WorldWideScience

Sample records for regulating primary cilium

  1. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    Science.gov (United States)

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Enteric neurons show a primary cilium.

    Science.gov (United States)

    Luesma, Ma José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia-Verdugo, José Manuel; Junquera, Concepción

    2013-01-01

    The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  3. New Roles of the Primary Cilium in Autophagy.

    Science.gov (United States)

    Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio; Morselli, Eugenia; Criollo, Alfredo

    2017-01-01

    The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies.

  4. CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium

    DEFF Research Database (Denmark)

    Mönnich, Maren; Borgeskov, Louise; Breslin, Loretta

    2018-01-01

    The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends...... on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling. Loss of CEP128 did not grossly affect centrosomal or ciliary structure...... but caused impaired transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) signaling in zebrafish and at the primary cilium in cultured mammalian cells. This phenotype is likely the result of defective vesicle trafficking at the cilium as ciliary localization of RAB11 was impaired upon loss...

  5. Neoexpression of a functional primary cilium in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Blanche Sénicourt

    2016-05-01

    Full Text Available The Hedgehog (HH signaling pathway is involved in the maintenance of numerous cell types both during development and in the adult. Often deregulated in cancers, its involvement in colorectal cancer has come into view during the last few years, although its role remains poorly defined. In most tissues, the HH pathway is highly connected to the primary cilium (PC, an organelle that recruits functional components and regulates the HH pathway. However, normal epithelial cells of the colon display an inactive HH pathway and lack a PC. In this study, we report the presence of the PC in adenocarcinoma cells of primary colorectal tumors at all stages. Using human colorectal cancer cell lines we found a clear correlation between the presence of the PC and the expression of the final HH effector, GLI1, and provide evidence of a functional link between the two by demonstrating the recruitment of the SMO receptor to the membrane of the primary cilium. We conclude that the primary cilium directly participates in the HH pathway in colorectal cancer cells.

  6. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

    DEFF Research Database (Denmark)

    Clement, Christian A; Kristensen, Stine G; Møllgård, Kjeld

    2009-01-01

    Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent...... P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine...... development. These data support the conclusion that cardiac primary cilia are crucial in early heart development, where they partly coordinate hedgehog signaling....

  7. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    International Nuclear Information System (INIS)

    Dvorak, J; Kasaova, L; Filip, S; Petera, J; Sitorova, V; Nikolov, D Hadzi; Ryska, A; Mokry, J; Richter, I

    2011-01-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G 1 (G 0 ) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  8. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    Science.gov (United States)

    Dvorak, J.; Sitorova, V.; Hadzi Nikolov, D.; Mokry, J.; Richter, I.; Kasaova, L.; Filip, S.; Ryska, A.; Petera, J.

    2011-12-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G1(G0) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  9. PDGFR alpha signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90(RSK) and AKT signaling pathways

    DEFF Research Database (Denmark)

    Clement, Ditte L.; Mally, Sabine; Stock, Christian

    2013-01-01

    In fibroblasts, platelet-derived growth factor receptor alpha (PDGFR alpha) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 path...

  10. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Jinah Kim

    Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

  11. Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control.

    Directory of Open Access Journals (Sweden)

    Anahi Molla-Herman

    Full Text Available The primary cilium is a sensory organelle generated from the centrosome in quiescent cells and found at the surface of most cell types, from where it controls important physiological processes. Specific sets of membrane proteins involved in sensing the extracellular milieu are concentrated within cilia, including G protein coupled receptors (GPCRs. Most GPCRs are regulated by beta-arrestins, betaarr1 and betaarr2, which control both their signalling and endocytosis, suggesting that betaarrs may also function at primary cilium.In cycling cells, betaarr2 was observed at the centrosome, at the proximal region of the centrioles, in a microtubule independent manner. However, betaarr2 did not appear to be involved in classical centrosome-associated functions. In quiescent cells, both in vitro and in vivo, betaarr2 was found at the basal body and axoneme of primary cilia. Interestingly, betaarr2 was found to interact and colocalize with 14-3-3 proteins and Kif3A, two proteins known to be involved in ciliogenesis and intraciliary transport. In addition, as suggested for other centrosome or cilia-associated proteins, betaarrs appear to control cell cycle progression. Indeed, cells lacking betaarr2 were unable to properly respond to serum starvation and formed less primary cilia in these conditions.Our results show that betaarr2 is localized to the centrosome in cycling cells and to the primary cilium in quiescent cells, a feature shared with other proteins known to be involved in ciliogenesis or primary cilium function. Within cilia, betaarr2 may participate in the signaling of cilia-associated GPCRs and, therefore, in the sensory functions of this cell "antenna".

  12. Characterization of membrane protein trafficking and cellular signaling at the primary cilium

    DEFF Research Database (Denmark)

    Mogensen, Johanne Bay

    Primary cilia are microtubule-based, non-motile, sensory organelles emerging in a single copy from the surface of most quiescent cells in vertebrates. They emanate from the centrosomal mother centriole and are assembled and maintained by a bidirectional transport process termed intraflagellar...... transport. Specific receptors, ion channels and downstream signaling components are localized along the cilium-centrosome axis, enabling the cilium to function as a hot spot for the balanced coordination of multiple signaling pathways to control cell cycle entry, differentiation and migration during...... differentiation of mouse stem cells into cardiomyocytes. These results support the conclusion that Tab2 functions at the primary cilium to coordinate specified signaling events, which when defective may lead to congenital heart disease Collectively, the results presented in this PhD thesis provide new insights...

  13. The primary cilium as sensor of fluid flow: new building blocks to the model

    DEFF Research Database (Denmark)

    Prætorius, Helle

    2015-01-01

    functionally as an organelle that makes cells more susceptible to changes in fluid flow. Thus the primary cilium was suggested to function as a flow-sensing device. This characterization has been substantiated for many epithelial cell types over the years. Nevertheless, part of the central mechanism of signal...

  14. Chapter 10 the primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Stine F; Satir, Peter

    2008-01-01

    Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present...... an overview of the function of primary cilia and the centrosome in the signaling pathways that regulate cell cycle control and migration with focus on ciliary signaling via platelet-derived growth factor receptor alpha (PDGFRalpha). We also consider how the primary cilium and the centrosome interact...... with the extracellular matrix, coordinate Wnt signaling, and modulate cytoskeletal changes that impinge on both cell cycle control and cell migration....

  15. Chemical-Free Technique to Study the Ultrastructure of Primary Cilium.

    Science.gov (United States)

    Mohieldin, Ashraf M; AbouAlaiwi, Wissam A; Gao, Min; Nauli, Surya M

    2015-11-02

    A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our results showed that a cilium has a swelling-like structure (termed bulb), which was previously considered a fixation artifact. The intramembrane particles observed via HPF/FFTEM indicated the presence of integral membrane proteins and soluble matrix proteins along the ciliary bulb, which is part of an integral structure within the ciliary membrane. We propose that HPF/FFTEM is an important and more suitable chemical-free method to study the ultrastructure of primary cilia.

  16. Betal-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signalling

    DEFF Research Database (Denmark)

    Prætorius, Helle; Prætorius, Jeppe; Nielsen, Søren

    2004-01-01

    observed that β1-integrin, α3-integrin, and perhaps α5-integrin were localized to the primary cilium of MDCK cells by combining lectin and immunofluorescence confocal microscopy. β1-Integrin was also colocalized with tubulin to the primary cilia of the rat renal collecting ducts, as well as to the cilia...

  17. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Cammer, Michael; Lehman, Jonathan

    2010-01-01

    Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration....... Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA...

  18. The primary cilium of telocytes in the vasculature: electron microscope imaging.

    Science.gov (United States)

    Cantarero, I; Luesma, M J; Junquera, C

    2011-12-01

    Blood vessels are highly organized and complex structure, which are far more than simple tubes conducting the blood to almost any tissue of the body. The fine structure of the wall of blood vessels has been studied previously using the electron microscope, but the presence the telocytes associated with vasculature, a specific new cellular entity, has not been studied in depth. Interestingly, telocytes have been recently found in the epicardium, myocardium, endocardium, human term placenta, duodenal lamina propria and pleura. We show the presence of telocytes located on the extracellular matrix of blood vessels (arterioles, venules and capillaries) by immunohistochemistry and transmission electron microscopy. Also, we demonstrated the first evidence of a primary cilium in telocytes. Several functions have been proposed for these cells. Here, the telocyte-blood vessels cell proximity, the relationship between telocytes, exosomes and nervous trunks may have a special significance. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  19. Exploration of Self-Regulation in the Natural Swimming of the Paramecium’s Cilium

    Science.gov (United States)

    2012-02-01

    aquatic environments. These animals propel themselves, albeit with limited maneuverability, by the synchronous motion of numerous tiny cilia...microtubule pairs are the source of cilium hardness during the power stroke ; there is a critical phase near the end of the power stroke where one cross...return stroke ; therefore, in each beat cycle, there must be a reattachment process of the cross-bridge links and re-hardening of the cilium during the

  20. Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.

    Directory of Open Access Journals (Sweden)

    Bomi Jung

    Full Text Available The seven-transmembrane receptor Smoothened (Smo activates all Hedgehog (Hh signaling by translocation into the primary cilia (PC, but how this is regulated is not well understood. Here we show that Pitchfork (Pifo and the G protein-coupled receptor associated sorting protein 2 (Gprasp2 are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation.

  1. The primary cilium as a multiple cellular signaling scaffold in development and disease

    Directory of Open Access Journals (Sweden)

    Hyuk Wan Ko*

    2012-08-01

    Full Text Available Primary cilia, single hair-like appendage on the surface of themost mammalian cells, were once considered to be vestigialcellular organelles for a past century because of their tinystructure and unknown function. Although they lack ancestralmotility function of cilia or flagella, they share common groundwith multiciliated motile cilia and flagella on internal structuresuch as microtubule based nine outer doublets nucleated from thebase of mother centrioles called basal body. Making cilia,ciliogenesis, in cells depends on the cell cycle stage due to reuseof centrioles for cell division forming mitotic spindle pole (Mphase and assembling cilia from basal body (starting G1 phaseand maintaining most of interphase. Ciliary assembly requiredtwo conflicting processes such as assembly and disassembly andbalance between these two processes determines the length ofcilia. Both process required highly conserved transport system tosupply needed substance to grow tip of cilia and bring ciliaryturnover product back to the base of cilia using motor protein,kinesin and dynein, and transport protein complex, IFT particles.Disruption of ciliary structure or function causes multiple humandisorder called ciliopathies affecting disease of diverse ciliatedtissues ranging from eye, kidney, respiratory tract and brain.Recent explosion of research on the primary cilia and theirinvolvement on animal development and disease attracts scientificinterest on how extensively the function of cilia related to specificcell physiology and signaling pathway. In this review, I introducegeneral features of primary cilia and recent progress inunderstanding of the ciliary length control and signaling pathwaystransduced through primary cilia in vertebrates.

  2. Reactive carbonyl compounds impair wound healing by vimentin collapse and loss of the primary cilium.

    Science.gov (United States)

    Rodríguez-Ribera, Lara; Slattery, Craig; Mc Morrow, Tara; Marcos, Ricard; Pastor, Susana

    2017-10-01

    In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients. In this study we evaluated reactive carbonyl compounds (RCC) effects on renal wound healing. The compounds resulting from carbonyl stress evaluated in this study were glyoxal (GO), methylglyoxal (MGO), malondialdehyde (MDA) and 4-hydroxy-hexenal (HHE). Wound repair ability was evaluated by the wound healing assay using HK-2 cells. EMT was evaluated by morphological, protein and transcriptional changes using microscopy, western blot, zymography and RT-qPCR. Changes in the vimentin network and primary cilia were assessed by immunofluorescence. Our data demonstrated that MDA and GO delay wound closure mediated by vimentin disruption, which caused collagen I mRNA decrease, and deciliation. In contrast, HHE treatment (and MGO to a minor degree) induced morphological changes and increased mesenchymal marker expression and gelatinase activity in HK-2 cells. In this study, we have demonstrated for the first time that exposure to RCC differentially affects wound healing in proximal tubular epithelia. A better comprehension of effects of uremic toxins on wound healing and fibrosis and migration is necessary to seek mechanisms to slow down renal fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

    Science.gov (United States)

    Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

    2017-11-01

    Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

  4. Renal Cell Regulation and Cancer: Tumor Suppressor Networks and the Primary Cilium

    NARCIS (Netherlands)

    Klasson, TD

    2017-01-01

    Cancer affects a large number of people the world over. Cancer is a class of extremely complex diseases that arise from malfunctions in otherwise vital cellular processes, especially those that govern aspects of cellular functions like proliferation, apoptosis or the cell cycle. These processes are

  5. Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which Mycoplasma hyopneumoniae regulates surface topography.

    Science.gov (United States)

    Bogema, Daniel R; Deutscher, Ania T; Woolley, Lauren K; Seymour, Lisa M; Raymond, Benjamin B A; Tacchi, Jessica L; Padula, Matthew P; Dixon, Nicholas E; Minion, F Chris; Jenkins, Cheryl; Walker, Mark J; Djordjevic, Steven P

    2012-01-01

    Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50(P146), P40(P146), and P85(P146) that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence (672)ATEF↓QQ(677), consistent with a cleavage motif resembling S/T-X-F↓X-D/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1(P146)-F3(P146) that mimic P50(P146), P40(P146), and P85(P146) were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3(P146) generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography. Vaccines used to control Mycoplasma

  6. Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

    Science.gov (United States)

    McMurray, R. J.; Wann, A. K. T.; Thompson, C. L.; Connelly, J. T.; Knight, M. M.

    2013-01-01

    The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation. PMID:24346024

  7. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

    Science.gov (United States)

    Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

    2016-01-01

    The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

  8. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

    Directory of Open Access Journals (Sweden)

    Hyunjung Choi

    Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

  9. Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling.

    Science.gov (United States)

    Wang, Hongzhong; Zou, Xinle; Wei, Zhuang; Wu, Yuan; Li, Rongxia; Zeng, Rong; Chen, Zhengjun; Liao, Kan

    2015-01-01

    The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90α clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90α forms a stable ring around the axoneme. Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. We further identify that Hsp90α at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling. © 2015. Published by The Company of Biologists Ltd.

  10. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  11. Adenylate cyclase regulates elongation of mammalian primary cilia

    International Nuclear Information System (INIS)

    Ou, Young; Ruan, Yibing; Cheng, Min; Moser, Joanna J.; Rattner, Jerome B.; Hoorn, Frans A. van der

    2009-01-01

    The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3β by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1-2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII-cAMP signaling pathway.

  12. Adenylate cyclase regulates elongation of mammalian primary cilia

    Energy Technology Data Exchange (ETDEWEB)

    Ou, Young; Ruan, Yibing; Cheng, Min; Moser, Joanna J. [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Rattner, Jerome B. [Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Hoorn, Frans A. van der, E-mail: fvdhoorn@ucalgary.ca [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada)

    2009-10-01

    The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3{beta} by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1-2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII-cAMP signaling pathway.

  13. Imaging intraflagellar transport in mammalian primary cilia.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Roy, Barnali; Shah, Jagesh V

    2009-01-01

    The primary cilium is a specialized organelle that projects from the surface of many cell types. Unlike its motile counterpart it cannot beat but does transduce extracellular stimuli into intracellular signals and acts as a specialized subcellular compartment. The cilium is built and maintained by the transport of proteins and other biomolecules into and out of this compartment. The trafficking machinery for the cilium is referred to as IFT or intraflagellar transport. It was originally identified in the green algae Chlamydomonas and has been discovered throughout the evolutionary tree. The IFT machinery is widely conserved and acts to establish, maintain, and disassemble cilia and flagella. Understanding the role of IFT in cilium signaling and regulation requires a methodology for observing it directly. Here we describe current methods for observing the IFT process in mammalian primary cilia through the generation of fluorescent protein fusions and their expression in ciliated cell lines. The observation protocol uses high-resolution time-lapse microscopy to provide detailed quantitative measurements of IFT particle velocities in wild-type cells or in the context of genetic or other perturbations. Direct observation of IFT trafficking will provide a unique tool to dissect the processes that govern cilium regulation and signaling. 2009 Elsevier Inc. All rights reserved.

  14. Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.

    Science.gov (United States)

    Zhang, Jingwei; Dalbay, Melis T; Luo, Xiaoman; Vrij, Erik; Barbieri, Davide; Moroni, Lorenzo; de Bruijn, Joost D; van Blitterswijk, Clemens A; Chapple, J Paul; Knight, Martin M; Yuan, Huipin

    2017-07-15

    The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery

  15. Analysis of fluid flow around a beating artificial cilium

    Directory of Open Access Journals (Sweden)

    Mojca Vilfan

    2012-02-01

    Full Text Available Biological cilia are found on surfaces of some microorganisms and on surfaces of many eukaryotic cells where they interact with the surrounding fluid. The periodic beating of the cilia is asymmetric, resulting in directed swimming of unicellular organisms or in generation of a fluid flow above a ciliated surface in multicellular ones. Following the biological example, externally driven artificial cilia have recently been successfully implemented as micropumps and mixers. However, biomimetic systems are useful not only in microfluidic applications, but can also serve as model systems for the study of fundamental hydrodynamic phenomena in biological samples. To gain insight into the basic principles governing propulsion and fluid pumping on a micron level, we investigated hydrodynamics around one beating artificial cilium. The cilium was composed of superparamagnetic particles and driven along a tilted cone by a varying external magnetic field. Nonmagnetic tracer particles were used for monitoring the fluid flow generated by the cilium. The average flow velocity in the pumping direction was obtained as a function of different parameters, such as the rotation frequency, the asymmetry of the beat pattern, and the cilium length. We also calculated the velocity field around the beating cilium by using the analytical far-field expansion. The measured average flow velocity and the theoretical prediction show an excellent agreement.

  16. Oscillatory fluid flow influences primary cilia and microtubule mechanics.

    Science.gov (United States)

    Espinha, Lina C; Hoey, David A; Fernandes, Paulo R; Rodrigues, Hélder C; Jacobs, Christopher R

    2014-07-01

    Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity. Copyright © 2014 Wiley Periodicals, Inc.

  17. Live imaging of individual cell divisions in mouse neuroepithelium shows asymmetry in cilium formation and Sonic hedgehog response

    Directory of Open Access Journals (Sweden)

    Piotrowska-Nitsche Karolina

    2012-05-01

    Full Text Available Abstract Background Primary cilia are microtubule-based sensory organelles that play important roles in developmental signaling pathways. Recent work demonstrated that, in cell culture, the daughter cell that inherits the older mother centriole generates a primary cilium and responds to external stimuli prior to its sister cell. This asynchrony in timing of cilia formation could be especially critical during development as cell divisions are required for both differentiation and maintenance of progenitor cell niches. Methods Here we integrate several fluorescent markers and use ex vivo live imaging of a single cell division within the mouse E8.5 neuroepithelium to reveal both the formation of a primary cilium and the transcriptional response to Sonic hedgehog in the daughter cells. Results We show that, upon cell division, cilia formation and the Sonic hedgehog response are asynchronous between the daughter cells. Conclusions Our results demonstrate that we can directly observe single cell divisions within the developing neuroepithelium and concomitantly monitor cilium formation or Sonic hedgehog response. We expect this method to be especially powerful in examining whether cellular behavior can lead to both differentiation and maintenance of cells in a progenitor niche.

  18. Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis.

    Directory of Open Access Journals (Sweden)

    Josephine C Bodle

    Full Text Available Adipose-derived stem cells (ASC are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1, polycystin-2 (PC2 and intraflagellar transport protein-88 (IFT88, in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical

  19. Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.

    Directory of Open Access Journals (Sweden)

    Ramona A Hoh

    Full Text Available Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP. The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.

  20. Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish

    Directory of Open Access Journals (Sweden)

    van Eeden Freek

    2010-04-01

    Full Text Available Abstract Background In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. Results Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation. Conclusion Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.

  1. Photoreceptor Sensory Cilium: Traversing the Ciliary Gate

    Directory of Open Access Journals (Sweden)

    Hemant Khanna

    2015-10-01

    Full Text Available Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal.

  2. Primary Auditory Cortex Regulates Threat Memory Specificity

    Science.gov (United States)

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  3. Analysis of primary cilia in directional cell migration in fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

  4. Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

    Czech Academy of Sciences Publication Activity Database

    Dean, S.; Moreira-Leite, F.; Varga, Vladimír; Gull, K.

    2016-01-01

    Roč. 113, č. 35 (2016), E5135-E5143 ISSN 0027-8424 Institutional support: RVO:68378050 Keywords : transition zone * cilium/flagellum * BBSome * MKS/B9 complex * trypanosome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.661, year: 2016

  5. Breakup and then makeup: a predictive model of how cilia self-regulate hardness for posture control.

    Science.gov (United States)

    Bandyopadhyay, Promode R; Hansen, Joshua C

    2013-01-01

    Functioning as sensors and propulsors, cilia are evolutionarily conserved organelles having a highly organized internal structure. How a paramecium's cilium produces off-propulsion-plane curvature during its return stroke for symmetry breaking and drag reduction is not known. We explain these cilium deformations by developing a torsional pendulum model of beat frequency dependence on viscosity and an olivo-cerebellar model of self-regulation of posture control. The phase dependence of cilia torsion is determined, and a bio-physical model of hardness control with predictive features is offered. Crossbridge links between the central microtubule pair harden the cilium during the power stroke; this stroke's end is a critical phase during which ATP molecules soften the crossbridge-microtubule attachment at the cilium inflection point where torsion is at its maximum. A precipitous reduction in hardness ensues, signaling the start of ATP hydrolysis that re-hardens the cilium. The cilium attractor basin could be used as reference for perturbation sensing.

  6. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

    NARCIS (Netherlands)

    Wheway, Gabrielle; Schmidts, Miriam; Mans, Dorus A; Szymanska, Katarzyna; Nguyen, Thanh-Minh T; Racher, Hilary; Phelps, Ian G; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A; Sorusch, Nasrin; Abdelhamed, Zakia A; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A; Letteboer, Stef J F; Roosing, Susanne; Adams, Matthew; Bell, Sandra M; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E; Tomlinson, Darren C; Slaats, Gisela G; van Dam, Teunis J P; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V; Boyle, Evan A; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A; Chodirker, Bernard N; Chudley, Albert E; Lamont, Ryan; Bernier, Francois P; Beaulieu, Chandree L; Gordon, Paul; Pon, Richard T; Donahue, Clem; Barkovich, A James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T; Boycott, Kym M; McKibbin, Martin; Inglehearn, Chris F; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A; Sergouniotis, Panagiotis I; Alkuraya, Fowzan S; Parboosingh, Jillian S; Innes, A Micheil; Willoughby, Colin E; Giles, Rachel H; Webster, Andrew R; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G; Wolfrum, Uwe; Beales, Philip L; Gibson, Toby; Doherty, Dan; Mitchison, Hannah M; Roepman, Ronald; Johnson, Colin A

    Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis

  7. Regulative Discourses of Primary Schooling in Greece: Memories of Punishment

    Science.gov (United States)

    Asimaki, Anna; Koustourakis, Gerasimos; Vergidis, Dimitris

    2016-01-01

    The mechanisms of discipline and power within the institution of the school constitute, in part, the relationship between society and childhood. This article traces the relationship between official regulative discourses of control and punishment practices over students in primary school. It focuses on the memories of schooling of first-year…

  8. High expression of the taurine transporter TauT in primary cilia of NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Voss, Jesper W.; Teilmann, Stefan C.

    2005-01-01

    Taurine, present in high concentrations in various mammalian cells, is essential for regulation of cell volume, cellular oxidative status as well as the cellular Ca2+ homeostasis. Cellular taurine content is a balance between active uptake through the saturable, Na+-dependent taurine transporter...... TauT expression and (iii) long-term exposure to hypertonic taurine medium, i.e., growth medium supplemented with 100 mM taurine, reduces ciliary TauT expression. These results point to an important role of taurine in the regulation of physiological processes located to the primary cilium....

  9. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  10. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

    Science.gov (United States)

    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  11. Regulation of primary productivity rate in the equatorial Pacific

    International Nuclear Information System (INIS)

    Barber, R.T.; Chavez, F.P.

    1991-01-01

    Analysis of the Chl-specific rate of primary productivity (P B ) as a function of subsurface nutrient concentration at >300 equatorial stations provides an answer to the question: What processes regulate primary productivity rate in the high-nutrient, low-chlorophyll waters of the equatorial Pacific? In the western Pacific where there is a gradient in 60-m [NO 3 ] from 0 to ∼12 μM, the productivity rate is a linear function of nutrient concentration; in the eastern Pacific where the gradient is from 12 to 28 μM, the productivity rate is independent of nutrient concentration and limited to ∼36 mg C(mg Chl) -1 d -1 , or a mean euphotic zone C-specific growth rate (μ) of 0.47 d -1 . However, rates downstream of the Galapagos Islands are not limited; they are 46.4 mg C(mg Chl) -1 d -1 and μ = 0.57 d -1 , very close to the predicted nutrient-regulated rates in the absence of other limitation. This pattern of rate regulation can be accounted for by a combination of eolian Fe, subsurface nutrients, and sedimentary Fe derived from the Galapagos platform. In the low-nutrient western Pacific the eolian supply of Fe is adequate to allow productivity rate to be set by subsurface nutrient concentration. In the nutrient-rich easter equatorial region eolian Fe is inadequate to support productivity rates proportional to the higher nutrient concentrations, so in this region eolian Fe is rate limiting. Around the Galapagos Islands productivity rates reach levels consistent with nutrient concentrations; sedimentary Fe from the Galapagos platform seems adequate to support increased nutrient-regulated productivity rates in this region

  12. Regulation of human renin expression in chorion cell primary cultures

    International Nuclear Information System (INIS)

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

    1990-01-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

  13. Implications of the Primary Cilium in Cellular Signaling and Brain Development

    DEFF Research Database (Denmark)

    Lindbæk, Louise

    neurogenesis. In addition, analysis of patient dermal fibroblasts show, that RRP7A localizes to nucleoli, centrosomes, and cilia, and that patient cells carrying a single amino acid substitution in RRP7A display reduced nucleoli localization. Moreover, patient-derived fibroblasts display defects in ribosomal...

  14. Emotion Regulation Characteristics Development in Iranian Primary School Pupils

    Directory of Open Access Journals (Sweden)

    Asghar Dadkhah

    2014-12-01

    Full Text Available Objectives: Emotion regulations refer to the ability of experiencing emotions as a basic human capacity and the experience of the basic emotions happiness, anger, sadness and fear are considered as reular characteristics among nations. In school-age children, problems in socioemotional development typically shows themselves as challenging, socially disruptive paterns of behavior. The purpose of the present study was to understand Emotion Regulation characteristics in Iranian primary school pupils and whether Iranian children enable to identify common emotions. Methods: Participants included 900 children, 9 to 10 years, from elementary schools from 21 provinces in Iran. In pilot work we presented 200 children with four hypothetical vignettes of the kind typically used in display rule research. In the main study children’s knowledge regarding hiding their emotions was assessed through a structured interview. The participants were presented with the interview questions after the vignettes. The answers were coded by two people and the interrater reliability was high. The children were assessed on the basis of four common emotions:Happiness, Anger,Fear,and, Sadness. Results: The analysis of the data indicated that: 1 all children were enabled to identify and differentiate all four emotions from each other, most of students hide their happiness, anger, fear and sadness, they hide their emotions in specific situation such as school and home, hide happiness and anger against peers and hide fear and sadness in front of adults. Discussion: The study indicates that Iranian children not only differ from other culture peers in the amount of display rule use in daily life, but also in the situations they report using it and their motives for doing so they suppress their overall emotions more frequently, especially in presence of family and for pro-social and self-protective reasons. These findings provides the basic knowledge about Iranian children

  15. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  16. Overview of the current National Primary Drinking Water Regulations and regulation development process

    International Nuclear Information System (INIS)

    Cotruvo, J.A.; Regelski, M.

    1989-01-01

    The promulgation of the National Primary Drinking Water Regulations (NPDWR) follows specific steps. First, the Advance Notice of Proposed Rule Making (ANPRM) is published. Second, the EPA, as mandated by the SDWA Amendments, proposes maximum contaminant levels (MCLs), (enforceable standards) and maximum contaminant level goals (MCLGs) simultaneously. The Office of Drinking Water developed a six-phase schedule that has attempted to parallel the SDWA-specified deadlines: Phase I - Voltile organic chemicals - July 8, 1987; Phase II - Synthetic organic chemicals and inorganic chemicals - June 1989, microbials and surface water treatment - June 1989, and Lead/copper - December 1988; Phase III - Radionuclides - December 1988; Phase IV - Disinfectants and disinfection by-products - June 1989; Phase V - Other inorganic chemicals, synthetic organic chemicals, and pesticides - June 1989; and Phase VI - 25 additional chemicals - January 199. In selecting contaminants for regulation, the most relevant criteria are (1) potential health risk; (2) ability to detect a contaminant in the drinking water; and (3) occurrence or potential occurrence in drinking water. The EPA uses a three category approach for setting maximum contaminant level goals for carcinogens: Category I, strong evidence of carcinogenicity-zero; Category II, equivocal evidence - reference dose (RfD) approach or 0.00001 to 0.000001 cancer risk range; and Category III, inadequate or no evidence from animal studies - RfD approach. 10 refs., 5 tabs

  17. 78 FR 10269 - National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule

    Science.gov (United States)

    2013-02-13

    ... Illness CWS--Community Water System DBP--Disinfection Byproduct DWC--Drinking Water Committee EA--Economic... 141 and 142 National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule; Final...-9684-8] RIN 2040-AD94 National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule...

  18. Local translation in primary afferent fibers regulates nociception.

    Directory of Open Access Journals (Sweden)

    Lydia Jiménez-Díaz

    2008-04-01

    Full Text Available Recent studies have demonstrated the importance of local protein synthesis for neuronal plasticity. In particular, local mRNA translation through the mammalian target of rapamycin (mTOR has been shown to play a key role in regulating dendrite excitability and modulating long-term synaptic plasticity associated with learning and memory. There is also increased evidence to suggest that intact adult mammalian axons have a functional requirement for local protein synthesis in vivo. Here we show that the translational machinery is present in some myelinated sensory fibers and that active mTOR-dependent pathways participate in maintaining the sensitivity of a subpopulation of fast-conducting nociceptors in vivo. Phosphorylated mTOR together with other downstream components of the translational machinery were localized to a subset of myelinated sensory fibers in rat cutaneous tissue. We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Behavioural studies confirmed that local treatment with rapamycin significantly attenuated persistent pain that follows tissue injury, but not acute pain. Specifically, we found that rapamycin blunted the heightened response to mechanical stimulation that develops around a site of injury and reduced the long-term mechanical hypersensitivity that follows partial peripheral nerve damage--a widely used model of chronic pain. Our results show that the sensitivity of a subset of sensory fibers is maintained by ongoing mTOR-mediated local protein synthesis and uncover a novel target for the control of long-term pain states.

  19. The Rab GTPase Rab8 as a shared regulator of ciliogenesis and immune synapse assembly: From a conserved pathway to diverse cellular structures.

    Science.gov (United States)

    Patrussi, Laura; Baldari, Cosima T

    2016-01-01

    Rab GTPases, which form the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Among them, Rab8 is an essential participant in primary cilium formation. In a report recently published in the Journal of Cell Science, Finetti and colleagues identify Rab8 as a novel player in vesicular traffic in the non-ciliated T lymphocytes, which contributes to the assembly of the specialized signaling platform known as the immune synapse. By interacting with the v-SNARE VAMP-3, Rab8 is indeed responsible for the final docking/fusion step in T cell receptor (TCR) recycling to the immune synapse. A second important take-home message which comes to light from this work is that VAMP-3 also interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of Smoothened at the plasma membrane. Hence the data presented in this report, in addition to identifying Rab8 as a novel player in vesicular traffic to the immune synapse, reveal how both ciliated and non-ciliated cells take advantage of a conserved pathway to build highly specific cellular structures.

  20. Field Experience from Li-Ion BESS Delivering Primary Frequency Regulation in the Danish Energy Market

    DEFF Research Database (Denmark)

    Swierczynski, Maciej Jozef; Stroe, Daniel Ioan; Lærke, Rasmus

    2014-01-01

    In this paper it is presented the practical experience from operating a 1.6 MW/ 0.4 MWh lithium ion battery energy storage system, which is providing primary frequency regulation service on the Danish energy market. Aspects of the battery system requirements and the used control strategy...

  1. Primary cilia function regulates the length of the embryonic trunk axis and urogenital field in mice

    DEFF Research Database (Denmark)

    Wainwright, Elanor N.; Svingen, Terje; Ting Ng, Ee

    2014-01-01

    The issues of whether and how some organs coordinate their size and shape with the blueprint of the embryo axis, while others appear to regulate their morphogenesis autonomously, remain poorly understood. Mutations in Ift144, encoding a component of the trafficking machinery of primary cilia asse...

  2. Using online learning networks to promote self-regulated learning in primary teacher education

    NARCIS (Netherlands)

    Vrieling, Emmy; Bastiaens, Theo; Stijnen, Sjef

    2017-01-01

    Many recent studies have stressed the importance of students’ self-regulated learning (SRL) skills for successful learning. Consequently, teacher educators have begun to increase student teachers’ SRL opportunities in educational pre-service programs. Although primary teacher educators are aware of

  3. Control mechanisms for battery energy storage system performing primary frequency regulation and self-consumption optimization

    NARCIS (Netherlands)

    Pliatskas Stylianidis, A.

    2016-01-01

    This report contains the design of a model for the integration of a battery energy system in a household level and its use for primary frequency regulation and self-consumption optimization. The main goal of this project was to investigate what are the possible applications and the most suitable for

  4. Self-Regulation of the Primary Auditory Cortex Attention Via Directed Attention Mediated By Real Time fMRI Neurofeedback

    Science.gov (United States)

    2017-05-05

    NELSON FROM: 59 MDW /SGYU SUBJECT: Professional Presentation Approval 1. Your paper, entitled Self - regulation of the Primary Auditory Cortex Attention via...DATE Sherwood - p.1 Self - regulation of the primary auditory cortex attention via directed attention mediated by real-time fMRI neurofeedback M S...auditory cortex hyperactivity by self - regulation of the primary auditory cortex (A 1) based on real-time functional magnetic resonance imaging neurofeedback

  5. ABI4 regulates primary seed dormancy by regulating the biogenesis of abscisic acid and gibberellins in arabidopsis.

    Directory of Open Access Journals (Sweden)

    Kai Shu

    2013-06-01

    Full Text Available Seed dormancy is an important economic trait for agricultural production. Abscisic acid (ABA and Gibberellins (GA are the primary factors that regulate the transition from dormancy to germination, and they regulate this process antagonistically. The detailed regulatory mechanism involving crosstalk between ABA and GA, which underlies seed dormancy, requires further elucidation. Here, we report that ABI4 positively regulates primary seed dormancy, while negatively regulating cotyledon greening, by mediating the biogenesis of ABA and GA. Seeds of the Arabidopsis abi4 mutant that were subjected to short-term storage (one or two weeks germinated significantly more quickly than Wild-Type (WT, and abi4 cotyledons greened markedly more quickly than WT, while the rates of germination and greening were comparable when the seeds were subjected to longer-term storage (six months. The ABA content of dry abi4 seeds was remarkably lower than that of WT, but the amounts were comparable after stratification. Consistently, the GA level of abi4 seeds was increased compared to WT. Further analysis showed that abi4 was resistant to treatment with paclobutrazol (PAC, a GA biosynthesis inhibitor, during germination, while OE-ABI4 was sensitive to PAC, and exogenous GA rescued the delayed germination phenotype of OE-ABI4. Analysis by qRT-PCR showed that the expression of genes involved in ABA and GA metabolism in dry and germinating seeds corresponded to hormonal measurements. Moreover, chromatin immunoprecipitation qPCR (ChIP-qPCR and transient expression analysis showed that ABI4 repressed CYP707A1 and CYP707A2 expression by directly binding to those promoters, and the ABI4 binding elements are essential for this repression. Accordingly, further genetic analysis showed that abi4 recovered the delayed germination phenotype of cyp707a1 and cyp707a2 and further, rescued the non-germinating phenotype of ga1-t. Taken together, this study suggests that ABI4 is a key

  6. REGULATION OF BLOOD PRESSURE IN PATIENTS WITH PRIMARY HYPERTENSION WITH SMOOTHIE BANANA (MUSA PARADISIACA

    Directory of Open Access Journals (Sweden)

    Eni Puji Lestari

    2017-04-01

    Full Text Available Introduction: Hypertension is a major problem that often happen in Indonesia. Hypertension can cause many complications. In Indonesia almost patients with hypertension got farmacologic therapy, but there is no difference. Banana smoothie is one of nonfarmacologic therapy that can be used to lower blood pressure. The purpose of this study was to analyze the effect of banana smoothie on regulation in patients with primary hypertension. Method: This study used quasy experimental design. The population in this study were patients with primary hypertension in Kedungturi village Taman Sidoarjo. The sampling technique used nonprobability sampling type of purposive sampling. The total number of sample were 16 respondents who were selected based on inclusion and exclusion criteria. Result:The Result of paired t-test at the systolic blood pressure and diastolic blood pressure in experiment group showed p value = 0.000. Independent t test between experiment group post-test and control group post-test showed p value = 0.000 for systolic blood pressure and p value = 0.002 for diastolic blood pressure. This result showed that there was a difference value of pretest and post-test systolic and diastolic blood pressure. With the result of independen t-test we know that there is a difference value between exsperiment and control blood pressure. Discussion: This study explain that there was significant effect of banana smoothie to regulate blood pressure in patients with primary hypertention. Banana smoothie can regulate the blood pressure because of high kalium substance. The function of kalium is to reduce the effect of natrium so the blood pressure can down. It can be conclude that banana smoothie can regulate the blood pressure in patients with primary hypertention. In further day patients with hypertension can choose banana smoothie to regulate their blood pressure.

