogenic Pb is lost during soil maturation. Radiogenic Pb is present in mineral grains and may be lost by solar wind sputtering (or volatilization) and not resupplied. 204 Pb coating grain surfaces acts as a reservoir to provide the 204 Pb being extracted in the Fe 0 formation process. Venting or some other volatile source may replenish the surface 204 Pb. 1 figure

  8. Predictive Capability Maturity Model for computational modeling and simulation.

    Energy Technology Data Exchange (ETDEWEB)

    Oberkampf, William Louis; Trucano, Timothy Guy; Pilch, Martin M.

    2007-10-01

    The Predictive Capability Maturity Model (PCMM) is a new model that can be used to assess the level of maturity of computational modeling and simulation (M&S) efforts. The development of the model is based on both the authors experience and their analysis of similar investigations in the past. The perspective taken in this report is one of judging the usefulness of a predictive capability that relies on the numerical solution to partial differential equations to better inform and improve decision making. The review of past investigations, such as the Software Engineering Institute's Capability Maturity Model Integration and the National Aeronautics and Space Administration and Department of Defense Technology Readiness Levels, indicates that a more restricted, more interpretable method is needed to assess the maturity of an M&S effort. The PCMM addresses six contributing elements to M&S: (1) representation and geometric fidelity, (2) physics and material model fidelity, (3) code verification, (4) solution verification, (5) model validation, and (6) uncertainty quantification and sensitivity analysis. For each of these elements, attributes are identified that characterize four increasing levels of maturity. Importantly, the PCMM is a structured method for assessing the maturity of an M&S effort that is directed toward an engineering application of interest. The PCMM does not assess whether the M&S effort, the accuracy of the predictions, or the performance of the engineering system satisfies or does not satisfy specified application requirements.

  9. Developing the Value Management Maturity Model (VM3©

    Directory of Open Access Journals (Sweden)

    Saipol Bari Abd Karim

    2013-06-01

    Full Text Available Value management (VM practices have been expanded and became a well-received technique globally. Organisations are now progressing towards a better implementation of VM and should be assessing their strengths and weaknesses in order to move forward competitively. There is a need to benchmark the existing VM practices to reflect their maturing levels which is currently not available. This paper outlines the concept of Value Management Maturity Model (VM3' as a structured plan of maturity and performance growth for businesses. It proposes five levels of maturity and each level has its own criteria or attributes to be achieved before progressing to a higher level. The framework for VM3' has been developed based on the review of literatures related to VM and maturity models (MM. Data is collected through questionnaire surveys to organisations that have implemented VM methodology. Additionally, semi-structured interviews were conducted to select individuals involved in implementing VM. The questions were developed to achieve the research objectives; investigating the current implementation of VM and, exploring the organisation's MM knowledge and practices. However, this research was limited to VM implementation in the Malaysian government's projects and programmes. VM3' introduces a new paradigm in VM as it provides a rating method for capabilities or performance. It is advocated that this VM3' framework is still being refined in the advance stage in order to provide a comprehensive and well accepted method to provide ratings for organisations' maturity.

  10. Quality Management Systems Implementation Compared With Organizational Maturity in Hospital.

    Science.gov (United States)

    Moradi, Tayebeh; Jafari, Mehdi; Maleki, Mohammad Reza; Naghdi, Seyran; Ghiasvand, Hesam

    2015-07-27

    A quality management system can provide a framework for continuous improvement in order to increase the probability of customers and other stakeholders' satisfaction. The test maturity model helps organizations to assess the degree of maturity in implementing effective and sustained quality management systems; plan based on the current realities of the organization and prioritize their improvement programs. We aim to investigate and compare the level of organizational maturity in hospitals with the status of quality management systems implementation. This analytical cross sectional study was conducted among hospital administrators and quality experts working in hospitals with over 200 beds located in Tehran. In the first step, 32 hospitals were selected and then 96 employees working in the selected hospitals were studied. The data were gathered using the implementation checklist of quality management systems and the organization maturity questionnaire derived from ISO 10014. The content validity was calculated using Lawshe method and the reliability was estimated using test - retest method and calculation of Cronbach's alpha coefficient. The descriptive and inferential statistics were used to analyze the data using SPSS 18 software. According to the table, the mean score of organizational maturity among hospitals in the first stage of quality management systems implementation was equal to those in the third stage and hypothesis was rejected (p-value = 0.093). In general, there is no significant difference in the organizational maturity between the first and third level hospitals (in terms of implementation of quality management systems). Overall, the findings of the study show that there is no significant difference in the organizational maturity between the hospitals in different levels of the quality management systems implementation and in fact, the maturity of the organizations cannot be attributed to the implementation of such systems. As a result, hospitals

  11. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    Science.gov (United States)

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  12. Debt Maturity: Is Long-Term Debt Optimal?

    OpenAIRE

    Laura Alfaro; Fabio Kanczuk

    2007-01-01

    We model and calibrate the arguments in favor and against short-term and long-term debt. These arguments broadly include: maturity premium, sustainability, and service smoothing. We use a dynamic equilibrium model with tax distortions and government outlays uncertainty, and model maturity as the fraction of debt that needs to be rolled over every period. In the model, the benefits of defaulting are tempered by higher future interest rates. We then calibrate our artificial economy and solve fo...

  13. Relationship between viticultural climatic indices and grape maturity in Australia

    Science.gov (United States)

    Jarvis, C.; Barlow, E.; Darbyshire, R.; Eckard, R.; Goodwin, I.

    2017-10-01

    Historical temperature data and maturity records were analyzed for 45 vineyard blocks in 15 winegrowing regions across Australia in order to evaluate the suitability of common viticultural indices to estimate date of grape maturity. Five temperature-based viticultural indices (mean January temperature, mean growing season temperature, growing degree days, biologically effective degree days, Huglin Index) along with four springtime temperature indices (mean and maximum temperature summations for September, October, and November; growing degree days and biologically effective degree days modified to include September) were compared to maturity data in order to investigate index relationship to observed maturity timing. Daily heat summations for the months of September, October, and November showed the best correlation to day of year of maturity, suggesting that springtime temperatures are important relative to the timing of grape maturity. Mean January temperature, a commonly used index, had the poorest correlation with day of year of maturity of all the indices included in this study. Indices that included the month of April had poorer correlation than indices that shifted the months included in the growing season to be from September to March inclusive. Calculated index values for the past 30 years for every region included in this study showed increasing temporal trends to various degrees, indicating that all regions studied are experiencing warming temperatures during the growing season. These results emphasize the need to reevaluate viticultural indices in the context of a changing climate.

  14. The Ikaros transcription factor regulates responsiveness to IL-12 and expression of IL-2 receptor alpha in mature, activated CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Eric T Clambey

    Full Text Available The Ikaros family of transcription factors is critical for normal T cell development while limiting malignant transformation. Mature CD8 T cells express multiple Ikaros family members, yet little is known about their function in this context. To test the functions of this gene family, we used retroviral transduction to express a naturally occurring, dominant negative (DN isoform of Ikaros in activated CD8 T cells. Notably, expression of DN Ikaros profoundly enhanced the competitive advantage of activated CD8 T cells cultured in IL-12, such that by 6 days of culture, DN Ikaros-transduced cells were 100-fold more abundant than control cells. Expression of a DN isoform of Helios, a related Ikaros-family transcription factor, conferred a similar advantage to transduced cells in IL-12. While DN Ikaros-transduced cells had higher expression of the IL-2 receptor alpha chain, DN Ikaros-transduced cells achieved their competitive advantage through an IL-2 independent mechanism. Finally, the competitive advantage of DN Ikaros-transduced cells was manifested in vivo, following adoptive transfer of transduced cells. These data identify the Ikaros family of transcription factors as regulators of cytokine responsiveness in activated CD8 T cells, and suggest a role for this family in influencing effector and memory CD8 T cell differentiation.

