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  1. Connexin 32 and connexin 43 are involved in lineage restriction of hepatic progenitor cells to hepatocytes

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    Haiyun Pei

    2017-11-01

    Full Text Available Abstract Background Bi-potential hepatic progenitor cells can give rise to both hepatocytes and cholangiocytes, which is the last phase and critical juncture in terms of sequentially hepatic lineage restriction from any kind of stem cells. If their differentiation can be controlled, it might access to functional hepatocytes to develop pharmaceutical and biotechnology industries as well as cell therapies for end-stage liver diseases. Methods In this study, we investigated the influence of Cx32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses. An inhibitor of Cx32 was also used to make further clarification. To reveal p38 MAPK pathway is closely related to Cxs, rats with 70% partial hepatectomy were injected intraperitoneally with a p38 inhibitor, SB203580. Besides, the effects of p38 MAPK pathway on differentiation of hepatoblasts isolated from fetal rat livers were evaluated by addition of SB203580 in culture medium. Results In vitro gain and loss of function analyses showed overexpression of Connexin 32 and knockdown of Connexin 43 promoted hepatocytes differentiation from hepatic progenitor cells. In addition, in vitro and ex vivo research revealed inhibition of p38 mitogen-activated protein kinase pathway can improve hepatocytes differentiation correlating with upregulation of Connexin 32 expression and downregulation of Connexin 43 expression. Conclusions Here we demonstrate that Connexins play crucial roles in facilitating differentiation of hepatic progenitors. Our work further implicates that regulators of Connexins and their related pathways might provide new insights to improve lineage restriction of stem cells to mature hepatocytes.

  2. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

    Science.gov (United States)

    Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-01-01

    Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

  3. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

    Science.gov (United States)

    Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-07-01

    The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de

  4. Connexin43 orthologues in vertebrates: phylogeny from fish to man

    NARCIS (Netherlands)

    van der Heyden, Marcel A. G.; van Eijk, Marleen; Wilders, Ronald; de Bakker, Jacques M. T.; Opthof, Tobias

    2004-01-01

    The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization

  5. Connexin43 gene and its irradiation-induced expression

    International Nuclear Information System (INIS)

    Long Xianhui; Zhou Pingkun

    2005-01-01

    Gap junctions, composed of connexin protein subunits, provide the important channel for the intercellular communication. Connexin43, the most popular component of the connexin protein family, is widely expressed in multiple tissues and cell lines and plays an important role in cell proliferation, differention and tissue homeostasis. Recently it was reported that the expression of connexin43 gene is remarkedly up-regulated by low dose ionizing radiation, the available data suggest connexin43 gene to be a poten-tial sensitive bio-marker in radiation damage. (authors)

  6. Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

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    Hossein Mostafavi

    2014-02-01

    Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

  7. Gap junction protein connexin-43 interacts directly with microtubules

    NARCIS (Netherlands)

    Giepmans, B N; Verlaan, I; Hengeveld, T; Janssen, H; Calafat, J; Falk, M M; Moolenaar, W H

    2001-01-01

    Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated

  8. Association of connexin43 with a receptor protein tyrosine phosphatase

    NARCIS (Netherlands)

    Giepmans, Ben N G; Feiken, Elles; Gebbink, Martijn F B G; Moolenaar, Wouter H

    2003-01-01

    Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap

  9. Gap junction protein connexin43 exacerbates lung vascular permeability.

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    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  10. Targeting connexin 43 in diabetic wound healing: Future perspectives

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    Bajpai S

    2009-01-01

    Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

  11. Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

    International Nuclear Information System (INIS)

    Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

    2010-01-01

    Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

  12. Control of Vascular Smooth Muscle Cell Growth by Connexin 43

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    Chintamani eJoshi

    2012-06-01

    Full Text Available Connexin 43 (Cx43, the principal gap junction protein in vascular smooth muscle cells (VSMCs, regulates movement of ions and other signaling molecules through gap junction intercellular communication (GJIC and plays important roles in maintaining normal vessel function; however, many of the signaling mechanisms controlling Cx43 in VSMCs are not clearly described. The goal of this study was to investigate mechanisms of Cx43 regulation with respect to VSMC proliferation. Treatment of rat primary VSMCs with the cAMP analog 8Br-cAMP, the soluble guanylate cyclase (sGC stimulator BAY 41-2272 (BAY, or the Cx inducer diallyl disulfide (DADS significantly reduced proliferation after 72 h compared to vehicle controls. Bromodeoxyuridine uptake revealed reduction (p<.001 in DNA synthesis after 6 h and flow cytometry showed reduced (40% S phase cell numbers after 16 h in DADS-treated cells compared to controls. Cx43 expression significantly increased after 270 min treatment with 8Br-cAMP, 8Br-cGMP, BAY or DADS. Inhibition of PKA, PKG or PKC reversed 8Br-cAMP-stimulated increases in Cx43 expression, whereas only PKG or PKC inhibition reversed 8Br-cGMP- and BAY-stimulated increases in total Cx43. Interestingly, stimulation of Cx43 expression by DADS was not dependent on PKA, PKG or PKC. Using fluorescence recovery after photobleaching, only 8Br-cAMP or DADS increased GJIC with 8Br-cAMP mediated by PKC and DADS mediated by PKG. Further, DADS significantly increased phosphorylation at the MAPK-sensitive serine (Ser255 and Ser279, the cell cycle regulatory kinase-sensitive Ser262 and the PKC-sensitive Ser368 after 30 min while 8Br-cAMP significantly increased phosphorylation only at Ser279 compared to controls. This study demonstrates that 8Br-cAMP- and DADS-enhanced GJIC rather than Cx43 expression and/or phosphorylation plays an important role in regulation of VSMC proliferation and provides new insights into the growth-regulatory capacities of Cx43 in VSMCs.