  7. Ionizing radiation increases primary cilia incidence and induces multiciliation in C2C12 myoblasts

    Czech Academy of Sciences Publication Activity Database

    Filipová, A.; Diaz-Garcia, D.; Bezrouk, A.; Čížková, D.; Havelek, R.; Vávrová, J.; Dayanithi, Govindan; Řezáčová, M.

    2015-01-01

    Roč. 39, č. 8 (2015), s. 943-953 ISSN 1065-6995 Institutional support: RVO:68378041 Keywords : cell line * ionizing radiation * multiple cilia * myoblast * primary cilium * serum starvation stress Subject RIV: FP - Other Medical Disciplines Impact factor: 1.663, year: 2015

  8. IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

    DEFF Research Database (Denmark)

    Schmid, Fabian Marc; Schou, Kenneth Bødtker; Vilhelm, Martin Juel

    2018-01-01

    ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport...... protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor...

  9. UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes.

    Directory of Open Access Journals (Sweden)

    Anne Kraemer

    Full Text Available MicroRNA (miRNA-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2, which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.

  10. UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

    Science.gov (United States)

    Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

    2013-01-01

    MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

  11. Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes

    Science.gov (United States)

    Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Petzold-Quinque, Stefanie; Damm, Georg; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2014-01-01

    Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells. PMID:24603648

  12. Combustor with two stage primary fuel tube with concentric members and flow regulating

    Science.gov (United States)

    Parker, David Marchant; Whidden, Graydon Lane; Zolyomi, Wendel

    1999-01-01

    A combustor for a gas turbine having a centrally located fuel nozzle and inner, middle and outer concentric cylindrical liners, the inner liner enclosing a primary combustion zone. The combustor has an air inlet that forms two passages for pre-mixing primary fuel and air to be supplied to the primary combustion zone. Each of the pre-mixing passages has a circumferential array of swirl vanes. A plurality of primary fuel tube assemblies extend through both pre-mixing passages, with each primary fuel tube assembly located between a pair of swirl vanes. Each primary fuel tube assembly is comprised of two tubular members. The first member supplies fuel to the first pre-mixing passage, while the second member, which extends through the first member, supplies fuel to the second pre-mixing passage. An annular fuel manifold is divided into first and second chambers by a circumferentially extending baffle. The proximal end of the first member is attached to the manifold itself while the proximal end of the second member is attached to the baffle. The distal end of the first member is attached directly to the second member at around its mid-point. The inlets of the first and second members are in flow communication with the first and second manifold chambers, respectively. Control valves separately regulate the flow of fuel to the two chambers and, therefore, to the two members of the fuel tube assemblies, thereby allowing the flow of fuel to the first and second pre-mixing passages to be separately controlled.

  13. Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Susanne Schuster

    Full Text Available Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382. Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells.

  14. Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons.

    Science.gov (United States)

    Bao, Lan

    2015-09-30

    Voltage-gated sodium channels (Navs) comprise at least nine pore-forming α subunits. Of these, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 are the most frequently studied in primary sensory neurons located in the dorsal root ganglion and are mainly localized to the cytoplasm. A large pool of intracellular Navs raises the possibility that changes in Nav trafficking could alter channel function. The molecular mediators of Nav trafficking mainly consist of signals within the Navs themselves, interacting proteins and extracellular factors. The surface expression of Navs is achieved by escape from the endoplasmic reticulum and proteasome degradation, forward trafficking and plasma membrane anchoring, and it is also regulated by channel phosphorylation and ubiquitination in primary sensory neurons. Axonal transport and localization of Navs in afferent fibers involves the motor protein KIF5B and scaffold proteins, including contactin and PDZ domain containing 2. Localization of Nav1.6 to the nodes of Ranvier in myelinated fibers of primary sensory neurons requires node formation and the submembrane cytoskeletal protein complex. These findings inform our understanding of the molecular and cellular mechanisms underlying Nav trafficking in primary sensory neurons.

  15. Operation of Grid -Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Loan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2017-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  16. Suggested Operation Grid-Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Ioan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2015-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  17. PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

    International Nuclear Information System (INIS)

    Du, Jing; Zhang, Lang; Liu, Shubo; Zhang, Chi; Huang, Xiuqing; Li, Jian; Zhao, Nanming; Wang, Zhao

    2009-01-01

    Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a key role in degrading both Aβ and insulin and deficient in IDE function is associated with Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) pathology. However, little is known about the cellular and molecular regulation of IDE expression. Here we show IDE levels are markedly decreased in DM2 patients and positively correlated with the peroxisome proliferator-activated receptor γ (PPARγ) levels. Further studies show that PPARγ plays an important role in regulating IDE expression in rat primary neurons through binding to a functional peroxisome proliferator-response element (PPRE) in IDE promoter and promoting IDE gene transcription. Finally, we demonstrate that PPARγ participates in the insulin-induced IDE expression in neurons. These results suggest that PPARγ transcriptionally induces IDE expression which provides a novel mechanism for the use of PPARγ agonists in both DM2 and AD therapies.

  18. Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity

    Directory of Open Access Journals (Sweden)

    Zhenwei Su

    2017-12-01

    Full Text Available Summary: The brain regulates food intake by processing sensory cues and peripheral physiological signals, but the neural basis of this integration remains unclear. Hypothalamic, agouti-related protein (AgRP-expressing neurons are critical regulators of food intake. AgRP neuron activity is high during hunger and is rapidly reduced by the sight and smell of food. Here, we reveal two distinct components of AgRP neuron activity regulation: a rapid but transient sensory-driven signal and a slower, sustained calorie-dependent signal. We discovered that nutrients are necessary and sufficient for sustained reductions in AgRP neuron activity and that activity reductions are proportional to the calories obtained. This change in activity is recapitulated by exogenous administration of gut-derived satiation signals. Furthermore, we showed that the nutritive value of food trains sensory systems—in a single trial—to drive rapid, anticipatory AgRP neuron activity inhibition. Together, these data demonstrate that nutrients are the primary regulators of AgRP neuron activity. : Su et al. demonstrate that nutrient content in the GI tract is rapidly signaled to hypothalamic neurons activated by hunger. This rapid effect is mediated by three satiation signals that synergistically reduce the activity of AgRP neurons. These findings uncover how hunger circuits in the brain are regulated and raise the possibility that hunger can be pharmacologically controlled. Keywords: calcium imaging, AgRP neurons, calories, satiation signals, sensory regulation, single trial learning, cholecystokinin, CCK, peptide tyrosine tyrosine, PYY, amylin, homeostasis

  19. Primary frequency regulation with Li-ion battery energy storage system: A case study for Denmark

    DEFF Research Database (Denmark)

    Swierczynski, Maciej Jozef; Stroe, Daniel Ioan; Stan, Ana-Irina

    2013-01-01

    Meeting ambitious goals of transition to distributed and environmentally-friendly renewable energy generation can be difficult to achieve without energy storage systems due to technical and economical challenges. Moreover, energy storage systems have a high potential of not only smoothing and imp...... electricity market. Moreover, in this paper a possible improvement of the Li-ion BESS energy management strategy is shown, which allows for obtaining the higher NPV....... lifetime, which introduces significant risk into the business model. This paper deals with the investigation of the lifetime of LiFeP04/C battery systems when they are used to provide primary frequency regulation service. A semi-empirical lifetime model for these battery cells was developed based...... on the results obtained from accelerated lifetime testing. The developed Li­-ion battery lifetime model is later a base for the analyses of the economic profitability of the investment in the Li-ion battery energy storage system (BESS), which delivers the primary frequency regulation service on the Danish...

  20. Unique properties of Drosophila spermatocyte primary cilia

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Riparbelli

    2013-09-01

    The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

  1. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

    Science.gov (United States)

    Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

    2012-01-01

    Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

    Science.gov (United States)

    Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

    2011-01-01

    Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

  3. Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules

    Directory of Open Access Journals (Sweden)

    Teresa Mendes Maia

    2014-01-01

    Cilia and flagella are organelles essential for motility and sensing of environmental stimuli. Depending on the cell type, cilia acquire a defined set of functions and, accordingly, are built with an appropriate length and molecular composition. Several ciliary proteins display a high degree of conservation throughout evolution and mutations in ciliary genes are associated with various diseases such as ciliopathies and infertility. Here, we describe the role of the highly conserved ciliary protein, Bug22, in Drosophila. Previous studies in unicellular organisms have shown that Bug22 is required for proper cilia function, but its exact role in ciliogenesis has not been investigated yet. Null Bug22 mutant flies display cilia-associated phenotypes and nervous system defects. Furthermore, sperm differentiation is blocked at the individualization stage, due to impaired migration of the individualization machinery. Tubulin post-translational modifications (PTMs such as polyglycylation, polyglutamylation or acetylation, are determinants of microtubule (MT functions and stability in centrioles, cilia and neurons. We found defects in the timely incorporation of polyglycylation in sperm axonemal MTs of Bug22 mutants. In addition, we found that depletion of human Bug22 in RPE1 cells resulted in the appearance of longer cilia and reduced axonemal polyglutamylation. Our work identifies Bug22 as a protein that plays a conserved role in the regulation of PTMs of the ciliary axoneme.

  4. MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents.

    Science.gov (United States)

    Kawauchi, Daisuke; Kobayashi, Hiroaki; Sekine-Aizawa, Yoko; Fujita, Shinobu C; Murakami, Fujio

    2003-10-01

    Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.

  5. Characterization of herpes simplex virus 2 primary microRNA Transcript regulation.

    Science.gov (United States)

    Tang, Shuang; Bosch-Marce, Marta; Patel, Amita; Margolis, Todd P; Krause, Philip R

    2015-05-01

    In order to understand factors that may influence latency-associated transcription and latency-associated transcript (LAT) phenotypes, we studied the expression of the herpes simplex virus 2 (HSV-2) LAT-associated microRNAs (miRNAs). We mapped the transcription initiation sites of all three primary miRNA transcripts and identified the ICP4-binding sequences at the transcription initiation sites of both HSV-2 LAT (pri-miRNA for miR-I and miR-II, which target ICP34.5, and miR-III, which targets ICP0) and L/ST (a pri-miRNA for miR-I and miR-II) but not at that of the primary miR-H6 (for which the target is unknown). We confirmed activity of the putative HSV-2 L/ST promoter and found that ICP4 trans-activates the L/ST promoter when the ICP4-binding site at its transcription initiation site is mutated, suggesting that ICP4 may play a dual role in regulating transcription of L/ST and, consequently, of miR-I and miR-II. LAT exon 1 (containing LAT enhancer sequences), together with the LAT promoter region, comprises a bidirectional promoter required for the expression of both LAT-encoded miRNAs and miR-H6 in latently infected mouse ganglia. The ability of ICP4 to suppress ICP34.5-targeting miRNAs and to activate lytic viral genes suggests that ICP4 could play a key role in the switch between latency and reactivation. The HSV-2 LAT and viral miRNAs expressed in the LAT region are the most abundant viral transcripts during HSV latency. The balance between the expression of LAT and LAT-associated miRNAs and the expression of lytic viral transcripts from the opposite strand appears to influence whether individual HSV-infected neurons will be latently or productively infected. The outcome of neuronal infection may thus depend on regulation of gene expression of the corresponding primary miRNAs. In the present study, we characterize promoter sequences responsible for miRNA expression, including identification of the primary miRNA 5' ends and evaluation of ICP4 response. These

  6. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    Directory of Open Access Journals (Sweden)

    Paola Brun

    Full Text Available Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and

  7. INPP5E Preserves Genomic Stability through Regulation of Mitosis.

    Science.gov (United States)

    Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

    2017-03-15

    The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

  8. Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma

    Science.gov (United States)

    Qin, Z; Dai, L; Bratoeva, M; Slomiany, MG; Toole, BP; Parsons, C

    2013-01-01

    The Kaposi’s sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), for which cytotoxic chemotherapy represents the standard of care. The high mortality associated with PEL may be explained in part by resistance of these tumors to chemotherapy. The membrane-bound glycoprotein emmprin (CD147) enhances chemoresistance in tumors through effects on transporter expression, trafficking and interactions. Interactions between hyaluronan and hyaluronan receptors on the cell surface also facilitate emmprin-mediated chemoresistance. Whether emmprin or hyaluronan-receptor interactions regulate chemotherapeutic resistance for virus-associated malignancies is unknown. Using human PEL tumor cells, we found that PEL sensitivity to chemotherapy is directly proportional to expression of emmprin, the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and a drug transporter known as the breast cancer resistance protein/ABCG2 (BCRP), and that emmprin, LYVE-1 and BCRP interact with each other and colocalize on the PEL cell surface. In addition, we found that emmprin induces chemoresistance in PEL cells through upregulation of BCRP expression, and RNA interference targeting of emmprin, LYVE-1 or BCRP enhances PEL cell apoptosis induced by chemotherapy. Finally, disruption of hyaluronan-receptor interactions using small hyaluronan oligosaccharides reduces expression of emmprin and BCRP while sensitizing PEL cells to chemotherapy. Collectively, these data support interdependent roles for emmprin, LYVE-1 and BCRP in chemotherapeutic resistance for PEL. PMID:21660043

  9. Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.

    Science.gov (United States)

    Inaba, Hironori; Goto, Hidemasa; Kasahara, Kousuke; Kumamoto, Kanako; Yonemura, Shigenobu; Inoko, Akihito; Yamano, Shotaro; Wanibuchi, Hideki; He, Dongwei; Goshima, Naoki; Kiyono, Tohru; Hirotsune, Shinji; Inagaki, Masaki

    2016-02-15

    Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. © 2016 Inaba et al.

  10. Dissecting Sequences of Regulation and Cognition: Statistical Discourse Analysis of Primary School Children's Collaborative Learning

    Science.gov (United States)

    Molenaar, Inge; Chiu, Ming Ming

    2014-01-01

    Extending past research showing that regulative activities (metacognitive and relational) can aid learning, this study tests whether sequences of cognitive, metacognitive and relational activities affect subsequent cognition. Scaffolded by a computer avatar, 54 primary school students (working in 18 groups of 3) discussed writing a report about a…

  11. MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2014-07-01

    Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

  12. Fabrication and characterization of a magnetic micro-actuator based on deformable Fe-doped PDMS artificial cilium using 3D printing

    Science.gov (United States)

    Liu, Fengli; Alici, Gursel; Zhang, Binbin; Beirne, Stephen; Li, Weihua

    2015-03-01

    This paper proposes the use of a 3D extrusion printer to fabricate artificial magnetic cilium. The cilia are fabricated using polydimethylsiloxane (PDMS) doped with iron particles so that they remain slender and flexible. They can be driven by a magnetic field to closely mimic the behaviour of biological cilia. Doping iron particles to the polymers has already been done; however, to the best of our knowledge, printing such active and soft magnetic structures has not. The existing methods for manufacturing magnetic polymeric structures are complex and difficult to use for the fabrication of micro-sized high-aspect-ratio cilia. The 3D printing technique we propose here is simple and inexpensive compared to previously suggested fabrication methods. In this study, free-standing magnetic PDMS cilia were fabricated in different sizes up to 5 mm in length and 1 mm in width. The stress-strain curves of the PDMS cilia were experimentally obtained to quantify the effect of the concentration of the iron particles on the modulus of elasticity of the cilia. The higher the iron concentration, the higher the modulus of elasticity. We have quantified the characteristics of the cilia made of 40% w/w iron particles in PDMS. A single cilium (5 × 1 × 0.0035 mm) can output up to 27 μN blocking force under a magnetic field of 160 mT. These cilia can be used as a mixer in lap-on-chip applications and as the anchoring and propulsion legs of endoscopic capsule robots operating within the gastrointestinal tract of humans. Analytical expressions estimating the blocking force are established and compared with the experimental results.

  13. Fabrication and characterization of a magnetic micro-actuator based on deformable Fe-doped PDMS artificial cilium using 3D printing

    International Nuclear Information System (INIS)

    Liu, Fengli; Alici, Gursel; Li, Weihua; Zhang, Binbin; Beirne, Stephen

    2015-01-01

    This paper proposes the use of a 3D extrusion printer to fabricate artificial magnetic cilium. The cilia are fabricated using polydimethylsiloxane (PDMS) doped with iron particles so that they remain slender and flexible. They can be driven by a magnetic field to closely mimic the behaviour of biological cilia. Doping iron particles to the polymers has already been done; however, to the best of our knowledge, printing such active and soft magnetic structures has not. The existing methods for manufacturing magnetic polymeric structures are complex and difficult to use for the fabrication of micro-sized high-aspect-ratio cilia. The 3D printing technique we propose here is simple and inexpensive compared to previously suggested fabrication methods. In this study, free-standing magnetic PDMS cilia were fabricated in different sizes up to 5 mm in length and 1 mm in width. The stress-strain curves of the PDMS cilia were experimentally obtained to quantify the effect of the concentration of the iron particles on the modulus of elasticity of the cilia. The higher the iron concentration, the higher the modulus of elasticity. We have quantified the characteristics of the cilia made of 40% w/w iron particles in PDMS. A single cilium (5 × 1 × 0.0035 mm) can output up to 27 μN blocking force under a magnetic field of 160 mT. These cilia can be used as a mixer in lap-on-chip applications and as the anchoring and propulsion legs of endoscopic capsule robots operating within the gastrointestinal tract of humans. Analytical expressions estimating the blocking force are established and compared with the experimental results. (paper)

  14. Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients.

    Science.gov (United States)

    Roth, Patrick; Keller, Andreas; Hoheisel, Jörg D; Codo, Paula; Bauer, Andrea S; Backes, Christina; Leidinger, Petra; Meese, Eckart; Thiel, Eckhard; Korfel, Agnieszka; Weller, Michael

    2015-02-01

    Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Application of the regulations on pressurized components or light water reactor primary coolant circuits

    International Nuclear Information System (INIS)

    Barthelemy, F.; Menjon, G.

    1977-01-01

    This paper describes the philosophy and the provisions of the Order of 26 February 1974 concerning application of the regulations on pressurized components for light water reactor steam supply systems. The aim is to show how these regulations which differ from other regulations on pressurized components and is more detailed on many points, is applied in practice in France in the various stages of the design, construction and operation of PWRs. (NEA) [fr

  16. Influence of Mothers' Parenting Styles on Self-Regulated Academic Learning among Saudi Primary School Students

    Science.gov (United States)

    Alnafea, Tahany; Curtis, David D.

    2017-01-01

    Much of the research on self-regulation has investigated the influence of school settings. However, fewer studies have concentrated on the home environment and its influence on student's academic behaviour in school. The present research investigates the influence of mothers' parenting styles on students' self-regulated learning behaviours in…

  17. Accurate calibration of steam turbine speed control system and its influence on primary regulation at electric grid

    Energy Technology Data Exchange (ETDEWEB)

    Irrazabal Bohorquez, Washington Orlando; Barbosa, Joao Roberto [Technological Institute of Aeronautics (ITA/CTA), Sao Jose dos Campos, SP (Brazil). Center for Reference on Gas Turbine and Energy], E-mail: barbosa@ita.br

    2010-07-01

    In an interconnected electric system there are two very important parameters: the field voltage and the frequency system. The frequency system is very important for the primary regulation of the electric grid. Each turbomachine actuating as generator interconnected to the grid has an automatic speed regulator to keep the rotational speed and mechanical power of the prime machine operating at the set conditions and stable frequency. The electric grid is a dynamical system and in every moment the power units are exposed to several types of disturbances, which cause unbalance of the mechanical power developed by prime machine and the consumed electric power at the grid. The steam turbine speed control system controls the turbine speed to support the electric grid primary frequency at the same time it controls the frequency of the prime machine. Using a mathematical model for the speed control system, the transfer functions were calculated, as well as the proportionality constants of each element of the steam turbine automatic speed regulator. Among other parameters, the droop characteristic of steam turbine and the dynamic characteristics of the automatic speed regulator elements were calculated. Another important result was the determination of the behavior of the speed control when disturbances occur with the improvement of the calibration precision of the control system. (author)

  18. WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT- beta-catenin-TCF signaling pathway.

    Science.gov (United States)

    Katoh, M; Kirikoshi, H; Terasaki, H; Shiokawa, K

    2001-12-21

    Genetic alterations of WNT signaling molecules lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway. We have previously cloned and characterized WNT2B/WNT13 gene on human chromosome 1p13, which is homologous to proto-oncogene WNT2 on human chromosome 7q31. WNT2B1 and WNT2B2 mRNAs, generated from the WNT2B gene due to alternative splicing of the alternative promoter type, encode almost identical polypeptides with divergence in the N-terminal region. WNT2B2 mRNA rather than WNT2B1 mRNA is preferentially expressed in NT2 cells with the potential of neuronal differentiation. Here, we describe our investigations of expression of WNT2B mRNAs in various types of human primary cancer. Matched tumor/normal expression array analysis revealed that WNT2B mRNAs were significantly up-regulated in 2 of 8 cases of primary gastric cancer. WNT2B2 mRNA rather than WNT2B1 mRNA was found to be preferentially up-regulated in a case of primary gastric cancer (signet ring cell carcinoma). Function of WNT2B1 mRNA and that of WNT2B2 mRNA were investigated by using Xenopus axis duplication assay. Injection of synthetic WNT2B1 mRNA into the ventral marginal zone of fertilized Xenopus eggs at the 4-cell stage did not induce axis duplication. In contrast, ventral injection of synthetic WNT2B2 mRNA induced axis duplication in 90% of embryos (complete axis duplication, 24%). These results strongly suggest that WNT2B2 up-regulation in some cases of gastric cancer might lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway.

  19. Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity

    Directory of Open Access Journals (Sweden)

    Gallagher Iain J

    2011-03-01

    Full Text Available Abstract Background Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components of the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Methods Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation to yield global profiles of miRNAs. Results We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided. Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p Conclusion In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of

  20. Role of Ocrl1 and Inpp5E in primary cilia assembly and maintenance: a phosphatidylinositol phosphatase relay system?

    Directory of Open Access Journals (Sweden)

    Madhivanan K

    2016-02-01

    Full Text Available Kayalvizhi Madhivanan,* Swetha Ramadesikan,* R Claudio Aguilar Department of Biological Sciences, Purdue University, West Lafayette, IN, USA *These authors contributed equally to this work Abstract: The primary cilium (PC is a plasma membrane-derived structure of great importance for cell and organismal physiology. Indeed, abnormalities in assembly or function of the PC trigger the onset of a group of genetic diseases collectively known as ciliopathies. In recent years, it has become evident that the integrity and function of the PC depends substantially on signaling elements such as phosphoinositides (PI and their regulators. Because phospholipids such as PI(4,5P2 constitute recruitment platforms for cytoskeleton, signaling, and trafficking machinery, control over their levels is critical for PC function. Although information about phosphoinositol phosphate (PIP kinases in the PC is scarce, a growing body of evidence supports a role for PIP phosphatases in cilia assembly/maintenance. Indeed, deficiencies in two 5′ PIP phosphatases, Inpp5E and Ocrl1, are clearly linked to ciliopathies like Joubert/MORM syndromes, or ciliopathy-associated diseases like Lowe syndrome. Here, we review the unique roles of these proteins and their specific site of action for ensuring ciliary integrity. Further, we discuss the possibility that a phosphatase relay system able to pass PI control from a preciliary to an intraciliary compartment is in place to ensure PC integrity/function. Keywords: primary cilia, Ocrl1, Inpp5E, Pip2, Pip3

  1. Transcriptomics insights into the genetic regulation of root apical meristem exhaustion and determinate primary root growth in Pachycereus pringlei (Cactaceae).

    Science.gov (United States)

    Rodriguez-Alonso, Gustavo; Matvienko, Marta; López-Valle, Mayra L; Lázaro-Mixteco, Pedro E; Napsucialy-Mendivil, Selene; Dubrovsky, Joseph G; Shishkova, Svetlana

    2018-06-04

    Many Cactaceae species exhibit determinate growth of the primary root as a consequence of root apical meristem (RAM) exhaustion. The genetic regulation of this growth pattern is unknown. Here, we de novo assembled and annotated the root apex transcriptome of the Pachycereus pringlei primary root at three developmental stages, with active or exhausted RAM. The assembled transcriptome is robust and comprehensive, and was used to infer a transcriptional regulatory network of the primary root apex. Putative orthologues of Arabidopsis regulators of RAM maintenance, as well as putative lineage-specific transcripts were identified. The transcriptome revealed putative orthologues of most proteins involved in housekeeping processes, hormone signalling, and metabolic pathways. Our results suggest that specific transcriptional programs operate in the root apex at specific developmental time points. Moreover, the transcriptional state of the P. pringlei root apex as the RAM becomes exhausted is comparable to the transcriptional state of cells from the meristematic, elongation, and differentiation zones of Arabidopsis roots along the root axis. We suggest that the transcriptional program underlying the drought stress response is induced during Cactaceae root development, and that lineage-specific transcripts could contribute to RAM exhaustion in Cactaceae.

  2. Fact sheet: National primary drinking water regulations for lead and copper

    International Nuclear Information System (INIS)

    1991-05-01

    The Fact Sheet contains a summary of what the regulations will do, establish, and provide; regulatory impact in regards to benefits and costs; treatment technique requirements; tap water monitoring for lead and copper; water quality monitoring (other than lead and copper); monitoring schedules, regulatory schedules for large, medium-sized, and small systems

  3. The Influence of Interactive Learning Materials on Self-Regulated Learning and Learning Satisfaction of Primary School Teachers in Mongolia

    Directory of Open Access Journals (Sweden)

    Shengru Li

    2018-04-01

    Full Text Available The purpose of this study was to investigate the effects of interactive learning materials on learners’ self-regulated learning processes and learning satisfaction. A two-group experimental design was employed for 285 primary school teachers involved in teacher training. Teachers in the experimental group utilised interactive learning materials along with training videos and guidelines for their self-development at the school level. Teachers in the control group conducted self-development only with training videos and guidelines. The result was analysed using self-regulated learning theory explaining how one’s self-regulation processes affect learning satisfaction. Five self-regulation processes were identified in this study: internal motivation, motivation for better assessment, planning and organizing skills, critical and positive thinking skills, and effort regulation. The analysis was conducted in two steps. First, t-test analysis was used to identify the significant differences between the experimental group and the control group. The analysis revealed: (1 teachers conducting self-development with interactive learning materials were highly motivated to achieve better teacher assessment, (2 teachers with interactive learning materials had higher learning satisfaction. Second, the study further investigated the effect of interactive materials on the relationship between self-regulation processes and learning satisfaction, using moderation analysis. The results showed that interactive materials significantly affect the relationship between motivation for better assessment and learning satisfaction, as well as the relationship between internal motivation and learning satisfaction. These results were complemented by qualitative analysis including interviews and focus group discussions with teachers.

  4. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  5. Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes

    International Nuclear Information System (INIS)

    Kern, P.A.; Marshall, S.; Eckel, R.H.

    1985-01-01

    To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific 125 I-insulin binding. In addition, chloroquine induced an increase in cell-associated 125 I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, there was a marked stimulation of CM and HR. The secretory response to serum (CM) correlated strongly with HR 24 h after preparation. In addition, HR was found to correlate logarithmically and inversely with body mass index. Insulin, at 400 ng/ml only, increased HR by 36 +/- 10%, an effect simulated by lower concentrations of insulin-like growth factor-1 (IGF1). Thus, LPL is produced and regulated in isolated human adipocytes. The degree of adiposity and serum are important regulators of HR activity, whereas insulin is stimulatory only at a pharmacologic concentration. This effect of insulin may be mediated through the IGF1 receptor. Isolated human adipocytes represent a novel and useful system for the study of LPL and lipid metabolism as well as for other aspects of adipocyte biology

  6. NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.

    Directory of Open Access Journals (Sweden)

    Shahin Ranjbar

    2006-12-01

    Full Text Available To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5, which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.

  7. Primary cilia and coordination of signaling pathways in heart development and tissue Homeostasis

    DEFF Research Database (Denmark)

    Clement, Christian Alexandro

    of primary cilia in coordinating Hh signaling in human pancreatic development and postnatal tissue homeostasis. In cultures of human pancreatic duct adenocarcinoma cell lines PANC-1 and CFPAC-1, Ptc in addition to Gli2 and Smo localize to primary cilia. These findings are consistent with the idea...... that the primary cilium continues to coordinate Hh signaling in cells derived from the mature pancreas. The fact that the Hh signaling pathway is active in the CFPAC-1 and PANC-1 cell lines without Hh stimulation suggests that ciliary Hh signaling plays a potential role in tumorigenesis. In conclusion, this thesis...

  8. Optimal Control and Operation Strategy for Wind Turbines Contributing to Grid Primary Frequency Regulation

    Directory of Open Access Journals (Sweden)

    Mun-Kyeom Kim

    2017-09-01

    Full Text Available This study introduces a frequency regulation strategy to enable the participation of wind turbines with permanent magnet synchronous generators (PMSGs. The optimal strategy focuses on developing the frequency support capability of PMSGs connected to the power system. Active power control is performed using maximum power point tracking (MPPT and de-loaded control to supply the required power reserve following a disturbance. A kinetic energy (KE reserve control is developed to enhance the frequency regulation capability of wind turbines. The coordination with the de-loaded control prevents instability in the PMSG wind system due to excessive KE discharge. A KE optimization method that maximizes the sum of the KE reserves at wind farms is also adopted to determine the de-loaded power reference for each PMSG wind turbine using the particle swarm optimization (PSO algorithm. To validate the effectiveness of the proposed optimal control and operation strategy, three different case studies are conducted using the PSCAD/EMTDC simulation tool. The results demonstrate that the optimal strategy enhances the frequency support contribution from PMSG wind turbines.

  9. Dormancy and activation of human oocytes from primordial and primary follicles: molecular clues to oocyte regulation

    DEFF Research Database (Denmark)

    Ernst, Emil Hagen; Grøndahl, Marie Louise; Grund, Simon

    2017-01-01

    ® software. Finally, qPCR and immunohistochemistry were employed to explore expression and localization of selected genes and products in human ovarian tissue. MAIN RESULTS AND THE ROLE OF CHANCE: We found 223 and 268 genes down-regulated and up-regulated, respectively, in the oocytes during the human...... SCALE DATA: http://users-birc.au.dk/biopv/published_data/ernst_2017/. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis and no functional studies were performed. The study was based on a limited number of patients and the experimental design could not take into account the natural.......H. and S.F. were supported by an MRC (UK) project grant MR/M012638/1. K.L.H. was supported by grants from Fonden til Lægevidenskabens Fremme, Kong Christian Den Tiendes Fond. K.L.H. and L.S. were supported by the IDEAS grant from Aarhus University Research Foundation (AUFF). There are no conflicts...

  10. Regulation of proximal tubular cell differentiation and proliferation in primary culture by matrix stiffness and ECM components.

    Science.gov (United States)

    Chen, Wan-Chun; Lin, Hsi-Hui; Tang, Ming-Jer

    2014-09-15

    To explore whether matrix stiffness affects cell differentiation, proliferation, and transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in primary cultures of mouse proximal tubular epithelial cells (mPTECs), we used a soft matrix made from monomeric collagen type I-coated polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary mPTECs to retain tubular-like morphology with differentiation and growth arrest and to evade TGF-β1-induced EMT. However, the potent effect of MG on mPTEC differentiation was suppressed by glutaraldehyde-induced cross-linking and subsequently stiffening MG or by an increasing ratio of collagen in the soft mixed gel. Culture media supplemented with MG also helped mPTECs to retain tubular-like morphology and a differentiated phenotype on stiff culture dishes as soft MG did. We further found that the protein level and activity of ERK were scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff matrix-induced dedifferentiation and proliferation. These data suggest that the ERK signaling pathway plays a vital role in matrix stiffness-regulated cell growth and differentiation. Taken together, both compliant property and specific MG signals from the matrix are required for the regulation of epithelial differentiation and proliferation. This study provides a basic understanding of how physical and chemical cues derived from the extracellular matrix regulate the physiological function of proximal tubules and the pathological development of renal fibrosis. Copyright © 2014 the American Physiological Society.

  11. CDK2 phosphorylation of Smad2 disrupts TGF-beta transcriptional regulation in resistant primary bone marrow myeloma cells.

    Science.gov (United States)

    Baughn, Linda B; Di Liberto, Maurizio; Niesvizky, Ruben; Cho, Hearn J; Jayabalan, David; Lane, Joseph; Liu, Fang; Chen-Kiang, Selina

    2009-02-15

    Resistance to growth suppression by TGF-beta1 is common in cancer; however, mutations in this pathway are rare in hematopoietic malignancies. In multiple myeloma, a fatal cancer of plasma cells, malignant cells accumulate in the TGF-beta-rich bone marrow due to loss of both cell cycle and apoptotic controls. Herein we show that TGF-beta activates Smad2 but fails to induce cell cycle arrest or apoptosis in primary bone marrow myeloma and human myeloma cell lines due to its inability to activate G(1) cyclin-dependent kinase (CDK) inhibitors (p15(INK4b), p21(CIP1/WAF1), p27(KIP1), p57(KIP2)) or to repress c-myc and Bcl-2 transcription. Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr(8) (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. Our findings provide the first direct evidence that pT8 Smad2 couples dysregulation of CDK2 to TGF-beta resistance in primary cancer cells, and they suggest that disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma.

  12. Functions and Epigenetic Regulation of Wwox in Bone Metastasis from Breast Carcinoma: Comparison with Primary Tumors

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2017-01-01

    Full Text Available Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox. The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1 affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma. In hypoxic-bone metastatic cells, Wwox enhances HIF-1α stabilization, phosphorylation, and nuclear translocation. Consistently, in bone-metastasis specimens Wwox localizes in cytosolic/perinuclear area, while TAZ (transcriptional co-activator with PDZ-binding motif and HIF-1α co-localize in nuclei, playing specific regulatory mechanisms: TAZ is a co-factor of HIF-1, and Wwox regulates HIF-1 activity by controlling HIF-1α. In vitro, DNA methylation affects Wwox-protein synthesis; hypoxia decreases Wwox-protein level; hepatocyte growth factor (HGF phosphorylates Wwox driving its nuclear shuttle, and counteracting a Twist program important for the epithelial phenotype and metastasis colonization. In agreement, in 1833-xenograft mice under DNA-methyltransferase blockade with decitabine, Wwox increases in nuclei/cytosol counteracting bone metastasis with prolongation of the survival. However, Wwox seems relevant for the autophagic process which sustains metastasis, enhancing more Beclin-1 than p62 protein levels, and p62 accumulates under decitabine consistent with adaptability of metastasis to therapy. In conclusion, Wwox methylation as a bone-metastasis therapeutic target would depend on autophagy conditions, and epigenetic mechanisms regulating Wwox may influence the phenotype of bone metastasis.

  13. Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA, total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL and fatty (ZF rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA. We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

  14. Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.

    Science.gov (United States)

    Gil-Ibañez, Pilar; García-García, Francisco; Dopazo, Joaquín; Bernal, Juan; Morte, Beatriz

    2017-01-01

    Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases.

    Science.gov (United States)

    Itoh, Masayuki; Ide, Shuhei; Iwasaki, Yuji; Saito, Takashi; Narita, Keishi; Dai, Hongmei; Yamakura, Shinji; Furue, Takeki; Kitayama, Hirotsugu; Maeda, Keiko; Takahashi, Eihiko; Matsui, Kiyoshi; Goto, Yu-Ichi; Takeda, Sen; Arima, Masataka

    2018-04-01

    Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients. All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm. AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Molecular imaging of the transcription factor NF-κB, a primary regulator of stress response

    International Nuclear Information System (INIS)

    Carlsen, Harald; Alexander, George; Austenaa, Liv M.I.; Ebihara, Kanae; Blomhoff, Rune

    2004-01-01

    A wide range of environmental stress and human disorders involves inappropriate regulation of NF-κB, including cancers and numerous inflammatory conditions. We have developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time non-invasive imaging of NF-κB activity in intact animals. We show that, in the absence of stimulation, strong, intrinsic luminescence is evident in lymph nodes in the neck region, thymus, and Peyer's patches. Treating mice with stressors, such as TNF-α, IL-1α, or lipopolysaccharide (LPS) increases the luminescence in a tissue-specific manner, with the strongest activity observable in the skin, lungs, spleen, Peyer's patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue exhibit less intense activities. Exposure of the skin to a low dose of UV-B radiation increases luminescence in the exposed areas. In ocular experiments, LPS- and TNF-α injected NF-κB-luciferase transgenic mice exhibit a 20-40-fold increase in lens NF-κB activity, similar to other LPS- and TNF-α-responsive organs. Peak NF-κB activity occurs 6 h after injection of TNF-α and 12 h after injection of LPS. Peak activities occur, respectively, 3 and 6 h later than that in other tissues. Mice exposed to 360 J/m 2 of UV-B exhibit a 16-fold increase in NF-κB activity 6 h after exposure, characteristically similar to TNF-α-exposed mice. Thus, in NF-κB-luciferase transgenic mice, NF-κB activity also occurs in lens epithelial tissue and is activated when the intact mouse is exposed to classical stressors. Furthermore, as revealed by real-time non-invasive imaging, induction of chronic inflammation resembling rheumatoid arthritis produces strong NF-κB activity in the affected joints. Finally, we have used the model to demonstrate NF-κB regulation by manipulating the Vitamin A status in mice. NF-κB activity is elevated in mice fed a Vitamin A deficient (VAD) diet, and suppressed by surplus doses of

  17. Immunosenescence Is Associated With Altered Gene Expression And Epigenetic Regulation In Primary And Secondary Immune Organs

    Directory of Open Access Journals (Sweden)

    Corinne eSidler

    2013-10-01

    Full Text Available Deterioration of the immune system (immunosenescence with age is associated with an increased susceptibility to infection, autoimmune disease and cancer, and reduced responsiveness to vaccination. Immunosenescence entails a reduced supply of naïve T cells from the thymus and increased specialization of peripheral T cell clones. Both thymic involution and peripheral T cell homeostasis are thought to involve cellular senescence. In order to analyze this at the molecular level, we studied gene expression profiles, epigenetic status and genome stability in the thymus and spleen of 1-month, 4-month and 18-month-old Long Evans rats. In the thymus, altered gene expression, DNA and histone hypomethylation, increased genome instability and apoptosis were observed in 18-month-old animals compared to 1- and 4-month-old animals. In the spleen, alterations in gene expression and epigenetic regulation occurred already by the age of 4 months compared to 1 month and persisted in 18-month-old compared to 1-month-old rats. In both organs, these changes were accompanied by the altered composition of resident T cell populations. Our study suggests that both senescence and apoptosis may be involved in altered organ function.