  15. Polysaccharide purified from Ganoderma atrum induced activation and maturation of murine myeloid-derived dendritic cells.

    Science.gov (United States)

    Wang, Hui; Yu, Qiang; Nie, Shao-Ping; Xiang, Quan-Dan; Zhao, Ming-Ming; Liu, Shi-Yu; Xie, Ming-Yong; Wang, Shun-Qi

    2017-10-01

    Ganoderma atrum (G. atrum), a member of the genus Ganoderma, is an edible and medicinal fungus. In this study, we investigated the direct and indirect effects of G. atrum polysaccharide (PSG-1) on dendritic cells (DCs). Firstly, flow cytometric and ELISA analysis showed that PSG-1 increased cell surface molecule expression of MHC-II, CD80 and CD86, and enhanced the production of IL-12 p70, IL-6, IL-10, RANTES, MIP-1α and MCP-1 in DCs. PSG-1-treated DCs promoted the proliferation of splenic T lymphocyte of mouse in mixed lymphocyte reaction. The above results demonstrated that PSG-1 induced the maturation of DCs. Secondly, PSG-1 increased the phosphorylation of p38, ERK and JNK determined by western blot. Inhibitors of p38, ERK and JNK decreased PSG-1-induced expression of MHC-II, CD80 and CD86 and production of IL-6 and IL-10 by DCs. These results suggested that PSG-1 induced mitogen-activated protein kinase (MAPK) activation was involved in the regulation of maturation markers and cytokines expression in DCs. Finally, PSG-1 increased expression of MHC-II of DCs in a DCs-Caco-2 co-culture model, suggesting that PSG-1 could indirectly influence DCs. In summary, our data suggested that PSG-1 directly induced DCs maturation via activating MAPK pathways, and indirectly stimulated DCs separated by intestinal epithelial cells. Copyright © 2017. Published by Elsevier Ltd.

  16. The role of GABA in the regulation of GnRH neurons

    Directory of Open Access Journals (Sweden)

    Miho eWatanabe

    2014-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

  17. Effects of mixing and covering with mature compost on gaseous emissions during composting.

    Science.gov (United States)

    Luo, Wen Hai; Yuan, Jing; Luo, Yi Ming; Li, Guo Xue; Nghiem, Long D; Price, William E

    2014-12-01

    This study investigated effects of mature compost on gaseous emissions during composting using pig manure amended with corn stalks. Apart from a control treatment, three treatments were conducted with the addition of 5% (wet weight of raw materials) of mature compost: (a) mixing raw materials with mature compost at the beginning of composting; (b) covering raw materials with mature compost throughout the experimental period; and (c) covering raw materials with mature compost at the start of composting, but incorporating it into composting pile on day 6 of composting. Mature compost used for the last treatment was inoculated with 2% (wet weight) of raw materials of strain M5 (a methanotrophic bacterium) solution. During 30-d of composting, three treatments with the addition of mature compost could reduce CH4 emission by 53-64% and N2O emission by 43-71%. However, covering with mature compost throughout the experimental period increased cumulative NH3 emission by 61%, although it could reduce 34% NH3 emission in the first 3d. Inoculating strain M5 in mature compost covered on the top of composting pile within first 6d enhanced CH4 oxidation, but simultaneously increased N2O emission. In addition, mixing with mature compost could improve compost maturity. Given the operational convenience in practice, covering with mature compost and then incorporating it into composting pile is a suitable approach to mitigate gaseous emissions during composting. Copyright © 2014. Published by Elsevier Ltd.

  18. Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation

    International Nuclear Information System (INIS)

    Han, Jun; Wang, Qiao-Chu; Zhu, Cheng-Cheng; Liu, Jun; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2016-01-01

    Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates agricultural staples and elicits a complex spectrum of toxic effects on humans and animals. It has been shown that DON impairs oocyte maturation, reproductive function and causes abnormal fetal development in mammals; however, the mechanisms remain unclear. In the present study, we investigate the possible reasons of the toxic effects of DON on porcine oocytes. Our results showed that DON significantly inhibited porcine oocyte maturation and disrupted meiotic spindle by reducing p-MAPK protein level, which caused retardation of cell cycle progression. In addition, up-regulated LC3 protein expression and aberrant Lamp2, LC3 and mTOR mRNA levels were observed with DON exposure, together with Annexin V-FITC staining assay analysis, these results indicated that DON treatment induced autophagy/apoptosis in porcine oocytes. We also showed that DON exposure increased DNA methylation level in porcine oocytes through altering DNMT3A mRNA levels. Histone methylation levels were also changed showing with increased H3K27me3 and H3K4me2 protein levels, and mRNA levels of their relative methyltransferase genes, indicating that epigenetic modifications were affected. Taken together, our results suggested that DON exposure reduced porcine oocytes maturation capability through affecting cytoskeletal dynamics, cell cycle, autophagy/apoptosis and epigenetic modifications. - Highlights: • DON exposure disrupted meiotic spindle by reducing p-MAPK expression. • DON exposure caused retardation of cell cycle progression in porcine oocytes. • DON triggered autophagy and early-apoptosis in porcine oocytes. • DON exposure led to aberrant epigenetic modifications in porcine oocytes.

  19. Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jun; Wang, Qiao-Chu; Zhu, Cheng-Cheng; Liu, Jun; Zhang, Yu [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Cui, Xiang-Shun; Kim, Nam-Hyung [Department of Animal Science, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Sun, Shao-Chen, E-mail: sunsc@njau.edu.cn [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China)

    2016-06-01

    Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates agricultural staples and elicits a complex spectrum of toxic effects on humans and animals. It has been shown that DON impairs oocyte maturation, reproductive function and causes abnormal fetal development in mammals; however, the mechanisms remain unclear. In the present study, we investigate the possible reasons of the toxic effects of DON on porcine oocytes. Our results showed that DON significantly inhibited porcine oocyte maturation and disrupted meiotic spindle by reducing p-MAPK protein level, which caused retardation of cell cycle progression. In addition, up-regulated LC3 protein expression and aberrant Lamp2, LC3 and mTOR mRNA levels were observed with DON exposure, together with Annexin V-FITC staining assay analysis, these results indicated that DON treatment induced autophagy/apoptosis in porcine oocytes. We also showed that DON exposure increased DNA methylation level in porcine oocytes through altering DNMT3A mRNA levels. Histone methylation levels were also changed showing with increased H3K27me3 and H3K4me2 protein levels, and mRNA levels of their relative methyltransferase genes, indicating that epigenetic modifications were affected. Taken together, our results suggested that DON exposure reduced porcine oocytes maturation capability through affecting cytoskeletal dynamics, cell cycle, autophagy/apoptosis and epigenetic modifications. - Highlights: • DON exposure disrupted meiotic spindle by reducing p-MAPK expression. • DON exposure caused retardation of cell cycle progression in porcine oocytes. • DON triggered autophagy and early-apoptosis in porcine oocytes. • DON exposure led to aberrant epigenetic modifications in porcine oocytes.