  13. Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

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    Malmström Anders

    2006-05-01

    Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

  14. Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias

    NARCIS (Netherlands)

    Fernandes, Sarah; van Rijen, Harold V. M.; Forest, Virginie; Evain, Stéphane; Leblond, Anne-Laure; Mérot, Jean; Charpentier, Flavien; de Bakker, Jacques M. T.; Lemarchand, Patricia

    2009-01-01

    Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients

  15. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

    NARCIS (Netherlands)

    van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R; Várnai, Péter; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H

    2007-01-01

    Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol

  16. Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin

    NARCIS (Netherlands)

    Giepmans, B N; Verlaan, I; Moolenaar, W H

    2001-01-01

    Gap junctions are composed of connexins that form transmembrane channels between adjacent cells. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated in the regulation of Cx43 channel gating. Interestingly, channel-independent processes regulated

  17. Sex differences in connexin-43 expression in left ventricles of aging rats

    Czech Academy of Sciences Publication Activity Database

    Tribulová, N.; Dupont, E.; Soukup, Tomáš; Okruhlicová, L.; Severs, N. J.

    2005-01-01

    Roč. 54, č. 6 (2005), s. 705-708 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/05/0327 Grant - others:MYORES(XE) 511978; CZ-SK(CZ) 02-2004-05 Institutional research plan: CEZ:AV0Z50110509 Keywords : connexin-43 * rat cardiomyocytes * male and female specificity Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  18. Studies on level of cytokines and expression of connexin43 in tumor and normal cells in culture conditions

    International Nuclear Information System (INIS)

    Asati, V.; Pandey, B.N.

    2016-01-01

    Factors secreted from the tumor cells in culture medium have been known to facilitate the growth of fresh cultures and also to affect the cellular radio-sensitivity. Moreover, expression of gap junction proteins like connexin-43 is known as a key player in cell survival and proliferation. The present study is aimed to evaluate the effects of conditioned medium on the growth of respective tumor/normal cells and the expression of connexin-43 in these cells

  19. Effect of Beta-Carotene on Oxidative Stress and Expression of Cardiac Connexin 43

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    Novo, Rosangela; Azevedo, Paula S.; Minicucci, Marcos F.; Zornoff, Leonardo A. M., E-mail: lzornoff@fmb.unesp.br; Paiva, Sergio A. R. [Faculdade de Medicina de Botucatu - Universidade Estadual Paulista ' Júlio de Mesquita Filho' , Botucatu, SP (Brazil)

    2013-09-15

    Intervention studies have shown an increased mortality in patients who received beta-carotene. However, the mechanisms involved in this phenomenon are still unknown. Evaluate the influence of beta-carotene on oxidative stress and the expression of connexin 43 in rat hearts. Wistar rats, weighing approximately 100 g, were allocated in two groups: Control Group (n = 30), that received the diet routinely used in our laboratory, and Beta-Carotene Group (n = 28), which received beta-carotene (in crystal form, added and mixed to the diet) at a dose of 500 mg of beta carotene/kg of diet. The animals received the treatment until they reached 200-250g, when they were sacrificed. Samples of blood, liver and heart were collected to perform Western blotting and immunohistochemistry for connexin 43; morphometric studies, dosages of beta carotene by high performance liquid chromatography as well as reduced glutathione, oxidized glutathione and lipids hydroperoxides were performed by biochemical analysis. Beta-carotene was detected only in the liver of Beta-Carotene Group animals (288 ± 94.7 μg/kg). Levels of reduced/ oxidized glutathione were higher in the liver and heart of Beta-Carotene Group animals (liver - Control Group: 42.60 ± 1.62; liver - Beta-Carotene Group: 57.40 ± 5.90; p = 0.04; heart: - Control Group: 117.40 ± 1.01; heart - Beta-Carotene Group: 121.81 ± 1.32 nmol/mg protein; p = 0.03). The content of total connexin 43 was larger in Beta-Carotene Group. Beta-carotene demonstrated a positive effect, characterized by the increase of intercellular communication and improvement of anti-oxidizing defense system. In this model, mechanism does not explain the increased mortality rate observed with the beta-carotene supplementation in clinical studies.

  20. Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

    Science.gov (United States)

    Clasadonte, Jerome; Scemes, Eliana; Wang, Zhongya; Boison, Detlev; Haydon, Philip G

    2017-09-13

    Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

    DEFF Research Database (Denmark)

    Alstrøm, Jette Skov; Stroemlund, Line Waring; Nielsen, Morten Schak

    2015-01-01

    Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix...... and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current...... knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results....