  18. National radiation exposures and risks caused by implementing EPA's proposed revised national primary drinking water regulations

    International Nuclear Information System (INIS)

    Morris, S.C.; Rowe, M.D.; Holtzman, S.; Meinhold, A.F.

    1993-05-01

    This report estimates risks to workers and the public associated with treatment processes and their associated waste products that would be mandated under proposed regulations of radium, radon, and uranium in drinking water. Three scenarios were examined: (1) all wastes flushed to the sanitary sewer; (2) all wastes disposed on land; (3) similar to (2) but radon removal by granulated activated carbon rather than packed tower aeration. Risks considered included accidental injury and cancer. Worker risks for both scenarios I and II were estimated to be 0.025 and 0.01 deaths per year of operation for radium-226 and radium-228, respectively. Worker risks for uranium were estimated to be 0.13 deaths/year of operation for scenario I and 0.5 deaths/year of operation for scenario II. Worker risks for radon removal were estimated to be 1.7 deaths/year of operation for scenario I and 2.2 deaths/year of operation for scenario II. Risks to the public for scenarios I and II for radium-226 were 4 x 10 -4 and for radium-228 were 9 x 10 -5 deaths/year of operation. Risks to the public for scenarios I and II for uranium were 7.3 x 10 -2 and 2 x 10 -4 , respectively. Risks to the public for scenario I and II for radon were 24 deaths/year of operation and for scenario III were nil. Public risks were quantified only for people exposed during a year of operation. For example, effects of public exposures in future years via groundwater contamination associated with landfill of treatment waste were not considered

  19. Primary Frequency Regulation with Li-Ion Battery Energy Storage System - Evaluation and Comparison of Different Control Strategies

    DEFF Research Database (Denmark)

    Thorbergsson, Egill; Knap, Vaclav; Swierczynski, Maciej Jozef

    2013-01-01

    devices is becoming more attractive, the aim of this paper is to analyse the viability of providing primary frequency regulation with Lithium-ion based energy storage systems. Three control strategies of the energy storage system are analysed and compared in terms of economic benefits on the Danish energy...... market. The revenues and degradation of the Lithium-ion batteries are obtained by simulations. Furthermore, an energy management strategy based on variable state-of-charge (SOC) set-point is evaluated. Preliminary, the influence of different state-of-charge levels on the cycle lifetime is estimated......The increased grid penetration levels of renewable sources are at the expense of the conventional power plants. This means that the grid support functions, traditionally achieved by the conventional power plants, need to be provided by new technologies. Since grid support with energy storage...

  20. The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

    Directory of Open Access Journals (Sweden)

    Proud Christopher G

    2002-05-01

    Full Text Available Abstract Background Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16–24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using αCD3 antibody to stimulate the T cell receptor and αCD28 antibody to provide the co-stimulus. Results Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with αCD3 and αCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK α/β pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F. Conclusions Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.

  1. A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons.

    Science.gov (United States)

    Leighton, Laura J; Zhao, Qiongyi; Li, Xiang; Dai, Chuanyang; Marshall, Paul R; Liu, Sha; Wang, Yi; Zajaczkowski, Esmi L; Khandelwal, Nitin; Kumar, Arvind; Bredy, Timothy W; Wei, Wei

    2018-01-15

    Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin, Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) of Ppp3r1 depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

    Science.gov (United States)

    Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

    2015-01-01

    Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

  3. Coactivator PGC-1α regulates the fasting inducible xenobiotic-metabolizing enzyme CYP2A5 in mouse primary hepatocytes

    International Nuclear Information System (INIS)

    Arpiainen, Satu; Jaervenpaeae, Sanna-Mari; Manninen, Aki; Viitala, Pirkko; Lang, Matti A.; Pelkonen, Olavi; Hakkola, Jukka

    2008-01-01

    The nutritional state of organisms and energy balance related diseases such as diabetes regulate the metabolism of xenobiotics such as drugs, toxins and carcinogens. However, the mechanisms behind this regulation are mostly unknown. The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. Peroxisome proliferator-activated receptor γ coactivator (PGC)-1α triggers many of the important hepatic fasting effects in response to elevated cAMP levels. In the present study, we were able to show that cAMP causes a coordinated induction of PGC-1α and CYP2A5 mRNAs in murine primary hepatocytes. Furthermore, the elevation of the PGC-1α expression level by adenovirus mediated gene transfer increased CYP2A5 transcription. Co-transfection of Cyp2a5 5' promoter constructs with the PGC-1α expression vector demonstrated that PGC-1α is able to activate Cyp2a5 transcription through the hepatocyte nuclear factor (HNF)-4α response element in the proximal promoter of the Cyp2a5 gene. Chromatin immunoprecipitation assays showed that PGC-1α binds, together with HNF-4α, to the same region at the Cyp2a5 proximal promoter. In conclusion, PGC-1α mediates the expression of CYP2A5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4α. This strongly suggests that PGC-1α is the major factor mediating the fasting response of CYP2A5

  4. Comprehensive Transcriptome Analysis Unravels the Existence of Crucial Genes Regulating Primary Metabolism during Adventitious Root Formation in Petunia hybrida

    Science.gov (United States)

    Ahkami, Amirhossein; Scholz, Uwe; Steuernagel, Burkhard; Strickert, Marc; Haensch, Klaus-Thomas; Druege, Uwe; Reinhardt, Didier; Nouri, Eva; von Wirén, Nicolaus; Franken, Philipp; Hajirezaei, Mohammad-Reza

    2014-01-01

    To identify specific genes determining the initiation and formation of adventitious roots (AR), a microarray-based transcriptome analysis in the stem base of the cuttings of Petunia hybrida (line W115) was conducted. A microarray carrying 24,816 unique, non-redundant annotated sequences was hybridized to probes derived from different stages of AR formation. After exclusion of wound-responsive and root-regulated genes, 1,354 of them were identified which were significantly and specifically induced during various phases of AR formation. Based on a recent physiological model distinguishing three metabolic phases in AR formation, the present paper focuses on the response of genes related to particular metabolic pathways. Key genes involved in primary carbohydrate metabolism such as those mediating apoplastic sucrose unloading were induced at the early sink establishment phase of AR formation. Transcriptome changes also pointed to a possible role of trehalose metabolism and SnRK1 (sucrose non-fermenting 1- related protein kinase) in sugar sensing during this early step of AR formation. Symplastic sucrose unloading and nucleotide biosynthesis were the major processes induced during the later recovery and maintenance phases. Moreover, transcripts involved in peroxisomal beta-oxidation were up-regulated during different phases of AR formation. In addition to metabolic pathways, the analysis revealed the activation of cell division at the two later phases and in particular the induction of G1-specific genes in the maintenance phase. Furthermore, results point towards a specific demand for certain mineral nutrients starting in the recovery phase. PMID:24978694

  5. Comprehensive transcriptome analysis unravels the existence of crucial genes regulating primary metabolism during adventitious root formation in Petunia hybrida.

    Science.gov (United States)

    Ahkami, Amirhossein; Scholz, Uwe; Steuernagel, Burkhard; Strickert, Marc; Haensch, Klaus-Thomas; Druege, Uwe; Reinhardt, Didier; Nouri, Eva; von Wirén, Nicolaus; Franken, Philipp; Hajirezaei, Mohammad-Reza

    2014-01-01

    To identify specific genes determining the initiation and formation of adventitious roots (AR), a microarray-based transcriptome analysis in the stem base of the cuttings of Petunia hybrida (line W115) was conducted. A microarray carrying 24,816 unique, non-redundant annotated sequences was hybridized to probes derived from different stages of AR formation. After exclusion of wound-responsive and root-regulated genes, 1,354 of them were identified which were significantly and specifically induced during various phases of AR formation. Based on a recent physiological model distinguishing three metabolic phases in AR formation, the present paper focuses on the response of genes related to particular metabolic pathways. Key genes involved in primary carbohydrate metabolism such as those mediating apoplastic sucrose unloading were induced at the early sink establishment phase of AR formation. Transcriptome changes also pointed to a possible role of trehalose metabolism and SnRK1 (sucrose non-fermenting 1- related protein kinase) in sugar sensing during this early step of AR formation. Symplastic sucrose unloading and nucleotide biosynthesis were the major processes induced during the later recovery and maintenance phases. Moreover, transcripts involved in peroxisomal beta-oxidation were up-regulated during different phases of AR formation. In addition to metabolic pathways, the analysis revealed the activation of cell division at the two later phases and in particular the induction of G1-specific genes in the maintenance phase. Furthermore, results point towards a specific demand for certain mineral nutrients starting in the recovery phase.

  6. Comprehensive transcriptome analysis unravels the existence of crucial genes regulating primary metabolism during adventitious root formation in Petunia hybrida.

    Directory of Open Access Journals (Sweden)

    Amirhossein Ahkami

    Full Text Available To identify specific genes determining the initiation and formation of adventitious roots (AR, a microarray-based transcriptome analysis in the stem base of the cuttings of Petunia hybrida (line W115 was conducted. A microarray carrying 24,816 unique, non-redundant annotated sequences was hybridized to probes derived from different stages of AR formation. After exclusion of wound-responsive and root-regulated genes, 1,354 of them were identified which were significantly and specifically induced during various phases of AR formation. Based on a recent physiological model distinguishing three metabolic phases in AR formation, the present paper focuses on the response of genes related to particular metabolic pathways. Key genes involved in primary carbohydrate metabolism such as those mediating apoplastic sucrose unloading were induced at the early sink establishment phase of AR formation. Transcriptome changes also pointed to a possible role of trehalose metabolism and SnRK1 (sucrose non-fermenting 1- related protein kinase in sugar sensing during this early step of AR formation. Symplastic sucrose unloading and nucleotide biosynthesis were the major processes induced during the later recovery and maintenance phases. Moreover, transcripts involved in peroxisomal beta-oxidation were up-regulated during different phases of AR formation. In addition to metabolic pathways, the analysis revealed the activation of cell division at the two later phases and in particular the induction of G1-specific genes in the maintenance phase. Furthermore, results point towards a specific demand for certain mineral nutrients starting in the recovery phase.

  7. Reconfigurable Resonant Regulating Rectifier With Primary Equalization for Extended Coupling- and Loading-Range in Bio-Implant Wireless Power Transfer.

    Science.gov (United States)

    Li, Xing; Meng, Xiaodong; Tsui, Chi-Ying; Ki, Wing-Hung

    2015-12-01

    Wireless power transfer using reconfigurable resonant regulating (R(3)) rectification suffers from limited range in accommodating varying coupling and loading conditions. A primary-assisted regulation principle is proposed to mitigate these limitations, of which the amplitude of the rectifier input voltage on the secondary side is regulated by accordingly adjusting the voltage amplitude Veq on the primary side. A novel current-sensing method and calibration scheme track Veq on the primary side. A ramp generator simultaneously provides three clock signals for different modules. Both the primary equalizer and the R(3) rectifier are implemented as custom integrated circuits fabricated in a 0.35 μm CMOS process, with the global control implemented in FPGA. Measurements show that with the primary equalizer, the workable coupling and loading ranges are extended by 250% at 120 mW load and 300% at 1.2 cm coil distance compared to the same system without the primary equalizer. A maximum rectifier efficiency of 92.5% and a total system efficiency of 62.4% are demonstrated.

  8. Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

    Science.gov (United States)

    Thorpe, Stephen D; Gambassi, Silvia; Thompson, Clare L; Chandrakumar, Charmilie; Santucci, Annalisa; Knight, Martin M

    2017-09-01

    Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

  9. Differential feedback regulation of cholesterol 7α-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes

    NARCIS (Netherlands)

    Twisk, J.; Lehmann, E.M.; Princen, H.M.G.

    1993-01-01

    We have used primary monolayer cultures of rat hepatocytes to study the effects of physiological concentrations of various bile acids, commonly found in bile of normal rats, on the mechanism of regulation of cholesterol 7α-hydroxylase and bile acid synthesis. Addition of taurocholic acid, the most

  10. Effect of brain-derived neurotrophic factor on activity-regulated cytoskeleton-associated protein gene expression in primary frontal cortical neurons. Comparison with NMDA and AMPA

    DEFF Research Database (Denmark)

    El-Sayed, Mona; Hofman-Bang, Jacob; Mikkelsen, Jens D

    2011-01-01

    The effect of brain-derived neurotrophic factor (BDNF) on activity-regulated cytoskeleton-associated protein (Arc) mRNA levels in primary neuronal cultures of rat frontal cortex was characterized pharmacologically and compared to the effect on expression of c-fos, bdnf, neuritin, cox-2 as examples...

  11. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan); Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan)

    2009-10-30

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  12. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    International Nuclear Information System (INIS)

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

    2009-01-01

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li 2 CO 3 were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  13. Glial cell line-derived neurotrophic factor up-regulates GTP-cyclohydrolase I activity and tetrahydrobiopterin levels in primary dopaminergic neurones

    DEFF Research Database (Denmark)

    Bauer, M; Suppmann, S; Meyer, M

    2002-01-01

    in tetrahydrobiopterin levels whereas tyrosine 3-monooxygenase activity was not altered. Actinomycin D, asan inhibitor of de novo biosynthesis, abolished any GDNF-mediated up-regulation of GTPCH I activity. However, GTPCH I mRNA levels in primary dopaminergic neurones were not altered by GDNF treatment, suggesting...... by triggering activation of GTP-cyclohydrolase I (GTPCH I), a key enzyme in catecholamine biosynthesis. GDNF stimulation of primary dopaminergic neurones expressing both tyrosine 3-monooxygenase and GTPCH I resulted in a dose-dependent doubling of GTPCH I activity, and a concomitant increase...... that the mode of action for that up-regulation is not directly connected to the regulation of GTPCH I transcription. We conclude that GDNF, in addition to its action in structural differentiation, also promotes differentiation regarding expression and enzymatic activity of a crucial component...

  14. The Construct Validity of the German Academic Self-regulation Questionnaire (SRQ-A within Primary and Secondary School Children

    Directory of Open Access Journals (Sweden)

    Julia Kröner

    2017-06-01

    Full Text Available The assessment of students' motivation can be a powerful tool in enhancing and understanding students' learning. One valid and often applied self-report measure is the Academic Self-Regulation Questionnaire (SRQ-A which is grounded in the self-determination theory. However, to date, there is still no German equivalent to the English version of this questionnaire. Therefore, the aim of the present study was to adapt and validate the SRQ-A on a representative German student sample, consisting of 672 children (327 girls, ages 8–14 from one primary and two secondary German schools. First, the translation-back-translation method was used to ensure the linguistic equivalence of the German questionnaire. Second, item analysis of the generated scores of the German SRQ-A were conducted. Third, the multidimensional factorial structure of the original measure was tested with confirmatory factor analysis (CFA using maximum likelihood estimation. Last, additional construct validity of the German SRQ-A was tested using correlational analyses with convergent and divergent measures. After conducting CFA, four items were excluded from the original questionnaire, due to loadings lower than 0.40, resulting in 28 items. The German SRQ-A showed good internal consistency for all subscales, with Chronbach's α ranging between 0.75 and 0.88. The simplex-structure of the original measurement could also be confirmed, however, the four-factorial model could not be replicated. The measurement showed good convergent and discriminant validity with other related questionnaires. In summary, the German SRQ-A is a reliable and valid self-report instrument for the assessment of self-determined motivational styles within the school context.

  15. Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation.

    Directory of Open Access Journals (Sweden)

    Pooja Singhmar

    Full Text Available Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

  16. Evaluation of compliance with the self-regulation agreement of the food and drink vending machine sector in primary schools in Madrid, Spain, in 2008.

    Science.gov (United States)

    Royo-Bordonada, Miguel A; Martínez-Huedo, María A

    2014-01-01

    To evaluate compliance with the self-regulation agreement of the food and drink vending machine sector in primary schools in Madrid, Spain. Cross-sectional study of the prevalence of vending machines in 558 primary schools in 2008. Using the directory of all registered primary schools in Madrid, we identified the presence of machines by telephone interviews and evaluated compliance with the agreement by visiting the schools and assessing accessibility, type of publicity, the products offered and knowledge of the agreement. The prevalence of schools with vending machines was 5.8%. None of the schools reported knowledge of the agreement or of its nutritional guidelines, and most machines were accessible to primary school pupils (79.3%) and packed with high-calorie, low-nutrient-dense foods (58.6%). Compliance with the self-regulation agreement of the vending machines sector was low. Stricter regulation should receive priority in the battle against the obesity epidemic. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  17. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  18. Systematic Multi-variable H-infinity Control Design for Primary Frequency Regulation in Stand-alone Microgrids with High Penetration of Renewable Energy Sources

    OpenAIRE

    Lam , Quang Linh; Bratcu , Antoneta Iuliana; Riu , Delphine

    2016-01-01

    International audience; In this paper, a systematic design of a robust multi-variable control structure for primary frequency regulation in microgrids with high rate of renewable source penetration is proposed. The considered microgrid represents a diesel-photovoltaic-supercapacitor hybrid power generation system operating in stand-alone mode. The proposed control structure relies on a two-level architecture: classical PI-based current tracking controllers are placed on the low control level ...

  19. Field tests experience from 1.6MW/400kWh Li-ion battery energy storage system providing primary frequency regulation service

    DEFF Research Database (Denmark)

    Swierczynski, Maciej Jozef; Stroe, Daniel Ioan; Stan, Ana-Irina

    2013-01-01

    Lithium-ion battery energy storage systems (BESSs) represent suitable alternatives to conventional generating units for providing primary frequency regulation on the Danish market. This paper presents aspects concerning the operation of the BESSs in the Danish energy market while providing upwards...... on the BESS demonstrator located in Western Denmark and initial results are introduced and discussed. These measurements can be used to validate models for battery ageing during realistic operation or to develop the diagnostic tools for the BESS....

  20. Evaluation of different operational strategies for lithium ion battery systems connected to a wind turbine for primary frequency regulation and wind power forecast accuracy improvement

    Energy Technology Data Exchange (ETDEWEB)

    Swierczynski, Maciej; Stroe, Daniel Ioan; Stan, Ana Irina; Teodorescu, Remus; Andreasen, Soeren Juhl [Aalborg Univ. (Denmark). Dept. of Energy Technology

    2012-07-01

    High penetration levels of variable wind energy sources can cause problems with their grid integration. Energy storage systems connected to wind turbine/wind power plants can improve predictability of the wind power production and provide ancillary services to the grid. This paper investigates economics of different operational strategies for Li-ion systems connected to wind turbines for wind power forecast accuracy improvement and primary frequency regulation. (orig.)

  1. Revealing the Molecular Structure and the Transport Mechanism at the Base of Primary Cilia Using Superresolution STED Microscopy

    Science.gov (United States)

    Yang, Tung-Lin

    The primary cilium is an organelle that serves as a signaling center of the cell and is involved in the hedgehog signaling, cAMP pathway, Wnt pathways, etc. Ciliary function relies on the transportation of molecules between the primary cilium and the cell, which is facilitated by intraflagellar transport (IFT). IFT88, one of the important IFT proteins in complex B, is known to play a role in the formation and maintenance of cilia in various types of organisms. The ciliary transition zone (TZ), which is part of the gating apparatus at the ciliary base, is home to a large number of ciliopathy molecules. Recent studies have identified important regulating elements for TZ gating in cilia. However, the architecture of the TZ region and its arrangement relative to intraflagellar transport (IFT) proteins remain largely unknown, hindering the mechanistic understanding of the regulation processes. One of the major challenges comes from the tiny volume at the ciliary base packed with numerous proteins, with the diameter of the TZ close to the diffraction limit of conventional microscopes. Using a series of stimulated emission depletion (STED) superresolution images mapped to electron microscopy images, we analyzed the structural organization of the ciliary base. Subdiffraction imaging of TZ components defines novel geometric distributions of RPGRIP1L, MKS1, CEP290, TCTN2 and TMEM67, shedding light on their roles in TZ structure, assembly, and function. We found TCTN2 at the outmost periphery of the TZ close to the ciliary membrane, with a 227+/-18 nm diameter. TMEM67 was adjacent to TCTN2, with a 205+/-20 nm diameter. RPGRIP1L was localized toward the axoneme at the same axial level as TCTN2 and TMEM67, with a 165+/-8 nm diameter. MKS1 was situated between TMEM67 and RPGRIP1L, with an 186+/-21 nm diameter. Surprisingly, CEP290 was localized at the proximal side of the TZ close to the distal end of the centrin-labeled basal body. The lateral width was unexpectedly close to

  2. The Research on Second-Order ADRC Algorithm of Using Wind Turbine Virtual Inertia to Participate in Primary Frequency Regulation in a Small Stand-Alone Microgrid

    Directory of Open Access Journals (Sweden)

    Wang Yi

    2018-01-01

    Full Text Available In order to improve the transient stability of frequency in a small stand-alone microgrid (SSM, this paper takes a SSM composed of a direct-drive permanent magnet synchronous generator (D-PMSG and a micro gas turbine (MGT as the background and uses wind turbine generator (WTG virtual inertia (VI to participate in the primary (short-term system frequency regulation. First of all, this paper constructs a grid-connected model composed of a WTG and a MGT, analyzes the WTG virtual inertia frequency regulation mechanism, and explains the principle of proportional-differentiation (PD virtual inertia control (VIC and its shortcomings. Secondly, the paper introduces the structure principle of n-order active disturbance rejection control (ADRC and deduces the design process of second-order ADRC-VIC. Finally, through the simulation and experimental verification, comparing the frequency perturbation of without-VIC, PD-VIC, and ADRC-VIC, it is concluded that PD-VIC and ADRC-VIC both can use the WTG virtual inertia to participate in the primary frequency regulation. The frequency regulation effect of ADRC-VIC is better than PD-VIC, ADRC-VIC can extend the rotor speed recovery time and avoid overshoot, and its frequency fluctuation amplitude and settling time are obviously improved, and ADRC-VIC can effectively avoid the overshoot phenomenon of the MGT output power.

  3. A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta.

    Science.gov (United States)

    Simon, Bailey; Bucher, Matthew; Maloyan, Alina

    2017-09-27

    Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture. This is followed by a method for simulating the inflammatory milieu in the obese intrauterine environment by treating primary trophoblasts from lean pregnancies with tumor necrosis factor alpha (TNFα), a proinflammatory cytokine that is elevated in obesity and in pregnancy. Through the implementation of the protocol described here, it is found that exposure to exogenous TNFα regulates the expression of Rubicon, a negative regulator of autophagy, in trophoblasts from lean pregnancies with female fetuses. While a variety of biological factors in the obese intrauterine environment maintain the potential to modulate critical pathways in trophoblasts, this ex vivo system is especially useful for determining if expression patterns observed in vivo in human placentas with maternal obesity are a direct result of TNFα signaling. Ultimately, this approach affords the opportunity to parse out the regulatory and molecular implications of inflammation associated with maternal obesity on autophagy and other critical cellular pathways in trophoblasts that have the potential to impact placental function.

  4. DIAGNOSIS OF EMOTIONAL AND VOLITIONAL SELF-REGULATION OF PRIMARY SCHOOL AGED PUPILS’ IN TERMS OF THE VOCAL AND CHORAL ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Olga A. Malakhova

    2015-01-01

    Full Text Available The aim of the study is to investigate emotional and volitional self-regulation of primary school children during musical activities such as a choral performance.Methods. The proposed method of diagnosing emotional and volitional selfregulation in the process of choral activities, and methods of mathematical statistics are applied. Results and scientific novelty. The author formulates the definition of emotional and volitional self-regulation; criteria and indicators for its diagnosis are developed. The main criteria for the development of emotional and volitional selfregulation are: «self-control in the process of hearing musical performance», «emotional performance of a musical work», and «arbitrary regulation of psychophysiological state». The data obtained in the course of diagnosis in the Ural College of Music in vocal and choral activities at primary school children are analyzed. The use of mathematical statistics to summarize the data is justified.Practical significance. The development techniques of emotional and volitional self-regulation of future musicians to choral exercises are described; this technology may be used in music colleges, children’s art schools, as well as the highest level of musical performing and musical-pedagogical education. Research materials can be useful both to psychologists, and experts in the field of music education.

  5. Dealing with emotions when the ability to cry is hampered: emotion processing and regulation in patients with primary Sjögren's syndrome.

    Science.gov (United States)

    van Leeuwen, Ninke; Bossema, Ercolie R; van Middendorp, Henriët; Kruize, Aike A; Bootsma, Hendrika; Bijlsma, Johannes W J; Geenen, Rinie

    2012-01-01

    The hampered ability to cry in patients with Sjögren's syndrome may affect their ways of dealing with emotions. The aim of this study was to examine differences in emotion processing and regulation between people with and without Sjögren's syndrome and correlations of emotion processing and regulation with mental well-being. In 300 patients with primary Sjögren's syndrome and 100 demographically matched control participants (mean age 56.8 years, 93% female), emotion processing (affect intensity and alexithymia, i.e. difficulty identifying and describing feelings), emotion regulation (cognitive reappraisal, suppression and expression of emotions), and mental well-being were assessed. Criteria for clinical alexithymia applied to 22% of the patients and 12% of the control participants; patients had significantly more difficulty identifying feelings than control participants. No other significant differences in emotion processing and emotion regulation were found. In patients, the emotion processing styles affect intensity and alexithymia (0.32emotion regulation strategy suppression of emotions (r=0.13) significantly correlated with worse mental well-being, which is about similar to control participants. Processing and regulating emotions in patients with Sjögren's syndrome does not deviate from normal with one exception: a relatively large number of patients is alexithymic. As in the general population, in patients with Sjögren's syndrome the more intense and deficient processing and regulation of emotions is associated with worse mental well-being. This study indicates that, except for selected patients, processing and regulation of emotions is not a key therapeutic issue for the majority of patients with Sjögren's syndrome.

  6. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    International Nuclear Information System (INIS)

    Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

    2011-01-01

    Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  7. TGFβ1-induced down-regulation of microRNA-138 contributes to epithelial-mesenchymal transition in primary lung cancer cells.

    Science.gov (United States)

    Zhang, Fang; Li, Tiepeng; Han, Lu; Qin, Peng; Wu, Zhao; Xu, Benling; Gao, Quanli; Song, Yongping

    2018-02-19

    The existence of cancer stem cells within the tumor could lead to cancer therapy resistance. TGFβ1 is considered as one of the most powerful players in the generation of CSCs through induction of epithelial-mesenchymal transition in different types of cancer including lung cancer, however, the detailed mechanisms by which TGFβ1 contribute to EMT induction and CSC maintenance remains unclear. Here, we showed primary lung cancer cells treated by TGFβ1 exhibit mesenchymal features, including morphology and expression of mesenchymal marker in a time-dependent manner. We also observed long-term TGFβ1 exposure leads to an enrichment of a sub-population of CD44 + CD90 + cells which represent CSCs in lung cancer cells. Moreover, the differential expression microRNAs between CSCs and non-CSCs were identified using next-generation sequencing to screen key miRNAs which might contribute to TGFβ1-induced EMT and CSCs generation. Among those differentially expressed miRNAs, the expression of microRNA-138 was time-dependently down-regulated by TGFβ1 treatment. We further demonstrated primary lung cancer cells, in which we knockdown the expression of miR-138, exhibit mesenchymal phenotypes and stem cell properties. Taken together, these findings indicate TGFβ1-induced down-regulation of microRNA-138 contributes to EMT in primary lung cancer cells, and suggest that miR-138 might serve as a potential therapeutic target. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Early Central Regulation, Slow Financial Participation: Relations between Primary Education and the Dutch State from ± 1750-1920

    Science.gov (United States)

    van Gijlswijk, Dick

    2016-01-01

    The declining economy of the Dutch Republic obliged city governments in the eighteenth century to take measures to undo the effects of the social deterioration. They therefore founded schools for the poor and sometimes gave full financial support. After 1795, the Batavian Revolution proclaimed that primary education was a state affair, but after a…

  9. DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

    International Nuclear Information System (INIS)

    Li, C.-C.; Lii, C.-K.; Liu, K.-L.; Yang, J.-J.; Chen, H.-W.

    2007-01-01

    The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 μM arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression

  10. Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Rasmussen, Anders Aamann; Byriel, Lene

    2013-01-01

    In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim...... of this study was to determine in detail how DNA methylation regulates MLH1 expression and impacts clinical management....

  11. Dealing with emotions when the ability to cry is hampered: emotion processing and regulation in patients with primary Sjogren's syndrome

    NARCIS (Netherlands)

    Leeuwen, N. van; Bossema, E.R.; Middendorp, H. van; Kruize, A.A.; Bootsma, H.; Bijlsma, J.W.J.; Geenen, R.

    2012-01-01

    OBJECTIVES: The hampered ability to cry in patients with Sjogren's syndrome may affect their ways of dealing with emotions. The aim of this study was to examine differences in emotion processing and regulation between people with and without Sjogren's syndrome and correlations of emotion processing

  12. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  13. Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

    Science.gov (United States)

    Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

    2014-08-01

    The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

  14. Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

    Science.gov (United States)

    Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

    2017-02-28

    Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

  15. Identification of transcripts regulated by CUG-BP, Elav-like family member 1 (CELF1 in primary embryonic cardiomyocytes by RNA-seq

    Directory of Open Access Journals (Sweden)

    Yotam Blech-Hermoni

    2015-12-01

    Full Text Available CUG-BP, Elav-like family member 1 (CELF1 is a multi-functional RNA binding protein that regulates pre-mRNA alternative splicing in the nucleus, as well as polyadenylation status, mRNA stability, and translation in the cytoplasm [1]. Dysregulation of CELF1 has been implicated in cardiomyopathies in myotonic dystrophy type 1 and diabetes [2–5], but the targets of CELF1 regulation in the heart have not been systematically investigated. We previously demonstrated that in the developing heart CELF1 expression is restricted to the myocardium and peaks during embryogenesis [6–8]. To identify transcripts regulated by CELF1 in the embryonic myocardium, RNA-seq was used to compare the transcriptome of primary embryonic cardiomyocytes following siRNA-mediated knockdown of CELF1 to that of controls. Raw data files of the RNA-seq reads have been deposited in NCBI's Gene Expression Omnibus [9] under the GEO Series accession number GSE67360. These data can be used to identify transcripts whose levels or alternative processing (i.e., alternative splicing or polyadenylation site usage are regulated by CELF1, and should provide insight into the pathways and processes modulated by this important RNA binding protein during normal heart development and during cardiac pathogenesis.

  16. Systematically reviewing the potential of concept mapping technologies to promote self-regulated learning in primary and secondary science education

    DEFF Research Database (Denmark)

    Stevenson, Matt P.; Hartmeyer, Rikke; Bentsen, Peter

    2017-01-01

    We systematically searched five databases to assess the potential of concept mapping-based technologies to promote self-regulated learning in science education. Our search uncovered 17 relevant studies that investigated seven different types of learning technologies. We performed a narrative....... Computer software was particularly useful for developing cognitive strategies through ease of use. Teaching agents were particularly useful for developing metacognitive strategies by coupling visualisation of knowledge patterns with performance monitoring, aided by a teaching metaphor. Finally, mobile...... devices and teaching agents were most effective in enhancing motivation. Effects on knowledge gains remain unclear due to small sample sizes....

  17. Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model.

    Science.gov (United States)

    Wang, C C; Guo, L; Tian, F D; An, N; Luo, L; Hao, R H; Wang, B; Zhou, Z H

    2017-03-23

    Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

  18. Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

    Directory of Open Access Journals (Sweden)

    C.C. Wang

    Full Text Available Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4 and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

  19. Activation of Nrf2 is required for up-regulation of the π class of glutathione S-transferase in rat primary hepatocytes with L-methionine starvation.

    Science.gov (United States)

    Lin, Ai-Hsuan; Chen, Haw-Wen; Liu, Cheng-Tze; Tsai, Chia-Wen; Lii, Chong-Kuei

    2012-07-04

    Numerous genes expression is regulated in response to amino acid shortage, which helps organisms adapt to amino acid limitation. The expression of the π class of glutathione (GSH) S-transferase (GSTP), a highly inducible phase II detoxification enzyme, is regulated mainly by activates activating protein 1 (AP-1) binding to the enhancer I of GSTP (GPEI). Here we show the critical role of nuclear factor erythroid-2-related factor 2 (Nrf2) in up-regulating GSTP gene transcription. Primary rat hepatocytes were cultured in a methionine-restricted medium, and immunoblotting and RT-PCR analyses showed that methionine restriction time-dependently increased GSTP protein and mRNA expression over a 48 h period. Nrf2 translocation to the nucleus, nuclear proteins binding to GPEI, and antioxidant response element (ARE) luciferase reporter activity were increased by methionine restriction as well as by l-buthionine sulfoximine (BSO), a GSH synthesis inhibitor. Transfection with Nrf2 siRNA knocked down Nrf2 expression and reversed the methionine-induced GSTP expression and GPEI binding activity. Chromatin immunoprecipitation assay confirmed the binding of Nrf2 to the GPEI. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells. ERK2 siRNA abolished methionine restriction-induced Nrf2 nuclear translocation, GPEI binding activity, ARE-luciferase reporter activity, and GSTP expression. Our results suggest that the up-regulation of GSTP gene transcription in response to methionine restriction likely occurs via the ERK-Nrf2-GPEI signaling pathway.

  20. Potential Role of Vδ2+ γδ T Cells in Regulation of Immune Activation in Primary HIV Infection

    Directory of Open Access Journals (Sweden)

    Nupur Bhatnagar

    2017-09-01

    Full Text Available Although conventional regulatory T cells (Tregs are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI. Our previous data suggested that double negative (DN T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI. In a cross-sectional study of 58 HIV-infected patients, in the primary and the chronic phase either ART-treated or untreated (UT, we analyzed phenotype and cytokine production of γδ T cells using flow cytometry. Cytokine production was assessed following in vitro stimulation with isopentenyl pyrophosphate or plate-bound anti-CD3/anti-CD28 monoclonal antibodies. We found that the proportion of γδ T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the Vδ2 receptor bearing (Vδ2+ γδ T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-β. In contrast, in UT-CHI, we observed a remarkable expansion of γδ T cells, where the Vδ2+ γδ T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-γ but very low levels of TGF-β. We also found that this loss of regulatory feature of γδ T cells in CHI was a lasting impairment as we did not find recovery of TGF-β production even in ART-CHI patients successfully treated for more than 5 years. Our data therefore suggest that during the primary HIV infection, Vδ2+ γδ T cells may act as Tregs controlling immune activation through production of TGF-β. However, in CHI, γδ T cells transform from an anti-inflammatory into pro

  1. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus.

    Science.gov (United States)

    Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J

    2014-04-03

    Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.

  2. Transcriptome Analyses Shed New Insights into Primary Metabolism and Regulation of Blumeria graminis f. sp. tritici during Conidiation

    Directory of Open Access Journals (Sweden)

    Fan-Song Zeng

    2017-06-01

    Full Text Available Conidia of the obligate biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt play a vital role in its survival and rapid dispersal. However, little is known about the genetic basis for its asexual reproduction. To uncover the primary metabolic and regulatory events during conidiation, we sequenced the transcriptome of Bgt epiphytic structures at 3 (vegetative hyphae growth, 4 (foot cells initiation, and 5 (conidiophore erection days post-inoculation (dpi. RNA-seq analyses identified 556 and 404 (combined 685 differentially expressed genes (DEGs at 4 and 5 dpi compared with their expression levels at 3 dpi, respectively. We found that several genes involved in the conversion from a variety of sugars to glucose, glycolysis, the tricarboxylic acid cycle (TAC, the electron transport chain (ETC, and unsaturated fatty acid oxidation were activated during conidiation, suggesting that more energy supply is required during this process. Moreover, we found that glucose was converted into glycogen, which was accumulated in developing conidiophores, indicating that it could be the primary energy storage molecule in Bgt conidia. Clustering for the expression profiles of 91 regulatory genes showed that calcium (Ca2+, H2O2, and phosphoinositide (PIP signaling were involved in Bgt conidiation. Furthermore, a strong accumulation of H2O2 in developing conidiophores was detected. Application of EGTA, a Ca2+ chelator, and trifluoperazine dihydrochloride (TFP, a calmodulin (CaM antagonist, markedly suppressed the generation of H2O2, affected foot cell and conidiophore development and reduced conidia production significantly. These results suggest that Ca2+ and H2O2 signaling play important roles in conidiogenesis and a crosslink between them is present. In addition to some conidiation-related orthologs known in other fungi, such as the velvet complex components, we identified several other novel B. graminis-specific genes that have not been previously

  3. Dorsal Medial Habenula Regulation of Mood-Related Behaviors and Primary Reinforcement by Tachykinin-Expressing Habenula Neurons

    Science.gov (United States)

    Hsu, Yun-Wei A.