  20. Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Otani, Satoshi [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Kakinuma, Sei, E-mail: skakinuma.gast@tmd.ac.jp [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo (Japan); Kamiya, Akihide [Institute of Innovative Science and Technology, Tokai University, Isehara (Japan); Goto, Fumio; Kaneko, Shun; Miyoshi, Masato; Tsunoda, Tomoyuki; Asano, Yu; Kawai-Kitahata, Fukiko; Nitta, Sayuri; Nakata, Toru; Okamoto, Ryuichi; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Asahina, Yasuhiro [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Tomoyuki [Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); Koshikawa, Naohiko [Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); Seiki, Motoharu [Medical School, Kanazawa University, Kanazawa (Japan); Nakauchi, Hiromitsu [Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); and others

    2016-01-22

    Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver development; however, the molecular mechanisms regulating the phenotype of these cells have not been completely elucidated. Matrix metalloproteinase (MMP)-14 is a type I transmembrane proteinase regulating pericellular proteolysis of the extracellular matrix and is essential for the activation of several MMPs and cytokines. However, the physiological functions of MMP-14 in liver development are unknown. Here we describe a functional role for MMP-14 in hepatic and biliary differentiation of mouse hepatoblasts. MMP-14 was upregulated in cells around the portal vein in perinatal stage liver. Formation of bile duct-like structures in MMP-14–deficient livers was significantly delayed compared with wild-type livers in vivo. In vitro biliary differentiation assays showed that formation of cholangiocytic cysts derived from MMP-14–deficient hepatoblasts was completely impaired, and that overexpression of MMP-14 in hepatoblasts promoted the formation of bile duct-like cysts. In contrast, the expression of molecules associated with metabolic functions in hepatocytes, including hepatic nuclear factor 4α and tryptophan 2,3-dioxygenase, were significantly increased in MMP-14–deficient livers. Expression of the epidermal growth factor receptor and phosphorylation of mitogen-activated protein kinases were significantly upregulated in MMP-14–deficient livers. We demonstrate that MMP-14–mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes. - Highlights: • Loss of MMP-14 delayed formation of bile duct-like structures in perinatal liver. • Overexpression of MMP-14 in hepatobalsts promoted the biliary formation in vitro. • Loss of MMP-14 promoted hepatocyte maturation of hepatoblasts in vivo. • MMP-14–mediated signaling regulates terminal differentiation of

  1. Adipocytokine and ghrelin responses to acute exercise and sport training in children during growth and maturation.

    Science.gov (United States)

    Jürimäe, Jaak

    2014-11-01

    Physical exercise is known to regulate energy balance. Important to this regulatory system is the existence of several peptides that communicate the status of body energy stores to the brain and are related to the body fatness including leptin, adiponectin and ghrelin. These hormones assist in regulating energy balance as well as somatic and pubertal growth in children. It appears that rather few studies have investigated the responses of leptin, adiponectin and ghrelin to acute exercise and these studies have demonstrated no changes in these peptides as a result of exercise. Leptin levels are decreased and may remain unchanged advancing from prepuberty to pubertal maturation in young male and female athletes. A limited number of studies indicate that adiponectin levels are not different between prepubertal and pubertal athletes and untrained controls. However, in certain circumstances circulating adiponectin could be increased in young athletes after onset of puberty as a result of heavily increased energy expenditure. Ghrelin levels are elevated in young sportsmen. However, pubertal onset decreases ghrelin levels in boys and girls even in the presence of chronically elevated energy expenditure as seen in young athletes. Ghrelin may also be used as an indicator of energy imbalance across the menstrual cycle in adolescent athletes. There are no studies with high-molecular-weight adiponectin and only very few studies with acylated ghrelin responses to acute exercise and chronic training have been performed in young athletes. Since these forms of adiponectin and ghrelin have been thought to be bioactive forms, further studies with these specific forms of adiponectin and ghrelin are needed. In conclusion, further studies should be conducted to investigate the response of these hormones to acute and chronic negative energy balance to better understand their role in regulating energy balance during growth and maturation in young athletes.

  2. ICoNOs MM: The IT-enabled Collaborative Networked Organizations Maturity Model

    NARCIS (Netherlands)

    Santana Tapia, R.G.

    2009-01-01

    The focus of this paper is to introduce a comprehensive model for assessing and improving maturity of business-IT alignment (B-ITa) in collaborative networked organizations (CNOs): the ICoNOs MM. This two dimensional maturity model (MM) addresses five levels of maturity as well as four domains to

  3. The Relationship between Emotional Maturity, Intelligence and Creativity in Gifted Children.

    Science.gov (United States)

    Landau, Erika; Weissler, Kineret

    1998-01-01

    This study examined the relationships among emotional maturity, intelligence, and creativity in 221 gifted children at a special school in Israel. Emotional maturity was defined as the strength and courage to actualize individual abilities within the frame of social demands. Highly intelligent and emotionally mature children were more creative…

  4. Regulation of carotenoid and ABA accumulation during the development and germination of Nicotiana plumbaginifolia seeds.

    Science.gov (United States)

    Frey, Anne; Boutin, Jean-Pierre; Sotta, Bruno; Mercier, Raphaël; Marion-Poll, Annie

    2006-08-01

    Abscisic acid (ABA) is derived from epoxycarotenoid cleavage and regulates seed development and maturation. A detailed carotenoid analysis was undertaken to study the contribution of epoxycarotenoid synthesis to the regulation of ABA accumulation in Nicotiana plumbaginifolia developing seeds. Maximal accumulation of xanthophylls occurred at mid-development in wild type seeds, when total ABA levels also peaked. In contrast, in ABA-deficient mutants xanthophyll synthesis was delayed, in agreement with the retardation in seed maturation. Seed dormancy was restored in mutants impaired in the conversion of zeaxanthin into violaxanthin by zeaxanthin epoxidase (ZEP), by the introduction of the Arabidopsis AtZEP gene under the control of promoters inducing expression during later stages of seed development compared to wild type NpZEP, and in dry and imbibed seeds. Alterations in the timing and level of ZEP expression did not highly affect the temporal regulation of ABA accumulation in transgenic seeds, despite notable perturbations in xanthophyll accumulation. Therefore, major regulatory control of ABA accumulation might occur downstream of epoxycarotenoid synthesis.

  5. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  6. Salmon louse (Lepeophtheirus salmonis transcriptomes during post molting maturation and egg production, revealed using EST-sequencing and microarray analysis

    Directory of Open Access Journals (Sweden)

    Jonassen Inge

    2008-03-01

    Full Text Available Abstract Background Lepeophtheirus salmonis is an ectoparasitic copepod feeding on skin, mucus and blood from salmonid hosts. Initial analysis of EST sequences from pre adult and adult stages of L. salmonis revealed a large proportion of novel transcripts. In order to link unknown transcripts to biological functions we have combined EST sequencing and microarray analysis to characterize female salmon louse transcriptomes during post molting maturation and egg production. Results EST sequence analysis shows that 43% of the ESTs have no significant hits in GenBank. Sequenced ESTs assembled into 556 contigs and 1614 singletons and whenever homologous genes were identified no clear correlation with homologous genes from any specific animal group was evident. Sequence comparison of 27 L. salmonis proteins with homologous proteins in humans, zebrafish, insects and crustaceans revealed an almost identical sequence identity with all species. Microarray analysis of maturing female adult salmon lice revealed two major transcription patterns; up-regulation during the final molting followed by down regulation and female specific up regulation during post molting growth and egg production. For a third minor group of ESTs transcription decreased during molting from pre-adult II to immature adults. Genes regulated during molting typically gave hits with cuticula proteins whilst transcripts up regulated during post molting growth were female specific, including two vitellogenins. Conclusion The copepod L.salmonis contains high a level of novel genes. Among analyzed L.salmonis proteins, sequence identities with homologous proteins in crustaceans are no higher than to homologous proteins in humans. Three distinct processes, molting, post molting growth and egg production correlate with transcriptional regulation of three groups of transcripts; two including genes related to growth, one including genes related to egg production. The function of the regulated

  7. Jealousy and Moral Maturity.

    Science.gov (United States)

    Mathes, Eugene W.; Deuger, Donna J.