  2. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43

    NARCIS (Netherlands)

    Boogerd, Kees-Jan; Wong, L. Y. Elaine; Christoffels, Vincent M.; Klarenbeek, Meinke; Ruijter, Jan M.; Moorman, Antoon F. M.; Barnett, Phil

    2008-01-01

    AIMS: T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering

  3. The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

    NARCIS (Netherlands)

    Giepmans, B N; Moolenaar, W H

    1998-01-01

    Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

  4. Modulation of cardiac connexin-43 by omega-3 fatty acid ethyl-ester supplementation demonstrated in spontaneously diabetic rats

    Czech Academy of Sciences Publication Activity Database

    Radošinská, J.; Kurahara, L. H.; Hiraishi, K.; Viczenczová, C.; Egan Beňová, T.; Szeiffová Bačová, B.; Dosenko, V.; Navarová, J.; Obšitník, B.; Imanaga, I.; Soukup, Tomáš; Tribulová, N.

    2015-01-01

    Roč. 64, č. 6 (2015), s. 795-806 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 7AMB14SK123 Institutional support: RVO:67985823 Keywords : diabetes * omega-3 fatty acids * cardiac connexin-43 * PKC * ultrastructure Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  5. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    International Nuclear Information System (INIS)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue; Panda, Satya P.

    2011-01-01

    Highlights: → Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. → First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. → Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. → Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. → Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b 5 and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  6. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    Energy Technology Data Exchange (ETDEWEB)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States); Panda, Satya P., E-mail: panda@uthscsa.edu [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States)

    2011-08-05

    Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  7. Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

    International Nuclear Information System (INIS)

    Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

    2015-01-01

    Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

  8. Molecular cloning and evolutionary analysis of the GJA1 (connexin43) gene from bats (Chiroptera).

    Science.gov (United States)

    Wang, Li; Li, Gang; Wang, Jinhong; Ye, Shaohui; Jones, Gareth; Zhang, Shuyi

    2009-04-01

    Gap junction protein connexin43 (Cx43), encoded by the GJA1 gene, is the most abundant connexin in the cardiovascular system and was reported as a crucial factor maintaining cardiac electrical conduction, as well as having a very important function in facilitating the recycling of potassium ions from hair cells in the cochlea back into the cochlear endolymph during auditory transduction processes. In mammals, bats are the only taxon possessing powered flight, placing exceptional demand on many organismal processes. To meet the demands of flying, the hearts of bats show many specialties. Moreover, ultrasonic echolocation allows bat species to orientate and often detect and locate food in darkness. In this study, we cloned the full-length coding region of GJA1 gene from 12 different species of bats and obtained orthologous sequences from other mammals. We used the maximum likelihood method to analyse the evolution of GJA1 gene in mammals and the lineage of bats. Our results showed this gene is much conserved in mammals, as well as in bats' lineage. Compared with other mammals, we found one private amino acid substitution shared by bats, which is located on the inner loop domain, as well as some species-specific amino acid substitutions. The evolution rate analyses showed the signature of purifying selection on not only different classification level lineages but also the different domains and amino acid residue sites of this gene. Also, we suggested that GJA1 gene could be used as a good molecular marker to do the phylogenetic reconstruction.

  9. The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mélanie Busby

    2018-02-01

    Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

  10. Connexin 43 Gene Therapy Delivered by Polymer-Modified Salmonella in Murine Tumor Models

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    Wei-Kuang Wang

    2014-04-01

    Full Text Available The use of preferentially tumor-targeting bacteria as vectors is one of the most innovative approaches for the treatment of cancer. This method is based on the observation that some obligate or facultative anaerobic bacteria are capable of selectively multiplying in tumors and inhibiting their growth. Previously, we found that the tumor-targeting efficiency of Salmonella could be modulated by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride (PAH, and these organisms are designated PAH-S.C. (S. choleraesuis. PAH can provide a useful platform for the chemical modification of Salmonella, perhaps by allowing a therapeutic gene to bind to tumor-targeting Salmonella. This study aimed to investigate the benefits of the use of PAH-S.C. for gene delivery. To evaluate this modulation, the invasion activity and gene transfer of DNA-PAH-S.C. were measured in vitro and in vivo. Treatment with PAH-S.C. carrying a tumor suppressor gene (connexin 43 resulted in inhibition of tumor growth, which suggested that tumor-targeted gene therapy using PAH-S.C. carrying a therapeutic gene could exert antitumor activities. This technique represents a promising strategy for the treatment of tumors.

  11. Connexin 43 Communication Channels in Follicular Dendritic Cell Development and in Follicular Lymphomas

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    Hajnalka Rajnai

    2015-01-01

    Full Text Available Follicular dendritic cells (FDC show homo- and heterocellular metabolic coupling through connexin 43 (Cx43 gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to “ex vivo” germinal centers with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and “ex vivo” germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.

  12. Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

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    Laura Walrave

    2016-12-01

    Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

  13. Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment.