    2016-01-01

    Abstract Animal models have been developed to investigate aspects of stress, anxiety, and depression, but our understanding of the circuitry underlying these models remains incomplete. Prior studies of the habenula, a poorly understood nucleus in the dorsal diencephalon, suggest that projections to the medial habenula (MHb) regulate fear and anxiety responses, whereas the lateral habenula (LHb) is involved in the expression of learned helplessness, a model of depression. Tissue-specific deletion of the transcription factor Pou4f1 in the dorsal MHb (dMHb) results in a developmental lesion of this subnucleus. These dMHb-ablated mice show deficits in voluntary exercise, a possible correlate of depression. Here we explore the role of the dMHb in mood-related behaviors and intrinsic reinforcement. Lesions of the dMHb do not elicit changes in contextual conditioned fear. However, dMHb-lesioned mice exhibit shorter immobility time in the tail suspension test, another model of depression. dMHb-lesioned mice also display increased vulnerability to the induction of learned helplessness. However, this effect is not due specifically to the dMHb lesion, but appears to result from Pou4f1 haploinsufficiency elsewhere in the nervous system. Pou4f1 haploinsufficiency does not produce the other phenotypes associated with dMHb lesions. Using optogenetic intracranial self-stimulation, intrinsic reinforcement by the dMHb can be mapped to a specific population of neurokinin-expressing habenula neurons. Together, our data show that the dMHb is involved in the regulation of multiple mood-related behaviors, but also support the idea that these behaviors do not reflect a single functional pathway. PMID:27482535

  4. Activity-dependent regulation of MHC class I expression in the developing primary visual cortex of the common marmoset monkey

    Directory of Open Access Journals (Sweden)

    Schlumbohm Christina

    2011-01-01

    Full Text Available Abstract Background Several recent studies have highlighted the important role of immunity-related molecules in synaptic plasticity processes in the developing and adult mammalian brains. It has been suggested that neuronal MHCI (major histocompatibility complex class I genes play a role in the refinement and pruning of synapses in the developing visual system. As a fast evolutionary rate may generate distinct properties of molecules in different mammalian species, we studied the expression of MHCI molecules in a nonhuman primate, the common marmoset monkey (Callithrix jacchus. Methods and results Analysis of expression levels of MHCI molecules in the developing visual cortex of the common marmoset monkeys revealed a distinct spatio-temporal pattern. High levels of expression were detected very early in postnatal development, at a stage when synaptogenesis takes place and ocular dominance columns are formed. To determine whether the expression of MHCI molecules is regulated by retinal activity, animals were subjected to monocular enucleation. Levels of MHCI heavy chain subunit transcripts in the visual cortex were found to be elevated in response to monocular enucleation. Furthermore, MHCI heavy chain immunoreactivity revealed a banded pattern in layer IV of the visual cortex in enucleated animals, which was not observed in control animals. This pattern of immunoreactivity indicated that higher expression levels were associated with retinal activity coming from the intact eye. Conclusions These data demonstrate that, in the nonhuman primate brain, expression of MHCI molecules is regulated by neuronal activity. Moreover, this study extends previous findings by suggesting a role for neuronal MHCI molecules during synaptogenesis in the visual cortex.

  5. Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes.

    Science.gov (United States)

    Wong, Siew Ying; Tan, Michelle G K; Banks, William A; Wong, W S Fred; Wong, Peter T-H; Lai, Mitchell K P

    2016-02-09

    Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In this study, we aimed to assess andrographolide's potential utility as an anti-neuroinflammatory therapeutic. The effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocytes were measured, including cytokine profiling, gene expression, and, in cultured astrocytes, activation of putative signaling regulators. Orally administered andrographolide significantly attenuated mouse cortical chemokine levels from the C-C and C-X-C subfamilies. Similarly, andrographolide abrogated a range of LPS-induced chemokines as well as tumor necrosis factor (TNF)-α in astrocytes. In astrocytes, the inhibitory actions of andrographolide on chemokine and TNF-α up-regulation appeared to be mediated by nuclear factor-κB (NF-κB) or c-Jun N-terminal kinase (JNK) activation. These results suggest that andrographolide may be useful as a therapeutic for neuroinflammatory diseases, especially those characterized by chemokine dysregulation.

  6. Interleukin-1β regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    International Nuclear Information System (INIS)

    Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2010-01-01

    Research highlights: → Levels of IL-1β are increased in the pig myocardium after infarction. → Cultured pig heart cells possess IL-1 receptors. → IL-1β increases cell proliferation of pig heart cells in-vitro. → IL-1β increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. → IL-1β may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1β is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1β on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1β. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1β resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1β plays a major role in the events of tissue remodelling in the heart. Combined with our recently published in vivo data (Meybohm et al., PLoS One

  7. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    Energy Technology Data Exchange (ETDEWEB)

    Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  8. Maintaining protein composition in cilia.

    Science.gov (United States)

    Stephen, Louise A; Elmaghloob, Yasmin; Ismail, Shehab

    2017-12-20

    The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.

  9. Role of the dorsal medial habenula in the regulation of voluntary activity, motor function, hedonic state, and primary reinforcement.

    Science.gov (United States)

    Hsu, Yun-Wei A; Wang, Si D; Wang, Shirong; Morton, Glenn; Zariwala, Hatim A; de la Iglesia, Horacio O; Turner, Eric E

    2014-08-20

    The habenular complex in the epithalamus consists of distinct regions with diverse neuronal populations. Past studies have suggested a role for the habenula in voluntary exercise motivation and reinforcement of intracranial self-stimulation but have not assigned these effects to specific habenula subnuclei. Here, we have developed a genetic model in which neurons of the dorsal medial habenula (dMHb) are developmentally eliminated, via tissue-specific deletion of the transcription factor Pou4f1 (Brn3a). Mice with dMHb lesions perform poorly in motivation-based locomotor behaviors, such as voluntary wheel running and the accelerating rotarod, but show only minor abnormalities in gait and balance and exhibit normal levels of basal locomotion. These mice also show deficits in sucrose preference, but not in the forced swim test, two measures of depression-related phenotypes in rodents. We have also used Cre recombinase-mediated expression of channelrhodopsin-2 and halorhodopsin to activate dMHb neurons or silence their output in freely moving mice, respectively. Optical activation of the dMHb in vivo supports intracranial self-stimulation, showing that dMHb activity is intrinsically reinforcing, whereas optical silencing of dMHb outputs is aversive. Together, our findings demonstrate that the dMHb is involved in exercise motivation and the regulation of hedonic state, and is part of an intrinsic reinforcement circuit. Copyright © 2014 the authors 0270-6474/14/3411366-19$15.00/0.

  10. Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows.

    Science.gov (United States)

    Li, Xinwei; Li, Yu; Ding, Hongyan; Dong, Jihong; Zhang, Renhe; Huang, Dan; Lei, Lin; Wang, Zhe; Liu, Guowen; Li, Xiaobing

    2018-05-01

    Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.

  11. A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.

    Directory of Open Access Journals (Sweden)

    Nathan Steere

    Full Text Available The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages, which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby, a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx, which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.

  12. A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.

    Science.gov (United States)

    Steere, Nathan; Chae, Vanessa; Burke, Michael; Li, Feng-Qian; Takemaru, Ken-ichi; Kuriyama, Ryoko

    2012-01-01

    The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages), which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby), a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx), which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.

  13. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

    International Nuclear Information System (INIS)

    Park, Jin-Sun; Kim, Hee-Sun

    2014-01-01

    Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes

  14. The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

    International Nuclear Information System (INIS)

    Robinson, G.S.

    1989-01-01

    The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

  15. Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.

    Science.gov (United States)

    Regan, Andrew D; Cohen, Rebecca D; Whittaker, Gary R

    2009-02-05

    Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

  16. Regulation of galactokinase gene expression in Tetrahymena thermophila. II. Identification of 3,4-dihydroxyphenylalanine as a primary effector of adrenergic control of galactokinase expression.

    Science.gov (United States)

    Ness, J C; Morse, D E

    1985-08-25

    Intracellular concentrations of catecholamines were determined in wild-type and mutant Tetrahymena thermophila, using the highly sensitive techniques of high-performance liquid chromatography and electro-chemical detection. Catecholamines were determined in these cell strains grown under various steady-state conditions, including those which initiate and maintain repression of galactokinase gene expression. Wild-type cells grown in defined minimal medium supplemented with 1% glycerol, exhibiting derepressed galactokinase synthesis, were found to contain considerable quantities of dopa (3,4-dihydroxyphenylalanine) and dopamine, but no detectable levels of either norepinephrine or epinephrine. Analyses of wild-type cells revealed a strong positive correlation between the internal concentration of dopa and expression of the galactokinase gene, both of which are regulated by exogenous carbohydrates, catecholamine agonists, or dibutyryl-cAMP; an analogous relationship between intracellular dopamine concentrations and galactokinase activity was not found. In addition, a correlation between intracellular dopa content and the phenotypic expression of galactokinase in various mutants deficient in the catecholamine biosynthetic pathway or in glucokinase further confirms the role of dopa as a primary effector in the regulation of galactokinase gene expression.

  17. Spatial variability of primary organic sources regulates ichthyofauna distribution despite seasonal influence in Terminos lagoon and continental shelf of Campeche, Mexico

    Science.gov (United States)

    Romo Rios, J. A.; Aguíñiga-García, S.; Sanchez, A.; Zetina-Rejón, M.; Arreguín-Sánchez, F.; Tripp-Valdéz, A.; Galeana-Cortazár, A.

    2013-05-01

    Human activities have strong impacts on coastal ecosystems functioning through their effect on primary organic sources distributions and resulting biodiversity. Hence, it appears to be of utmost importance to quantify contribution of primary producers to sediment organic matter (SOM) spatial variability and its associated ichthyofauna. The Terminos lagoon (Gulf of Mexico) is a tropical estuary severely impacted by human activities even though of primary concern for its biodiversity, its habitats, and its resource supply. Stable isotope data (d13C, d15N) from mangrove, seaweed, seagrass, phytoplankton, ichthyofauna and SOM were sampled in four zones of the lagoon and the continental shelf through windy (November to February), dry (March to June) and rainy (July to October) seasons. Stable Isotope Analysis in R (SIAR) mixing model were used to determine relative contributions of the autotrophic sources to the ichthyofauna and SOM. Analysis of variance of ichthyofauna isotopic values showed significant differences (P < 0.001) in the four zones of lagoon despite the variability introduced by the windy, dry and rainy seasons. In lagoons rivers discharge zone, the mangrove contribution to ichthyofauna was 40% and 84% to SOM. Alternative use of habitat by ichthyofauna was evidenced since in the deep area of the lagoon (4 m), the contribution of mangrove to fish is 50%, and meanwhile contribution to SOM is only 77%. Although phytoplankton (43%) and seaweed (41%) contributions to the adjacent continental shelf ichthyofauna were the main organic sources, there was 37% mangrove contribution to SOM, demonstrating conspicuous terrigenous influence from lagoon ecosystem. Our results point toward organic sources spatial variations that regulate fish distribution. In Terminos lagoon, significant correlation (p-value = 0.2141 and r=0.79) of Ariopsis felis and Sphoeroides testudineus abundances and seaweed and seagrasses contributions (30-35%) during both dry and rainy seasons

  18. Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Long, Cong; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Wang, Huan; Wang, Chao; Liu, Yu [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan, 430072 (China)

    2016-01-01

    Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated that triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells. - Highlights: • Triptolide reduces expression of hTERT by decreasing its transcription level. • Triptolide reduces promoter activity and stability of hTERT. • Triptolide down-regulates expression of Sp1. • Special Sp1 shRNAs inhibit transcription and protein expression of hTERT. • Triptolide and Sp1 shRNA2 induce cell proliferation inhibition and apoptosis.

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

    Directory of Open Access Journals (Sweden)

    Seema Singh

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

  20. Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release

    Directory of Open Access Journals (Sweden)

    Zhang YueMei

    2005-02-01

    Full Text Available Abstract Background Apoptosis plays a key role in cell death observed in neurodegenerative diseases marked by a progressive loss of neurons as seen in Alzheimer's disease. Although the exact cause of apoptosis is not known, a number of factors such as free radicals, insufficient levels of nerve growth factors and excessive levels of glutamate have been implicated. We and others, have previously reported that in a stable HT22 neuronal cell line, glutamate induces apoptosis as indicated by DNA fragmentation and up- and down-regulation of Bax (pro-apoptotic, and Bcl-2 (anti-apoptotic genes respectively. Furthermore, these changes were reversed/inhibited by estrogens. Several lines of evidence also indicate that a family of cysteine proteases (caspases appear to play a critical role in neuronal apoptosis. The purpose of the present study is to determine in primary cultures of cortical cells, if glutamate-induced neuronal apoptosis and its inhibition by estrogens involve changes in caspase-3 protease and whether this process is mediated by Fas receptor and/or mitochondrial signal transduction pathways involving release of cytochrome c. Results In primary cultures of rat cortical cells, glutamate induced apoptosis that was associated with enhanced DNA fragmentation, morphological changes, and up-regulation of pro-caspase-3. Exposure of cortical cells to glutamate resulted in a time-dependent cell death and an increase in caspase-3 protein levels. Although the increase in caspase-3 levels was evident after 3 h, cell death was only significantly increased after 6 h. Treatment of cells for 6 h with 1 to 20 mM glutamate resulted in a 35 to 45% cell death that was associated with a 45 to 65% increase in the expression of caspase-3 protein. Pretreatment with caspase-3-protease inhibitor z-DEVD or pan-caspase inhibitor z-VAD significantly decreased glutamate-induced cell death of cortical cells. Exposure of cells to glutamate for 6 h in the presence or

  1. ABA and GA3 regulate the synthesis of primary and secondary metabolites related to alleviation from biotic and abiotic stresses in grapevine.

    Science.gov (United States)

    Murcia, Germán; Fontana, Ariel; Pontin, Mariela; Baraldi, Rita; Bertazza, Gianpaolo; Piccoli, Patricia N

    2017-03-01

    Plants are able to synthesize a large number of organic compounds. Among them, primary metabolites are known to participate in plant growth and development, whereas secondary metabolites are mostly involved in defense and other facultative processes. In grapevine, one of the major fruit crops in the world, secondary metabolites, mainly polyphenols, are of great interest for the wine industry. Even though there is an extensive literature on the content and profile of those compounds in berries, scarce or no information is available regarding polyphenols in other organs. In addition, little is known about the effect of plant growth regulators (PGRs), ABA and GA 3 (extensively used in table grapes) on the synthesis of primary and secondary metabolites in wine grapes. In table grapes, cultural practices include the use of GA 3 sprays shortly before veraison, to increase berry and bunch size, and sugar content in fruits. Meanwhile, ABA applications to the berries on pre-veraison improve the skin coloring and sugar accumulation, anticipating the onset of veraison. Accordingly, the aim of this study was to assess and characterize primary and secondary metabolites in leaves, berries and roots of grapevine plants cv. Malbec at veraison, and changes in compositions after ABA and GA 3 aerial sprayings. Metabolic profiling was conducted using GC-MS, GC-FID and HPLC-MWD. A large set of metabolites was identified: sugars, alditols, organic acids, amino acids, polyphenols (flavonoids and non-flavonoids) and terpenes (mono-, sesqui-, di- and triterpenes). The obtained results showed that ABA applications elicited synthesis of mono- and sesquiterpenes in all assessed tissues, as well as L-proline, acidic amino acids and anthocyanins in leaves. Additionally, applications with GA 3 elicited synthesis of L-proline in berries, and mono- and sesquiterpenes in all the tissues. However, treatment with GA 3 seemed to block polyphenol synthesis, mainly in berries. In conclusion, ABA and GA

  2. Polycystin-1 Cleavage and the Regulation of Transcriptional Pathways

    Science.gov (United States)

    Merrick, David; Bertuccio, Claudia A.; Chapin, Hannah C.; Lal, Mark; Chauvet, Veronique; Caplan, Michael J.

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease, affecting ~1 in 1,000 people. The disease is characterized by the development of numerous large fluid filled renal cysts over the course of decades. These cysts compress the surrounding renal parenchyma and impair its function. Mutations in two genes are responsible for ADPKD. The protein products of both of these genes, polycystin-1 and polycystin-2, localize to the primary cilium and participate in a wide variety of signaling pathways. Polycystin-1 undergoes several proteolytic cleavages that produce fragments that manifest biological activities. Recent results suggest that the production of polycystin-1 cleavage fragments is necessary and sufficient to account for at least some, although certainly not all, of the physiological functions of the parent protein. PMID:23824180

  3. Proteolytic processing of the cilium adhesin MHJ_0194 (P123J ) in Mycoplasma hyopneumoniae generates a functionally diverse array of cleavage fragments that bind multiple host molecules.

    Science.gov (United States)

    Raymond, Benjamin B A; Jenkins, Cheryl; Seymour, Lisa M; Tacchi, Jessica L; Widjaja, Michael; Jarocki, Veronica M; Deutscher, Ania T; Turnbull, Lynne; Whitchurch, Cynthia B; Padula, Matthew P; Djordjevic, Steven P

    2015-03-01

    Mycoplasma hyopneumoniae, the aetiological agent of porcine enzootic pneumonia, regulates the presentation of proteins on its cell surface via endoproteolysis, including those of the cilial adhesin P123 (MHJ_0194). These proteolytic cleavage events create functional adhesins that bind to proteoglycans and glycoproteins on the surface of ciliated and non-ciliated epithelial cells and to the circulatory host molecule plasminogen. Two dominant cleavage events of the P123 preprotein have been previously characterized; however, immunoblotting studies suggest that more complex processing events occur. These extensive processing events are characterized here. The functional significance of the P97 cleavage fragments is also poorly understood. Affinity chromatography using heparin, fibronectin and plasminogen as bait and peptide arrays were used to expand our knowledge of the adhesive capabilities of P123 cleavage fragments and characterize a novel binding motif in the C-terminus of P123. Further, we use immunohistochemistry to examine in vivo, the biological significance of interactions between M. hyopneumoniae and fibronectin and show that M. hyopneumoniae induces fibronectin deposition at the site of infection on the ciliated epithelium. Our data supports the hypothesis that M. hyopneumoniae possesses the molecular machinery to influence key molecular communication pathways in host cells. © 2014 John Wiley & Sons Ltd.

  4. Reduction of the immunostainable length of the hippocampal dentate granule cells’ primary cilia in 3xAD-transgenic mice producing human Aβ1-42 and tau

    International Nuclear Information System (INIS)

    Chakravarthy, Balu; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Atkinson, Trevor; LaFerla, Frank M.; Ito, Shingo; Armato, Ubaldo; Dal Prà, Ilaria; Whitfield, James

    2012-01-01

    Highlights: ► Aβ and tau-induced neurofibrillary tangles play a key role in Alzheimer’s disease. ► Aβ 1-42 and mutant tau protein together reduce the primary cilium length. ► This shortening likely reduces cilium-dependent neurogenesis and memory function. ► This provides a model of an Aβ/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75 NTR ). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6–24-months-old triple transgenic Alzheimer’s disease model mice (3xTg-AD) producing both Aβ 1-42 and the mutant human tau protein tau P301L, the dentate granule cells still had immunostainable SSTR3- and p75 NTR -bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of Aβ 1-42 or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of Aβ 1-42 and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  5. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  6. Primary microcephaly gene MCPH1 shows signatures of tumor suppressors and is regulated by miR-27a in oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thejaswini Venkatesh

    Full Text Available Mutations in the MCPH1 (microcephalin 1 gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC samples, and observed that 14/71 (19.72% informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22% and 19/25 (76% OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10% tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3'-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.

  7. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells.

    Science.gov (United States)

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S

    2016-04-15

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells*

    Science.gov (United States)

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.

    2016-01-01

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca2+] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca2+-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca2+ entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca2+-dependent up-regulation of AQP5. These important findings reveal that the Ca2+-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. PMID:26903518

  9. HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements.

    Science.gov (United States)

    Young, George R; Terry, Sandra N; Manganaro, Lara; Cuesta-Dominguez, Alvaro; Deikus, Gintaras; Bernal-Rubio, Dabeiba; Campisi, Laura; Fernandez-Sesma, Ana; Sebra, Robert; Simon, Viviana; Mulder, Lubbertus C F

    2018-01-01

    Endogenous retroviruses (ERVs) occupy extensive regions of the human genome. Although many of these retroviral elements have lost their ability to replicate, those whose insertion took place more recently, such as the HML-2 group of HERV-K elements, still retain intact open reading frames and the capacity to produce certain viral RNA and/or proteins. Transcription of these ERVs is, however, tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has been reported that some pathological states, such as viral infections and certain cancers, coincide with ERV expression, suggesting that transcriptional reawakening is possible. HML-2 elements are reportedly induced during HIV-1 infection, but the conserved nature of these elements has, until recently, rendered their expression profiling problematic. Here, we provide comprehensive HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary human CD4 + T cells. We combined enrichment of HIV-1 infected cells using a reporter virus expressing a surface reporter for gentle and efficient purification with long-read single-molecule real-time sequencing. We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average between 3- and 5-fold in HIV-1-infected CD4 + T cells. One provirus, HML-2 12q24.33, in contrast, was repressed in the presence of active HIV replication. In conclusion, this report identifies the HERV-K HML-2 loci whose expression profiles differ upon HIV-1 infection in primary human CD4 + T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication. IMPORTANCE Endogenous retroviruses inhabit big portions of our genome. Moreover, although they are mainly inert, some of the evolutionarily younger members maintain the ability to express both RNA and proteins. We have developed an approach using long-read single-molecule real-time (SMRT) sequencing that produces long reads that

  10. Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

    DEFF Research Database (Denmark)

    Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We...... are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

  11. Frequency primary regulation (FPR). Implications of the down stream flow variations. Operation methodology; Regulacion primaria de frecuencia (RPF). Implicancia por las variaciones del caudal aguas abajo. Metodologia de operacion

    Energy Technology Data Exchange (ETDEWEB)

    Morandi, Hector Enrique; Martelli, Jose Francisco [Ente Ejecutivo Presa Embalse Casa de Piedra, Buenos Aires (Argentina)]. E-mail: cdpba@impsat1.com.br

    1998-07-01

    This paper describes the Frequency Primary Regulation - FPR, determining that the operator running of a hydroelectric power plant must observe a set of norms, actions, etc, aiming to reduce as much as possible the environmental impact following the important modifications introduced. The regulation of the water flux downstream is one of the priority imposed to the project of a hydroelectric power plant. The regulation also allows other benefits as follows: the use of potentially or effectively flooded increasing the productive area; the efficient operation of water influx for various uses; the elimination of crop losses due to lack of irrigation water during certain seasons.

  12. Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B.

    Science.gov (United States)

    Sugimoto, Naotoshi; Miwa, Shinji; Hitomi, Yoshiaki; Nakamura, Hiroyuki; Tsuchiya, Hiroyuki; Yachie, Akihiro

    2014-01-01

    Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. We previously showed that methylxanthines, including caffeine and theophylline, have antitumor and antiinflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE). A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor. The purpose of this study was to determine whether theobromine could exert growth inhibitory effects on U87-MG, a cell line derived from human malignant glioma. We show that theobromine treatment elevates intracellular cAMP levels and increases the activity of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, whereas it attenuates p44/42 extracellular signal-regulated kinase activity and the Akt/mammalian target of rapamycin kinase and nuclear factor-kappa B signal pathways. It also inhibits cell proliferation. These results suggest that foods and beverages containing cocoa bean extracts, including theobromine, might be extremely effective in preventing human glioblastoma.

  13. Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer

    International Nuclear Information System (INIS)

    Senchenko, Vera N; Zabarovsky, Eugene R; Anedchenko, Ekaterina A; Kondratieva, Tatiana T; Krasnov, George S; Dmitriev, Alexei A; Zabarovska, Veronika I; Pavlova, Tatiana V; Kashuba, Vladimir I; Lerman, Michael I

    2010-01-01

    The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region),NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10 -6 ). We estimated the quantity of RBSP3, NPRL2, RASSF1A, GAPDH, RPN1 mRNA and RBSP3 DNA copy number in 59 primary non-small cell lung cancers, including 41 squamous cell and 18 adenocarcinomas by real-time reverse transcription-polymerase chain reaction based on TaqMan technology and relative quantification. We evaluated the relationship between mRNA level and clinicopathologic characteristics in non-small cell lung cancer. A significant expression decrease (≥2) was found for all three genes early in tumor development: in 85% of cases for RBSP3; 73% for NPRL2 and 67% for RASSF1A (P < 0.001), more strongly pronounced in squamous cell than in adenocarcinomas. Strong suppression of both, NPRL2 and RBSP3 was seen in 100% of cases already at Stage I of squamous cell carcinomas. Deregulation of RASSF1A correlated with tumor progression of squamous cell (P = 0.196) and adenocarcinomas (P < 0.05). Most likely, genetic and epigenetic mechanisms might be responsible for transcriptional inactivation of RBSP3 in non-small cell lung cancers as promoter methylation of RBSP3 according to NotI microarrays data was detected in 80% of squamous cell and in 38% of adenocarcinomas. With NotI microarrays we tested how often LUCA (NPRL2, RASSF1A) and AP20 (RBSP3) regions were deleted or methylated in the same tumor sample and found that this occured in 39% of all studied samples (P < 0.05). Our data support the hypothesis that these TSG are involved in tumorigenesis of NSCLC. Both genetic and epigenetic mechanisms contribute to down-regulation of these three genes representing two tumor suppressor clusters in 3p21

  14. Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

    Directory of Open Access Journals (Sweden)

    Fernandez Pedro L

    2005-08-01

    Full Text Available Abstract Background We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1 highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3. Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer.

  15. Deciphering the Temporal and Spatial Complexity in Submarine Canyons in Antarctica: the Role of Mixed Layer Depth in Regulating Primary Production

    Science.gov (United States)

    Carvalho, F.; Kohut, J. T.; Schofield, O.; Oliver, M. J.; Gorbunov, M. Y.

    2016-02-01

    There is a high spatial and temporal variability in the biophysical processes regulating primary productivity in submarine canyons in the West Antarctic Peninsula (WAP). WAP canyon heads are considered biological "hotspots" by providing predictable food resource and driving penguin foraging locations. Because the physiology and composition of the phytoplankton blooms and the physical mechanisms driving them aren't well understood, we aim to characterize the dynamics of the spring phytoplankton bloom at the head of a canyon in the WAP. A 6-year record of Slocum glider deployments is analyzed, corresponding to over 16,000 water column profiles. The mixed layer depth (MLD), determined by the maximum of the buoyancy frequency criteria, was found to be the MLD definition with the highest ecological relevance. The same holds true for other regions in Antarctica such as the Ross and Amundsen Seas. A FIRe sensor on a glider was used to evaluate physiological responses of phytoplankton to canyon dynamics using fluorescence kinetics. Initial results show a spatial influence, with increased photosynthetic efficiencies found at the canyon head. The strongest signal was the seasonal cycle. The shoaling of the MLD in early January results in increased chlorophyll a concentrations and as MLD deepens in mid season due to wind forcing, phytoplankton concentrations decrease, likely due to decreased light availability. A consistent secondary peak in chlorophyll matches a shoaling in MLD later in the growth season. A steady warming and increase in salinity of the MLD is seen throughout the season. Spatial differences were recorded at the head of the canyon and result from the local circulation. Shallower MLD found on the northern region are consistent with a fresher surface ocean (coastal influence) and increased chlorophyll concentrations. The southern region is thought to be more oceanic influenced as intrusions of warm deep water (mUCDW) to the upper water column were recorded

  16. Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing.

    Science.gov (United States)

    Wang, Binbin; Li, Lin; Zhu, Ying; Zhang, Wei; Wang, Xi; Chen, Beili; Li, Tengyan; Pan, Hong; Wang, Jing; Kee, Kehkooi; Cao, Yunxia

    2017-10-01

    Does a novel heterozygous KHDRBS1 variant, identified using whole-exome sequencing (WES) in two patients with primary ovarian insufficiency (POI) in a pedigree, cause defects in mRNA alternative splicing? The heterozygous variant of KHDRBS1 was confirmed to cause defects in alternative splicing of many genes involved in DNA replication and repair. Studies in mice revealed that Khdrbs1 deficient females are subfertile, which manifests as delayed sexual maturity and significantly reduced numbers of secondary and pre-antral follicles. No mutation of KHDRBS1, however, has been reported in patients with POI. This genetic and functional study used WES to find putative mutations in a POI pedigree. Altogether, 215 idiopathic POI patients and 400 healthy controls were screened for KHDRBS1 mutations. Two POI patients were subjected to WES to identify sequence variants. Mutational analysis of the KHDRBS1 gene in 215 idiopathic POI patients and 400 healthy controls were performed. RNA-sequencing was carried out to find the mis-regulation of gene expression due to KHDRBS1 mutation. Bioinformatics was used to analyze the change in alternative splicing events. We identified a heterozygous mutation (c.460A > G, p.M154V) in KHDRBS1 in two patients. Further mutational analysis of 215 idiopathic POI patients with the KHDRBS1 gene found one heterozygous mutation (c.263C > T, p.P88L). We failed to find these two mutations in 400 healthy control women. Using RNA-sequencing, we found that the KGN cells expressing the M154V KHDRBS1 mutant had different expression of 66 genes compared with wild-type (WT) cells. Furthermore, 145 genes were alternatively spliced in M154V cells, and these genes were enriched for DNA replication and repair function, revealing a potential underlying mechanism of the pathology that leads to POI. Although the in vitro assays demonstrated the effect of the KHDRBS1 variant on alternative splicing, further studies are needed to validate the in vivo effects on germ

  17. DMPD: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and con...cott J. Biochem Pharmacol. 2006 Nov 30;72(11):1469-76. Epub 2006 Jul 17. (.png) (.svg) (.html) (.csml) Show Distinct function...anti-tumor activity in primary macrophages. PubmedID 16846591 Title Distinct functions of IRF-3 and IRF-7 in

  18. Post-transcriptional regulation of osteoblastic platelet-derived growth factor receptor-alpha expression by co-cultured primary endothelial cells

    DEFF Research Database (Denmark)

    Finkenzeller, Günter; Mehlhorn, Alexander T; Schmal, Hagen

    2010-01-01

    -alpha downregulation is dependent on time and cell number. This effect was specific to endothelial cells and was not observed when hOBs were co-cultured with human primary chondrocytes or fibroblasts. Likewise, HUVEC-mediated suppression of PDGFR-alpha expression was only seen in hOBs and mesenchymal stem cells......Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in osteoblast function. Inhibition of PDGFR activity leads to a suppression of osteoblast proliferation, whereas mineralized matrix production is enhanced. In previous experiments, we showed that co......-cultivation of human primary endothelial cells and human primary osteoblasts (hOBs) leads to a cell contact-dependent downregulation of PDGFR-alpha expression in the osteoblasts. In this study, we investigated this effect in more detail, revealing that human umbilical vein endothelial cell (HUVEC)-mediated PDGFR...

  19. Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

    DEFF Research Database (Denmark)

    Milani, Lili; Lundmark, Anders; Nordlund, Jessica

    2008-01-01

    To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood...

  20. Regulation of primary cytotoxic T lymphocyte responses generated during mixed leukocyte culture with H-2d identical Qa-1-disparate cells

    International Nuclear Information System (INIS)

    Huston, D.P.; Tavana, G.; Rich, R.R.; Gressens, S.E.

    1986-01-01

    Cytotoxic lymphocyte (CTL) responses are not usually generated during primary mixed leukocyte culture (MLC) with H-2 identical cells. Thus NZB mice are unusual in that their spleen cells do mount CTL responses during primary MLC with H-2d identical stimulator cells; the predominant target antigen for these NZB responses is Qa-1b. Considering the numerous immunoregulatory defects in NZB mice, we postulated that these NZB anti-Qa-1 primary CTL responses were due to an abnormality in T suppressor cell activity. Cellular interactions capable of suppressing NZB anti-Qa-1 primary CTL responses were investigated by using one-way and two-way MLC with spleen cells from NZB mice and other H-2d strains. Although H-2d identical one-way MLC with the use of NZB responders resulted in substantial CTL responses, only minimal CTL responses were detected from two-way MLC with the use of NZB spleen cells plus nonirradiated spleen cells from other H-2d mice. Thus the presence of non-NZB spleen cells in the two-way H-2d identical MLC prevented the generation of NZB CTL. Noncytotoxic mechanisms were implicated in the suppression of the NZB CTL responses during two-way MLC, because only minimal CTL activity was generated when NZB spleen cells were cultured with semiallogeneic, H-2d identical (e.g., NZB X BALB) F1 spleen cells. The observed suppression could be abrogated with as little as 100 rad gamma-irradiation to the non-NZB spleen cells. The phenotype of these highly radiosensitive spleen cells was Thy-1+, Lyt-1+, Lyt-2-, L3T4+. The functional presence of these cells in the spleens of semiallogeneic, H-2d identical F1 mice indicated that their deficiency in NZB mice was a recessive trait. These data suggest that NZB mice lack an L3T4+ cell present in the spleens of normal mice that is capable of suppressing primary anti-Qa-1 CTL responses

  1. Arabidopsis Histone Demethylases LDL1 and LDL2 Control Primary Seed Dormancy by Regulating DELAY OF GERMINATION 1 and ABA Signaling-Related Genes

    Directory of Open Access Journals (Sweden)

    Ming lei Zhao

    2015-03-01

    Full Text Available Seed dormancy controls germination and plays a critical role in regulating the beginning of the life cycle of plants. Seed dormancy is established and maintained during seed maturation and is gradually broken during dry storage (after-ripening. The plant hormone abscisic acid (ABA and DELAY OF GERMINATION1 (DOG1 protein are essential regulators of seed dormancy. Recent studies revealed that chromatin modifications are also involved in the transcription regulation of seed dormancy. Here, we showed that two Arabidopsis histone demethylases, LYSINESPECIFIC DEMETHYLASE LIKE 1 and 2 (LDL1 and LDL2 act redundantly in repressing of seed dormancy. LDL1 and LDL2 are highly expressed in the early silique developing stage. The ldl1 ldl2 double mutant displays increased seed dormancy, whereas overexpression of LDL1 or LDL2 in Arabidopsis causes reduced dormancy. Furthermore, we showed that LDL1 and LDL2 repress the expression of seed dormancy-related genes, including DOG1, ABA2 and ABI3 during seed dormancy establishment. Furthermore, genetic analysis revealed that the repression of seed dormancy by LDL1 and LDL2 requires DOG1, ABA2 and ABI3. Taken together, our findings revealed that LDL1 and LDL2 play an essential role in seed dormancy.

  2. Amenorrhea - primary

    Science.gov (United States)

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  3. RNAi screening in primary human hepatocytes of genes implicated in genome-wide association studies for roles in type 2 diabetes identifies roles for CAMK1D and CDKAL1, among others, in hepatic glucose regulation.

    Directory of Open Access Journals (Sweden)

    Steven Haney

    Full Text Available Genome-wide association (GWA studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D. In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.

  4. Drinking Water Contaminants -- Standards and Regulations

    Science.gov (United States)

    ... and Research Centers Contact Us Share Drinking Water Contaminants – Standards and Regulations EPA identifies contaminants to regulate ... other partners to implement these SDWA provisions. Regulated Contaminants National Primary Drinking Water Regulations (NPDWRs) - table of ...

  5. Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Naamane, Najib; Flamez, Daisy

    2010-01-01

    by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h......-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression...... of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine...

  6. Self-regulation of primary motor cortex activity with motor imagery induces functional connectivity modulation: A real-time fMRI neurofeedback study.

    Science.gov (United States)

    Makary, Meena M; Seulgi, Eun; Kyungmo Park

    2017-07-01

    Recent developments in data acquisition of functional magnetic resonance imaging (fMRI) have led to rapid preprocessing and analysis of brain activity in a quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB). This information is fed back to subjects allowing them to gain a voluntary control over their own region-specific brain activity. Forty-one healthy participants were randomized into an experimental (NFB) group, who received a feedback directly proportional to their brain activity from the primary motor cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI was functionally localized during motor execution and imagery tasks. A resting-state functional run was performed before and after the neurofeedback training to investigate the default mode network (DMN) modulation after training. The NFB group revealed increased DMN functional connectivity after training to the cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus, respectively), which may be associated with sensorimotor processing of learning in the resting state. These results show that motor imagery training through rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas, suggesting that this modulation potentially subserved the establishment of motor learning in the NFB group.

  7. Expression of the potential therapeutic target CXXC5 in primary acute myeloid leukemia cells - high expression is associated with adverse prognosis as well as altered intracellular signaling and transcriptional regulation.