    Jealousy may be perceived as either good or bad depending upon the moral maturity of the individual. To investigate this conclusion, a study was conducted testing two hypothesis: a positive relationship exists between conventional moral reasoning (reference to norms and laws) and the endorsement and level of jealousy; and a negative relationship…

  8. Bone Morphogenetic Protein Signaling and Olig1/2 Interact to Regulate the Differentiation and Maturation of Adult Oligodendrocyte Precursor Cells

    OpenAIRE

    Cheng, Xiaoxin; Wang, Yaping; He, Qian; Qiu, Mengsheng; Whittemore, Scott R.; Cao, Qilin

    2007-01-01

    Promotion of remyelination is an important therapeutic strategy for the treatment of the demyelinating neurological disorders. Adult oligodendrocyte precursor cells (OPCs), which normally reside quiescently in the adult central nervous system (CNS), become activated and proliferative after demyelinating lesions. However, the extent of endogenous remyelination is limited because of the failure of adult OPCs to mature into myelinating oligodendrocytes (OLs) in the demyelinated CNS. Understandin...

  9. Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity.

    Science.gov (United States)

    Kraft, David C E; Bindslev, Dorthe A; Melsen, Birte; Abdallah, Basem M; Kassem, Moustapha; Klein-Nulend, Jenneke

    2010-02-01

    For engineering bone tissue, mechanosensitive cells are needed for bone (re)modelling. Local bone mass and architecture are affected by mechanical loading, which provokes a cellular response via loading-induced interstitial fluid flow. We studied whether human dental pulp-derived mesenchymal stem cells (PDSCs) portraying mature (PDSC-mature) or immature (PDSC-immature) bone cell characteristics are responsive to pulsating fluid flow (PFF) in vitro. We also assessed bone formation by PDSCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Cultured PDSC-mature exhibited higher osteocalcin and alkaline phosphatase gene expression and activity than PDSC-immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5 min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced prostaglandin E(2) production, and cyclooxygenase 2 gene expression was higher than in PDSC-immature. Implantation of PDSC-mature resulted in more osteoid deposition and lamellar bone formation than PDSC-immature. We conclude that PDSCs with a mature osteogenic phenotype are more responsive to pulsating fluid shear stress than osteogenically immature PDSCs and produce more bone in vivo. These data suggest that PDSCs with a mature osteogenic phenotype might be preferable for bone tissue engineering to restore, for example, maxillofacial defects, because they might be able to perform mature bone cell-specific functions during bone adaptation to mechanical loading in vivo.

  10. Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network.

    Science.gov (United States)

    Perdigoto, Carolina N; Bardot, Evan S; Valdes, Victor J; Santoriello, Francis J; Ezhkova, Elena

    2014-12-01

    Merkel cell-neurite complexes are located in touch-sensitive areas of the mammalian skin and are involved in recognition of the texture and shape of objects. Merkel cells are essential for these tactile discriminations, as they generate action potentials in response to touch stimuli and induce the firing of innervating afferent nerves. It has been shown that Merkel cells originate from epidermal stem cells, but the cellular and molecular mechanisms of their development are largely unknown. In this study, we analyzed Merkel cell differentiation during development and found that it is a temporally regulated maturation process characterized by a sequential activation of Merkel cell-specific genes. We uncovered key transcription factors controlling this process and showed that the transcription factor Atoh1 is required for initial Merkel cell specification. The subsequent maturation steps of Merkel cell differentiation are controlled by cooperative function of the transcription factors Sox2 and Isl1, which physically interact and work to sustain Atoh1 expression. These findings reveal the presence of a robust transcriptional network required to produce functional Merkel cells that are required for tactile discrimination. © 2014. Published by The Company of Biologists Ltd.

  11. Social and moral maturity of high-school students

    Directory of Open Access Journals (Sweden)

    Silvana Gasar

    2005-02-01

    Full Text Available The level of social and moral maturity of high-school students was examined. There were almost no significant differences between the students of two different educational programs. In general, the students' level of social and moral maturity is satisfyingly high, but their social skills are not quite appropriately developed. The results of behaviour in school situations reveal a quite unpleasant picture of interpersonal relations, which is probably a reflection of social relations in society. The absence of correlations between both components of maturity and social skills shows the gap between human's reasoning and behaviour. Students know, which behaviour is moral and socially adapted, but they do not always act in congruence with that, because existing social relations often encourage different behaviour.

  12. Ecological and evolutionary patterns of freshwater maturation in Pacific and Atlantic salmonines

    Science.gov (United States)

    Sloat, Matthew R.; Fraser, Dylan J.; Dunham, Jason B.; Falke, Jeffery A.; Jordan, Chris E.; McMillan, John R.; Ohms, Haley A.

    2014-01-01

    Reproductive tactics and migratory strategies in Pacific and Atlantic salmonines are inextricably linked through the effects of migration (or lack thereof) on age and size at maturity. In this review, we focus on the ecological and evolutionary patterns of freshwater maturation in salmonines, a key process resulting in the diversification of their life histories. We demonstrate that the energetics of maturation and reproduction provides a unifying theme for understanding both the proximate and ultimate causes of variation in reproductive schedules among species, populations, and the sexes. We use probabilistic maturation reaction norms to illustrate how variation in individual condition, in terms of body size, growth rate, and lipid storage, influences the timing of maturation. This useful framework integrates both genetic and environmental contributions to conditional strategies for maturation and, in doing so, demonstrates how flexible life histories can be both heritable and subject to strong environmental influences. We review evidence that the propensity for freshwater maturation in partially anadromous species is predictable across environmental gradients at geographic and local spatial scales. We note that growth is commonly associated with the propensity for freshwater maturation, but that life-history responses to changes in growth caused by temperature may be strikingly different than changes caused by differences in food availability. We conclude by exploring how contemporary management actions can constrain or promote the diversity of maturation phenotypes in Pacific and Atlantic salmonines and caution against underestimating the role of freshwater maturing forms in maintaining the resiliency of these iconic species.

  13. Aerobic fitness, maturation, and training experience in youth basketball.

    Science.gov (United States)

    Carvalho, Humberto M; Coelho-e-Silva, Manuel J; Eisenmann, Joey C; Malina, Robert M

    2013-07-01

    Relationships among chronological age (CA), maturation, training experience, and body dimensions with peak oxygen uptake (VO2max) were considered in male basketball players 14-16 y of age. Data for all players included maturity status estimated as percentage of predicted adult height attained at the time of the study (Khamis-Roche protocol), years of training, body dimensions, and VO2max (incremental maximal test on a treadmill). Proportional allometric models derived from stepwise regressions were used to incorporate either CA or maturity status and to incorporate years of formal training in basketball. Estimates for size exponents (95% CI) from the separate allometric models for VO2max were height 2.16 (1.23-3.09), body mass 0.65 (0.37-0.93), and fat-free mass 0.73 (0.46-1.02). Body dimensions explained 39% to 44% of variance. The independent variables in the proportional allometric models explained 47% to 60% of variance in VO2max. Estimated maturity status (11-16% of explained variance) and training experience (7-11% of explained variance) were significant predictors with either body mass or estimated fat-free mass (P ≤ .01) but not with height. Biological maturity status and training experience in basketball had a significant contribution to VO2max via body mass and fat-free fat mass and also had an independent positive relation with aerobic performance. The results highlight the importance of considering variation associated with biological maturation in aerobic performance of late-adolescent boys.