    Science.gov (United States)

    Pecoraro, Michela; Rodríguez-Sinovas, Antonio; Marzocco, Stefania; Ciccarelli, Michele; Iaccarino, Guido; Pinto, Aldo; Popolo, Ada

    2017-10-11

    The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca 2+ ] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca 2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca 2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.

  14. Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

    Science.gov (United States)

    Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2016-06-15

    Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Ultrastructure and regulation of lateralized connexin43 in the failing heart.

    Science.gov (United States)

    Hesketh, Geoffrey G; Shah, Manish H; Halperin, Victoria L; Cooke, Carol A; Akar, Fadi G; Yen, Timothy E; Kass, David A; Machamer, Carolyn E; Van Eyk, Jennifer E; Tomaselli, Gordon F

    2010-04-02

    Gap junctions mediate cell-to-cell electric coupling of cardiomyocytes. The primary gap junction protein in the working myocardium, connexin43 (Cx43), exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases, although the precise location and function of this population is unknown. To define the subcellular location of lateralized gap junctions at the light and electron microscopic level, and further characterize the biochemical regulation of gap junction turnover. By electron microscopy, we characterized gap junctions formed between cardiomyocyte lateral membranes in failing canine ventricular myocardium. These gap junctions were varied in structure and appeared to be extensively internalizing. Internalized gap junctions were incorporated into multilamellar membrane structures, with features characteristic of autophagosomes. Intracellular Cx43 extensively colocalized with the autophagosome marker GFP-LC3 when both proteins were exogenously expressed in HeLa cells, and endogenous Cx43 colocalized with GFP-LC3 in neonatal rat ventricular myocytes. Furthermore, a distinct phosphorylated form of Cx43, as well as the autophagosome-targeted form of LC3 (microtubule-associated protein light chain 3) targeted to lipid rafts in cardiac tissue, and both were increased in heart failure. Our data demonstrate a previously unrecognized pathway of gap junction internalization and degradation in the heart and identify a cellular pathway with potential therapeutic implications.

  16. Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones.

    Science.gov (United States)

    Grümmer, R; Chwalisz, K; Mulholland, J; Traub, O; Winterhager, E

    1994-12-01

    A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy.

  17. Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

    Science.gov (United States)

    Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

    2014-01-01

    Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

  18. Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

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    Mauricio A. Retamal

    2017-11-01

    Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

  19. Effects of androgen on immunohistochemical localization of androgen receptor and Connexin 43 in mouse ovary.

    Science.gov (United States)

    Yang, Mei; Li, Jianhua; An, Yulin; Zhang, Shuiwen

    2015-10-01

    Androgens have essential roles in the regulation of follicular development and female fertility. Androgen excess is the leading defect in polycystic ovary syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this study was to elucidate the regarding regulatory role of androgen in the follicular development of female mouse. Immunohistochemical staining and Western blot analyses were performed to detect androgen receptor (AR) and Connexin 43 (Cx43) expression in ovaries from both control and testosterone-treated group mice. In this study, localizations of AR and Cx43 were dramatically altered in testosterone-treated mouse ovaries. In addition, AR expression was significantly increased, whereas Cx43 expression was markedly decreased after testosterone treatment. Alterations of AR and Cx43 expression by testosterone with concomitant reduction of MII oocytes. Overall, these results suggest the involvement of androgen in the regulation of AR and Cx43 localizations in mouse ovary. Alterations of AR and Cx43 expression by testosterone may affect normal folliculogenesis. Together these findings will enable us to begin understanding the important roles of AR and Cx43 actions in the regulation of follicular development, as well as providing insights into the role of AR and Cx43 actions in the androgen-associated reproductive diseases such as PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

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    Miaki Uzu

    2015-05-01

    Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

  1. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

    Science.gov (United States)

    Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

    2018-01-01

    Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

  2. Cardiac Connexin-43 and PKC Signaling in Rats With Altered Thyroid Status Without and With Omega-3 Fatty Acids Intake

    Czech Academy of Sciences Publication Activity Database

    Szeiffová Bačová, B.; Egan Beňová, T.; Viczenczová, C.; Soukup, Tomáš; Rauchová, Hana; Pavelka, Stanislav; Knezl, V.; Barančík, M.; Tribulová, N.

    2016-01-01

    Roč. 65, Suppl.1 (2016), S77-S90 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * Connexin-43 * omega-3 polyunsaturated fatty acids Subject RIV: ED - Physiology Impact factor: 1.461, year: 2016

  3. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian; Wang, Xuhui; Wang, Guangchao; Wu, Junhua

    2013-01-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication

  4. Friend or foe: Endoplasmic reticulum protein 29 (ERp29) in epithelial cancer

    Science.gov (United States)

    Chen, Shaohua; Zhang, Daohai

    2015-01-01

    The endoplasmic reticulum (ER) protein 29 (ERp29) is a molecular chaperone that plays a critical role in protein secretion from the ER in eukaryotic cells. Recent studies have also shown that ERp29 plays a role in cancer. It has been demonstrated that ERp29 is inversely associated with primary tumor development and functions as a tumor suppressor by inducing cell growth arrest in breast cancer. However, ERp29 has also been reported to promote epithelial cell morphogenesis, cell survival against genotoxic stress and distant metastasis. In this review, we summarize the current understanding on the biological and pathological functions of ERp29 in cancer and discuss the pivotal aspects of ERp29 as “friend or foe” in epithelial cancer. PMID:25709888

  5. Connexin 43 expression in human and mouse testes with impaired spermatogenesis

    Directory of Open Access Journals (Sweden)

    M Kotula-Balak

    2009-08-01

    Full Text Available Connexin 43 (Cx43 belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter’s syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter’s patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter’s patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought.