    Science.gov (United States)

    Bruserud, Øystein; Reikvam, Håkon; Fredly, Hanne; Skavland, Jørn; Hagen, Karen-Marie; van Hoang, Tuyen Thy; Brenner, Annette K; Kadi, Amir; Astori, Audrey; Gjertsen, Bjørn Tore; Pendino, Frederic

    2015-02-20

    The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and high expression in human acute myeloid leukemia (AML) cells is associated with adverse prognosis. We now characterized the biological context of CXXC5 expression in primary human AML cells. The global gene expression profile of AML cells derived from 48 consecutive patients was analyzed; cells with high and low CXXC5 expression then showed major differences with regard to extracellular communication and intracellular signaling. We observed significant differences in the phosphorylation status of several intracellular signaling mediators (CREB, PDK1, SRC, STAT1, p38, STAT3, rpS6) that are important for PI3K-Akt-mTOR signaling and/or transcriptional regulation. High CXXC5 expression was also associated with high mRNA expression of several stem cell-associated transcriptional regulators, the strongest associations being with WT1, GATA2, RUNX1, LYL1, DNMT3, SPI1, and MYB. Finally, CXXC5 knockdown in human AML cell lines caused significantly increased expression of the potential tumor suppressor gene TSC22 and genes encoding the growth factor receptor KIT, the cytokine Angiopoietin 1 and the selenium-containing glycoprotein Selenoprotein P. Thus, high CXXC5 expression seems to affect several steps in human leukemogenesis, including intracellular events as well as extracellular communication.

  8. Primary explosives

    Energy Technology Data Exchange (ETDEWEB)

    Matyas, Robert; Pachman, Jiri [Pardubice Univ. (Czech Republic). Faculty of Chemical Technology

    2013-06-01

    The first chapter provides background such as the basics of initiation and differences between requirements on primary explosives used in detonators and igniters. The authors then clarify the influence of physical characteristics on explosive properties, focusing on those properties required for primary explosives. Furthermore, the issue of sensitivity is discussed. All the chapters on particular groups of primary explosives are structured in the same way, including introduction, physical and chemical properties, explosive properties, preparation and documented use.

  9. Primary fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, S; Jensen, L T; Foldager, M

    1990-01-01

    Serum concentrations of procollagen type III aminoterminal peptide have previously been reported to be low in some patients with primary fibromyalgia and the aim of this study was to determine if such patients differ clinically from primary fibromyalgia patients with normal levels of procollagen...... type III aminoterminal peptide. Subjective symptoms, tender points and dynamic muscle strength in 45 women with primary fibromyalgia were related to serum concentrations of procollagen type III aminoterminal peptide. Patients with low serum concentrations of procollagen type III aminoterminal peptide...... concentrations of procollagen type III aminoterminal peptide of primary fibromyalgia patients are connected to the disease impact....

  10. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C on the regulation of Toll-like receptors, adaptor proteins and inflammatory response

    Directory of Open Access Journals (Sweden)

    Weith Andreas

    2005-11-01

    Full Text Available Abstract Background Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR. Methods The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Results Our data demonstrate that poly(I:C, a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C decreased the expression of TLR5, TLR6 and TOLLIP. Conclusion Poly(I:C, an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type

  11. Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human A{beta}{sub 1-42} and tau

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarthy, Balu, E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Gaudet, Chantal; Menard, Michel; Brown, Leslie; Atkinson, Trevor [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); LaFerla, Frank M. [Department of Neurobiology and Behavior, University of California, Irvine, CA (United States); Ito, Shingo [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Armato, Ubaldo; Dal Pra, Ilaria [Department of Life and Reproduction Sciences, University of Verona Medical School, Verona (Italy); Whitfield, James [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  12. Primary productivity

    Digital Repository Service at National Institute of Oceanography (India)

    Verlecar, X.N.; Parulekar, A.H.

    Photosynthetic production in the oceans in relation to light, nutrients and mixing processes is discussed. Primary productivity in the estuarine region is reported to be high in comparison to coastal and oceanic waters. Upwelling phenomenon...

  13. Primary Hyperparathyroidism

    Science.gov (United States)

    ... Neoplasia Type 1 Thyroid Disease & Pregnancy Primary Hyperparathyroidism Prolactinoma National Hormone and Pituitary Program (NHPP): Information for ... qualified health care provider nearby. Eating, Diet, and Nutrition Eating, diet, and nutrition have not been shown ...

  14. Primary Myelofibrosis

    Science.gov (United States)

    ... attack is higher. Patients also have an increased risk of acute myeloid leukemia or primary myelofibrosis . Symptoms of polycythemia vera include headaches and a feeling of fullness below the ribs on the left ...

  15. Normocalcemic primary hyperparathyroidism

    Science.gov (United States)

    Bilezikian, John P.; Silverberg, Shonni J.

    2011-01-01

    SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

  16. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Science.gov (United States)

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. [Hypertension: once primary, always primary?

    NARCIS (Netherlands)

    Braam, R.L.; Pieters, G.F.F.M.; Thien, Th.

    2002-01-01

    Three patients diagnosed with primary hypertension suddenly developed hard-to-treat blood pressure after several years of stable blood pressure. One patient, a man aged 48 years, had developed a renal artery stenosis, which had not been present five years earlier. The other two patients, a man aged

  18. Hyperthyroidism (primary)

    OpenAIRE

    Nygaard, Birte

    2010-01-01

    Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone (TSH). Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.About 20 times more women than men have hyperthyroidism.

  19. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  20. [Primary care in Ireland].

    Science.gov (United States)

    Sánchez-Sagrado, T

    Spanish doctors are still leaving the country to look for quality work. Ireland is not a country with many Spanish professionals but it is interesting to know its particular Health care system. Ireland is one of the countries with a national health care system, although it has a mixture of private health care insurance schemes. People have a right to health care if they have been living in Ireland at least for a year. Access to the primary care health system depends on age and income: free of charge for Category 1 and co-payments for the rest. This division generates great inequalities among the population. Primary Care doctors are self-employed, and they work independently. However, since 2001 they have tended to work in multidisciplinary teams in order to strengthen the Primary Care practice. Salary is gained from a combination of public and private incomes which are not differentiated. The role of the General Practitioner consists in the treatment of acute and chronic diseases, minor surgery, child care, etc. There is no coordination between Primary and Secondary care. Access to specialised medicine is regulated by the price of consultation. Primary Care doctors are not gatekeepers. To be able to work here, doctors must have three years of training after medical school. After that, Continuing Medical Education is compulsory, and the college of general practitioners monitors it annually. The Irish health care system does not fit into the European model. Lack of a clear separation between public and private health care generates great inequalities. The non-existence of coordination between primary and specialised care leads to inefficiencies, which Ireland cannot allow itself after a decade of economic crisis. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  1. [Primary care in France].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2016-01-01

    The poor planning of health care professionals in Spain has led to an exodus of doctors leaving the country. France is one of the chosen countries for Spanish doctors to develop their professional career. The French health care system belongs to the Bismarck model. In this model, health care system is financed jointly by workers and employers through payroll deduction. The right to health care is linked to the job, and provision of services is done by sickness-funds controlled by the Government. Primary care in France is quite different from Spanish primary care. General practitioners are independent workers who have the right to set up a practice anywhere in France. This lack of regulation has generated a great problem of "medical desertification" with problems of health care access and inequalities in health. French doctors do not want to work in rural areas or outside cities because "they are not value for money". Medical salary is linked to professional activity. The role of doctors is to give punctual care. Team work team does not exist, and coordination between primary and secondary care is lacking. Access to diagnostic tests, hospitals and specialists is unlimited. Duplicity of services, adverse events and inefficiencies are the norm. Patients can freely choose their doctor, and they have a co-payment for visits and hospital care settings. Two years training is required to become a general practitioner. After that, continuing medical education is compulsory, but it is not regulated. Although the French medical Health System was named by the WHO in 2000 as the best health care system in the world, is it not that good. While primary care in Spain has room for improvement, there is a long way for France to be like Spain. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

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

  3. Patient evaluations of primary care.

    NARCIS (Netherlands)

    Schäfer, W.L.A.; Boerma, W.G.W.; Schellevis, F.G.; Groenewegen, P.P.

    2012-01-01

    Background: So far, studies about people’s appreciation of primary care services has shown that patient satisfaction seems to be lower in health care systems with regulated access to specialist services by gate keeping. Nevertheless, international comparative research about patients’ expectations

  4. Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

    Science.gov (United States)

    Ruiz-Perez, Victor L; Blair, Helen J; Rodriguez-Andres, M Elena; Blanco, Maria Jose; Wilson, Amy; Liu, Yu-Ning; Miles, Colin; Peters, Heiko; Goodship, Judith A

    2007-08-01

    EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.

  5. [Primary care in Italy].

    Science.gov (United States)

    Sánchez-Sagrado, T

    Italy is not a country where Spanish doctors emigrate, as there is an over-supply of health care professionals. The Italian Servizio Sanitario Nazionale has some differences compared to the Spanish National Health System. The Servizio Sanitario Nazionale is financed by national and regional taxes and co-payments. There are taxes earmarked for health, and Primary Care receives 50% of the total funds. Italian citizens and residents in Italy have the right to free health cover. However, there are co-payments for laboratory and imaging tests, pharmaceuticals, specialist ambulatory services, and emergencies. Co-payments vary in the different regions. The provision of services is regional, and thus fragmentation and major inequities are the norm. Doctors in Primary Care are self-employed and from 2000 onwards, there are incentives to work in multidisciplinary teams. Salary is regulated by a national contract and it is the sum of per-capita payments and extra resources for specific activities. Responsibilities are similar to those of Spanish professionals. However, medical care is more personal. Relationships between Primary Care and specialised care depend on the doctors' relationships. Primary Care doctors are gatekeepers for specialised care, except for gynaecology, obstetrics and paediatrics. Specialised training is compulsory in order to work as general practitioner. The Italian Health Care System is a national health system like the Spanish one. However, health care professionals are self-employed, and there are co-payments. In spite of co-payments, Italians have one of the highest average life expectancy, and they support a universal and publicly funded health-care system. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Self-regulation processes in the life-course: primary and secondary control / Processos de auto-regulação no curso de vida: controle primário e controle secundário

    Directory of Open Access Journals (Sweden)

    Hilma Tereza Tôrres Khoury

    2009-01-01

    Full Text Available This article discusses relevant concepts of life course perspective which are not very much diffused in Brazil: primary and secondary control. The former refers to efforts to change the environment so that it fits individual's needs. The latter involves efforts to fit in with the environment. The original definitions are presented as a two-process model of control in contrast to one-process models such as learned helplessness. Furthermore, it discusses a conceptual revision, which modified and expanded these constructs as a bi-dimensional model that relates primary and secondary control to the concepts of selection and compensation. In process of arguing about those, suggestions are presented for thinking and expanding the theoretical and conceptual discussion of these constructs.

  7. Partridgeberry polyphenols protect rat primary cortical neurons from oxygen-glucose deprivation-reperfusion-induced injury via suppression of inflammatory adipokines and regulation of HIF-1α and PPARγ.

    Science.gov (United States)

    Bhullar, Khushwant S; Rupasinghe, H P Vasantha

    2016-07-01

    The aim of this study was to investigate the neuroprotective ability of partridgeberry polyphenols in rat primary cortical neurons against oxygen-glucose deprivation/reperfusion (OGD/R) injury in vitro and explore the underlying therapeutic mechanism(s). The OGD/R injury was induced in rat primary cortical neurons by incubation with deoxygenated glucose-free medium in a hypoxia chamber. The strongest activity in this regard was exhibited by partridgeberry-derived PPF2 and PPF3, i.e. the flavan-3-ol- and flavonol-rich polyphenol fractions of partridgeberry (P ≤ 0.05). Moreover, partridgeberry polyphenol pre-treatment reduced the membrane damage in primary neurons, as measured by the lactose dehydrogenase (LDH) release assay (P ≤ 0.05). Furthermore, PPF2 and PPF3 pre-treatment (100 µg ml(-1)) for 24 hours, before OGD/R, resulted in the strongest suppression of interleukin (IL)-6 and tumor necrosis factor-α induction by OGD/R injury, compared with the control group (P ≤ 0.05). Additionally, the protein levels of hypoxia-inducible factor (HIF-1α) and PPARγ, quantified by ELISA presented a significant modulation following PPFs treatment (100 µg ml(-1)), favorably toward neuroprotection, compared with the respective controls after OGD/R injury in vitro (P ≤ 0.05). In summary, partridgeberry polyphenols at concentrations of 1-100 µg ml(-1), significantly induced a decline in OGD/R injury-triggered apoptosis in vitro, suppressed the inflammatory biomarkers in primary neurons, and modulated the activity of HIF-1α and proliferator-activated receptor gamma (PPARγ) following hypoxic injury.

  8. Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom.

    Science.gov (United States)

    Berger, Philipp; Sirkowski, Erich E; Scherer, Steven S; Suter, Ueli

    2004-11-01

    Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.

  9. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    Tomain, J.P.

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  10. Nuclear regulation in transition

    Energy Technology Data Exchange (ETDEWEB)

    Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.

  11. 75 FR 16645 - Increase in the Primary Nuclear Liability Insurance Premium

    Science.gov (United States)

    2010-04-02

    ... Primary Nuclear Liability Insurance Premium AGENCY: Nuclear Regulatory Commission. ACTION: Final rule... impractical. The NRC is amending its regulations to increase the primary premium for liability insurance... protection requirements and indemnity agreements to increase the primary nuclear liability insurance layer...

  12. Radiation regulation

    International Nuclear Information System (INIS)

    Braithwaite, J.; Grabosky, P.

    1985-01-01

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  13. Histone deacetylases 1 and 3 but not 2 mediate cytokine-induced beta cell apoptosis in INS-1 cells and dispersed primary islets from rats and are differentially regulated in the islets of type 1 diabetic children

    DEFF Research Database (Denmark)

    Lundh, M; Christensen, D P; Damgaard Nielsen, M

    2012-01-01

    onset, HDAC1 was upregulated in beta cells whereas HDAC2 and -3 were downregulated in comparison with five paediatric controls. CONCLUSIONS/INTERPRETATION: These data demonstrate non-redundant functions of islet class I HDACs and suggest that targeting HDAC1 and HDAC3 would provide optimal protection......AIMS/HYPOTHESIS: Histone deacetylases (HDACs) are promising pharmacological targets in cancer and autoimmune diseases. All 11 classical HDACs (HDAC1-11) are found in the pancreatic beta cell, and HDAC inhibitors (HDACi) protect beta cells from inflammatory insults. We investigated which HDACs...... of HDAC1, -2 and -3 rescued INS-1 cells from inflammatory damage. Small hairpin RNAs against HDAC1 and -3, but not HDAC2, reduced pro-inflammatory cytokine-induced beta cell apoptosis in INS-1 and primary rat islets. The protective properties of specific HDAC knock-down correlated with attenuated cytokine...

  14. Processos de auto-regulação no curso de vida: controle primário e controle secundário Self-regulation processes in the life-course: primary and secondary control

    Directory of Open Access Journals (Sweden)

    Hilma Tereza Tôrres Khoury

    2009-01-01

    Full Text Available Este artigo discute conceitos relevantes à perspectiva do curso de vida, porém pouco difundidos no Brasil: controle primário e controle secundário. O primeiro se refere aos esforços que o indivíduo empreende para adaptar o ambiente às suas necessidades; o segundo, para se adaptar ao ambiente. Apresenta-se a formulação original dos conceitos como modelo de dois processos de controle, em oposição a modelos de processo único, como o do desamparo aprendido. Em seguida, discute-se revisão conceitual que trouxe modificação e ampliação para estes construtos, concebendo-os em um modelo bidimensional que articula controle primário e secundário com os conceitos de seleção e compensação. Nesse processo, apresentam-se contribuições no intuito de estimular a reflexão e expandir a discussão teórico-conceitual que envolve estes construtos.This article discusses relevant concepts of life course perspective which are not very much diffused in Brazil: primary and secondary control. The former refers to efforts to change the environment so that it fits individual's needs. The latter involves efforts to fit in with the environment. The original definitions are presented as a two-process model of control in contrast to one-process models such as learned helplessness. Furthermore, it discusses a conceptual revision, which modified and expanded these constructs as a bi-dimensional model that relates primary and secondary control to the concepts of selection and compensation. In process of arguing about those, suggestions are presented for thinking and expanding the theoretical and conceptual discussion of these constructs.

  15. The assessment on impact of essential drugs policy on primary health care system in rural areas of Shandong Province policy and regulation division of the Health Department of Shandong Province.

    Science.gov (United States)

    Li, Zhuge; Shu, Defeng; Xia, Mei; Gao, Dehai; Lu, Dan; Huang, Ning; Tian, Xiaoqing; An, Limei; Li, Shixue; Li, Sheng

    2015-01-01

    At present, China has achieved an initial establishment and gradual implementation of a framework for national essential drugs policy. With the further implementation of the national essential drugs policy, it is not clear how the policy works, whether it achieves the original intention of essential drugs policy, and what impact essential drugs policy exerts on the primary health care system. In view of it, we conducted a field research on sample areas of Shandong Province to understand the conditions of the implementation of the essential drugs policy in Shandong Province. From three perspectives of medical institutions, patients and medical staff, this thesis analyzes the impact of essential drugs policy on village-level and township-level health service system, summarizes the effectiveness of implementing essential drugs policy, discovers the problems of various aspects and conducts an in-depth analysis of the causes, and puts forward feasible suggestions to provide reference for improving the essential drugs policy. The assessment results show that the implementation of essential drugs policy in Shandong Province has played a positive role in promoting the sound development of the primary health care system, changed the situation of covering hospital expenses with medicine revenue in the past, contributed to the return of medical institutions to public welfare, and reduced the patient's economic burden of disease. But there emerge many problems as follows: impact on the doctor's diagnosis and treatment due to incompleteness of drug types, and distribution not in place, patient loss and operational difficulty of village clinic. Thus, this thesis makes recommendations of drugs catalog formulation, drug procurement, sales and use, and meanwhile points out that the supporting financial compensation policy and performance appraisal policy and other measures in place are a prerequisite for a positive role of essential drugs policy.

  16. 77 FR 60948 - Stress Testing of Regulated Entities

    Science.gov (United States)

    2012-10-05

    ... regulated by a primary federal financial regulatory agency, to conduct annual stress tests to determine... the regulated entities under the Federal Housing Enterprises Financial Safety and Soundness Act of... regulated by a primary Federal financial regulatory agency shall conduct annual stress tests * * * (emphasis...

  17. [Primary care in Portugal].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2018-04-01

    The economic crisis and deterioration of the Portuguese National Health service has forced professionals to leave the country. The Portuguese National Health System was introduced in 1976, but it has been unable to provide citizens with the social and health advantages of an equality of access and free national health system. The Portuguese National Health System is financed by taxes. However, a 35% of its incomes are from private sources. The health minister decides the budget, and it is based on an historical financing plus a per capita system. Portuguese citizens and immigrants are entitled to free health care, but there is a co-payment for care, diagnostic, pharmacy, and emergency care. Health care provision is a mixture of public and private health care at a regional level. It leads to fragmentation of services and greater inequalities. Doctors are civil servants. Salary is regulated and it depends on seniority and on-call shifts. Primary care activities are similar to those of their Spanish counterparts. General practitioners have gatekeeper function, but the system is imperfect, and patients with private insurance get direct access to the specialist. Specialist training is similar to the training system in Spain. Continuing education is not regulated. The Portuguese Health System has been trying to become a national health system since 1979. Political instability, fragmentation of services, lack of clarity between public and private and co-payments are important constraints. Inequalities are an important problem to reconsider while discussing a national health system. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Regulative environmental policy. Regulative Umweltpolitik

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

    1991-01-01

    Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

  19. Functional characterization of the vertebrate primary ureter: Structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia

    Directory of Open Access Journals (Sweden)

    Prehn Lea R

    2010-05-01

    Full Text Available Abstract Background Three kidney systems appear during vertebrate development: the pronephroi, mesonephroi and metanephroi. The pronephric duct is the first or primary ureter of these kidney systems. Its role as a key player in the induction of nephrogenic mesenchyme is well established. Here we investigate whether the duct is involved in urine modification using larvae of the freshwater amphibian Ambystoma mexicanum (axolotl as model. Results We investigated structural as well as physiological properties of the pronephric duct. The key elements of our methodology were: using histology, light and transmission electron microscopy as well as confocal laser scanning microscopy on fixed tissue and applying the microperfusion technique on isolated pronephric ducts in combination with single cell microelectrode impalements. Our data show that the fully differentiated pronephric duct is composed of a single layered epithelium consisting of one cell type comparable to the principal cell of the renal collecting duct system. The cells are characterized by a prominent basolateral labyrinth and a relatively smooth apical surface with one central cilium. Cellular impalements demonstrate the presence of apical Na+ and K+ conductances, as well as a large K+ conductance in the basolateral cell membrane. Immunolabeling experiments indicate heavy expression of Na+/K+-ATPase in the basolateral labyrinth. Conclusions We propose that the pronephric duct is important for the subsequent modification of urine produced by the pronephros. Our results indicate that it reabsorbs sodium and secretes potassium via channels present in the apical cell membrane with the driving force for ion movement provided by the Na+/K+ pump. This is to our knowledge the first characterization of the pronephric duct, the precursor of the collecting duct system, which provides a model of cell structure and basic mechanisms for ion transport. Such information may be important in understanding

  20. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

    Science.gov (United States)

    Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

    2016-09-01

    Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

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

  2. Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

    Science.gov (United States)

    Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

    2015-12-01

    The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. © The Author 2015. Published by Oxford

  3. Fisheries regulation

    DEFF Research Database (Denmark)

    Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

    2017-01-01

    Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

  4. PPARγ regulates exocrine pancreas lipase.

    Science.gov (United States)

    Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

    2016-12-01

    Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Regulating nuclear fuel waste

    International Nuclear Information System (INIS)

    1995-01-01

    When Parliament passed the Atomic Energy Control Act in 1946, it erected the framework for nuclear safety in Canada. Under the Act, the government created the Atomic Energy Control Board and gave it the authority to make and enforce regulations governing every aspect of nuclear power production and use in this country. The Act gives the Control Board the flexibility to amend its regulations to adapt to changes in technology, health and safety standards, co-operative agreements with provincial agencies and policy regarding trade in nuclear materials. This flexibility has allowed the Control Board to successfully regulate the nuclear industry for more than 40 years. Its mission statement 'to ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment' concisely states the Control Board's primary objective. The Atomic Energy Control Board regulates all aspects of nuclear energy in Canada to ensure there is no undue risk to health, safety, security or the environment. It does this through a multi-stage licensing process

  6. Primary Progressive Aphasia

    Science.gov (United States)

    ... which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: Comprehending spoken or written ... word meanings Naming objects Logopenic variant primary progressive aphasia Symptoms include: Having difficulty retrieving words Frequently pausing ...

  7. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  8. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  9. French regulations

    International Nuclear Information System (INIS)

    Ballereau, P.

    1998-01-01

    In this issue are given the new French regulations relative to radiation protection of temporary personnel, the licensing to release gaseous and liquid wastes and the licensing granted to thirty two laboratories using beta and gamma decay radioisotopes. (N.C.)

  10. Investigating Primary Source Literacy

    Science.gov (United States)

    Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

    2009-01-01

    Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

  11. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Cheng Cui

    2013-11-01

    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  12. Primary prevention of adolescent pregnancy.

    Science.gov (United States)

    Schinke, S P; Blythe, B J; Gilchrist, L D; Burt, G A

    1981-01-01

    Teenage pregnancy is associated with many health, emotional and socioeconomic problems including higher rates of anemia, labor complications, mortality, legal and social struggles and hhigher divorce rates. Professional social workers need strategies to help teenagers avoid early, unwanted pregnancy. This paper offers promising experential and research backing for a primary prevention group work strategy for all adolescents. Social and health programs overlook educational, cognitive anc interpersonal factors biasing youths' ability to comprehend and regulate contraception. Primary prevention to assist adolescents in thinking analytically about their sexual behavior must stress problem solving and decision-making as well as facts about human reproduction and birth control. To implement decisions, youths also need interpersonal communication skills. Small groups are ideal for delivering cognitive-behavioral primary prevention. This approach is based on the premise that youths become pregnant not because of a lack of relevant information, but because they lack cognitive and behavioral skills necessary to use information. Group work involving role-playing helps develop communication skills. Results from 2 field studies describe short-term and longitudinal benefits of the prevention strategy. Professionals can reach significant numbers of youth in this way. By treating sexual issues and the risk of pregnancy as normal in adolescence, social workers can introduce information and pertinent skills to all teenagers. No one is singled out as deviant and the group format enables young people to discuss taboo topics, discovering what the norms are and gradually learning how to deal with peers, family members, techers and others. Adolescents in primary prevention groups gained knowledge, cognitive skills and communication acumen. Improved attitudes toward family planning, increased regular contraception and less unsafe sex resulted from this cognitive-behavioral approach

  13. Primary Hyperparathyroidism: An Overview

    Directory of Open Access Journals (Sweden)

    Jessica MacKenzie-Feder

    2011-01-01

    Full Text Available Primary hyperparathyroidism is a common condition that affects 0.3% of the general population. Primary and tertiary care specialists can encounter patients with primary hyperparathyroidism, and prompt recognition and treatment can greatly reduce morbidity and mortality from this disease. In this paper we will review the basic physiology of calcium homeostasis and then consider genetic associations as well as common etiologies and presentations of primary hyperparathyroidism. We will consider emerging trends in detection and measurement of parathyroid hormone as well as available imaging modalities for the parathyroid glands. Surgical indications and approach will be reviewed as well as medical management of primary hyperparathyroidism with bisphosphonates and calcimimetics.

  14. Normocalcemic Primary Hyperparathyroidism

    Science.gov (United States)

    Cusano, Natalie E.; Silverberg, Shonni J.; Bilezikian, John P.

    2013-01-01

    Primary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and elevated levels of parathyroid hormone (PTH). A newer presentation of primary hyperparathyroidism has been described over the past decade, in which PTH is elevated but serum calcium is consistently normal, in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency. Recognition of this phenotype of primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, supports a biphasic chronological time course in some individuals in which PTH levels are first elevated but serum calcium is normal, followed by the development of frank hypercalcemia. This review focuses on the available literature regarding this newly described phenotype of primary hyperparathyroidism. PMID:23374739

  15. Regulating Internalities

    OpenAIRE

    Sunstein, Cass Robert; Allcott, Hunt

    2015-01-01

    This paper offers a framework for regulating internalities. Using a simple economic model, we provide four principles for designing and evaluating behaviorally-motivated policy. We then outline rules for determining which contexts reliably reflect true preferences and discuss empirical strategies for measuring internalities. As a case study, we focus on energy efficiency policy, including Corporate Average Fuel Economy (CAFE) standards and appliance and lighting energy efficiency standards.

  16. Multiple primary cancer

    International Nuclear Information System (INIS)

    Jung, Gyu Sik; Lee, Ouk; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duck

    1989-01-01

    It is rare for one human being to be afflicted with more than one cancer. However with further advances in therapeutic regimens, histopathologic observation, diagnostic modalities, and increased curiosity, there are increasing number of case reports of multiple primary cancer. The present study evaluates 25 histologically confirmed cases of multiple primary cancer from 1974 to 1988 at Kosin Medical Center. The most frequent site of the first primary cancer in male was stomach and in female, uterine cervix. The first primary cancer in female occurred in endocrine-related organs (breast, uterus and thyroid) in 63.6 percent. Synchronous cancers are diagnosed simultaneously or within an interval of about six months and synchronous cancers were 16 out of 25 cases. Metachronous cancers are diagnosed at interval of more than six months. There were 9 metachronous cancers and average interval between the first and second primary cancer was 22.8 months. The incidence of multiple primary cancer was 0.11 percent. The average age was 51.9 years at the time of the first primary cancer (53.1 years in male and 50.3 years in female). CT scan was most helpful in early detection of multiple primary cancers facilitating biopsy and surgery. Multiple primary cancers are beyond the medical curiosity. Early diagnosis of the disease and careful follow-up study, based on an awareness of the possibility of second cancers, will substantially increase the survival of these patients

  17. Arf4 is required for Mammalian development but dispensable for ciliary assembly.

    Directory of Open Access Journals (Sweden)

    John A Follit

    2014-02-01

    Full Text Available The primary cilium is a sensory organelle, defects in which cause a wide range of human diseases including retinal degeneration, polycystic kidney disease and birth defects. The sensory functions of cilia require specific receptors to be targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed to sort cargo destined for the cilium at the Golgi complex and deemed a key regulator of ciliary protein trafficking. In this work, we show that Arf4 binds to the ciliary targeting sequence (CTS of fibrocystin. Knockdown of Arf4 indicates that it is not absolutely required for trafficking of the fibrocystin CTS to cilia as steady-state CTS levels are unaffected. However, we did observe a delay in delivery of newly synthesized CTS from the Golgi complex to the cilium when Arf4 was reduced. Arf4 mutant mice are embryonic lethal and die at mid-gestation shortly after node formation. Nodal cilia appeared normal and functioned properly to break left-right symmetry in Arf4 mutant embryos. At this stage of development Arf4 expression is highest in the visceral endoderm but we did not detect cilia on these cells. In the visceral endoderm, the lack of Arf4 caused defects in cell structure and apical protein localization. This work suggests that while Arf4 is not required for ciliary assembly, it is important for the efficient transport of fibrocystin to cilia, and also plays critical roles in non-ciliary processes.

  18. CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function

    Directory of Open Access Journals (Sweden)

    Peter Canning

    2018-01-01

    Full Text Available Various kinases, including a cyclin-dependent kinase (CDK family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs, including an unusual αJ helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1–4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and αJ helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy.

  19. Using Primary Source Documents.

    Science.gov (United States)

    Mintz, Steven

    2003-01-01

    Explores the use of primary sources when teaching about U.S. slavery. Includes primary sources from the Gilder Lehrman Documents Collection (New York Historical Society) to teach about the role of slaves in the Revolutionary War, such as a proclamation from Lord Dunmore offering freedom to slaves who joined his army. (CMK)

  20. Medics in Primary School

    Science.gov (United States)

    Press, Colin

    2003-01-01

    Some time ago a flyer on "Medics in Primary School" came the author's way. It described a programme for making placements in primary schools available to medical students. The benefits of the program to medical students and participating schools were highlighted, including opportunities to develop communication skills and demystify…

  1. Primary Sclerosing Cholangitis (PSC)

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Primary Sclerosing Cholangitis Back ...

  2. Primary cultures of astrocytes

    DEFF Research Database (Denmark)

    Lange, Sofie C; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    During the past few decades of astrocyte research it has become increasingly clear that astrocytes have taken a central position in all central nervous system activities. Much of our new understanding of astrocytes has been derived from studies conducted with primary cultures of astrocytes...... subsequently found in vivo. Nevertheless, primary cultures of astrocytes are an in vitro model that does not fully mimic the complex events occurring in vivo. Here we present an overview of the numerous contributions generated by the use of primary astrocyte cultures to uncover the diverse functions...... of astrocytes. Many of these discoveries would not have been possible to achieve without the use of astrocyte cultures. Additionally, we address and discuss the concerns that have been raised regarding the use of primary cultures of astrocytes as an experimental model system....

  3. Primary Meningeal Rhabdomyosarcoma

    Science.gov (United States)

    Palta, Manisha; Riedel, Richard F.; Vredenburgh, James J.; Cummings, Thomas J.; Green, Scott; Chang, Zheng; Kirkpatrick, John P.

    2011-01-01

    Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy. PMID:21772793

  4. Primary Meningeal Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Manisha Palta

    2011-01-01

    Full Text Available Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13. Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC systemic therapy.

  5. Primary meningeal rhabdomyosarcoma.

    Science.gov (United States)

    Palta, Manisha; Riedel, Richard F; Vredenburgh, James J; Cummings, Thomas J; Green, Scott; Chang, Zheng; Kirkpatrick, John P

    2011-01-01

    Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

  6. Primary Nurse - Role Evolution

    Science.gov (United States)

    Mundinger, Mary O'Neil

    1973-01-01

    Primary nursing means that each patient has an individual nurse who is responsible for assessing his nursing needs and planning and evaluating his nursing care. The article describes the advantages and problems connected with this approach to patient care. (AG)

  7. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  8. Primary infertility (image)

    Science.gov (United States)

    Primary infertility is a term used to describe a couple that has never been able to conceive a pregnancy ... to do so through unprotected intercourse. Causes of infertility include a wide range of physical as well ...

  9. Primary Intraorbital Ectopic Meningioma

    Science.gov (United States)

    Yokoyama, Tetsuo; Nishizawa, Shigeru; Sugiyama, Kenji; Yokota, Noki; Ohta, Seiji; Uemura, Kenichi; Hinokuma, Kaoru; Inenaga, Chikanori

    1999-01-01

    We report a case of intraorbital meningioma. Operative findings and histopathological examination revealed the tumoc to be meningothelial meningloma and to be located entirely outside the optic dura. This case demonstrates the occurrence of primary intraorbital ectopic meningioma, and the tumor was removed through a modified Dolenc approach. The primary intraorbital ectopic meningioma is discussed and the surgical approach to the orbital apex region is reviewed. ImagesFigure 1Figure 2Figure 4Figure 5 PMID:17171081

  10. Primary leiomyosarcoma of epididymis

    Directory of Open Access Journals (Sweden)

    Dillip Kumar Muduly

    2012-01-01

    Full Text Available Primary leiomyosarcomas rarely arise from epididymis. But they are the most common histopathological types of sarcoma arising from the epididymis. Primary epididymal leiomyosarcoma occurs usually in older patients. We report a young patient of 35 years presenting with leiomyosarcoma of left epididymis. He did not have any metastasis and underwent left high inguinal orchiectomy. He is on regular follow-up and disease free for last two years.

  11. Primary care ... where?

    Science.gov (United States)

    Adcock, G B

    1999-07-01

    Corporate-based nurse managed centers are not the national norm. More prevalent is the use of an occupational health or physician-directed medical model of care. The author describes how a 14-year-old primary care center at a North Carolina computer software company is just "business as usual" when viewed in the context of the company's philosophy, goals, and culture. Included are considerations for nurse practitioners interested in the successful transplantation of this primary care model to other settings.

  12. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  13. Other primary headaches

    Directory of Open Access Journals (Sweden)

    Anish Bahra

    2012-01-01

    Full Text Available The ′Other Primary Headaches′ include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed ′alarm clock headache′, exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review.

  14. Primary Ectopic Ethmoidal Craniopharyngioma.

    Science.gov (United States)

    Preti, Andrea; Karligkiotis, Apostolos; Facco, Carla; Ottini, Giorgia; Volpi, Luca; Castelnuovo, Paolo

    2017-06-01

    Craniopharyngiomas are benign but aggressive epithelial tumors usually originating in the anterior lobe of the pituitary gland from squamous remnants of an incompletely involuted craniopharingeal duct developing from the Rathke pouch. To the authors' knowledge only 1 patient of a primary isolated ethmoidal craniopharyngioma has been reported in the literature.The authors report the case of a 17-year-old boy with a primary extracranial ethmoidal craniopharyngioma. An endoscopic endonasal approach was employed to resect the tumor. After 2 years of clinical and radiological follow-up no recurrence of disease was observed.Primary ethmoidal craniopharyngiomas are rare entities and biopsy is necessary for diagnosis. However, a preoperative assessment by means of nasal endoscopy, computed tomography scan, and enhanced magnetic resonance imaging is mandatory to better evaluate the extension and characteristics of the tumor. The endoscopic endonasal technique is a safe and effective approach for the treatment of these lesions.

  15. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  16. Primary headaches in children

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Pan

    2015-01-01

    Full Text Available Headache is a widespread clinical problem; the prevalence is high in all age groups, from which children and teenagers are not spared. It has been reported that, as many as 75% of school-age children may experience headache infrequently, among them 10% have recurrent headaches. [1],[2] The vast majority of headaches are primary and classified as migraine, tension-type headache (TTH, cluster headache, and other trigeminal autonomic cephalgias. The type of primary headaches could usually be diagnosed by a thorough and careful history taking, and physical examination. Once the diagnosis of migraine is established and appropriate reassurance provided, a balanced and individually tailored treatment plan can be instituted. The goal of treatment includes abortive or acute pain treatment, preventive long-term treatment, and biobehavioral therapy. Knowledge of precise impact of primary headaches on child′s quality of life helps to design a proper comprehensive treatment plan.

  17. Thoughts on primary care.

    Science.gov (United States)

    Raskin, Lynne

    2010-01-01

    The uptake of family health teams in Ontario has been tremendous. And the creation of group practices in primary care has taken root in other provinces as well. For many people, being involved with something new is exciting. At the same time, once they are committed, they discover the challenges that can be simultaneously exhilarating and frustrating. This issue of Healthcare Quarterly offers two articles that provide interesting reflections on what has been learned so far from the perspectives of both team leadership and the team members themselves within a transforming primary care system.

  18. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  19. Surgery of Primary Melanomas

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2010-05-01

    Full Text Available Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  20. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  1. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Zdzienicki, Marcin; Nowecki, Zbigniew I.; Akkooi, Alexander C. J. van

    2010-01-01

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  2. Primary intestinal lymphangiectasia.

    Science.gov (United States)

    Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi

    2009-10-01

    Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.