  14. Involvement of PLA2, COX and LOX in Rhinella arenarum oocyte maturation.

    Science.gov (United States)

    Ortiz, Maria Eugenia; Bühler, Marta Inés; Zelarayán, Liliana Isabel

    2014-11-01

    In Rhinella arenarum, progesterone is the physiological nuclear maturation inducer that interacts with the oocyte surface and starts a cascade of events that leads to germinal vesicle breakdown (GVBD). Polyunsaturated fatty acids and their metabolites produced through cyclooxygenase (COX) and lipoxygenase (LOX) pathways play an important role in reproductive processes. In amphibians, to date, the role of arachidonic acid (AA) metabolites in progesterone (P4)-induced oocyte maturation has not been clarified. In this work we studied the participation of three enzymes involved in AA metabolism - phospholipase A2 (PLA2), COX and LOX in Rhinella arenarum oocyte maturation. PLA2 activation induced maturation in Rhinella arenarum oocytes in a dose-dependent manner. Oocytes when treated with 0.08 μM melittin showed the highest response (78 ± 6% GVBD). In follicles, PLA2 activation did not significantly induce maturation at the assayed doses (12 ± 3% GVBD). PLA2 inhibition with quinacrine prevented melittin-induced GVBD in a dose-dependent manner, however PLA2 inactivation did not affect P4-induced maturation. This finding suggests that PLA2 is not the only phospholipase involved in P4-induced maturation in this species. P4-induced oocyte maturation was inhibited by the COX inhibitors indomethacin and rofecoxib (65 ± 3% and 63 ± 3% GVBD, respectively), although COX activity was never blocked by their addition. Follicles showed a similar response following the addition of these inhibitors. Participation of LOX metabolites in maturation seems to be correlated with seasonal variation in ovarian response to P4. During the February to June period (low P4 response), LOX inhibition by nordihydroguaiaretic acid or lysine clonixinate increased maturation by up to 70%. In contrast, during the July to January period (high P4 response), LOX inhibition had no effect on hormone-induced maturation.

  15. Neuropsychological relationship between maturity and presence-absence of crawling behavior

    OpenAIRE

    Suárez, Alejandra; Lozada, Carlos

    2017-01-01

    Neuropsychological maturity is the level of organization and maturational development that allows the development of behavioral and cognitive age-appropriate individual functions, crawling behavior is the first harmonic motion in which the baby uses his head and his both lower extremities as superior, to support and move, it allows the establishment of connections between brain hemispheres, leading to the intercom that simplifies the work of the brain and promotes the maturation of the cognit...

  16. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras

    International Nuclear Information System (INIS)

    Mosley, R.L.; Styre, D.; Klein, J.R.

    1990-01-01

    The thymus dependency of murine intestinal intraepithelial lymphocytes (IEL) was studied in an athymic F1----parent radiation chimera model. IEL, although not splenic or lymph node lymphocytes, from athymic chimeras displayed normal levels of cells bearing the class-specific T cell Ag, CD4 and CD8; the TCR-associated molecule, CD3; and the Thy-1 Ag. Moreover, two-color flow cytometric analyses of IEL from athymic mice demonstrated regulated expression of T cell Ag characteristic of IEL subset populations from thymus-bearing mice. In immunoprecipitation experiments, surface TCR-alpha beta or TCR-gamma delta were expressed on IEL, although not on splenic lymphocytes, from athymic chimeras. That IEL from athymic chimeras constituted a population of functionally mature effector cells activated in situ, similar to IEL from thymus-bearing mice, was demonstrated by the presence of CD3-mediated lytic activity of athymic lethally irradiated bone marrow reconstituted IEL. These data provide compelling evidence that intestinal T cells do not require thymic influence for maturation and development, and demonstrate that the microenvironment of the intestinal epithelium is uniquely adapted to regulate IEL differentiation

  17. Water relations in culture media influence maturation of avocado somatic embryos.

    Science.gov (United States)

    Márquez-Martín, Belén; Sesmero, Rafael; Quesada, Miguel A; Pliego-Alfaro, Fernando; Sánchez-Romero, Carolina

    2011-11-15

    Application of transformation and other biotechnological tools in avocado (Persea americana Mill.) is hampered by difficulties in obtaining mature somatic embryos capable of germination at an acceptable rate. In this work, we evaluated the effect of different compounds affecting medium water relations on maturation of avocado somatic embryos. Culture media were characterized with respect to gel strength, water potential and osmotic potential. Improved production of mature somatic embryos was achieved with gelling agent concentrations higher than those considered standard. The osmotic agents such as sorbitol and PEG did not have positive effects on embryo maturation. The number of w-o mature somatic embryos per culture was positively correlated with medium gel strength. Gel strength was significantly affected by gelling agent type as well as by gelling agent and PEG concentration. Medium water potential was influenced by sorbitol concentration; incorporation of PEG to a culture medium did not affect medium water potential. The highest maturation results were achieved on a medium gelled with 10 gl(-1) agar. Moreover, these somatic embryos had improved germination rates. These results corroborate the role of water restriction as a key factor controlling maturation of somatic embryos. Copyright © 2011 Elsevier GmbH. All rights reserved.

  18. Slab replacement maturity guidelines : [summary].

    Science.gov (United States)

    2014-04-01

    Concrete sets in hours at moderate temperatures, : but the bonds that make concrete strong continue : to mature over days to years. However, for : replacement concrete slabs on highways, it is : crucial that concrete develop enough strength : within ...

  19. Comparative study of the nutritional composition of matured green ...

    African Journals Online (AJOL)

    peppery fruit”. The fruit serve as a stimulant and eaten raw. It is still green when matured and turn from yellow to red if left for sometime after reaching maturity. Dennettia tripetala is one of the most cherished stimulants. However, there is lack of ...

  20. E-learning process maturity level: a conceptual framework

    Science.gov (United States)

    Rahmah, A.; Santoso, H. B.; Hasibuan, Z. A.

    2018-03-01

    ICT advancement is a sure thing with the impact influencing many domains, including learning in both formal and informal situations. It leads to a new mindset that we should not only utilize the given ICT to support the learning process, but also improve it gradually involving a lot of factors. These phenomenon is called e-learning process evolution. Accordingly, this study attempts to explore maturity level concept to provide the improvement direction gradually and progression monitoring for the individual e-learning process. Extensive literature review, observation, and forming constructs are conducted to develop a conceptual framework for e-learning process maturity level. The conceptual framework consists of learner, e-learning process, continuous improvement, evolution of e-learning process, technology, and learning objectives. Whilst, evolution of e-learning process depicted as current versus expected conditions of e-learning process maturity level. The study concludes that from the e-learning process maturity level conceptual framework, it may guide the evolution roadmap for e-learning process, accelerate the evolution, and decrease the negative impact of ICT. The conceptual framework will be verified and tested in the future study.