  6. TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

    Science.gov (United States)

    Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

    2014-01-01

    ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

  7. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

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    Zahra Moinfar

    Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

  8. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

    Science.gov (United States)

    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis.

    Science.gov (United States)

    Tsuchida, Shinji; Arai, Yuji; Kishida, Tsunao; Takahashi, Kenji A; Honjo, Kuniaki; Terauchi, Ryu; Inoue, Hiroaki; Oda, Ryo; Mazda, Osam; Kubo, Toshikazu

    2013-04-01

    The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies. Copyright © 2012 Orthopaedic Research Society.

  10. Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

    Science.gov (United States)

    Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

    2017-10-15

    Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Conflicting Roles of Connexin43 in Tumor Invasion and Growth in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Miaki Uzu

    2018-04-01

    Full Text Available The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs and hemichannels (HCs which are composed of hexamer of connexin43 (Cx43 protein. In particular, we discuss how GJ intercellular communication (GJIC in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are “hijacked” by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood–brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent on what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, needs to be revisited and understood together with new findings on Cx proteins and HC

  12. Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

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    Qin eXu

    2013-04-01

    Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

  13. Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

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    Rong-Hui Tu

    2017-11-01

    Full Text Available Background/Aims: Previous studies have shown that heat shock protein 90 (HSP90-mediated mitochondrial import of connexin 43 (Cx43 is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. Methods: Cellular models of hypoxic postconditioning (HPC from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS production was assessed with the peroxide-sensitive fluorescent probe 2′,7′-dichlorofluorescin in diacetate (DCFH-DA. The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA, ROS scavengers superoxide dismutase (SOD and catalase (CAT, and small interfering RNA (siRNA targeting Cx43 and HSP90 were also investigated. Results: HPC significantly reduced hypoxia/reoxygenation (H/R-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA or siRNA targeting

  14. Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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    Chen Li

    Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

  15. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

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    Shuo Liu

    Full Text Available Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases

  16. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

    Science.gov (United States)

    Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

    2015-01-01

    Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

  17. Na,K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase dependent connexin43 phosphorylation

    DEFF Research Database (Denmark)

    Hangaard, Lise; Bouzinova, Elena; Stæhr, Christian Albeck

    2017-01-01

    Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We...... coupling in rat mesenteric small arteries in vitro. Phosphorylation of cSrc kinase and connexin43 (Cx43) were semiquantified by Western blotting. Micromole concentration of ouabain reduced the amplitude of norepinephrine-induced vasomotion and desynchronized Ca2+ transients in VSMC in the arterial wall...

  18. Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

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    Fei Xiao

    Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

  19. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

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    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

    2016-04-01

    Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

  1. Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Steven C., E-mail: bug@uw.edu [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States); University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Kennedy, Brian K., E-mail: bkennedy@buckinstitute.org [University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945 (United States); Lampe, Paul D., E-mail: plampe@fhcrc.org [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2013-04-01

    An understanding of the molecular mechanism behind the arrhythmic phenotype associated with laminopathies has yet to emerge. A-type lamins have been shown to interact and sequester activated phospho-ERK1/2(pERK1/2) at the nucleus. The gap junction protein connexin43 (Cx43) can be phosphorylated by pERK1/2 on S279/282 (pS279/282), inhibiting intercellular communication. We hypothesized that without A-type lamins, pS279/282 Cx43 will increase due to inappropriate phosphorylation by pERK1/2, resulting in decreased gap junction function. We observed a 1.6-fold increase in pS279/282 Cx43 levels in Lmna{sup −/−} mouse embryonic fibroblasts (MEFs) compared to Lmna{sup +/+}, and 1.8-fold more pERK1/2 co-precipitated from Lmna{sup −/−} MEFs with Cx43 antibodies. We found a 3-fold increase in the fraction of non-nuclear pERK1/2 and a concomitant 2-fold increase in the fraction of pS279/282 Cx43 in Lmna{sup −/−} MEFs by immunofluorescence. In an assay of gap junctional function, Lmna{sup −/−} MEFs transferred dye to 60% fewer partners compared to Lmna{sup +/+} controls. These results are mirrored in 5–6 week-old Lmna{sup −/−} mice compared to their Lmna{sup +/+} littermates as we detect increased pS279/282 Cx43 in gap junctions by immunofluorescence and 1.7-fold increased levels by immunoblot. We conclude that increased pS279/282 Cx43 in the Lmna{sup −/−} background results in decreased cell communication and may contribute to the arrhythmic pathology in vivo. - Highlights: ► Connexin43 phosphorylation plays a role in laminopathy-associated conduction defects. ► Loss of A-type lamin activity results in release of pERK1/2 from the nucleus. ► Increased cytoplasmic localization of pERK1/2 acts to phosphorylate S279/282 of Cx43. ► Phosphorylation of S279/282 on Cx43 decreases gap junction activity in cell culture. ► Mice lacking A-type lamins have increased phosphorylation on S279/282 of Cx43.