  3. Healthcare is primary

    Directory of Open Access Journals (Sweden)

    Raman Kumar

    2015-01-01

    Full Text Available India is undergoing a rapid transformation in terms of governance, administrative reforms, newer policy develoment, and social movements. India is also considered one of the most vibrant economies in the world. The current discourse in public space is dominated by issues such as economic development, security, corruption free governance, gender equity, and women safety. Healthcare though remains a pressing need of population; seems to have taken a backseat. In the era of decreasing subsidies and cautious investment in social sectors, the 2 nd National Conference on Family Medicine and Primary Care 2015 (FMPC brought a focus on "healthcare" in India. The theme of this conference was "Healthcare is Primary." The conference participants discussed on the theme of why healthcare should be a national priority and why strong primary care should remain at the center of healthcare delivery system. The experts recommended that India needs to strengthen the "general health system" instead of focusing on disease based vertical programs. Public health system should have capacity and skill pool to be able to deliver person centered comprehensive health services to the community. Proactive implementation of policies towards human resource in health is the need of the hour. As the draft National Health Policy 2015 is being debated, "family medicine" (academic primary care, the unfinished agenda of National Health Policy 2002, remains a priority area of implementation.

  4. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... breast and ascending colon. KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous. Multiple Primary Tumors. MA Adeyanju, AA Ilori. Address for correspondence: Dr. MA Adeyanju,. Department of Surgery, Federal Medical Centre, Ebute Metta,. Lagos, Nigeria. E-mail: mbadeyanju@yahoo.

  5. Primary malignant intramedullary lymphoma

    International Nuclear Information System (INIS)

    Orrego P, E.; Heinicke Y, H.; Arbaiza A, D.; Yepez R, V.

    1999-01-01

    A case of primary malignant intramedullary lymphoma, localized in the dorsal part of the spinal cord is presented. The clinical symptoms were associated with motor and sensitive deficit. Clinical investigations excluded the presence of lymphoma in other locations in the central nervous system and the extra neural organs. Postoperative radiotherapy and chemotherapy improved relict neurological symptoms. (authors)

  6. Primary black holes

    International Nuclear Information System (INIS)

    Novikov, I.; Polnarev, A.

    1981-01-01

    Proves are searched for of the formation of the so-called primary black holes at the very origin of the universe. The black holes would weigh less than 10 13 kg. The formation of a primary black hole is conditional on strong fluctuations of the gravitational field corresponding roughly to a half of the fluctuation maximally permissible by the general relativity theory. Only big fluctuations of the gravitational field can overcome the forces of the hot gas pressure and compress the originally expanding matter into a black hole. Low-mass black holes have a temperature exceeding that of the black holes formed from stars. A quantum process of particle formation, the so-called evaporation takes place in the strong gravitational field of a black hole. The lower the mass of the black hole, the shorter the evaporation time. The analyses of processes taking place during the evaporation of low-mass primary black holes show that only a very small proportion of the total mass of the matter in the universe could turn into primary black holes. (M.D.)

  7. Familial primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Iqbal, P.; Javed, R.

    2007-01-01

    A case of primary hyperparathyroidism in a 17 years old female is described. Patient presented with severe abdominal and pelvic pains associate with discomfort. Diagnostic testing revealed multiple upper and lower limb fractures and renal stones. Case was self limiting. Patient's condition resolved on parathyroidectomy for adenoma and partial thyroidectomy. Follow-up showed familial links. (author)

  8. Multiple Primary Cancer Monograph

    Science.gov (United States)

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  9. Primary cosmic ray flux

    Energy Technology Data Exchange (ETDEWEB)

    Stanev, Todor

    2001-05-01

    We discuss the primary cosmic ray flux from the point of view of particle interactions and production of atmospheric neutrinos. The overall normalization of the cosmic ray flux and its time variations and site dependence are major ingredients of the atmospheric neutrino predictions and the basis for the derivation of the neutrino oscillation parameters.

  10. in primary care

    African Journals Online (AJOL)

    Claire van Deventer

    Keywords: child HIV, doctor involvement, primary health care, quality improvement ... expertise increased, PHC facilities are now expected to be able to .... organised patient documentation were revisited. .... Review: what can we learn from quality ... South Pacific: Review of evidence and lessons from an innovative.

  11. [Primary and secondary encopresis].

    Science.gov (United States)

    Lang-Langer, Ellen

    2007-01-01

    While the difficulty of the child to part with its faeces in primary encopresis is linked to the incapability to experience the object as separated and independent from himself, secondary encopresis is a progressed psychical state of development. In this case we have to deal with regression caused by conflict. Two case-studies show clearly the differences.

  12. Functional aspects of cilia and tumor suppressors

    NARCIS (Netherlands)

    Basten, S.G.

    2013-01-01

    Sensing the cellular environment and responding accordingly is pivotal for tissue development and homeostasis. One cellular structure that functions almost exclusively as a sensory organelle is the nearly ubiquitously present primary cilium, that has been implicated in orchestrating cellular

  13. [Primary care in the United Kingdom].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2016-03-01

    The inadequate planning of health professionals in Spain has boosted the way out of doctors overseas. The United Kingdom is one of the countries chosen by Spanish doctors to develop their job. The National Health Service is a health system similar to the Spanish one. Health care services are financing mainly through taxes. The right to health care is linked to the citizen condition. The provision of health care is a mix-up of public and private enterprises. Primary Care is much closed to Spanish Primary Care. Doctors are "self-employed like" professionals. They can set their surgeries in a free area previously designed by the government. They have the right to make their own team and to manage their own budget. Medical salary is linked to professional capability and curriculum vitae. The main role of a General Practitioner is the prevention. Team work and coordination within primary and specialised care is more developed than in Spain. The access to diagnostic tests and to the specialist is controlled through waiting lists. General Practitioners work as gate-keepers. Patients may choose freely their doctor and consultations and hospital care are free at the point of use. Within the United Kingdom there are also health regions with problems due to inequalities to access and to treatment. There is a training path and the access to it is by Curricula. The number of training jobs is regulated by the local needs. Continuing education is compulsory and strictly regulated local and nationally. The National Health Service was the example for the Spanish health reform in 1986. While Spanish Primary health care is of quality, the efficiency of the health system would improve if staff in Primary Care settings were managed in a similar way to the British's. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Spirometry in primary care

    Science.gov (United States)

    Coates, Allan L; Graham, Brian L; McFadden, Robin G; McParland, Colm; Moosa, Dilshad; Provencher, Steeve; Road, Jeremy

    2013-01-01

    Canadian Thoracic Society (CTS) clinical guidelines for asthma and chronic obstructive pulmonary disease (COPD) specify that spirometry should be used to diagnose these diseases. Given the burden of asthma and COPD, most people with these diseases will be diagnosed in the primary care setting. The present CTS position statement was developed to provide guidance on key factors affecting the quality of spirometry testing in the primary care setting. The present statement may also be used to inform and guide the accreditation process for spirometry in each province. Although many of the principles discussed are equally applicable to pulmonary function laboratories and interpretation of tests by respirologists, they are held to a higher standard and are outside the scope of the present statement. PMID:23457669

  15. Cancer of unknown primary

    DEFF Research Database (Denmark)

    Dyrvig, Anne-Kirstine; Yderstræde, Knud Bonnet; Gerke, Oke

    2017-01-01

    210 (38.7%) had a CUP diagnosis confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR matching with the NPR registration. Exposure to diagnostic procedures included biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor with 67 (12.4%) individuals alive...... after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less...... than 1 quarter had their primary identified and the 1-year survival was approximately 20%. Research is needed to develop efficacious methods for primary detection....

  16. Primary omental pregnancy

    International Nuclear Information System (INIS)

    Yildizhan, R.; Kurdoglu, M.; Kolusari, A.; Erten, R.

    2008-01-01

    Omental pregnancy is a rare form of ectopic pregnancy and can be seen primarily or secondary to a tubal pregnancy. A 25-yeal-old woman presented with abdominal distention with pain and anemia without vaginal bleeding. After a provisional diagnosis of ruptured ectopic pregnancy, laparotomy was performed. On surgical exploration, the bilateral tubes and ovaries were intact, however, an omental pregnancy was detected as the cause of hemoperitoneum. Partial omentectomy was performed. Although most cases are secondary, presented here is an additional case of primary omental pregnancy at 12 weeks according to Studdiford's criteria. Histological evidence of neovascularization into the supporting tissue confirmed our diagnosis. A primary omental pregnancy should always be considered as a possible explanation for severe hemoperitoneum in ectopic pregnancies presenting with acute abdomen and with intact adnexes on surgical exploration. (author)

  17. Basics of primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Martínez

    2016-05-01

    Full Text Available Primary immunodeficiencies (PID are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.

  18. Primary Tunnel Junction Thermometry

    International Nuclear Information System (INIS)

    Pekola, Jukka P.; Holmqvist, Tommy; Meschke, Matthias

    2008-01-01

    We describe the concept and experimental demonstration of primary thermometry based on a four-probe measurement of a single tunnel junction embedded within four arrays of junctions. We show that in this configuration random sample specific and environment-related errors can be avoided. This method relates temperature directly to Boltzmann constant, which will form the basis of the definition of temperature and realization of official temperature scales in the future

  19. Primary stabbing headache.

    Science.gov (United States)

    Pareja, Juan A; Sjaastad, Ottar

    2010-01-01

    Primary stabbing headache is characterized by transient, cephalic ultrashort stabs of pain. It is a frequent complaint with a prevalence of 35.2%, a female preponderance, and a mean age of onset of 28 years (Vågå study). Attacks are generally characterized by moderate to severe, jabbing or stabbing pain, lasting from a fraction of a second to 3s. Attack frequency is generally low, with one or a few attacks per day. The paroxysms generally occur spontaneously, during daytime. Most patients exhibit a sporadic pattern, with an erratic, unpredictable alternation between symptomatic and non-symptomatic periods. Paroxysms are almost invariably unilateral. Temporal and fronto-ocular areas are most frequently affected. Attacks tend to move from one area to another, in either the same or the opposite hemicranium. Jabs may be accompanied by a shock-like feeling and even by head movement - "jolts" -or vocalization. On rare occasions, conjunctival hemorrhage and monocular vision loss have been described as associated features. Primary stabbing headache may concur, synchronously or independently, with other primary headaches. In contrast to what is the case in adults, in childhood it is not usually associated with other headaches. Treatment is rarely necessary. Indomethacin, 75-150 mg daily, may seem to be of some avail. Celecoxib, nifedipine, melatonin, and gabapentin have been reported to be effective in isolated cases and small series of patients. The drug studies need corroboration. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. [Primary headache and depression].

    Science.gov (United States)

    Gesztelyi, Gyöngyi

    2004-11-28

    Primary headaches--mainly tension-type headache and migraine--affect a significant portion of the population. Depression is also highly prevalent. The co-existence of a primary headache and depression in the same patient therefore might be a coincidence due to the high prevalence of these conditions, but there might be a causal relationship between them, or headaches and depression might have a common background. This review of the literature summarizes the features of the relationship between primary headaches and depression. Depression is more prevalent in headache patients than in the headache-free population. Prospective epidemiological studies suggest a common genetic, biochemical or environmental background behind primary headaches and depression. This theory is supported by the role of the same neurotransmitter systems (mostly serotonin and dopamine) in headaches as well as in depression. Comorbid depression is associated with female gender, higher age, and higher frequency of headaches. Most depression inventories--questionnaires used to screen for the severity of depressive symptoms--contain transdiagnostic items, therefore their use in their original form is limited in organic diseases: due to the somatic items they might overestimate the severity of depression. When examining a headache patient special attention should be paid to the recognition of comorbid depression. The diagnosis of suspected mood disorder could be supported by using simple screening methods, such as the original or the abbreviated versions of standard depression inventories, but the final diagnosis of major depression needs psychiatric evaluation. Quality of life of the headache patient is affected not only by the characteristics of pain (frequency, duration, severity) but also by the disability caused by headache and the associating mood disorder. Recognizing coexisting mood disorder and disability helps to make the best treatment choice for the acute and preventive treatment of

  1. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  2. [Ghrelin: beyond hunger regulation].

    Science.gov (United States)

    Milke García, Maria del Pilar

    2005-01-01

    Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.

  3. EB1 is required for primary cilia assembly in fibroblasts

    DEFF Research Database (Denmark)

    Schrøder, Jacob M; Schneider, Linda; Christensen, Søren T

    2007-01-01

    EB1 is a small microtubule (MT)-binding protein that associates preferentially with MT plus ends and plays a role in regulating MT dynamics. EB1 also targets other MT-associated proteins to the plus end and thereby regulates interactions of MTs with the cell cortex, mitotic kinetochores, and diff...... that localization of EB1 at the centriole/basal body is required for primary cilia assembly in fibroblasts....

  4. Localization of primary aldosteronism

    International Nuclear Information System (INIS)

    Pagny, J.Y.; Chatellier, G.; Raynaud, A.; Plouin, P.F.; Corvol, P.

    1988-01-01

    After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. The efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism was reviewed. Diagnosis of Conn's adenoma (n=96) or Adrenal Hyperplasia (n=40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/ Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n=6) and adrenal haematoma (n=2) lead to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation [fr

  5. Teacher of primary English

    CERN Multimedia

    2003-01-01

    Part-time teacher of primary English needed for September 2003 to teach English National Curriculum (KS2) and NLS to mother tongue or good second language English-speakers aged 7-10. 4 hours contact time per week, team planning, marking and meetings. Candidates should be English mother tongue qualified teachers, confident, flexible classroom practitioners and team players. For further details and how to apply see http://enpferney.org/staff_vacancies.htm English National Programme, Lycée International, Ferney-Voltaire (http://enpferney.org/)

  6. Primary isolated hepatic tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

    2013-01-01

    Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

  7. PRIMARY CARIES: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Gaurav Solanki

    2012-01-01

    Full Text Available Primary caries is an initial lesions produced by direct extension from an external surface. Dental caries is called as tooth decay or a cavity is a disease in which bacterial processes changes carbohydrate to acid which than dematerializes the hard tooth structure like enamel, dentin and cementum. Streptococcus mutans and Lactobacillus are the bacteria responsible for the dental caries by acid production. This article throws light on the dental caries disease, its sign and symptoms, treatment and prevention of it. A review of some patents on dental caries is also provided that summarizes the recent technical advancements taken place in this area.

  8. Primary cutaneous lymphoma

    International Nuclear Information System (INIS)

    Nguyen, M. Connie; Cleary, Sean F.; Hoppe, Richard T.

    1995-01-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  9. Bellefonte primary containment structure

    International Nuclear Information System (INIS)

    Olyniec, J.H.

    1981-01-01

    Construction of the reactor building primary containment structure at the Bellefonte Nuclear Plant involved several specialized construction techniques. This two unit plant is one of the nine nuclear units at six different sites now under construction by the Tennessee Valley Authority (TVA). The post-Tensioned, cast-in-place interior steel lined containment structure is unique within TVA. Problems during construction were identified at weekly planning meetings, and options were discussed. Close coordination between craft supervisors and on-site engineering personnel drew together ''hands-on''experience and technical background. Details of the construction techniques, problems, and solutions are presented

  10. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

  11. Aspirin for Primary Prevention.

    Science.gov (United States)

    Richman, Ilana B; Owens, Douglas K

    2017-07-01

    Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Primary cutaneous lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, M Connie; Cleary, Sean F; Hoppe, Richard T

    1995-07-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  13. PRIMARY SCHOOL TEACHER

    CERN Multimedia

    Madeleine Dittus

    2002-01-01

    For January 2003, the A.P.E.G. has an opening for a primary school teacher in the German national language program. The position requires one afternoon of teaching (13:30 till 16:30) every Tuesday at the Collège in Prévessin. The candidate should be a native speaker of German and have some knowledge of French. If you are interested, please send your CV, a copy of your diploma, and a short letter of motivation, until December 9th, to the following address. Madeleine Dittus Présidente A.P.E.G. 5, La vie Destraz 01630 St. Genis-Pouilly (France)

  14. Primary Frequency Response with Aggregated DERs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guggilam, Swaroop S.; Dhople, Sairaj V.; Zhao, Changhong; Dall' Anese, Emiliano; Chen, Yu Christine

    2017-03-03

    Power networks have to withstand a variety of disturbances that affect system frequency, and the problem is compounded with the increasing integration of intermittent renewable generation. Following a large-signal generation or load disturbance, system frequency is arrested leveraging primary frequency control provided by governor action in synchronous generators. In this work, we propose a framework for distributed energy resources (DERs) deployed in distribution networks to provide (supplemental) primary frequency response. Particularly, we demonstrate how power-frequency droop slopes for individual DERs can be designed so that the distribution feeder presents a guaranteed frequency-regulation characteristic at the feeder head. Furthermore, the droop slopes are engineered such that injections of individual DERs conform to a well-defined fairness objective that does not penalize them for their location on the distribution feeder. Time-domain simulations for an illustrative network composed of a combined transmission network and distribution network with frequency-responsive DERs are provided to validate the approach.

  15. Competition between bank regulators

    OpenAIRE

    Schindler, Dirk; Eggert, Wolfgang

    2004-01-01

    This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

  16. Pattern of Primary Nocturnal Enuresis in Primary School Children ...

    African Journals Online (AJOL)

    Pattern of Primary Nocturnal Enuresis in Primary School Children (First Grade) in ... The control group consisting of 100 age-matched non-enuretic children ... was insignificantly associated with a positive family history, family size or birth rank.

  17. Primary iris leiomyoma.

    Science.gov (United States)

    Yeaney, Gabrielle A; Platt, Sean; Singh, Arun D

    Intraocular leiomyomas are uncommon and usually occur in the ciliary body. Primary leiomyoma of the iris is both rare and a difficult diagnosis to make, given melanocytic tumors are more common and may be amelanotic. The somewhat controversial diagnosis of iris leiomyoma requires further confirmation by immunohistochemistry and electron microscopy. Herein, we describe a 58-year-old man with a 2-mm round translucent pink lesion of the iris. The tumor was excised by sector iridectomy. Immunohistochemistry showed positivity for both smooth muscle actin and desmin and negativity for S-100, HMB45, SOX10, MelanA, CD31, CD34, and h-caldesmon. Epstein-Barr virus-associated smooth muscle tumor was excluded by chromogenic in situ hybridization-Epstein-Barr virus-encoded RNA. Ultrastructural analysis showed cytoplasmic myofilaments with focal fusiform densities and micropinocytotic vesicles. Our review of previous literature confirmed the unusual nature of this tumor. Primary iris leiomyoma should be considered in the differential of an amelanotic S-100-immunonegative iris tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Imaging in primary osteosarcomas

    International Nuclear Information System (INIS)

    Davies, A.M.

    1998-01-01

    Osteosarcoma is the most common primary malignant bone tumour with the exception of myeloma. The majority of osteosarcoma cases arise within bone and are called conventional osteosarcoma. Intraosseous variants include telangiectatic, small-cell, low-grade intraosseous and cortical osteosarcoma. Less than 10% of osteosarcomas arise on the surface of bone and are subdivided into periosteal, high-grade surface and parosteal varieties. The imaging features of these subtypes of osteosarcoma are described and the impact on diagnosis highlighted. Using material from over 750 osteosarcomas treated at the author's centre, this article reviews the role of imaging in the management of this condition. Detection still relies principally on the conventional radiograph with bone scintigraphy and MR imaging useful in occult tumours. Establishing the radiological diagnosis depends on careful analysis of the radiographs, with particular attention paid to the nature and extent of bone destruction, periosteal new bone formation and matrix mineralization. The prudent radiologist will be wary of those bone conditions, such as stress fractures and osteomyelitis, which are frequently mistaken for osteosarcoma. Appropriate surgical staging requires MR imaging of the primary tumour to show the bony and soft tissue extent of the lesion and to confirm/exclude skip metastases and local lymph-node involvement. Staging should also include bone scintigraphy to confirm/exclude multiple lesions and chest CT to confirm/exclude pulmonary metastases. Following definitive surgery, imaging is used in the follow-up to monitor potential local recurrence and the development of pulmonary or osseous metastases. (orig.) [de

  19. [Normocalcemic primary hyperparathyroidism].

    Science.gov (United States)

    Spivacow, Francisco R; Sapag Durán, Ana; Zanchetta, María B

    2014-01-01

    This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

  20. Asymptomatic Primary Hyperparathyroidism

    Science.gov (United States)

    Silverberg, Shonni J.; Walker, Marcella D.; Bilezikian, John P.

    2014-01-01

    The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term “asymptomatic primary hyperparathyroidism” was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease. PMID:23374736

  1. Regulating through leverage: Civil regulation in China

    NARCIS (Netherlands)

    Fürst, K.

    2016-01-01

    The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

  2. A Conceptual Framework for Lean Regulated Software Development

    DEFF Research Database (Denmark)

    Cawley, Oisin; Richardson, Ita; Wang, Xiaofeng

    2015-01-01

    for software development within a regulated environment? This poster presents the results of our empirical research into lean and regulated software development. Built from a combination of data sources, we have developed a conceptual framework comprising five primary components. In addition the relationships...... they have with both the central focus of the framework (the situated software development practices) and with each other are indicated....

  3. Preschoolers' Emotion Expression and Regulation: Relations with School Adjustment

    Science.gov (United States)

    Herndon, Kristina J.; Bailey, Craig S.; Shewark, Elizabeth A.; Denham, Susanne A.; Bassett, Hideko H.

    2013-01-01

    Children's expression and regulation of emotions are building blocks of their experiences in classrooms. Thus, the authors' primary goal was to investigate whether preschoolers' expression or ability to regulate emotions were associated with teachers' ratings of school adjustment. A secondary goal was to investigate how boys and girls differed…

  4. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    Journal of Community Medicine and Primary Health Care. ... Ladoke Akintola University of Technology, PMB 4400, Osogbo, Osun State. ... weak management and poor adherence to the basic infrastructure e.g. primary, secondary and tertiary.

  5. Bezafibrate for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena S; Poropat, Goran; Krstic, Miodrag N

    2012-01-01

    Treatment of primary biliary cirrhosis is complicated. There are studies suggesting that bezafibrate, alone or in combination with ursodeoxycholic acid (UDCA), is effective in the treatment of primary biliary cirrhosis, but no systematic review has summarised the evidence yet....

  6. BR-5 primary circuit decontamination

    International Nuclear Information System (INIS)

    Efimov, I.A.; Nikulin, M.P.; Smirnov-Averin, A.P.; Tymosh, B.S.; Shereshkov, V.S.

    1976-01-01

    Results and methodology of steam-water and acid decontamination of the primary coolant circuit SBR-5 reactor in 1971 are discussed. Regeneration process in a cold trap of the primary coolant circuit is discussed

  7. Primary Prevention With Statins

    DEFF Research Database (Denmark)

    Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. OBJECTIVES: This study...... the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin......-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC...

  8. Primary care guidelines

    DEFF Research Database (Denmark)

    Ijäs, Jarja; Alanen, Seija; Kaila, Minna

    2009-01-01

    OBJECTIVE: To describe the adoption of the national Hypertension Guideline in primary care and to evaluate the consistency of the views of the health centre senior executives on the guideline's impact on clinical practices in the treatment of hypertension in their health centres. DESIGN: A cross...... Guideline. RESULTS: Data were available from 143 health centres in Finland (49%). The views of head physicians and senior nursing officers on the adoption of the Hypertension Guideline were not consistent. Head physicians more often than senior nursing officers (44% vs. 29%, p ...: Hypertension Guideline recommendations that require joint agreements between professionals are less often adopted than simple, precise recommendations. More emphasis on effective multidisciplinary collaboration is needed....

  9. Adrenal incidentalomas. Primary hyperaldosteronism

    International Nuclear Information System (INIS)

    Murat, A.; Dupas, B.; Zenatti, M.; Aupetit-Faisant, B.; Tenenbaum, F.; Tabarin, A.; Barrat, J.L.; Gosse, P.; Olivier-Puel, F.; Leprat, F.; Trouette, H.; Laurent, F.; Roger, P.

    1993-01-01

    Adrenal incidentalomas are masses incidentally discovered at X rays, ultrasound or MRI examination of the abdomen. In 100 CT scans, one can expect to find two incidentalomas on average. The article by Murat and Dupas is dealing with the strategy of biological, morphological and scintigraphic examinations to be performed in such patients, to assess whether the tumor is of a benign or a malignant nature. Zenatti et al propose a detailed exploration of the aldosterone pathways, since adrenal carcinoma may be responsible for a specific profile of the serum concentrations of mineralo-steroids, compatible with a blockade of the last step of the aldosterone synthesis. The exploration of primary hyperaldosteronism requires biological and imaging techniques. Tabarin et al summarize the main biological parameters and tests available for the diagnosis of this condition and delineate the indications of imaging techniques, associated to hormonal tests to distinguish between adenoma and bilateral adrenal hyperplasia. (author). 104 refs

  10. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  11. Primary conjunctival amyloidosis

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2014-01-01

    Full Text Available A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid.On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

  12. Prostaglandins and primary dysmenorrhea

    International Nuclear Information System (INIS)

    Seifert, B.; Liedtke, M.P.; Kempf, H.J.; Richter, H.; Alexander, H.; Herter, U.

    1978-01-01

    In 100 patients a total of 171 PG determinations in the menstrual blood was performed under standardized conditions. The primary PGE 1 and PGFsub(2α) were determined by RIA. The evaluation of the analysis of the sexual hormones resulted in a group with a biphasic cycle without dysmenorrhea and a group with a biphasic cycle with dysmenorrhea. Highly significant differences (p < 0.01) were found in the PGFsub(2α) concentration in menstrual blood between a group of healthy women and one of patients with dysmenorrhea. In dysmenorrhea the ratio of the PGs investigated is shifted in favor of PGFsub(2α). Indomethacin can decrease the PGFsub(2α) levels in dysmenorrhea up to 15% (p < 0.01). All treated patients reported that their conditions had improved. Five out of seven women were completely without any complaints. (author)

  13. PRIMARY SCHOOL TEACHER

    CERN Multimedia

    Madeleine Dittus

    2002-01-01

    For the beginning of the school year 2002/2003, the A.P.E.G. has an opening for a primary school teacher in the German national language program. The position requires one afternoon of teaching (13:30 till 16:30) every Tuesday at the Collège in Prévessin. The candidate should be a native speaker of German and have some knowledge of French. If you are interested, please send your CV, a copy of your diploma, and a short letter of motivation, until March 10th, to the following address. Madeleine Dittus - Présidente A.P.E.G. 5, La vie Destraz 01630 St. Genis-Pouilly - France

  14. Primary Fallopian Tube Carcinoma

    Directory of Open Access Journals (Sweden)

    Prasad K Shetty

    2011-01-01

    Full Text Available Primary Fallopian Tube Carcinoma (PFTC is rare and accounts for about 0.3% of all gynecologic cancers. Less than 1500 cases have been reported in the literature. It arises in postmenopausal women and typically presents with abdominal pelvic pain, vaginal bleeding and watery discharge. However, a correct diagnosis is rarely achieved preoperative, and in many cases, the diagnosis is made after incidental surgery for unrelated conditions commonly being ovarian carcinoma . Compared with ovarian carcinoma, PFTC more often presents at early stages, but it has a worse prognosis. PFTC is usually managed in the same manner as ovarian cancer. We report a case of Left PFTC that presented as Left ovarian mass, and we briefly review the literature.

  15. Primary aldosteronism. Clinical management

    International Nuclear Information System (INIS)

    Grant, C.S.; Carpenter, P.; van Heerden, J.A.; Hamberger, B.

    1984-01-01

    We retrospectively reviewed the clinical features, methods of diagnosis and localization, and results of treatment in 105 patients with primary aldosteronism seen between 1969 and 1981. Coincident with the use of computed tomography (CT), 131 I-6-beta-iodomethyl norcholesterol scans (NP-59), and postural response studies, the study group was temporally divided into pre-1976 and post-1976 groups, and subdivided into groups with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. Our results indicate that aldosterone postural response studies and CT differentiate and localize APA and IHA reliably. Adrenalectomy is a safe and effective treatment for APA, whereas medical treatment alone is preferable for IHA

  16. Primary Identity in Literature

    DEFF Research Database (Denmark)

    Graham, Brian Russell

    In our times, literary criticism, as well as larger political and cultural developments, is characterized by identity politics, meaning that our discourses are structured around the notion of different socially identifiable populations in society. In relation to literature, this results in our...... viewing the characters in literature in terms of these political identities. Literature is consequently discussed in relation to political causes. Literary criticism is animated by the same causes, and is viewed as having a direct intervention in society in relation to them. In this paper, I will discuss......, in relation to Frye’s works, the idea that the primary identities of characters in literature were and, to a considerable extent, continue to be those of family-member identities. As such, literature should not be appropriated to a political context too readily. Whereas viewing characters in terms of...

  17. [Primary care in Belgium].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2017-09-01

    Belgium is an attractive country to work in, not just for doctors but for all Spanish workers, due to it having the headquarters of European Union. The health job allure is double; on the one hand, the opportunity to find a decent job, and on the other, because it is possible to develop their professional abilities with patients of the same nationality in a health system with a different way of working. The Belgium health care system is based on security social models. Health care is financed by the government, social security contributions, and voluntary private health insurance. Primary care in Belgium is very different to that in Spain. Citizens may freely choose their doctor (general practitioner or specialist) increasing the lack of coordination between primary and specialized care. This leads to serious patient safety problems and loss of efficiency within the system. Belgium is a European country with room to improve preventive coverage. General practitioners are self-employed professionals with free choice of setting, and their salary is linked to their professional activity. Ambulatory care is subjected to co-payment, and this fact leads to great inequities on access to care. The statistics say that there is universal coverage but, in 2010, 14% of the population did not seek medical contact due to economic problems. It takes 3 years to become a General Practitioner and continuing medical education is compulsory to be revalidated. In general, Belgian and Spaniards living and working in Belgium are happy with the functioning of the health care system. However, as doctors, we should be aware that it is a health care system in which access is constrained for some people, and preventive coverage could be improved. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Primary Teacher Education in Malaysia

    Science.gov (United States)

    Ching, Chin Phoi; Yee, Chin Peng

    2012-01-01

    In Malaysia the training of primary school teachers is solely carried out by teacher training institutes which offer the Bachelor of Teaching with Honors (Primary education) program and was first launched in 2007. This program prepares primary school teachers specializing in various subjects or major and is carried out in 27 teacher training…

  19. Atomic Energy Control Regulations

    International Nuclear Information System (INIS)

    1992-01-01

    This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

  20. Environmental regulation and competitiveness

    NARCIS (Netherlands)

    Mulatu, A.; Florax, R.J.G.M.; Withagen, C.A.A.M.

    2001-01-01

    The potential relationship between domestic environmental regulation and international competitiveness has evoked various speculations. The common neoclassical train of thought is that strict environmental regulation is detrimental to the competitiveness of industry, and that it induces phenomena

  1. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    1978-01-01

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  2. Regulation of Genetic Tests

    Science.gov (United States)

    ... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...

  3. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  4. Bilateral supernumerary primary maxillary canines

    Directory of Open Access Journals (Sweden)

    Santanu Mukhopadhyay

    2018-01-01

    Full Text Available Supernumerary teeth are more common in the permanent than in primary dentition. In the primary dentition, the anomaly is most frequently observed in the maxillary lateral incisor region, followed by the maxillary midline where they are termed as mesiodens. Supernumerary teeth in the primary canine region are rare. This paper describes a rare case of nonsyndromic supernumerary primary maxillary canine distributed bilaterally in a 4-year-old boy. Both the supernumeraries resembled size and shape of normal primary canine. The right supplemental canine is high labially placed, whereas the left one is seen normally aligned in the dental arch distal to lateral incisor. One of the most significant sequelae of primary supernumerary teeth is their duplication in the permanent series. Radiographic examination of supernumerary primary canine did not indicate any such anomaly in the permanent dentition. The patient was kept under observation.

  5. Comparison between Primary Teacher Educators' and Primary School Teachers' Beliefs of Primary Geography Education Quality

    Science.gov (United States)

    Bent, Gert Jan; Bakx, Anouke; den Brok, Perry

    2016-01-01

    In this study teacher educators' beliefs concerning primary geography education have been investigated and compared with primary school teachers' beliefs. In this study 45 teacher educators and 489 primary school teachers completed a questionnaire, and nine teacher educators have been interviewed as well. It has been found that teacher educators…

  6. Primary hepatic pheochromocytoma

    International Nuclear Information System (INIS)

    Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

    1996-01-01

    Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

  7. Primary intestinal lymphangiectasia: Minireview

    Science.gov (United States)

    Ingle, Sachin B; Hinge (Ingle), Chitra R

    2014-01-01

    Primary idiopathic intestinal lymphangiectasia is an unusual disease featured by the presence of dilated lymphatic channels which are located in the mucosa, submucosa or subserosa leading to protein loosing enteropathy.Most often affected were children and generally diagnosed before third year of life but may be rarely seen in adults too. Bilateral pitting oedema of lower limb is the main clinical manifestation mimicking the systemic disease and posing a real diagnostic dilemma to the clinicians to differentiate it from other common systemic diseases like Congestive cardiac failure, Nephrotic Syndrome, Protein Energy Malnutrition, etc. Diagnosis can be made on capsule endoscopy which can localise the lesion but unable to take biopsy samples. Thus, recently double-balloon enteroscopy and biopsy in combination can be used as an effective diagnostic tool to hit the correct diagnosis. Patients respond dramatically to diet constituting low long chain triglycerides and high protein content with supplements of medium chain triglyceride. So early diagnosis is important to prevent untoward complications related to disease or treatment for the sake of accurate pathological diagnosis. PMID:25325063

  8. Primary hyperoxaluria in infants

    Directory of Open Access Journals (Sweden)

    Manel Jellouli

    2016-01-01

    Full Text Available The infantile form of primary hyperoxaluria type-1 (PH-1 is characterized by a rapid progression to the end-stage renal disease (ESRD due to both increased oxalate load and reduced glomerular filtration rate. In the literature, data on this form are limited. The purpose of this study is to analyze retrospectively the clinical, biological, and radiological features of children who were diagnosed with PH-1 during the 1styear of life. We reviewed the records of all children with PH-1 diagnosed and followed-up at our department between January 1995 and December 2013. Among them, only infants younger than 12 months of age were retrospectively enrolled in the study. Fourteen infants with the median age of two months were enrolled in the study. At diagnosis, 11 patients had ESRD. All patients had nephrocalcinosis and two of them had calculi. The diagnosis was established in nine patients on the basis of the positive family history of PH-1, bilateral nephrocalcinosis, and quantitative crystalluria. In four patients, the diagnosis was made with molecular analysis of DNA. Kidney biopsy contributed to the diagnosis in one patient. During follow-up, two patients were pyridoxine sensitive and preserved renal function. Seven among 11 patients who had ESRD died, four patients are currently undergoing peritoneal dialysis. Children with infantile PH and ESRD are at high risk of early death. Peritoneal dialysis is not a treatment of choice. Combined liver-kidney transplantation is mandatory.

  9. Primary hyperparathyroidism: recent advances.

    Science.gov (United States)

    Walker, Marcella D; Bilezikian, John P

    2018-07-01

    The purpose of this review is to describe recent advances and changes in the evaluation and management of primary hyperparathyroidism (PHPT). Although it has long been recognized that asymptomatic PHPT is associated with bone loss, particularly at cortical skeletal sites when evaluated with dual-energy X-ray absorptiometry, new imaging techniques suggest that trabecular skeletal deterioration as well as clinically silent vertebral fractures and nephrolithiasis are common. Nonclassical targets of asymptomatic PHPT as well as the effect of vitamin D deficiency and treatment upon PHPT presentation have been the subject of recent intense investigation. Randomized clinical trials are now available regarding the effect of parathyroidectomy (PTX) upon both classical and nonclassical target organs. They have confirmed results from observational studies with regard to the skeletal benefits of PTX but have not consistently shown improvements in nonclassical symptoms. These findings have led to recommendations for more extensive renal and skeletal evaluation and broader criteria for PTX in PHPT. In addition to dual-energy X-ray absorptiometry, vertebral and renal imaging is recommended. When available, trabecular imaging techniques may be helpful. PTX criteria now include subclinical kidney stones, vertebral fractures and hypercalciuria, in addition to those based on age, serum calcium, bone densitometry and renal function.

  10. Primary sclerosing cholangitis

    Directory of Open Access Journals (Sweden)

    Marina G Silveira

    2008-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.

  11. Primary sclerosing cholangitis

    Directory of Open Access Journals (Sweden)

    Chapman Roger

    2006-10-01

    Full Text Available Abstract Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect.

  12. Consanguinity and primary immunodeficiencies.

    Science.gov (United States)

    Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima

    2014-01-01

    Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.

  13. Idiopathic (primary achalasia

    Directory of Open Access Journals (Sweden)

    Vaezi Michael F

    2007-09-01

    Full Text Available Abstract Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram, and esophageal motility testing (esophageal manometry. Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients.

  14. Idiopathic (primary) achalasia

    Science.gov (United States)

    Farrokhi, Farnoosh; Vaezi, Michael F

    2007-01-01

    Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES) relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg) is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram), and esophageal motility testing (esophageal manometry). Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients. PMID:17894899

  15. Achieving Value in Primary Care: The Primary Care Value Model.

    Science.gov (United States)

    Rollow, William; Cucchiara, Peter

    2016-03-01

    The patient-centered medical home (PCMH) model provides a compelling vision for primary care transformation, but studies of its impact have used insufficiently patient-centered metrics with inconsistent results. We propose a framework for defining patient-centered value and a new model for value-based primary care transformation: the primary care value model (PCVM). We advocate for use of patient-centered value when measuring the impact of primary care transformation, recognition, and performance-based payment; for financial support and research and development to better define primary care value-creating activities and their implementation; and for use of the model to support primary care organizations in transformation. © 2016 Annals of Family Medicine, Inc.