  1. Farmakologisk behandling af præmatur ejakulation

    DEFF Research Database (Denmark)

    Kuhlmann, Ida Berglund; Hedegaard, Ulla; Christensen, Mette Marie H

    2017-01-01

    Forfatterne anbefaler lokalanæstesi med lidokain og/eller prilokain som førstevalg. Andet valg til behandling vil være dapoxetin, som er en korttidsvirkende SSRI med indikationen præmatur ejakulation. Som tredje valg kan overvejes SSRI'et sertralin......Forfatterne anbefaler lokalanæstesi med lidokain og/eller prilokain som førstevalg. Andet valg til behandling vil være dapoxetin, som er en korttidsvirkende SSRI med indikationen præmatur ejakulation. Som tredje valg kan overvejes SSRI'et sertralin...

  2. Digital Maturity of the Firm's Business Model

    DEFF Research Database (Denmark)

    Groskovs, Sergejs; Vemula, Sreekanth

    We propose a digital maturity assessment model as an instrument for researchers and a strategic tool for managers. Existing literature lacks a conceptually clear way to measure the construct of digital maturity at the level of the firms business model. Our proposed instrument thus opens avenues...... for research into questions related to antecedents, process, and performance outcomes of the digitalization of business activities. The assessment follows the logic of first decomposing the business model into the underlying value creation activities and then evaluating the levels of automation...

  3. Evaluation of sexual maturity among adolescent male sickle cell ...

    African Journals Online (AJOL)

    Tanner staging and testicular volume assessment were both used as models for evaluating stages of sexual maturation among SCA patients and their normal counterparts matched for age and socioeconomic status. Results. SCA patients showed delayed onset and completion of sexual maturation. TV of subjects was ...

  4. Nicotine supplementation blocks oocyte maturation in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Meitria Syahadatina Noor

    2013-08-01

    Full Text Available Background Indonesia has the third largest tobacco consumption in the world after China and India. Nicotine as the main component of cigarette smoke has negative effects on the reproductive system, such as oocyte maturation, ovulation, and fertilization, and increasing the diploidy of oocytes. The goal of this research was to evaluate the effect of nicotine on oocyte maturation in Rattus norvegicus. Methods This was an experimental study with post test only control group design. The subjects were 40 rats selected homogenously and randomly. They were divided into a control group (receiving carboxy-methyl-cellulose sodium and 3 treatment groups (I-III receiving nicotine subcutaneously for 7 days at dosages of 21 mg/kgBW, 41 kg/kgBW and 84/kgBW, respectively. The observations comprised oocyte maturation stage, viz. germinal vesicle (GV, germinal vesicle breakdown (GVBD, metaphase I and metaphase II. Data were analyzed by one-way Anova with á=0.05, followed by Tukey’s HSD test. Results One-way Anova showed significant differences in oocyte maturation in all groups. Tukey’s HSD test showed that for GV, the differing groups were control and I, control and II, I and III. For GVBD, the differing groups were control and I, I and II, I and III. For metaphase I, the differing groups were control with I, II, and III, I and II, I and III. For metaphase II, the differing groups were control versus I, II, and III, I and II, I and III. Conclusion Low dose of nicotine is capable of affecting oocyte maturation in Rattus norvegicus.

  5. Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells.

    NARCIS (Netherlands)

    Berk, L.C.J. van den; Roelofs, H.; Huijs, T.; Siebers-Vermeulen, K.G.C.; Raymakers, R.A.P.; Kogler, G.; Figdor, C.G.; Torensma, R.

    2009-01-01

    Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord

  6. Dual Role for Hsc70 in the Biogenesis and Regulation of the Heme-Regulated Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2

    Science.gov (United States)

    Uma, Sheri; Thulasiraman, Vanitha; Matts, Robert L.

    1999-01-01

    The heme-regulated kinase of the α subunit of eukaryotic initiation factor 2 (HRI) is activated in rabbit reticulocyte lysate (RRL) in response to a number of environmental conditions, including heme deficiency, heat shock, and oxidative stress. Activation of HRI causes an arrest of initiation of protein synthesis. Recently, we have demonstrated that the heat shock cognate protein Hsc70 negatively modulates the activation of HRI in RRL in response to these environmental conditions. Hsc70 is also known to be a critical component of the Hsp90 chaperone machinery in RRL, which plays an obligatory role for HRI to acquire and maintain a conformation that is competent to activate. Using de novo-synthesized HRI in synchronized pulse-chase translations, we have examined the role of Hsc70 in the regulation of HRI biogenesis and activation. Like Hsp90, Hsc70 interacted with nascent HRI and HRI that was matured to a state which was competent to undergo stimulus-induced activation (mature-competent HRI). Interaction of HRI with Hsc70 was required for the transformation of HRI, as the Hsc70 antagonist clofibric acid inhibited the folding of HRI into a mature-competent conformation. Unlike Hsp90, Hsc70 also interacted with transformed HRI. Clofibric acid disrupted the interaction of Hsc70 with transformed HRI that had been matured and transformed in the absence of the drug. Disruption of Hsc70 interaction with transformed HRI in heme-deficient RRL resulted in its hyperactivation. Furthermore, activation of HRI in response to heat shock or denatured proteins also resulted in a similar blockage of Hsc70 interaction with transformed HRI. These results indicate that Hsc70 is required for the folding and transformation of HRI into an active kinase but is subsequently required to negatively attenuate the activation of transformed HRI. PMID:10454533

  7. In vivo and in vitro pollen maturation in Lilium: influence of carbohydrates

    Directory of Open Access Journals (Sweden)

    Christophe Clement

    2014-01-01

    Full Text Available The purpose of this study was to develop a protocol for in vitro conform pollen maturation, as a model to study the involvement of carbohydrates on pollen maturation in Lilium. In vivo and in vitro pollen maturations were followed and compared by transmission electron microscopy, and several in vitro parameters were tested in terms of carbohydrate physiology. In vivo, pollen maturation was initiated at the vacuolated microspore stage, and consisted of two successive phases. The first phase was characterized by reactivation of microspore organelles, followed by microspore mitosis, starch synthesis and vacuole breakdown. During the second phase, starch was progressively degraded whereas lipid and phytine reserves accumulated. In vivo, pollen maturation occured within 14 days and pollen germination rate was 73.6 ± 2.2%. We then attempted to realise in vitro pollen maturation starting from the vacuolated microspore stage. The best results were obtained with flower buds cultivated at 26oC, in 100 µmol/m2/s light, with a 16h/8h photoperiod on a modified Heller's medium supplemented with NAA (10-2 mg/l and sucrose (M/6. In these conditions, pollen maturation occured within 7 days only. In vitro matured pollen is cytologically comparable to in vivo developed pollen grains and the germination rate was 72.4 ± 3.7%. When flower buds were cultivated in the dark, the germination rate decreased, but this could be compensated by providing high sucrose concentrations (1M in the medium. Further, photosynthesis inhibitors had the same effect on pollen maturation than the darkness, strongly suggesting that photosynthesis occurs in the flower bud and is important for pollen maturation in Lilium.

  8. Maturation of pig oocytes in vitro in a medium with pyruvate

    Directory of Open Access Journals (Sweden)

    H. Gonzales-Figueroa

    2005-06-01

    Full Text Available The aim of in vitro maturation oocyte systems is to produce oocytes of comparable quality to those derived in vivo. The present study was designed to examine the surface morphological changes of the cumulus-oocyte complex (COC and nuclear maturation in a culture system containing pyruvate. Ovaries were obtained from a slaughterhouseand transported to the laboratory within 2 h at 35-39ºC,and rinsed three times in 0.9% NaCl. The COCs were harvested from the ovaries and in vitro maturation was evaluated in San Marcos (SM medium, a chemically defined culture system containing 22.3 mM sodium pyruvate. Oocytes were cultured in SM, SM + porcine follicular fluid (pFF and in SM + pFF + gonadotropins (eCG and hCG for 20-22 h and then without hormonal supplements for an additional 20-22 h. After culture, the degree of cumulus expansion and frequency of nuclear maturation were determined. Oocytes matured in SM (40.9% and SM + pFF (42.9% showed moderate cumulus expansion, whereas oocytes matured in SM + pFF + gonadotropins (54.6% showed high cumulus expansion. The maturation rate of cultured oocytes, measured in function of the presence of the polar corpuscle, did not differ significantly between SM (40.9 ± 3.6% and SM + pFF (42.9 ± 3.7%. These results indicate that pig oocytes can be successfully matured in a chemically definedmedium and suggest a possible bifunctional role of pyruvate as an energy substrate and as an antioxidant protecting oocytes against the stress of the in vitro environment.