  2. Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

    2016-07-01

    Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

  3. Green fluorescent protein changes the conductance of connexin 43 (Cx43) hemichannels reconstituted in planar lipid bilayers.

    Science.gov (United States)

    Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

    2012-01-20

    In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein.

  4. Green Fluorescent Protein Changes the Conductance of Connexin 43 (Cx43) Hemichannels Reconstituted in Planar Lipid Bilayers*

    Science.gov (United States)

    Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

    2012-01-01

    In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein. PMID:22139870

  5. The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis

    International Nuclear Information System (INIS)

    Tekpli, X.; Rivedal, E.; Gorria, M.; Landvik, N.E.; Rissel, M.; Dimanche-Boitrel, M.-T.; Baffet, G.; Holme, J.A.; Lagadic-Gossmann, D.

    2010-01-01

    Gap junctions are channels in plasma membrane composed of proteins called connexins. These channels are organized in special domains between cells, and provide for direct gap junctional intercellular communication (GJIC), allowing diffusion of signalling molecules < 1 kD. GJIC regulates cell homeostasis and notably the balance between proliferation, cell cycle arrest, cell survival and apoptosis. Here, we have investigated benzo[a]pyrene (B[a]P) effects on GJIC and on the subcellular localization of the major protein of gap junction: connexin-43 (Cx43). Our results showed that B[a]P increased GJIC between mouse hepatoma Hepa1c1c7 cells via translocation of Cx43 from Golgi apparatus and lipid rafts into gap junction plaques. Interestingly, inhibition of GJIC by chlordane or small interference RNA directed against Cx43 enhanced B[a]P-induced apoptosis in Hepa1c1c7 cells. The increased apoptosis caused by inhibition of GJIC appeared to be mediated by ERK/MAPK pathway. It is suggested that B[a]P could induce transfer of cell survival signal or dilute cell death signal via regulation of ERK/MAPK through GJIC.

  6. Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo.

    Science.gov (United States)

    Mancuso, M; Pasquali, E; Leonardi, S; Rebessi, S; Tanori, M; Giardullo, P; Borra, F; Pazzaglia, S; Naus, C C; Di Majo, V; Saran, A

    2011-11-10

    Ionizing radiation is a genotoxic agent and human carcinogen. Recent work has questioned long-held dogmas by showing that cancer-associated genetic alterations occur in cells and tissues not directly exposed to radiation, questioning the robustness of the current system of radiation risk assessment. In vitro, diverse mechanisms involving secreted soluble factors, gap junction intercellular communication (GJIC) and oxidative metabolism are proposed to mediate these indirect effects. In vivo, the mechanisms behind long-range 'bystander' responses remain largely unknown. Here, we investigate the role of GJIC in propagating radiation stress signals in vivo, and in mediating radiation-associated bystander tumorigenesis in mouse central nervous system using a mouse model in which intercellular communication is downregulated by targeted deletion of the connexin43 (Cx43) gene. We show that GJIC is critical for transmission of oncogenic radiation damage to the non-targeted cerebellum, and that a mechanism involving adenosine triphosphate release and upregulation of Cx43, the major GJIC constituent, regulates transduction of oncogenic damage to unirradiated tissues in vivo. Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role.

  7. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  8. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    International Nuclear Information System (INIS)

    Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

    2007-01-01

    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  9. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43.

    Science.gov (United States)

    Boogerd, Kees-Jan; Wong, L Y Elaine; Christoffels, Vincent M; Klarenbeek, Meinke; Ruijter, Jan M; Moorman, Antoon F M; Barnett, Phil

    2008-06-01

    T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering protein partners of Tbx2 and Tbx3 will shed light on the mechanisms by which these factors regulate these gene programs. Employing an yeast 2-hybrid screen and subsequent in vitro pull-down experiments we demonstrate that muscle segment homeobox genes Msx1 and Msx2 are able to bind the cardiac T-box proteins Tbx2, Tbx3, and Tbx5. This interaction, as that of the related Nkx2.5 protein, is supported by the T-box and homeodomain alone. Overlapping spatiotemporal expression patterns of Msx1 and Msx2 together with the T-box genes during cardiac development in mouse and chicken underscore the biological significance of this interaction. We demonstrate that Msx proteins together with Tbx2 and Tbx3 suppress Cx43 promoter activity and down regulate Cx43 gene activity in a rat heart-derived cell line. Using chromatin immunoprecipitation analysis we demonstrate that Msx1 can bind the Cx43 promoter at a conserved binding site located in close proximity to a previously defined T-box binding site, and that the activity of Msx proteins on this promoter appears dependent in the presence of Tbx3. Msx1 and Msx2 can function in concert with the T-box proteins to suppress Cx43 and other working myocardial genes.

  10. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication

    Science.gov (United States)

    Garciarena, Carolina D.; Malik, Akif; Swietach, Pawel; Moreno, Alonso P.; Vaughan-Jones, Richard D.