  16. Culture and emotion regulation.

    Science.gov (United States)

    Ford, Brett Q; Mauss, Iris B

    2015-06-01

    While anthropological research has long emphasized cultural differences in whether emotions are viewed as beneficial versus harmful, psychological science has only recently begun to systematically examine those differences and their implications for emotion regulation and well-being. Underscoring the pervasive role of culture in people's emotions, we summarize research that has examined links between culture, emotion regulation, and well-being. Specifically, we focus on two questions. First, how does culture lead individuals to regulate their emotions? And second, how does culture modulate the link between emotion regulation and well-being? We finish by suggesting directions for future research to advance the study of culture and emotion regulation.

  17. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    1993-01-01

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  18. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  19. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    to amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...... volume regulation. In the same cell, these functions may be maintained by different ion pathways that are separately regulated. RVD is often preceded by increase in cytosolic free Ca2+, probably via influx through TRP channels, but Ca2+ release from intracellular stores has also been observed. Cell...

  20. Voltage regulator for generator

    Energy Technology Data Exchange (ETDEWEB)

    Naoi, K

    1989-01-17

    It is an object of this invention to provide a voltage regulator for a generator charging a battery, wherein even if the ambient temperature at the voltage regulator rises abnormally high, possible thermal breakage of the semiconductor elements constituting the voltage regulator can be avoided. A feature of this invention is that the semiconductor elements can be protected from thermal breakage, even at an abnormal ambient temperature rise at the voltage regulator for the battery charging generator, by controlling a maximum conduction ratio of a power transistor in the voltage regulator in accordance with the temperature at the voltage regulator. This is achieved through a switching device connected in series to the field coil of the generator and adapted to be controlled in accordance with an output voltage of the generator and the ambient temperature at the voltage regulator. 6 figs.

  1. Primary intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

    1988-01-01

    Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found. (author)

  2. Primary cosmic radiation

    International Nuclear Information System (INIS)

    Anderson, H.R.

    1972-01-01

    The term cosmic radiation means the charged particle flux that reaches the earth from outside its magnetosphere with energies above the solar wind energy of a few keV. There are two sources of flux. Sporadically the sun produces such particles, generally within the energy range 1--200 MeV, and these solar cosmic rays arrive at the earth for a period ranging from hours to days. There may be a small, rather constant flux from the sun also, but the bulk of the steady flux originates outside the earth's orbit. Although some have conjectured that part of this latter flux may be accelerated in the outer portions of the solar system where the outward flowing interplanetary medium meets the interstellar medium, it is generally thought that most or all of it arises in unique systems such as supernovae, and is distributed throughout the galaxy. These galactic particles range in energy from a few MeV to at least 10 13 MeV and consist primarily of protons with significant numbers of heavier nuclei, positrons and electrons. They are supposed to fill our galaxy, or at least the disc, more or less uniformly. However, the flux with energies below a few GeV that reaches earth's orbit is modulated by the interplanetary medium so that the number at earth varies inversely with solar activity and is always somewhat below the interstellar flux. A discussion is presented of primary galactic radiation at earth, its modulation by solar activity, and its interaction with the geomagnetic field. (U.S.)

  3. APC sets the Wnt tone necessary for cerebral cortical progenitor development.

    Science.gov (United States)

    Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

    2017-08-15

    Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

  4. African Primary Care Research: qualitative interviewing in primary care.

    Science.gov (United States)

    Reid, Steve; Mash, Bob

    2014-06-05

    This article is part of a series on African Primary Care Research and focuses on the topic of qualitative interviewing in primary care. In particular it looks at issues of study design, sample size, sampling and interviewing in relation to individual and focus group interviews.There is a particular focus on helping postgraduate students at a Masters level to write their research proposals.

  5. DC microgrids providing frequency regulation in electrical power system - imperfect communication issues

    DEFF Research Database (Denmark)

    Bašić, Hrvoje; Dragicevic, Tomislav; Pandžić, Hrvoje

    2017-01-01

    This paper presents a model of multiple DC microgrids with battery energy storage systems and demand response capability, taking part in primary frequency regulation of electrical power system. Although DC microgrids can contribute to stability and efficiency of frequency regulation, these complex...... systems may cause serious stability issues due to the imperfect communication. This work presents possible scenarios of unstable primary frequency regulation in a simplified model of electrical power system with DC microgrids, which are controlled through communication network....

  6. [Healing garden: Primary concept].

    Science.gov (United States)

    Pringuey-Criou, F

    2015-10-01

    Since ancient times the relationship between mankind and plants occupies medicine and philosophy. From the first tablets of herbal medicine to Asclepius gardens, those of cloisters and bimaristans to cosmological gardens in Asia, from the largest public park to asylum institutions of the nineteenth century, the garden is proposed as a place of care, a promoter of restoration of the human being. If the advent of technology and drugs have for a time relegated it to the level of empirical care, results in neuroscience ultimately provide it on a scientific basis. The early evolutionary theories, the Savanah theory from Orians, the biophilia hypothesis from Wilson, are relayed by the famous Ulrich' study showing the positive influence of a view of nature through the window on the recovery of in patients. Mechanisms leading stress regulation, level of attention and organisation, focus and fascination, are recognized at the origin of restoration processes. Human capacities to respond to the recuperating function of a natural environment connect to grounded behaviour for adaptation to natural selection process and survival. The mechanisms of our immune system are essential to maintain our vitality. Phyto-resonance, felt or unconsciously perceived in appearance, according to Shepard is an emotion that structures well beyond the archaic behaviour. Recovery, in terms of phenomenological experience of the presence, is a philosophical demonstration of the environmental i.e. multisensory, spatial and temporal approach. Its emotional and affective experience connects to the vitality and creativity. The phyto-resonance hypothesis according to the Konrad Neuberger's point of view induces strategies catering to all levels of the organisation of the human being. It confirms the multidisciplinary nature of hortitherapy and places the mechanism of relationships between man and plant at the centre of discipline. It is also a source of inspiration and inexhaustible work for caregivers

  7. Cell swelling and volume regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay

    1992-01-01

    The extracellular space in the brain is typically 20% of the tissue volume and is reduced to at least half its size under conditions of neural insult. Whether there is a minimum size to the extracellular space was discussed. A general model for cell volume regulation was presented, followed...... by a discussion on how many of the generally involved mechanisms are identified in neural cells and (or) in astrocytes. There seems to be clear evidence suggesting that parallel K+ and Cl- channels mediate regulatory volume decrease in primary cultures of astrocytes, and a stretch-activated cation channel has...... been reported. The role of the different channels was discussed. A taurine leak pathway is clearly activated after cell swelling both in astrocytes and in neurones. The relations between the effect of glutamate and cell swelling were discussed. Discussion on the clearance of potassium from...

  8. Large-scale river regulation

    International Nuclear Information System (INIS)

    Petts, G.

    1994-01-01

    Recent concern over human impacts on the environment has tended to focus on climatic change, desertification, destruction of tropical rain forests, and pollution. Yet large-scale water projects such as dams, reservoirs, and inter-basin transfers are among the most dramatic and extensive ways in which our environment has been, and continues to be, transformed by human action. Water running to the sea is perceived as a lost resource, floods are viewed as major hazards, and wetlands are seen as wastelands. River regulation, involving the redistribution of water in time and space, is a key concept in socio-economic development. To achieve water and food security, to develop drylands, and to prevent desertification and drought are primary aims for many countries. A second key concept is ecological sustainability. Yet the ecology of rivers and their floodplains is dependent on the natural hydrological regime, and its related biochemical and geomorphological dynamics. (Author)

  9. Understanding purposes of regulation: a case example in mental health.

    Science.gov (United States)

    Ziegenfuss, J T; Hadley, T

    1980-01-01

    This paper reviews the purposes of governmental regulation and how an exploration of purpose can contribute to our understanding of specific regulations. The primary regulatory purpose is defined as the achievement of quality control of a subject system, its process or its product. Quality control via regulation is achieved through one or a combination of approaches: (1) accountability, (2) organizational development, (3) protectionism. Regulatory purpose and approach is illustrated by a case example of the development of regulations for partial hospitalization mental health services.

  10. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

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

  11. The development of regulations

    International Nuclear Information System (INIS)

    Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

    2003-01-01

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  12. Regulating hedge funds.

    OpenAIRE

    Daníelsson, J.; Zigrand, JP.

    2007-01-01

    Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on a misperception of the effectiveness of financial regulations, perhaps coupled with a lack of understand...

  13. Effective self-regulation change techniques to promote mental wellbeing among adolescents: a meta-analysis

    NARCIS (Netherlands)

    Genugten, L. van; Dusseldorp, E.; Massey, E.K.; Empelen, P. van

    2017-01-01

    Mental wellbeing is influenced by self-regulation processes. However, little is known on the efficacy of change techniques based on self-regulation to promote mental wellbeing. The aim of this meta-analysis is to identify effective self-regulation techniques (SRTs) in primary and secondary

  14. Primary epiploic appendagitis

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez

    2013-07-01

    Full Text Available Primary epiploic appendagitis (PEA is a seldom reported disease caused by spontaneous torsion of one or more epiploic appendices. The aim of this study is to describe two cases of PEA reviewing the main aspects of the diagnosis and treatment of disease. Case report: Case 1 Male patient, 55 years old, obese, with abdominal right iliac fossa (RIF pain for two days. Abdominal examination showed pain on palpation in the RIF with rebound tenderness. Abdominal computed tomography identified lobulated lesion in the cecum, measuring 4.5 cm in diameter, which was suggestive of PEA or early neoplasm of the colon wall. The lapa- roscopic assessment confirmed the diagnosis of PEA and the appendix was removed. The pa- tient had a satisfactory outcome, being discharged on the second postoperative day. Case 2 Female patient, obese, 47 years old, with abdominal pain for six days, with sudden RIF onset. She had pain at palpation with rebound tenderness. Acute diverticulitis was suspected and patient underwent abdominal CT that identified PEA in the sigmoid colon. After expectant management, the patient showed progressive improvement resuming her activities in seven days. PEA is a rarely recalled condition during the investigation of inflammatory acute abdo- men which can be easily recognized by modern imaging methods of assessment. Resumo: Apendagite epiplóica primária (AEP é uma enfermidade raramente descrita, ocasionada pela torção espontânea de um ou mais apêndices epiplóicos. O objetivo deste estudo é descrever dois casos de AEP revisando os principais aspectos do diagnóstico e tratamento da doença. Relato dos Casos: 1° Homem, 55 anos, obeso com dor abdominal em FID há dois dias. No exame do abdômen apresentava dor à palpação na FID e descompressão brusca presente. A tomografia computadorizada do abdômen identificou lesão expansiva no ceco, lobulada, medindo 4,5 cm de diâmetro, suspeitando-se de AEP ou neoplasia primitiva da parede c

  15. Regulating household financial advice

    Directory of Open Access Journals (Sweden)

    Benjamin F. Cummings

    2012-08-01

    Full Text Available This paper reviews economic theory related to investment advice. This theory explains 1 why financial advisors need to be carefully regulated for the benefit of both the investment advice industry and for consumers, 2 why principles-based regulation (e.g., a fiduciary standard is more efficient than rules-based regulation, 3 why dual regulation of financial professionals providing investment or insurance advice is inefficient and inequitable policy, and 4 why the application of a universal and uniform fiduciary standard will be difficult to implement.

  16. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    Within hunting, wildlife populations are estimated to be too high in many countries which is assumed to be due to the market failure, that each hunter harvests too little compared to what the regulator wants. This may be due to the existing regulation which, among other things, requires knowledge...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...... to the existing regulation....

  17. Nuclear safety and regulation

    International Nuclear Information System (INIS)

    Kim, Hho Jung

    2000-03-01

    This book contains 12 chapters, which are atom and radiation, nuclear reactor and kinds of nuclear power plant, safeguard actuation system and stability evaluation for rock foundation of nuclear power plant, nuclear safety and principle, safety analysis and classification of incident, probabilistic safety assessment and major incident, nuclear safety regulation, system of nuclear safety regulation, main function and subject of safety regulation in nuclear facilities, regulation of fuel cycle and a nuclear dump site, protection of radiation and, safety supervision and, safety supervision and measurement of environmental radioactivity.

  18. The strength of primary care in Europe: an international comparative study.

    Science.gov (United States)

    Kringos, Dionne; Boerma, Wienke; Bourgueil, Yann; Cartier, Thomas; Dedeu, Toni; Hasvold, Toralf; Hutchinson, Allen; Lember, Margus; Oleszczyk, Marek; Rotar Pavlic, Danica; Svab, Igor; Tedeschi, Paolo; Wilm, Stefan; Wilson, Andrew; Windak, Adam; Van der Zee, Jouke; Groenewegen, Peter

    2013-11-01

    A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking. Evaluation of strength of primary care in Europe. International comparative cross-sectional study performed in 2009-2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey. Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts' consultations. Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries. Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.

  19. Primary ectopic frontotemporal extradural craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Reza Pourkhalili

    2016-01-01

    Full Text Available We present a case of primary ectopic frontotemporal extradural craniopharyngioma. Primary ectopic craniopharyngiomas are very rare and have been reported involving the fourth ventricle, infrasellar region, lateral ventricle, temporal area, cerebellopontine angle, clivus, corpus callosum, and prepontine cistern. There was just 1 case of craniopharyngioma previously presented in the literature, with nearly same location as the presenting case.

  20. Methotrexate for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since...... that last review version, follow-up data of the included trials have been published....

  1. Primary Science Interview: Science Sparks

    Science.gov (United States)

    Bianchi, Lynne

    2016-01-01

    In this "Primary Science" interview, Lynne Bianchi talks with Emma Vanstone about "Science Sparks," which is a website full of creative, fun, and exciting science activity ideas for children of primary-school age. "Science Sparks" started with the aim of inspiring more parents to do science at home with their…

  2. Cardiovascular Risk in Primary Hyperaldosteronism

    NARCIS (Netherlands)

    Prejbisz, A.; Warchol-Celinska, E.; Lenders, J.W.M.; Januszewicz, A.

    2015-01-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary

  3. Primary care research in Denmark

    DEFF Research Database (Denmark)

    Vedsted, Peter; Kallestrup, Per

    2016-01-01

    International Perspectives on Primary Care Research examines how the evidence base from primary care research can strengthen health care services and delivery, tackle the growing burden of disease, improve quality and safety, and increase a person-centred focus to health care. Demonstrating...... the inter-professional nature of the discipline, the book also features a section on cross-nation organisations and primary care networks supporting research. National perspectives are offered from researchers in 20 countries that form part of the World Organization of Family Doctors, providing case...... histories from research-rich to resource-poor nations that illustrate the range of research development and capacity building. This book argues the importance of primary care research, especially to policy makers, decision makers and funders in informing best practice, training primary health care providers...

  4. Control Method for Variable Speed Wind Turbines to Support Temporary Primary Frequency Control

    DEFF Research Database (Denmark)

    Wang, Haijiao; Chen, Zhe; Jiang, Quanyuan

    2014-01-01

    This paper develops a control method for variable speed wind turbines (VSWTs) to support temporary primary frequency control of power system. The control method contains two parts: (1) up-regulate support control when a frequency drop event occurs; (2) down-regulate support control when a frequen...

  5. Radioactive waste management and regulation

    International Nuclear Information System (INIS)

    Willrich, M.; Lester, R.K.; Greenberg, S.C.; Mitchell, H.C.; Walker, D.A.

    1977-01-01

    Purpose of this book is to assist in developing public policy and institutions for the safe management of radioactive waste, currently and long term. Both high-level waste and low-level waste containing transuranium elements are covered. The following conclusions are drawn: the safe management of post-fission radioactive waste is already a present necessity and an irreversible long-term commitment; the basic goals of U.S. radioactive waste policy are unclear; the existing organization for radioactive waste management is likely to be unworkable if left unchanged; and the existing framework for radioactive waste regulation is likely to be ineffective if left unchanged. The following recommendations are made: a national Radioactive Waste Authority should be established as a federally chartered public corporation; with NRC as the primary agency, a comprehensive regulatory framework should be established to assure the safety of all radioactive waste management operations under U.S. jurisdiction or control; ERDA should continue to have primary government responsibility for R and D and demonstration of radioactive waste technology; and the U.S. government should propose that an international Radioactive Waste Commission be established under the IAEA

  6. Peak regulation right

    International Nuclear Information System (INIS)

    Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

    2005-01-01

    A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

  7. Soft Regulators, though judges

    NARCIS (Netherlands)

    de Geest, G.G.A.; Dari Mattiacci, G.

    Judges have a tendency to be more demanding than regulators. In the United States, a majority of the courts has adopted the rule that the unexcused violation of a statutory standard is negligence per se. However, the converse does not hold: compliance with regulation does not relieve the injurer of

  8. Mortgage market regulation: Europe

    NARCIS (Netherlands)

    Aalbers, M.B.; Smith, S.J.

    2012-01-01

    Despite several European Union (EU) initiatives, there is only limited pan-European mortgage market regulation. The EU strategy can be characterised as one of parallel liberalisation and consolidation. This article highlights the key differences in regulation among European mortgage markets.

  9. The Coming Primary Care Revolution.

    Science.gov (United States)

    Ellner, Andrew L; Phillips, Russell S

    2017-04-01

    The United States has the most expensive, technologically advanced, and sub-specialized healthcare system in the world, yet it has worse population health status than any other high-income country. Rising healthcare costs, high rates of waste, the continued trend towards chronic non-communicable disease, and the growth of new market entrants that compete with primary care services have set the stage for fundamental change in all of healthcare, driven by a revolution in primary care. We believe that the coming primary care revolution ought to be guided by the following design principles: 1) Payment must adequately support primary care and reward value, including non-visit-based care. 2) Relationships will serve as the bedrock of value in primary care, and will increasingly be fostered by teams, improved clinical operations, and technology, with patients and non-physicians assuming an ever-increasing role in most aspects of healthcare. 3) Generalist physicians will increasingly focus on high-acuity and high-complexity presentations, and primary care teams will increasingly manage conditions that specialists managed in the past. 4) Primary care will refocus on whole-person care, and address health behaviors as well as vision, hearing, dental, and social services. Design based on these principles should lead to higher-value healthcare, but will require new approaches to workforce training.

  10. Regulation as Rhetoric

    DEFF Research Database (Denmark)

    Boll, Karen; Györy, Csaba

    This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax...... and Customs Administration (SKAT) which is the national tax regulator in Denmark. SEC operates in a US context where the agency fights to get trust, while SKAT operates in a context where high trust in public agencies is a basic condition. We argue, however, that despite the radically different institutional...... engage reflectively in image promotion which serves two purposes: establishing and maintaining legitimacy in a particular social and political environment and producing compliance. Further, we argue that this regulation is a form of ‘post-bureaucratic’ regulation in which compliance is achieved...

  11. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera....... Finally, we argue that, in Asia, governments act as a structuration mechanism which challenges the current understanding of CSR.......This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... and environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  12. Primary amenorrhea: diagnosis and management.

    Science.gov (United States)

    Marsh, Courtney A; Grimstad, Frances W

    2014-10-01

    Puberty is a defining time of many adolescents' lives. It is a series of events that includes thelarche, pubarche, and menarche. Primary amenorrhea is the absence of menarche. There are numerous etiologies including outflow tract obstructions, gonadal dysgenesis, and anomalies of the hypothalamic axis. This review's aims are to define primary amenorrhea and describe the various causes, their workups, associated comorbidities, and treatment options. At the end, a generalist should be able to perform an assessment of an adolescent who presents with primary amenorrhea and, if warranted, begin initial treatment.

  13. Primary vertebral tumours in children

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Masel, J.; Diard, F.; Ferrari-Ciboldi, F.; Le Dosseur, P.; Labatut, J.

    1984-03-01

    20 cases of primary benign and malignant bone tumours in children were reported. The most common tumours were Ewing's sarcoma, aneurismal bone cyst, benign osteoblastoma and osteoid osteoma. Some rare primary bone tumours in children (osteochondroma, chondroblastoma 6F, primary lymphoma of bone and neurofibromatosis with unusual cervical spinal changes) were also reported. The authors believe that radiographic findings together with clinical history and clinical examination may yield a high percentage of accurate diagnoses. Although microscopy is essential in the final diagnosis, the microscopic report should be also accepted with caution.

  14. Primary Productivity (PP_Master)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set included primary production for each subregion in the study (Georges Bank, Gulf of Maine, Southern New England, Middle Atlantic Bight) . The data came...

  15. Problems of Primary Education Today

    Science.gov (United States)

    Dubova, M. V.

    2014-01-01

    Primary education in Russia has failed to adapt to the needs of post-Soviet society, and is still based on rote learning and memorization instead of learning through discovery and learning to use and apply what is learned.

  16. Primary sclerosing cholangitis and pregnancy

    Directory of Open Access Journals (Sweden)

    Casper Q. Kammeijer

    2011-08-01

    Full Text Available Primary sclerosing cholangitis is a progressive disease, and coincidentally in pregnancy it is rare. It is characterized by progressive inflammation and destruction of bile ducts finally resulting in liver failure. A rare case of primary sclerosing cholangitis in pregnancy is presented. The course of the pregnancy was marked by threatened preterm delivery and exacerbation of cholestasis. She was successfully treated with ursodeoxycholic acid (UDCA. Although, primary sclerosing cholangitis has both maternal and fetal effects on pregnancy, the overall outcome is favorable. Only few cases have been reported using high dose ursodeoxycholic acid for primary sclerosing cholangitis in pregnancy, it often improves pruritus but has no protection against stillbirth. Data on the safety to the fetus or neonate and long-term outcome are scarce.

  17. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    adedamla

    Quarry industry has become a major means of livelihood in Ebonyi state, but insufficient data exists on their operations ... of Dust Mask among Crushers of Selected Quarry (Crushed ... Journal of Community Medicine and Primary Health Care.

  18. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  19. Structures in the primary spectrum

    International Nuclear Information System (INIS)

    Kempa, J.; Knurenko, S.P.; Malecki, R.

    2009-01-01

    Structures in the energy spectrum of primary cosmic rays at the 'knee' region and for energies higher than 1 EeV are obtained through studying extensive air showers (EAS). The main problem of the research is the fact that we work in the ranges of highly fluctuating parameters used to obtain the primary energy spectrum. In this paper the log-normal distribution for the error function has been used in convolution with the power spectrum to explain the Yakutsk experimental data. Similar results have been obtained for the gamma distribution as the error function. Using the power law primary spectrum in the energy region around 10 19 eV we will argue that the primary Yakutsk spectrum is overestimated. In the best case this overestimation is not less than 42%.

  20. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    ajiboro

    3Department of Community and Primary Health Care, College of Medicine, University of Lagos, Idiaraba, ... Some of the participants (45.3%) carry out physical exercises such as walking ..... hypertension, continuous effective management of.

  1. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    2Primary Health Care Department, Ikpoba Okha Local Government Area, Benin City, ... selected from each of the ten wards in the LGA using multistage sampling technique. ..... Knowledge of HIV/AIDS Insurance Companies in Lagos State.

  2. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    Client Satisfaction with Antenatal Care Services in Primary Health Care. Centres in Sabon ... important information about how well clinicians and the population of women within child bearing. 8 ..... model. Health and Quality of Life outcomes.

  3. Primary optic nerve sheath meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Jeremic, Branislav [International Atomic Energy Agency, Vienna (Austria); Pitz, Susanne (eds.) [University Eye Hospital, Mainz (Germany)

    2008-07-01

    Optic nerve sheath meningioma (ONSM) is a rare tumour. Cases are usually separated into primary ONSM, which arises either intraorbitally or, less commonly, intracanalicularly, and secondary ONSM, which arises intracranially and subsequently invades the optic canal and orbit. This is the first book to cover all important aspects of the diagnosis and treatment of primary ONSM. After a general introduction, individual chapters discuss the clinical presentation, clinical examination and diagnosis, imaging, and histology. Treatment options are then addressed in detail, with special emphasis on external beam radiation therapy, and in particular stereotactic fractionated radiation therapy. The latter has recently produced consistently good results and is now considered the emerging treatment of choice for the vast majority of patients with primary ONSM. This well-illustrated book will prove invaluable to all practitioners who encounter primary ONSM in their clinical work. (orig.)

  4. Allegheny County Primary Care Access

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The data on health care facilities includes the name and location of all the hospitals and primary care facilities in Allegheny County. The current listing of...

  5. & PRIMARY HEALTH CARE COMMUNITY MEDICINE

    African Journals Online (AJOL)

    Family planning is an important preventive measure against maternal and child ... users of the services, desire for more children, fear of side effects and partner's ... It is an essential component of primary development across the regions .

  6. Risk-informed regulation

    International Nuclear Information System (INIS)

    Hoffman, D.R.

    2003-01-01

    In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

  7. Characteristics of Sissi primary beam

    International Nuclear Information System (INIS)

    Nghiem, P.; Payet, J.; Tkatchenko, A.

    1994-01-01

    This study concerns the definition of the Sissi primary beam characteristics. The calculations have been carried out in two steps : -a study of primary and secondary order with the help of BETA matrix code -a study of superior orders with the help of ZGOUBI code which is able to take into consideration the measured fields and in which the movement equations are integrated numerically. (O.L.). 9 figs., 3 tabs

  8. Insomnia (primary) in older people

    OpenAIRE

    Alessi, Cathy; Vitiello, Michael V

    2011-01-01

    Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include medical and psychiatric illnesses, psychological factors, stress, daytime napping, and hyperarousal.Primary insomnia is a chronic and relapsing condition that may increase the risks of accidents.Primary insomnia is chronic insomnia without specific underlying medical, psychiatric, or other sleep ...

  9. Hyperuricemia in Childhood Primary Hypertension

    OpenAIRE

    Feig, Daniel I.; Johnson, Richard J.

    2003-01-01

    Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18...

  10. Glucocorticosteroids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis...... sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis...

  11. Primary system boron dilution analysis

    International Nuclear Information System (INIS)

    Crump, R.J.; Naretto, C.J.; Borgen, R.A.; Rockhold, H.C.

    1978-01-01

    The results are presented for an analysis conducted to determine the potential paths through which nonborated water or water with insufficient boron concentration might enter the LOFT primary coolant piping system or reactor vessel to cause dilution of the borated primary coolant water. No attempt was made in the course of this analysis to identify possible design modifications nor to suggest changes in administrative procedures or controls

  12. Epigenetic Regulation of Adipokines

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  13. The power of regulation

    International Nuclear Information System (INIS)

    Lewis, M.G.

    1995-01-01

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  14. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  15. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2016-09-01

    regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

  16. Developing young adolescents’ self-regulation by means of formative assessment: A theoretical perspective

    OpenAIRE

    Meusen-Beekman, Kelly; Joosten-ten Brinke, Desirée; Boshuizen, Els

    2018-01-01

    Fostering self-regulated learning (SRL) has become increasingly important at various educational levels. Most studies on SRL have been conducted in higher education. The present literature study aims toward understanding self-regulation processes of students in primary and secondary education. We explored the development of young students’ self-regulation from a theoretical perspective. In addition, effective characteristics for an intervention to develop young students’ self-regulation were ...

  17. The Roles of Primary Cilia in Cardiovascular System

    Science.gov (United States)

    2016-10-01

    stages of heart development. An example is the Hedgehog (Hh) signaling pathway which regulates the L-R asymmetry in vertebrates and promotes the...Seol AD, So PL, et al. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 2009; 15(9): 1055-61. [29...Pauerstein CJ. Anatomy and physiology of the fallopian tube. Clin Obstet Gynecol 1980; 23(4): 1177-93. [38] Lyons RA, Saridogan E, Djahanbakhch O

  18. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray.

    Science.gov (United States)

    Xie, Wengui; Ji, Lixin; Zhao, Teng; Gao, Pengfei

    2015-05-09

    A number of genes have been identified to be related with primary osteoporosis while less is known about the comprehensive interactions between regulating genes and proteins. We aimed to identify the differentially expressed genes (DEGs) and regulatory effects of transcription factors (TFs) involved in primary osteoporosis. The gene expression profile GSE35958 was obtained from Gene Expression Omnibus database, including 5 primary osteoporosis and 4 normal bone tissues. The differentially expressed genes between primary osteoporosis and normal bone tissues were identified by the same package in R language. The TFs of these DEGs were predicted with the Essaghir A method. DAVID (The Database for Annotation, Visualization and Integrated Discovery) was applied to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DEGs. After analyzing regulatory effects, a regulatory network was built between TFs and the related DEGs. A total of 579 DEGs was screened, including 310 up-regulated genes and 269 down-regulated genes in primary osteoporosis samples. In GO terms, more up-regulated genes were enriched in transcription regulator activity, and secondly in transcription factor activity. A total 10 significant pathways were enriched in KEGG analysis, including colorectal cancer, Wnt signaling pathway, Focal adhesion, and MAPK signaling pathway. Moreover, total 7 TFs were enriched, of which CTNNB1, SP1, and TP53 regulated most up-regulated DEGs. The discovery of the enriched TFs might contribute to the understanding of the mechanism of primary osteoporosis. Further research on genes and TFs related to the WNT signaling pathway and MAPK pathway is urgent for clinical diagnosis and directing treatment of primary osteoporosis.

  19. Cardiac autonomic control in adolescents with primary hypertension

    Directory of Open Access Journals (Sweden)

    Havlíceková Z

    2009-12-01

    Full Text Available Abstract Background Impairment in cardiovascular autonomic regulation participates in the onset and maintenance of primary hypertension. Objective The aim of the present study was to evaluate cardiac autonomic control using long-term heart rate variability (HRV analysis in adolescents with primary hypertension. Subjects and methods Twenty two adolescent patients with primary hypertension (5 girls/17 boys aged 14-19 years and 22 healthy subjects matched for age and gender were enrolled. Two periods from 24-hour ECG recording were evaluated by HRV analysis: awake state and sleep. HRV analysis included spectral power in low frequency band (LF, in high frequency band (HF, and LF/HF ratio. Results In awake state, adolescents with primary hypertension had lower HF and higher LF and LF/HF ratio. During sleep, HF was lower and LF/HF ratio was higher in patients with primary hypertension. Conclusions A combination of sympathetic predominance and reduced vagal activity might represent a potential link between psychosocial factors and primary hypertension, associated with increased cardiovascular morbidity.

  20. Toward a Personalized Science of Emotion Regulation

    Science.gov (United States)

    Doré, Bruce P.; Silvers, Jennifer A.; Ochsner, Kevin N.

    2018-01-01

    The ability to successfully regulate emotion plays a key role in healthy development and the maintenance of psychological well-being. Although great strides have been made in understanding the nature of regulatory processes and the consequences of deploying them, a comprehensive understanding of emotion regulation that can specify what strategies are most beneficial for a given person in a given situation is still a far-off goal. In this review, we argue that moving toward this goal represents a central challenge for the future of the field. As an initial step, we propose a concrete framework that (i) explicitly considers emotion regulation as an interaction of person, situation, and strategy, (ii) assumes that regulatory effects vary according to these factors, and (iii) sets as a primary scientific goal the identification of person-, situation-, and strategy-based contingencies for successful emotion regulation. Guided by this framework, we review current questions facing the field, discuss examples of contextual variation in emotion regulation success, and offer practical suggestions for continued progress in this area. PMID:29750085

  1. Regulations and classification advice: transport safety

    International Nuclear Information System (INIS)

    Davies, M.; Owen, K.

    1990-01-01

    The packaging of radioactive material for transport must conform with the regulations of the International Atomic Energy Agency (IAEA). These regulations are extensive and complex and require specialist interpretation. Packaging must be designed to contain the material, to limit radiation to safe levels, and to maintain the material in a safe state under both normal and accident conditions. British Nuclear Fuels Ltd. (BNFL) developed the TRANAID expert system to provide automated expert advice on the subject. It is used at BNFL and by other users internationally. The system was produced to meet an internal BNFL emphasis on accurate consistent and reliable interpretation of the complex IAEA regulations; and to provide a commercial product which would meet an external need. TRANAID provides reliable and consistent advice on safe transport procedures which reduce the workload on scarce skilled personnel, and allows them to concentrate on their primary task of packaging design. TRANAID also avoids overclassifying radioactive shipments, which would lead to the use of more expensive packaging than strictly is required. The IAEA regulations are applied internationally, and so there is a large potential worldwide market. The indications from the initial response are that future sales and use are expected to more than cover the investment. Other non-quantifiable benefits include the provision of consistent advice within a uniform approach, the safe-guarding of knowledge of the IAEA regulations, training and improvement in the expertise of users, improved management control, and enhancement of the professional image of BNFL. (author)

  2. Legislation and regulation

    International Nuclear Information System (INIS)

    1998-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation

  3. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    . The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  4. Legislation and regulation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation.

  5. Spongiosa Primary Development: A Biochemical Hypothesis by Turing Patterns Formations

    Directory of Open Access Journals (Sweden)

    Oscar Rodrigo López-Vaca

    2012-01-01

    Full Text Available We propose a biochemical model describing the formation of primary spongiosa architecture through a bioregulatory model by metalloproteinase 13 (MMP13 and vascular endothelial growth factor (VEGF. It is assumed that MMP13 regulates cartilage degradation and the VEGF allows vascularization and advances in the ossification front through the presence of osteoblasts. The coupling of this set of molecules is represented by reaction-diffusion equations with parameters in the Turing space, creating a stable spatiotemporal pattern that leads to the formation of the trabeculae present in the spongy tissue. Experimental evidence has shown that the MMP13 regulates VEGF formation, and it is assumed that VEGF negatively regulates MMP13 formation. Thus, the patterns obtained by ossification may represent the primary spongiosa formation during endochondral ossification. Moreover, for the numerical solution, we used the finite element method with the Newton-Raphson method to approximate partial differential nonlinear equations. Ossification patterns obtained may represent the primary spongiosa formation during endochondral ossification.

  6. The regulation of appetite

    OpenAIRE

    Druce, M; Bloom, S R

    2006-01-01

    The worsening global obesity epidemic, particularly the increase in childhood obesity, has prompted research into the mechanisms of appetite regulation. Complex pathways modulate energy balance, involving appetite centres in the hypothalamus and brain stem, and hormonal signals of energy status released by the gut and by the periphery. Better understanding of appetite regulation improves understanding of the aetiology of obesity. Manipulation of this homoeostatic system offers potentially use...

  7. Corruption, Institutions and Regulation

    OpenAIRE

    Michael Breen; Robert Gillanders

    2011-01-01

    We analyze the effects of corruption and institutional quality on the quality of business regulation. Our key findings indicate that corruption negatively aspects the quality of regulation and that general institutional quality is insignificant once corruption is controlled for. These findings hold over a number of specifications which include additional exogenous historical and geographic controls. The findings imply that policy-makers should focus on curbing corruption to improve regulat...

  8. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  9. Gender equality in primary immunisation

    Directory of Open Access Journals (Sweden)

    Deepak S Khismatrao

    2015-01-01

    Full Text Available Context: Immunization, a well-known and effective method of preventing childhood illnesses is basic service under primary health care. Most surveys in India measure primary immunization coverage and quality, but no "Gender Equality." Aims: Assess "Gender Equality" in primary immunization with reference to coverage, quality, and place of immunization. Settings and Design: Cross-sectional survey in a primary health center, Pune, Maharashtra using World Health Organization 30-cluster sampling method with 14 beneficiaries (7 girls and 7 boys to be selected from each cluster. Instead of 420 children, data collected for 345 children, as requisite numbers of children were not available in low population villages and also children whose mothers were not present during survey were excluded. Materials and Methods: Vaccination data collected from either records and/or history by mother. Children born on or between 13-09-2009 and 13-09-2010, were included. Statistical Analysis Used: SPSS 14.01 version with Chi-square as test of significance. Results: Of the study population, 171 (49.6% were females and 174 (50.4% males. A total of 64.1% children had immunization records with female proportion 69.0% and males 59.2%. Primary immunization coverage was 80.0%, with female proportion 82.5% and males 77.6%. One male child was completely unimmunized and remaining partially immunized, with unaware of schedule and illness of child being major reasons for partial immunization. There was no gender wise statistically significant difference observed in Primary Immunization with reference to coverage, quality, and place of immunization. Conclusions: Immunization coverage is nearing 85% benchmark with major contribution from Universal Immunization Program. Gender Equality observed in primary immunization. Preservation of immunization records by community and timely vaccinations are areas for improvement.