  9. Thermal mud maturation: organic matter and biological activity.

    Science.gov (United States)

    Centini, M; Tredici, M R; Biondi, N; Buonocore, A; Maffei Facino, R; Anselmi, C

    2015-06-01

    Many of the therapeutic and cosmetic treatments offered in spas are centred on mud therapy, to moisturize the skin and prevent skin ageing and rheumatic diseases. Thermal mud is a complex matrix composed of organic and inorganic elements which contribute to its functions. It is a natural product derived from the long mixing of clay and thermal water. During its maturation, organic substances are provided by the microalgae, which develop characteristic of the composition of thermal water. The aim of this study was to identify methods for introducing objective parameters as a basis for characterizing thermal mud and assessing its efficacy. Samples of thermal mud were collected at the Saturnia spa, where there are several sulphureous pools. The maturation of the mud was evaluated by organic component determination using extractive methods and chromatographic analysis (HPLC, GC-MS, SPME). We also studied the radical scavenging activity of mud samples at different stages of maturation, in a homogeneous phase, using several tests (DPPH, ORAC, ABTS). We identified several classes of compounds: saturated and unsaturated fatty acids, hydroxyl acids, dicarboxylic acids, ketoacids, alcohols and others. SPME analysis showed the presence of various hydrocarbons compounds (C(11) -C(17)) and long-chain alcohols (C(12) -C(16)). Six or seven months seemed appropriate to complete the process of maturation, and the main effect of maturation time was the increase of lipids. Six-month mud showed the highest activity. The hydrophilic extract was more active than the lipophilic extract. The results indicate that maturation of thermal mud can be followed on the basis of the changes in its organic composition and antioxidant properties along the time. They also highlight the need to develop reference standards for thermal muds in relation to assess their use for therapeutic and cosmetic purposes. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  10. Effect of fertilization on the physiological maturation of sesame seeds

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    Erivan Isídio Ferreira

    2017-06-01

    Full Text Available Fertilization and harvest time may influence the formation and maturation processes, as well as the physiological quality of seeds. This study aimed at evaluating the effect of fertilization on the physiological maturation of sesame seeds. The following variables were evaluated: fruit color, dry mass and water content of fruits and seeds, germination, first germination count, germination speed, emergence and emergence speed. No significant fertilization effect was observed on fruit maturation for water content or dry mass. However, there was significance for these variables in the seeds. The harvest time had a significant effect on water content and dry mass of fruits and seeds. For the variables that evaluated the seed viability and vigor, both the fertilization and harvest time influenced the physiological maturation. The physiological maturity of the sesame seeds, whose plants were grown with and without fertilization, was reached between 52 and 54 days after anthesis, when the fruits were classified as yellow-greenish 7.5 Y 8/6 and yellow to yellow-red 10.R 4/6.

  11. Phytohormone and Light Regulation of Chlorophyll Degradation

    Directory of Open Access Journals (Sweden)

    Xiaoyu Zhu

    2017-11-01

    Full Text Available Degreening, due to the net loss of chlorophyll (Chl, is the most prominent symptom during the processes of leaf senescence, fruit ripening, and seed maturation. Over the last decade or so, extensive identifications of Chl catabolic genes (CCGs have led to the revelation of the biochemical pathway of Chl degradation. As such, exploration of the regulatory mechanism of the degreening process is greatly facilitated. During the past few years, substantial progress has been made in elucidating the regulation of Chl degradation, particularly via the mediation of major phytohormones' signaling. Intriguingly, ethylene and abscisic acid's signaling have been demonstrated to interweave with light signaling in mediating the regulation of Chl degradation. In this review, we briefly summarize this progress, with an effort on providing a framework for further investigation of multifaceted and hierarchical regulations of Chl degradation.

  12. The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus

    International Nuclear Information System (INIS)

    Ma Shiliang; Sorensen, Annette Balle; Kunder, Sandra; Sorensen, Karina Dalsgaard; Quintanilla-Martinez, Leticia; Morris, David W.; Schmidt, Joerg; Pedersen, Finn Skou

    2006-01-01

    ICSBP (interferon consensus sequence binding protein)/IRF8 (interferon regulatory factor 8) is an interferon gamma-inducible transcription factor expressed predominantly in hematopoietic cells, and down-regulation of this factor has been observed in chronic myelogenous leukemia and acute myeloid leukemia in man. By screening about 1200 murine leukemia virus (MLV)-induced lymphomas, we found proviral insertions at the Icsbp locus in 14 tumors, 13 of which were mature B-cell lymphomas or plasmacytomas. Only one was a T-cell lymphoma, although such tumors constituted about half of the samples screened. This indicates that the Icsbp locus can play a specific role in the development of mature B-lineage malignancies. Two proviral insertions in the last Icsbp exon were found to act by a poly(A)-insertion mechanism. The remaining insertions were found within or outside Icsbp. Since our results showed expression of Icsbp RNA and protein in all end-stage tumor samples, a simple tumor suppressor function of ICSBP is not likely. Interestingly, proviral insertions at Icsbp have not been reported from previous extensive screenings of mature B-cell lymphomas induced by endogenous MLVs. We propose that ICSBP might be involved in an early modulation of an immune response to exogenous MLVs that might also play a role in proliferation of the mature B-cell lymphomas

  13. Pricing constant maturity credit default swaps under jumo dynamics

    NARCIS (Netherlands)

    Jönsson, H.; Schoutens, W.

    2009-01-01

    In this paper we discuss the pricing of Constant Maturity Credit Default Swaps (CMCDS) under single sided jump models. The CMCDS offers default protection in exchange for a floating premium which is periodically reset and indexed to the market spread on a CDS with constant maturity tenor written on

  14. MRI quantitative assessment of brain maturation and prognosis in premature infants using total maturation score

    International Nuclear Information System (INIS)

    Qi Ying; Wang Xiaoming

    2009-01-01

    Objective: To quantitatively assess brain maturation and prognosis in premature infants on conventional MRI using total maturation score (TMS). Methods: Nineteen cases of sequelae of white matter damage (WMD group )and 21 cases of matched controls (control group) in premature infants confirmed by MRI examinations were included in the study. All cases underwent conventional MR imaging approximately during the perinatal period after birth. Brain development was quantitatively assessed using Childs AM's validated scoring system of TMS by two sophisticated radiology physicians. Interobserver agreement and reliability was evaluated by using intraclass correlation (ICC). Linear regression analysis between TMS and postmenstrual age (PMA) was made(Y: TMS, X: PMA). Independent-sample t test of the two groups' TMS was made. Results: Sixteen of 19 cases revealed MRI abnormalities. Lesions showing T 1 and T 2 shortening tended to occur in clusters or a linear pattern in the deep white matter of the centrum semiovale, periventricular white matter. Diffusion-weighted MR image (DWI) showed 3 cases with greater lesions and 4 cases with new lesions in corpus callosum. There was no abnormality in control group on MRI and DWI. The average numbers of TMS between the two observers were 7.13±2.27, 7.13±2.21. Interobservcer agreement was found to be high (ICC=0.990, P 2 =0.6401,0.5156 respectively, P 0.05). Conclusion: Conventional MRI is able to quantify the brain maturation and prognosis of premature infants using TMS. (authors)