    2018-01-01

    Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue’s metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels—the major isoform in the heart and brain—is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values. We demonstrate that Cx43 channels expressed in HeLa or N2a cell pairs are gated biphasically by pHi via a process that consists of activation by H+ ions at alkaline pHi and inhibition at more acidic pHi. For Cx43 channel–mediated solute/ion transmission, the ensemble of these effects produces a pHi optimum, near resting pHi. By using Cx43 mutants, we demonstrate that alkaline gating involves cysteine residues of the C terminus and is independent of motifs previously implicated in acidic gating. Thus, we present a molecular mechanism by which cytoplasmic acid–base chemistry fine tunes intercellular communication and establishes conditions for the optimal transmission of solutes and signals in tissues, such as the heart and brain.—Garciarena, C. D., Malik, A., Swietach, P., Moreno, A. P., Vaughan-Jones, R. D. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication. PMID:29183963

  11. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

    Science.gov (United States)

    Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

    2006-09-01

    Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

  12. Proinflammatory cytokines downregulate connexin 43-gap junctions via the ubiquitin-proteasome system in rat spinal astrocytes.

    Science.gov (United States)

    Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2015-09-04

    Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for intercellular communication between spinal cord astrocytes. Various neurological disorders are associated with dysfunctional Cx43-gap junctions. However, the mechanism modulating Cx43-gap junctions in spinal astrocytes under pathological conditions is not entirely clear. A previous study showed that treatment of spinal astrocytes in culture with pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased both Cx43 expression and gap junction intercellular communication (GJIC) via a c-jun N-terminal kinase (JNK)-dependent pathway. The current study further elaborates the intracellular mechanism that decreases Cx43 under an inflammatory condition. Cycloheximide chase analysis revealed that TNF-α (10 ng/ml) alone or in combination with IFN-γ (5 ng/ml) accelerated the degradation of Cx43 protein in cultured spinal astrocytes. The reduction of both Cx43 expression and GJIC induced by a mixture of TNF-α and IFN-γ were blocked by pretreatment with proteasome inhibitors MG132 (0.5 μM) and epoxomicin (25 nM), a mixture of TNF-α and IFN-γ significantly increased proteasome activity and Cx43 ubiquitination. In addition, TNF-α and IFN-γ-induced activation of ubiquitin-proteasome systems was prevented by SP600125, a JNK inhibitor. Together, these results indicate that a JNK-dependent ubiquitin-proteasome system is induced under an inflammatory condition that disrupts astrocytic gap junction expression and function, leading to astrocytic dysfunction and the maintenance of the neuroinflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

    Science.gov (United States)

    Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

    2014-01-17

    Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

  14. Irradiation-Induced Cardiac Connexin-43 and miR-21 Responses Are Hampered by Treatment with Atorvastatin and Aspirin

    Directory of Open Access Journals (Sweden)

    Csilla Viczenczova

    2018-04-01

    Full Text Available Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of irradiation has been shown to result in compensatory up-regulation of the myocardial connexin-43 (Cx43, activation of the protein kinase C (PKC signaling along with the decline of microRNA (miR-1 and an increase of miR-21 levels in the left ventricle (LV. We investigated whether drugs with antioxidant, anti-inflammatory or vasodilating properties, such as aspirin, atorvastatin, and sildenafil, may affect myocardial response in the LV and right ventricle (RV following chest irradiation. Adult, male Wistar rats were subjected to a single sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day, atorvastatin (0.25 mg/day, and sildenafil (0.3 mg/day for six weeks. Cx43, PKCε and PKCδ proteins expression and levels of miR-1 as well as miR-21 were determined in the LV and RV. Results showed that the suppression of miR-1 was associated with an increase of total and phosphorylated forms of Cx43 as well as PKCε expression in the LV while having no effect in the RV post-irradiation as compared to the non-irradiated rats. Treatment with aspirin and atorvastatin prevented an increase in the expression of Cx43 and PKCε without change in the miR-1 levels. Furthermore, treatment with aspirin, atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV while having partial effect in the RV post irradiation. The increase in pro-apoptotic PKCδ was not affected by any of the used treatment. In conclusion, irradiation and drug-induced changes were less pronounced in the RV as compared to the LV. Treatment with aspirin and atorvastatin interfered with irradiation-induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing their elevation, possibly via amelioration of oxidative stress and inflammation.

  15. Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

    Science.gov (United States)

    Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

    2016-02-01

    Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of

  16. Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

    Directory of Open Access Journals (Sweden)

    Isola A.M. Brown

    2016-01-01

    Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

  17. Altered thyroid status affects myocardial expression of connexin-43 and susceptibility of rat heart to malignant arrhythmias that can be partially normalized by red palm oil intake

    Czech Academy of Sciences Publication Activity Database

    Szeiffová Bačová, B.; Vinczenzová, C.; Žurmanová, J.; Kašparová, Dita; Knezl, V.; Egan Beňová, T.; Pavelka, Stanislav; Soukup, Tomáš; Tribulová, N.