  10. Interpersonal emotion regulation.

    Science.gov (United States)

    Zaki, Jamil; Williams, W Craig

    2013-10-01

    Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

  11. Abortion patients' perceptions of abortion regulation.

    Science.gov (United States)

    Cockrill, Kate; Weitz, Tracy A

    2010-01-01

    Most states regulate abortion differently than other health care services. Examples of these regulations include mandating waiting periods and the provision of state-authored information, and prohibiting private and public insurance coverage for abortion. The primary purpose of this paper is to explore abortion patients' perspectives on these regulations. We recruited 20 participants from three abortion providing facilities located in two states in the U.S. South and Midwest. Using a survey and semistructured interview, we collected information about women's knowledge of abortion regulation and policy preferences. During the interviews, women weighed the pros and cons of abortion regulations. We used grounded theory analytical techniques and matrix analysis to organize and interpret the data. We discovered five themes in these women's considerations of regulation: responsibility, empathy, safe and accessible health care, privacy, and equity. Women in the study generally supported policies that they felt protected women or informed decisions. However, most women also opposed laws mandating two-day abortion appointments for women who were traveling long distances. Women tended to favor financial coverage of abortion, arguing that it could help poor women afford abortion or reduce state expenditures. Overall the study participants' opinions on abortion policy reflect key values for advocates and policy makers to consider: responsibility, empathy, safe and accessible health care, privacy, and equity. Future work should examine abortion regulations in light of these shared values. Laws that promote misinformation or prohibit accommodations of unique circumstances are not consistent the positions articulated by the subjects in our study. Copyright 2010 Jacobs Institute of Women

  12. Cardiovascular Risk in Primary Hyperaldosteronism.

    Science.gov (United States)

    Prejbisz, A; Warchoł-Celińska, E; Lenders, J W M; Januszewicz, A

    2015-12-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary aldosteronism varies considerably between different studies among hypertensive patients, depending on patient selection, the used diagnostic methods, and the severity of hypertension. Prevalence rates vary from 4.6 to 16.6% in those studies in which confirmatory tests to diagnose primary aldosteronism were used. There is also growing evidence indicating that prolonged exposure to elevated aldosterone concentrations is associated with target organ damage in the heart, kidney, and arterial wall, and high cardiovascular risk in patients with primary aldosteronism. Therefore, the aim of treatment should not be confined to BP normalization and hypokalemia correction, but rather should focus on restoring the deleterious effects of excess aldosterone on the cardiovascular system. Current evidence convincingly demonstrates that both surgical and medical treatment strategies beneficially affect cardiovascular outcomes and mortality in the long term. Further studies can be expected to provide better insight into the relationship between cardiovascular risk and complications and the genetic background of primary aldosteronism. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Federal Aviation Regulations - National Aviation Regulations of Russia

    Science.gov (United States)

    Chernykh, O.; Bakiiev, M.

    2018-03-01

    Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

  14. Primary malignant small bowel tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

    1990-07-15

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

  15. Primary malignant small bowel tumor

    International Nuclear Information System (INIS)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

    1990-01-01

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings

  16. Primary thyroid lymphoma: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo-Cheol; Han, Moon Hee E-mail: hanmh@radcom.snu.ac.kr; Kim, Keon Ha; Jae, Hwan Jun; Lee, Sang Hyun; Kim, Sam Soo; Kim, Kwang Hyun; Chang, Kee-Hyun

    2003-06-01

    Introduction: To evaluate the computed tomographic (CT) findings of primary thyroid lymphoma. Methods and material: The clinicopathological data and CT images of nine patients with primary thyroid lymphoma were retrospectively reviewed. The CT appearances were classified into three types: type 1, a solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, a homogeneously enlarged both thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. Results: All patients had a rapidly enlarging thyroid mass and coexistent Hashimoto's thyroiditis. One patient showed type 1 pattern, three type 2, and five type 3. Six patients had homogeneous tumor isoattenuating to surrounding muscles. The tumors had a strong tendency to compress normal remnant thyroid and the surrounding structure without invasion. Conclusion: Primary thyroid lymphoma should be included in the differential diagnosis when old female had a homogeneous thyroidal mass isoattenuating to muscles, which does not invade surrounding structures.

  17. Recurrent Primary Spinal Hydatid Cyst

    Directory of Open Access Journals (Sweden)

    Okan Turk

    2015-03-01

    Full Text Available Primary hydatid disease of spine is rare and spinal hydatitosis constitute only 1% of all hydatitosis. We report a case of recurrent primary intraspinal extradural hydatid cyst of the thoracic region causing progressive paraparesis. The patient was operated 16 years ago for primary spinal hydatid disease involvement and was instrumented dorsally for stabilization. The magnetic resonance imaging (MRI of thoracic spine showed a cystic lesion at T11-12 level and compressed spinal cord posterolaterally. Intraspinal cyst was excised through T11-12 laminectomy which made formerly. The early postoperative period showed a progressive improvement of his neurological deficit and he was discharged with antihelmintic treatment consisting of albendazole and amoxicillin-sulbactam combination. [Cukurova Med J 2015; 40(Suppl 1: 84-89

  18. Primary prevention of chronic obstructive pulmonary disease in primary care.

    Science.gov (United States)

    van der Molen, Thys; Schokker, Siebrig

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is a prevalent disease, with cigarette smoking being the main risk factor. Prevention is crucial in the fight against COPD. Whereas primary prevention is targeted on whole populations, patient populations are the focus of primary care; therefore, prevention in this setting is mainly aimed at preventing further deterioration of the disease in patients who present with the first signs of disease (secondary prevention). Prevention of COPD in primary care requires detection of COPD at an early stage. An accurate definition of COPD is crucial in this identification process. The benefits of detecting new patients with COPD should be determined before recommending screening and case-finding programs in primary care. No evidence is available that screening by spirometry results in significant health gains. Effective treatment options in patients with mild disease are lacking. Smoking cessation is the cornerstone of COPD prevention. Because cigarette smoking is not only a major cause of COPD but is also a major cause of many other diseases, a decline in tobacco smoking would result in substantial health benefits.

  19. Summarizing primary and secondary effects

    DEFF Research Database (Denmark)

    Karlson, Kristian Bernt

    2013-01-01

    Current methods for decomposing class differentials in educational decisions into primary and secondary effects produce many parameters, rendering them ill-equipped for parsimonious comparisons across countries or birth cohorts. This paper develops a parametric method that provides an optimal...... summary of primary and secondary effects across discrete class origins. Under the testable assumption that the pattern of effects of class origins on academic ability is proportional to the pattern of effects of class origins on educational choice net of academic ability, the method returns a single...

  20. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  1. Primary carcinoma of the duodenum

    International Nuclear Information System (INIS)

    Steidle, B.; Huetter, B.; Ziegler, F.

    1984-01-01

    Primary carcinoma of the duodenum represents about 0.35% of all gastrointestinal carcinomas and is thus a rare disease. The radiological diagnosis of a duodenal origin is made more difficult by the close proximity of the pancreas, biliary system, right kidney and transverse colon. Histologically, duodenal malignant tumours are usually adenocarcinomas. Between 1973 and 1983, eight patients with primary duodenal carcinomas were diagnosed at the University of Tuebingen. Average age of the patients was 67 years. There was no sex difference. Average survival was 3.3 years. (orig.) [de

  2. Primary Posterior Mediastinum Hydatid Cyst

    International Nuclear Information System (INIS)

    Ahmed, M.; Eid, A. F.; Sheikh, M. Y.; Yiannakou, N.

    2014-01-01

    Primary posterior mediastinal hydatid cyst is a serious health problem for the Mediterranean countries. We diagnosed a case of a 46-year-old female with a primary posterior mediastinum hydatid cyst on CT and MRI. It was provisionally identified as either a hydatid cyst or bronchogenic cyst or neuroenteric cyst. CT guided aspiration with 18 gauge needle confirmed as hydatid sand. This is very rare in this population but it should be kept in mind when one is looking at any cyst in the posterior mediastinum. (author)

  3. Shoulder arthropathy in primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Nussbaum, A.J.; Doppman, J.L.

    1982-01-01

    An erosive arthropathy of the hands and wrists has been recognized in patients with primary and secondary hyperparathyroidism. Recently, intra-articular erosions of the humeral head were described in six patients who had been on chronic long-term hemodialysis with secondary hyperparathyroidism. We would like to present the finding of shoulder erosions in four patients with primary hyperparathyroidism and one patient with renal osteodystrophy and suggest that the humeral erosion can occur in both an intra-articular and peri-articular location. (orig.)

  4. Genetics Home Reference: primary spontaneous pneumothorax

    Science.gov (United States)

    ... Home Health Conditions Primary spontaneous pneumothorax Primary spontaneous pneumothorax Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Primary spontaneous pneumothorax is an abnormal accumulation of air in the ...

  5. To regulate or not to regulate?

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.; Wrixon, A. [IAEA, Vienna (Austria)

    2006-07-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on

  6. To regulate or not to regulate?

    International Nuclear Information System (INIS)

    Mason, G.; Wrixon, A.

    2006-01-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on

  7. The Ciliopathy Protein CC2D2A Associates with NINL and Functions in RAB8-MICAL3-Regulated Vesicle Trafficking.

    Directory of Open Access Journals (Sweden)

    Ruxandra Bachmann-Gagescu

    2015-10-01

    Full Text Available Ciliopathies are a group of human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in transduction of extra-cellular signals to the cell. This function requires the concentration of receptors and channels in the ciliary membrane, which is achieved by complex trafficking mechanisms, in part controlled by the small GTPase RAB8, and by sorting at the transition zone located at the entrance of the ciliary compartment. Mutations in the transition zone gene CC2D2A cause the related Joubert and Meckel syndromes, two typical ciliopathies characterized by central nervous system malformations, and result in loss of ciliary localization of multiple proteins in various models. The precise mechanisms by which CC2D2A and other transition zone proteins control protein entrance into the cilium and how they are linked to vesicular trafficking of incoming cargo remain largely unknown. In this work, we identify the centrosomal protein NINL as a physical interaction partner of CC2D2A. NINL partially co-localizes with CC2D2A at the base of cilia and ninl knockdown in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins and vesicle accumulation, similar to cc2d2a-/- phenotypes. Moreover, partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype of the mutants, indicating a genetic interaction in vivo, for which an illustration is found in patients from a Joubert Syndrome cohort. Similar to zebrafish cc2d2a mutants, ninl morphants display altered Rab8a localization. Further exploration of the NINL-associated interactome identifies MICAL3, a protein known to interact with Rab8 and to play an important role in vesicle docking and fusion. Together, these data support a model where CC2D2A associates with NINL to provide a docking point for cilia-directed cargo vesicles, suggesting a mechanism by which transition zone proteins can control the protein content of the ciliary

  8. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the ...

  9. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... mostly near the start of the gene known as the promoter. This region contains patterns scattered in the DNA that the TFs can recognize and bind to. Such binding can prompt the assembly of the pre-initiation complex which ultimately leads to transcription of the gene. In order to achieve the regulation...... on what characterizes a hippocampus promoter. Pairing CAGE with TF binding site prediction we identi¿ed a likely key regulator of hippocampus. Finally, we developed a method for CAGE exploration. While the DeepCAGE library characterized a full 1.4 million transcription initiation events it did not capture...

  10. Radiation emitting devices regulations

    International Nuclear Information System (INIS)

    1970-01-01

    The Radiation Emitting Devices Regulations are the regulations referred to in the Radiation Emitting Devices Act and relate to the operation of devices. They include standards of design and construction, standards of functioning, warning symbol specifications in addition to information relating to the seizure and detention of machines failing to comply with the regulations. The radiation emitting devices consist of the following: television receivers, extra-oral dental x-ray equipment, microwave ovens, baggage inspection x-ray devices, demonstration--type gas discharge devices, photofluorographic x-ray equipment, laser scanners, demonstration lasers, low energy electron microscopes, high intensity mercury vapour discharge lamps, sunlamps, diagnostic x-ray equipment, ultrasound therapy devices, x-ray diffraction equipment, cabinet x-ray equipment and therapeutic x-ray equipment

  11. Natural Gas Regulation

    International Nuclear Information System (INIS)

    1995-01-01

    The regulation of Natural Gas. Natural gas Regulation clarifies and consolidates the legal and institutional framework for development of the industry through six principal elements: 1) Establishment of a vision of the industry. 2) Development of regulatory objectives. 3) Determination of relationships among industry participants. 4) Clear specification of the role of PEMEX in the industry. 5) Definition of the functions of the Regulatory authority. 6) Creation of a transition regime. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implement the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

  12. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

  13. Primary pachydermoperiostosis: a case report.

    Science.gov (United States)

    Thappa, D M; Sethuraman, G; Kumar, G R; Elangovan, S

    2000-02-01

    Pachydermoperiostosis (PDP), a rare genodermatosis, occurred in a 38-year-old Indian male. He presented with progressive thickening of the skin on the face and scalp of 15 years duration. Widening of his wrists and ankles and broadening of the fingers and toes had also developed since then. He was born of a consanguineous marriage and had no family history of a similar disorder. He had the typical findings of complete form of PDP including cutis verticis gyrata, coarse facial features, clubbing of the digits in the skin, and periostosis and cortical thickening at the distal ends of long bones of the extremities and small bones of the hands and feet. PDP has two different forms--primary and secondary. These two entities are differentiated by family history and presence or absence of a primary lesion, usually in the lungs. Clinically, in secondary PDP, the cutaneous findings (pachydermia, seborrhoea, oiliness) are less severe than primary PDP; osteoarthropathy is more severe and painful in secondary PDP, especially with congenital heart disease. The present case was suffering from primary PDP that had expressed itself in its complete form.

  14. Primary syphilis of the fingers

    OpenAIRE

    Starzycki, Z

    1983-01-01

    Six patients were seen with primary syphilitic chancres on their fingers between 1965 and 1980. Of these, two had bipolar chancres on their fingers and genitals resulting from sexual foreplay. Because syphilis is rarely suspected in such cases diagnostic errors are common.

  15. Primary acalvaria: a case report

    International Nuclear Information System (INIS)

    Rios, Livia Teresa Moreira; Martins, Marilia da Gloria; Simoes, Vanda Maria Ferreira; Nunes, Marynea do Vale; Marques, Patricia Franco; Godoy, Silvia Helena Cavalcante de Souza

    2010-01-01

    Acalvaria is a rare congenital malformation of unknown pathogenesis characterized by the absence of the flat bones of the cranial vault, dura mater and associated muscles, while the central nervous system is usually preserved. The most accepted physiopathogenic theory suggests the presence of a post neurulation defect with normal placement the embryonic ectoderm. The present report describes neonatal imaging findings of primary acalvaria. (author)

  16. The Primary Dental Care Workforce.

    Science.gov (United States)

    Neenan, M. Elaine; And Others

    1993-01-01

    A study describes the characteristics of the current primary dental care workforce (dentists, hygienists, assistants), its distribution, and its delivery system in private and public sectors. Graduate dental school enrollments, trends in patient visits, employment patterns, state dental activities, and workforce issues related to health care…

  17. Primary Teachers Opinion about Homework

    Science.gov (United States)

    Matei, Stefania; Ciasca, Liliana

    2015-01-01

    Homework assignments trigger various perceptions and attitudes in students, parents or teachers: some overestimate them, others reject them, some do it with pleasure and to others they cause tears. Literature indicates both benefits and disadvantages of homework. In Romania, at primary level, homework is a systematic practice. The explanation is…

  18. Hypertrichosis due to primary hypothyroidism.

    OpenAIRE

    Stern, S R; Kelnar, C J

    1985-01-01

    A 10 year old girl with hypertrichosis associated with primary hypothyroidism that resolved after 6 months' replacement treatment with thyroxine is reported. It is important to consider the diagnosis of hypothyroidism in children with abnormal hairiness or distribution of body hair.

  19. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    ajiboro

    2Department of Community Medicine & Primary Care, Faculty of Clinical Sciences, ... It may result from road traffic accident, near saving basic principles in emergency care that even drowning, electric ... (4.3%) at place of work, 8 (11.4%) at.

  20. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    the_monk

    Journal of Community Medicine and Primary Health Care. 26 (1) 12-20 .... large proportions of the population work in the poor people use health care services far less than. 19 ... hypertension, cancers and road traffic accidents) below 1 dollar ...

  1. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    the_monk

    VPDs, this represents 17% of global total. 1 ... Knowledge, Attitude and Practice of Childhood Immunization ... Department of Community Health & Primary Care, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, ... include access to services, parental (maternal) ... Calmette Guerin (BCG) vaccine Oral Polio.

  2. Primary Boys and Hegemonic Masculinities.

    Science.gov (United States)

    Skelton, Christine

    1997-01-01

    Explores the relationships between primary-aged boys, hegemonic masculinities, and sexualized/violent behaviors in the school setting. Shows that hegemonic masculinities vary from school to school and that boys draw upon, negotiate, and reject aspects of the hegemonic masculinity of the school in the process of constructing their masculine…

  3. Primary Prevention of Eating Disorders.

    Science.gov (United States)

    Shisslak, Catherine M.; And Others

    1987-01-01

    Summarizes current understanding of anorexia nervosa and bulimia (clinical symptoms and outcome, prevalence and risk factors), offering suggestions for the primary prevention of these disorders at the individual, family, and community levels, and emphasizing prevention in the schools. (Author/KS)

  4. The Relevance of Primary Education

    Science.gov (United States)

    Coe, John

    2018-01-01

    This article sketches a vision of how primary education needs to be re-shaped to let schools focus more sharply on the development of children as individuals. Rapid social change requires a fundamental re-thinking of formal education and assessment. High-stakes testing must end. Greater weight must be given to the application of knowledge and…

  5. Primary Schooling in West Bengal

    Science.gov (United States)

    Sen, Amartya

    2010-01-01

    With his Nobel Prize award money, Amartya Sen set up the Pratichi Trust which carries out research, advocacy and experimental projects in basic education, primary health care, and women's development in West Bengal and Bangladesh. Professor Sen himself took active interest in this work--helping set the agenda, looking at the evidence from…

  6. Primary Sources and Inquiry Learning

    Science.gov (United States)

    Pappas, Marjorie L.

    2006-01-01

    In this article, the author discusses inquiry learning and primary sources. Inquiry learning puts students in the active role of investigators. Questioning, authentic and active learning, and interactivity are a few of the characteristics of inquiry learning that put the teacher and library media specialist in the role of coaches while students…

  7. Lead-free primary explosives

    Science.gov (United States)

    Huynh, My Hang V.

    2010-06-22

    Lead-free primary explosives of the formula (cat).sub.Y[M.sup.II(T).sub.X(H.sub.2O).sub.6-X].sub.Z, where T is 5-nitrotetrazolate, and syntheses thereof are described. Substantially stoichiometric equivalents of the reactants lead to high yields of pure compositions thereby avoiding dangerous purification steps.

  8. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    adedamla

    Background: The well-being of women and children is one of the major determinants ... The Sample for the study were women recruited from 11 primary health care ... respondents educational level and knowledge of preconception care (X =24.76, ... single adult or married couple) are in an optimal state .... The major site for.

  9. Primary Science Education in China

    Science.gov (United States)

    Pook, Gayle

    2013-01-01

    Consider the extent to which primary science teaching has evolved since it became a core subject in England with the introduction of the National Curriculum in 1988, and the pace at which theory-driven classroom practice has advanced. It is no wonder that, given the recent economic restructuring and boom in technological development in China,…

  10. Civil Engineering in Primary Schools

    Science.gov (United States)

    Brown, Martin; Strong, Alan

    2010-01-01

    For many children of primary school age, an engineer is the man who comes to service the central heating system or who fixes the family car when it breaks down. Most have never met a "real" professional engineer, and have no idea of what is involved in the exciting world of engineering. Most assume that engineers are men. To try to…

  11. Assessing primary care data quality.

    Science.gov (United States)

    Lim, Yvonne Mei Fong; Yusof, Maryati; Sivasampu, Sheamini

    2018-04-16

    Purpose The purpose of this paper is to assess National Medical Care Survey data quality. Design/methodology/approach Data completeness and representativeness were computed for all observations while other data quality measures were assessed using a 10 per cent sample from the National Medical Care Survey database; i.e., 12,569 primary care records from 189 public and private practices were included in the analysis. Findings Data field completion ranged from 69 to 100 per cent. Error rates for data transfer from paper to web-based application varied between 0.5 and 6.1 per cent. Error rates arising from diagnosis and clinical process coding were higher than medication coding. Data fields that involved free text entry were more prone to errors than those involving selection from menus. The authors found that completeness, accuracy, coding reliability and representativeness were generally good, while data timeliness needs to be improved. Research limitations/implications Only data entered into a web-based application were examined. Data omissions and errors in the original questionnaires were not covered. Practical implications Results from this study provided informative and practicable approaches to improve primary health care data completeness and accuracy especially in developing nations where resources are limited. Originality/value Primary care data quality studies in developing nations are limited. Understanding errors and missing data enables researchers and health service administrators to prevent quality-related problems in primary care data.

  12. Primary processes during water radiolysis

    International Nuclear Information System (INIS)

    Pikaev, A.K.

    1980-01-01

    Briefly reviewed are investigations of primary process mechanism taking place during radiolysis of water and similar systems, executed by direct and indirect methods. A conclusion is made on the important role of the water structure during radiolysis of aqueous solutions of some substances. A necessity to take account of this factor during consideration of radiolysis theoretical models is pointed out

  13. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    ajiboro

    Result: Majority of the mothers (89.2%) had primary/secondary education and 69.4% were traders. Most ... regards immunization, 22.7% of the children were not fully immunized. A total of 69 ..... Nigeria: Perception and Attitudes of the. 17.

  14. Primary acalvaria: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Rios, Livia Teresa Moreira, E-mail: ltlrios@terra.com.b [Universidade Federal do Maranhao (UFMA), Sao Luis, MA (Brazil). Hospital Universitario. Unidade de Diagnostico por Imagem; Martins, Marilia da Gloria [Universidade Federal do Maranhao (UFMA), Sao Luis, MA (Brazil). Hospital Universitario. Servico de Ginecologia e Obstetricia; Simoes, Vanda Maria Ferreira; Nunes, Marynea do Vale; Marques, Patricia Franco; Godoy, Silvia Helena Cavalcante de Souza [Universidade Federal do Maranhao (UFMA), Sao Luis, MA (Brazil). Hospital Universitario. Servico de Neonatologia

    2010-07-15

    Acalvaria is a rare congenital malformation of unknown pathogenesis characterized by the absence of the flat bones of the cranial vault, dura mater and associated muscles, while the central nervous system is usually preserved. The most accepted physiopathogenic theory suggests the presence of a post neurulation defect with normal placement the embryonic ectoderm. The present report describes neonatal imaging findings of primary acalvaria. (author)

  15. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    ajiboro

    ... Experience in a primary health care facility in Rivers State, South-South Nigeria. ... health center increased by 3.09% (p-value > 0.05); the patients that had their babies in the facility were ... 100, 000 live births, based on historical studies and.

  16. Phytotherapy in primary health care

    Science.gov (United States)

    Antonio, Gisele Damian; Tesser, Charles Dalcanale; Moretti-Pires, Rodrigo Otavio

    2014-01-01

    OBJECTIVE To characterize the integration of phytotherapy in primary health care in Brazil. METHODS Journal articles and theses and dissertations were searched for in the following databases: SciELO, Lilacs, PubMed, Scopus, Web of Science and Theses Portal Capes, between January 1988 and March 2013. We analyzed 53 original studies on actions, programs, acceptance and use of phytotherapy and medicinal plants in the Brazilian Unified Health System. Bibliometric data, characteristics of the actions/programs, places and subjects involved and type and focus of the selected studies were analyzed. RESULTS Between 2003 and 2013, there was an increase in publications in different areas of knowledge, compared with the 1990-2002 period. The objectives and actions of programs involving the integration of phytotherapy into primary health care varied: including other treatment options, reduce costs, reviving traditional knowledge, preserving biodiversity, promoting social development and stimulating inter-sectorial actions. CONCLUSIONS Over the past 25 years, there was a small increase in scientific production on actions/programs developed in primary care. Including phytotherapy in primary care services encourages interaction between health care users and professionals. It also contributes to the socialization of scientific research and the development of a critical vision about the use of phytotherapy and plant medicine, not only on the part of professionals but also of the population. PMID:25119949

  17. Primary pigmented nodular adrenocortical disease

    Directory of Open Access Journals (Sweden)

    Marie T Manipadam

    2011-01-01

    Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of ACTH-independent Cushing′s syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney′s complex. Bilateral adrenalectomy is the treatment of choice.

  18. Scenarios cancer in primary care.

    NARCIS (Netherlands)

    Velden, L.F.J. van der; Schellevis, F.G.

    2011-01-01

    Introduction: Previous studies predicted an increase in both the incidence and prevalence of cancer in the Netherlands. Other studies showed that cancer patients use primary care more frequently than non-cancer patients. Finally, during the “chronic phase” of the disease, task substitution from

  19. Second Languages in Primary Education.

    Science.gov (United States)

    Donoghue, Mildred R.; Kunkle, John F.

    A book on second languages in primary education, designed to assist both classroom teachers and language specialists, is presented. The following topics are addressed: (1) reasons for studying a second language; (2) reasons for children to learn a second language; (3) language choices; (4) qualifications of teachers; (5) FLES, bilingual education,…

  20. Primary Medical Care in Chile

    DEFF Research Database (Denmark)

    Scarpaci, Joseph L.

    Primary medical care in Chile: accessibility under military rule [Front Cover] [Front Matter] [Title Page] Contents Tables Figures Preface Chapter 1: Introduction Chapter 2: The Restructuring of Medical Care Financing in Chile Chapter 3: Inflation and Medical Care Accessibility Chapter 4: Help......-Seeking Behavior of the Urban Poor Chapter 5: Spatial Organization and Medical Care Accessibility Chapter 6: Conclusion...

  1. Primary Intradural Extraosseous Ewing's Sarcoma

    OpenAIRE

    Kim, Seok Won; Shin, Ho

    2009-01-01

    Ewing's sarcoma usually arises from skeletal bone, but rarely may have an extraskeletal origin. However, Ewing's sarcoma that originates around the spinal column, especially, the intradural extramedullary type is extremely rare. We report a rare case of primary intraspinal extraskeletal Ewing's sarcoma.

  2. QUANTITATIVE ANALYSIS OF FLUX REGULATION THROUGH HIERARCHICAL REGULATION ANALYSIS

    NARCIS (Netherlands)

    van Eunen, Karen; Rossell, Sergio; Bouwman, Jildau; Westerhoff, Hans V.; Bakker, Barbara M.; Jameson, D; Verma, M; Westerhoff, HV

    2011-01-01

    Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of V(max) can be dissected into the

  3. Quantitative analysis of flux regulation through hierarchical regulation analysis

    NARCIS (Netherlands)

    Eunen, K. van; Rossell, S.; Bouwman, J.; Westerhoff, H.V.; Bakker, B.M.

    2011-01-01

    Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of Vmax can be dissected into the

  4. The Impact of Regulating Social Science Research with Biomedical Regulations

    Science.gov (United States)

    Durosinmi, Brenda Braxton

    2011-01-01

    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  5. Public regulators and CSR

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2016-01-01

    The social licence to operate (SLO) concept is little developed in the academic literature so far. Deployment of the term was made by the United National (UN) Guiding Principles on Business and Human Rights and the UN ‘Protect, Respect and Remedy’ Framework, which apply SLO as an argument...... for responsible business conduct, connecting to social expectations and bridging to public regulation. This UN guidance has had a significant bearing on how public regulators seek to influence business conduct beyond Human Rights to broader Corporate Social Responsibility (CSR) concerns. Drawing on examples...

  6. Collaborative Tax Regulation

    DEFF Research Database (Denmark)

    Boll, Karen

    2016-01-01

    This article shows a new form of regulation within a tax administration where tax administrators abate tax evasion by nudging and motivating consumers to only purchase services from tax compliant businesses. This indirectly closes or forces tax evading businesses to change their practices, because...... stakeholders, i.e. the consumers, in the regulatory craft. The study is based on a qualitative methodology and draws on a unique case of regulation in the cleaning sector. This sector is at high risk of tax evasion and human exploitation of vulnerable workers operating in the informal economy. The article has...

  7. Public regulators and CSR

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2016-01-01

    of such public regulatory governance, this article explores and explains developments towards a juridification of CSR entailing efforts by public regulators to reach beyond jurisdictional and territorial limitations of conventional public law to address adverse effects of transnational economic activity. Through...... analysis of an expansion of law into the normative framing of what constitutes responsible business conduct, we demonstrate a process of juridification entailing a legal framing of social expectations of companies, a proliferation of law into the field of business ethics, and an increased regulation by law...

  8. Nuclear regulations and environment

    International Nuclear Information System (INIS)

    Oliveira, Antonio A.

    2001-01-01

    After an historical overview of the nuclear regulation system in Argentina a description is made of the country's Nuclear Regulatory Authority (ARN) and of its regulation and control functions. Its organic structure is also outlined. A detailed report is given of the environmental monitoring activities in the sites of the operating Argentine nuclear power plants as well as those of the nuclear research centres. A special reference is made of the monitoring of the relevant uranium mining districts in Argentina. The radon determination in houses of several regions of the country is also mentioned

  9. Nuclear regulation and safety

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed

  10. Regulated underground storage tanks

    International Nuclear Information System (INIS)

    1992-06-01

    This guidance package is designed to assist DOE Field operations by providing thorough guidance on the underground storage tank (UST) regulations. [40 CFR 280]. The guidance uses tables, flowcharts, and checklists to provide a ''roadmap'' for DOE staff who are responsible for supervising UST operations. This package is tailored to address the issues facing DOE facilities. DOE staff should use this guidance as: An overview of the regulations for UST installation and operation; a comprehensive step-by-step guidance for the process of owning and operating an UST, from installation to closure; and a quick, ready-reference guide for any specific topic concerning UST ownership or operation

  11. 78 FR 5997 - Amendments to National Marine Sanctuary Regulations

    Science.gov (United States)

    2013-01-28

    ...'' with ``in the aquarium trade''. The proposed change makes grammatical correction and updates the... and clarify regulations. 2. General Permit Categories ONMS has three ways by which it may authorize... are divided into several categories that correspond with the primary purpose of the proposed activity...

  12. On Secondary Control Approaches for Voltage Regulation in DC Microgrids

    DEFF Research Database (Denmark)

    Peyghami, Saeed; Mokhtari, Hossein; Davari, Pooya

    2017-01-01

    Centralized or decentralized secondary controller is commonly employed to regulate the voltage drop raised by the primary controller. However, in the case of high capacity MGs and long feeders with much voltage drop on the line resistances, the conventional methods may not guarantee the voltage r...

  13. On Secondary Control Approaches for Voltage Regulation in DC Microgrids

    DEFF Research Database (Denmark)

    Peyghami Akhuleh, Saeed; Mokhtari, Hossein; Davari, Pooya

    2017-01-01

    Centralized or decentralized secondary controller is commonly employed to regulate the voltage drop raised by the primary controller. However, in the case of high capacity MGs and long feeders with much voltage drop on the line resistances, the conventional methods may not guarantee the voltage...

  14. Primary extracranial vertebral artery aneurysms.

    Science.gov (United States)

    Morasch, Mark D; Phade, Sachin V; Naughton, Peter; Garcia-Toca, Manuel; Escobar, Guillermo; Berguer, Ramon

    2013-05-01

    Extracranial vertebral artery aneurysms are uncommon and are usually associated with trauma or dissection. Primary cervical vertebral aneurysms are even rarer and are not well described. The presentation and natural history are unknown and operative management can be difficult. Accessing aneurysms at the skull base can be difficult and, because the frail arteries are often afflicted with connective tissue abnormalities, direct repair can be particularly challenging. We describe the presentation and surgical management of patients with primary extracranial vertebral artery aneurysms. In this study we performed a retrospective, multi-institutional review of patients with primary aneurysms within the extracranial vertebral artery. Between January 2000 and January 2011, 7 patients, aged 12-56 years, were noted to have 9 primary extracranial vertebral artery aneurysms. All had underlying connective tissue or another hereditary disorder, including Ehler-Danlos syndrome (n=3), Marfan's disease (n=2), neurofibromatosis (n=1), and an unspecified connective tissue abnormality (n=1). Eight of 9 aneurysms were managed operatively, including an attempted bypass that ultimately required vertebral ligation; the contralateral aneurysm on this patient has not been treated. Open interventions included vertebral bypass with vein, external carotid autograft, and vertebral transposition to the internal carotid artery. Special techniques were used for handling the anastomoses in patients with Ehler-Danlos syndrome. Although endovascular exclusion was not performed in isolation, 2 hybrid procedures were performed. There were no instances of perioperative stroke or death. Primary extracranial vertebral artery aneurysms are rare and occur in patients with hereditary disorders. Operative intervention is warranted in symptomatic patients. Exclusion and reconstruction may be performed with open and hybrid techniques with low morbidity and mortality. Copyright © 2013 Elsevier Inc. All rights

  15. Primary closure in colon trauma.

    Science.gov (United States)

    Salinas-Aragón, Luis Enrique; Guevara-Torres, Lorenzo; Vaca-Pérez, Enrique; Belmares-Taboada, Jaime Arístides; Ortiz-Castillo, Fátima de Guadalupe; Sánchez-Aguilar, Martín

    2009-01-01

    Primary repair of colon injuries is an accepted therapeutic option; however, controversy persists regarding its safety. Our objective was to report the evolution and presence of complications in patients with colon injury who underwent primary closure and to determine if the time interval (>6 h), degree of injury, contamination, anatomic site injured, PATI (Penetrating Abdominal Trauma Index) >25, and the presence of other injuries in colon trauma are associated with increased morbidity and mortality. This was a prospective, observational, longitudinal and descriptive study conducted at the Central Hospital "Dr. Ignacio Morones Prieto," San Luis Potosí, Mexico, from January 1, 2003 to December 31, 2007. We included patients with abdominal trauma with colon injury subjected to surgical treatment. chi(2) was used for basic statistical analysis. There were 481 patients with abdominal trauma who underwent surgery; 77(16.1%) had colon injury. Ninety percent (n = 69) were treated in the first 6 h; 91% (n = 70) were due to penetrating injuries, and gunshot wound accounted for 48% (n = 37). Transverse colon was the most frequently injured (38%) (n = 29). Grade I and II injuries accounted for 75.3% (n = 58). Procedures included primary repair (76.66 %) (n = 46); resection with anastomosis (8.3%) (n = 5); and colostomy (15%) (n = 9). Associated injuries were present in 76.6% (n = 59). There was some degree of contamination in 85.7% (n = 66); 82.8% (58) had PATI colon injury. Primary repair is a safe procedure for treatment of colon injuries. Patients with primary repair had lower morbidity (p <0.009). Surgery during the first 6 h (p <0.006) and in hemodynamically stable patients (p <0.014) had a lower risk of complications.

  16. Dynamic loads on the primary system

    International Nuclear Information System (INIS)

    Rohde, J.

    1980-01-01

    As a result of pipe breaks f.ex. in the primary system of a PWR-plant dynamic forces act on the components of the system as well as on their support-structures and internals. The design basis must guarantee that LOCA or system-transient generated loads cannot produce deformations or fractures that endanger the coolability of the reactor, the emergency feedwater supply to the core-region and a safe shut-down of the reactor. In this lecture the first part of a LOCA will be discussed, where the highest dynamic loads on the primary system are expected. In this connection comments are given on the main assumptions and boundary conditions, the related regulations and guide-lines, as well as the possible consequences of an accident. Next, a review is presented of the analytical methods being used for the determination of thermohydraulic generated loads. The stress-calculations on the basis of these load-functions are discussed in the following lectures. The application of the analytical methods, i.e. the different computer codes, and the verification on the basis of the experimental results are described together with a discussion of the theoretical results. In addition a survey will be given of the research work done in connection with the problems of the dynamic loads under accident conditions. Finally, the problems of the fluid-structure interaction will be explained and comments made on computer code development now under way regarding this problem. A short film will be presented to provide a better understanding of fast transient phenomena. (orig./RW)

  17. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    the_monk

    one strategy that could be conducted anywhere, if the health care workers are trained and positively disposed ... places; regulate advertising, manufacturing. 13 .... Gender. Male. 52 (46.0). 61 (54.0). 0.0001. Significant. Female. 82 (73.2).

  18. Introducing Cooperative Learning to Primary 1 and Primary 2 Pupils

    Science.gov (United States)

    Fong, Salim; Ho, Linda; Chew, Lay See; Wong, Kok Wah; Wee, Sheila; Jacobs, George M.

    2000-01-01

    It was scary at first. Just getting P1 and 2 students to follow basic instructions is hard enough; trying to get them to work together in groups seemed like asking for extra trouble. But, a dash or two of trouble adds a bit of spice to a veteran teacher's life; so the four of us teachers at Mayflower Primary School--a neighbourhood school in Ang…

  19. Ketamine and international regulations.

    Science.gov (United States)

    Liao, Yanhui; Tang, Yi-Lang; Hao, Wei

    2017-09-01

    Ketamine is an anesthetic commonly used in low-income countries and has recently been shown to be effective for treatment-resistant depression. However, the illicit manufacturing, trafficking, and nonmedical use of ketamine are increasing globally, and its illicit use poses major public health challenges in many countries. To review the nonmedical use of ketamine in selected countries and its regulatory control. We conducted a review of literature identified from searches of the China National Knowledge Infrastructure (CNKI) (1979-2016) and PubMed databases, supplemented by additional references identified by the authors. Special attention was given to the regulation of ketamine. Illicit manufacturing, trafficking, and use of ketamine appear to have begun on a large scale in several Asian nations, and it has subsequently spread to other regions. Regulations governing availability of ketamine vary across countries, but there is a clear trend toward tighter regulations. As nonmedical use of ketamine and its harmful consequences have worsened globally, stricter controls are necessary. Appropriate regulation of ketamine is important for international efforts to control ketamine's cross-border trafficking and its nonmedical use.

  20. Federal Gasoline Regulations

    Science.gov (United States)

    The Clean Air Act requires EPA to regulate fuels and fuel additives for use in mobile sources if such fuel, fuel additive or any emission products causes or contributes to air or water pollution that may endanger the public health or welfare.