  15. Maturity Gonad Sea Cucumber Holothuria scabra Under The Month Cycle

    Science.gov (United States)

    Penina Tua Rahantoknam, Santi

    2017-10-01

    Gonad maturity level of the sea cucumber Holothuria scabra is important to note for selection of parent ready spawn. Sea cucumbers are giving a reaction to the treatment of excitatory spawn mature individuals only. For the determination of the level of maturity of gonads of sea cucumbers, the necessary observation of the gonads are microscopic, macroscopic and gonad maturity gonado somatic indeks (GSI). GSI value is important to know the changes that occur in the gonads quantitatively, so that time can be presumed spawning (Effendie, 1997). Reproductive cycle can be determined by observing the evolution of GSI. The study of sea cucumbers Holothuria scabra gonad maturity conducted in Langgur, Southeast Maluku. Observations were made at every cycle of the moon is the full moon phase (BP) and new moon (BB) in the period January 29, 2017 until July 23, 2017. Observations H. scabra gonad maturity level is done with surgery, observation and calculation GSI gonad histology. GSI highest value obtained in May that full moon cycle at 90% of individuals that are in the spawning stage (phase 5), then 70% of the individuals that are in the spawning stage (phase 5) in March that the full moon cycle. The results obtained show that the peak spawning H. scabra period January 2017 to July 2017 occurred on the full moon cycle in May.

  16. Proteome analysis during pod, zygotic and somatic embryo maturation of Theobroma cacao.

    Science.gov (United States)

    Niemenak, Nicolas; Kaiser, Edward; Maximova, Siela N; Laremore, Tatiana; Guiltinan, Mark J

    2015-05-15

    Two dimensional electrophoresis and nano-LC-MS were performed in order to identify alterations in protein abundance that correlate with maturation of cacao zygotic and somatic embryos. The cacao pod proteome was also characterized during development. The recently published cacao genome sequence was used to create a predicted proteolytic fragment database. Several hundred protein spots were resolved on each tissue analysis, of which 72 variable spots were subjected to MS analysis, resulting in 49 identifications. The identified proteins represent an array of functional categories, including seed storage, stress response, photosynthesis and translation factors. The seed storage protein was strongly accumulated in cacao zygotic embryos compared to their somatic counterpart. However, sucrose treatment (60 g L(-1)) allows up-regulation of storage protein in SE. A high similarity in the profiles of acidic proteins was observed in mature zygotic and somatic embryos. Differential expression in both tissues was observed in proteins having high pI. Several proteins were detected exclusively in fruit tissues, including a chitinase and a 14-3-3 protein. We also identified a novel cacao protein related to known mabinlin type sweet storage proteins. Moreover, the specific presence of thaumatin-like protein, another sweet protein, was also detected in fruit tissue. We discuss our observed correlations between protein expression profiles, developmental stage and stress responses. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. The tax aspects of mature fields of oil and the reduction of regional inequalities in Brazil; Aspectos fiscais dos campos maduros de petroleo e reducao das desigualdades regionais no Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Passeggi, Alicia Violeta B.S. [Instituto Brasileiro de Petroleo, Gas e Biocombustiveis (IBP), Rio de Janeiro, RJ (Brazil); Bichara, Jahyr-Philippe [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2008-07-01

    Considering the important role played in internalizing national development by the small and medium size oil producers, the work approaches the tax aspects in the activity of mature fields' exploitation, relating it to the constitutional principle of reduction of regional inequalities, which is deeply developed in the Brazilian Federal Constitution of 1988. The birth of a new class of independent producers, in a scene before dominated by one single actor, is a phenomena that demands special attention from the State as 'regulator', because it includes several relevant aspects to the achievement of national objectives, legally imposed, such as: free enterprise, the pursuit of plain employment, the reduction of regional inequalities, a favored treatment to enterprises of small size, the conservation of energy, the rational use of oil, among others. Despite its relevance, the exploitation of mature fields suffers an absence of specific regulation, e.g., in what concern the imprecise terminology of mature fields. It was verified through the research, that the tax regime does not take into consideration neither the reduced contributive capacity of the small and medium size producers, nor its important function in the regional and energy subjects. (author)

  18. Self-regulation of learning and performance level of elite youth soccer players

    NARCIS (Netherlands)

    Toering, Tynke; Elferink-Gemser, Marije T.; Jordet, Geir; Pepping, Gert-Jan; Visscher, Chris

    2012-01-01

    This study examined the relationship between self-regulated learning and performance level of 256 elite youth soccer players aged 12 to 17 years (M-age = 14.2; SD = 1.2). As relative age may affect this relationship through its association with maturation, experience, and performance level, we

  19. How to manage sustainable supply chain? The issue of maturity

    Directory of Open Access Journals (Sweden)

    Agata Rudnicka

    2016-12-01

    Full Text Available Background: The issue of managing sustainability in supply chain seems to be more and more complex. There are many aspects that need to be taken into consideration when planning, implementing and monitoring environmental and social conditions of supply chains. Despite many works, already published, on the concept of sustainable development (SD is seems that the issue of assessment and especially the issue of maturity in the light of the SD concept is still not developed enough. Methods: The general aim of the paper is the analysis of the maturity issue in the context of sustainability. The main objective is to conceptualize the idea of maturity in sustainable supply chain. Beside the literature research the own proposition of theoretical model was described. Results: The article describes the issue of maturity as an element of managing sustainable development in the supply chain. The author presented a theoretical model of the maturity. Moreover the author gave some recommendations how to manage the sustainability issues in supply chain in more mature approach and introduced some useful tools among which are: certification, code of conduct and code of ethics, audits, projects etc. Conclusions: The issue of maturity seems to be very useful for proper understanding the idea of sustainable development in supply chain. The developed model can be used as self-assessment method to check at which level of implementation the idea of SD is analyzed in supply chain. Furthermore, the next phase of the planned research in form of practical verification of the model was advised as well as a research of identification of new factors and tools in analyzed area.

  20. [Emotional experience and regulation across the adult lifespan: comparative analysis in three age groups].

    Science.gov (United States)

    Márquez-González, María; Izal Fernández de Trocóniz, María; Montorio Cerrato, Ignacio; Losada Baltar, Andrés

    2008-11-01

    The studies focused on age-related differences in emotional experience are still scarce, and most of them have been conducted with North-American samples. This study explores the presence of age-related differences in some facets of emotional experience (subjective well-being and emotional intensity), as well as in variables related to emotion regulation (subjective emotional control and three emotion-regulation mechanisms: situation selection, emotion suppression, rumination) in the Spanish population. One hundred and sixty people from three age groups (younger, middle-aged and older adults) participated in the study. Older participants reported lower levels of life satisfaction and positive emotional intensity than younger ones, as well as higher levels of perceived emotional control, emotional maturity and leveling of positive affect, and more use of emotion suppression. The results partially support the emotional maturity hypothesis of emotional functioning in old age, but also suggest that older adults' emotional regulation may present important peculiarities which have not yet been addressed in the extant literature, such as the moderation or limitation of emotional experience, especially positive emotions.