    2017-01-01

    Roč. 147, č. 1 (2017), s. 63-73 ISSN 0948-6143 R&D Projects: GA MŠk(CZ) LH15279; GA MŠk(CZ) 7AMB14SK123 Grant - others:AV ČR(CZ) SAV-15-03 Program:Bilaterální spolupráce Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * connexin-43 * PKC * red palm oil Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.553, year: 2016

  18. Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123)

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Stahlhut, Martin; Mohammed, Shabaz

    2006-01-01

    Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence...... and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass...... of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed...

  19. Knockdown of connexin43-mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation.

    Science.gov (United States)

    Law, Lee Yong; Lin, Jun Sheng; Becker, David L; Green, Colin R

    2002-12-01

    In the developing chick wing, the use of antisense oligodeoxynucleotides to transiently knock down the expression of the gap junction protein, connexin43 (Cx43), results in limb patterning defects, including deletion of the anterior digits. To understand more about how such defects arise, the effects of transient Cx43 knockdown on the expression patterns of several genes known to play pivotal roles in limb formation were examined. Sonic hedgehog (Shh), which is normally expressed in the zone of polarizing activity (ZPA) and is required to maintain both the ZPA and the apical ectodermal ridge (AER), was found to be downregulated in treated limbs within 30 h. Bone morphogenetic protein-2 (Bmp-2), a gene downstream of Shh, was similarly downregulated. Fibroblast growth factor-8 expression, however, was unaltered 30 h after treatment but was greatly reduced at 48 h post-treatment, when the AER begins to regress. Expressions of Bmp-4 and Muscle segment homeobox-like gene (Msx-1) were not affected at any of the time points examined. Cx43 expression is therefore involved in some, but not all patterning cascades, and appears to play a role in the regulation of ZPA activity.

  20. Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate

    Directory of Open Access Journals (Sweden)

    Anna Hejmej

    2013-01-01

    Full Text Available To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR and connexin 43 (Cx43 in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20, neonatal (PD2, and prepubertal (PD90 exposure to an antiandrogen flutamide (50 mg/kg bw. In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.

  1. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian

    2013-04-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.

  2. Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.

    Science.gov (United States)

    Grippo, Angela J; Moffitt, Julia A; Henry, Matthew K; Firkins, Rachel; Senkler, Jonathan; McNeal, Neal; Wardwell, Joshua; Scotti, Melissa-Ann L; Dotson, Ashley; Schultz, Rachel

    2015-01-01

    Exposure to social and environmental stressors may influence behavior as well as autonomic and cardiovascular regulation, potentially leading to depressive disorders and cardiac dysfunction including elevated sympathetic drive, reduced parasympathetic function, and ventricular arrhythmias. The cellular mechanisms that underlie these interactions are not well understood. One mechanism may involve alterations in the expression of Connexin43 (Cx43) and Connexin45 (Cx45), gap junction proteins in the heart that play an important role in ensuring efficient cell-to-cell coupling and the maintenance of cardiac rhythmicity. The present study investigated the hypothesis that long-term social isolation, combined with mild environmental stressors, would produce both depressive behaviors and altered Cx43 and Cx45 expression in the left ventricle of prairie voles - a socially monogamous rodent model. Adult, female prairie voles were exposed to either social isolation (n = 22) or control (paired, n = 23) conditions (4 weeks), alone or in combination with chronic mild stress (CMS) (1 week). Social isolation, versus paired control conditions, produced significantly (p Social isolation (alone) reduced (p social and environmental stress in the prairie vole.

  3. TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

    Science.gov (United States)

    Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

    2008-12-01

    One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

  4. Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation

    Directory of Open Access Journals (Sweden)

    Hongyan Xie

    2017-01-01

    Full Text Available Connexin 43 (Cx43 is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR or oxygen-glucose deprivation and reoxygenation (OGDR were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and MAPRE1 (microtubule-associated protein RP/EB family member 1 expression at different time points. The total number of Cx43 was unchanged in the normal and IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were significantly greater than that of the normal group. Particles in the cytoplasm were significantly fewer after endocytosis was blocked by dynasore. There was no difference among the groups at each time point regarding protein or gene expression of MAPRE1. We concluded that internalization of Cx43 into the cytoplasm occurred during ischemia, which was partially mediated through endocytosis, not by the change of Cx43 quantity. Moreover, internalization was not related to microtubule transport.

  5. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: marie-helene.durand@ens-lyon.fr [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)

    2013-04-01

    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  6. Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase-2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis

    Directory of Open Access Journals (Sweden)

    Aiudi Giulio

    2004-06-01

    Full Text Available Abstract The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC were cultured in a control defined medium supplemented with eFSH (0 to 5 micrograms/ml, Fetal Calf Serum (FCS, precursors for hyaluronic acid synthesis or glutamine according to the experiments. After in vitro maturation, the cumulus expansion rate was increased with 1 microgram/ml eFSH, and was the highest with 20% FCS. It was not influenced by precursors for hyaluronic acid synthesis or glutamine. The expression of transcripts related to cumulus expansion was analyzed in equine cumulus cells before maturation, and after in vivo and in vitro maturation, by using reverse transcription-polymerase chain reaction (RT-PCR with specific primers. Connexin 43, cyclooxygenase-2 (COX-2 and FSH receptor (FSHr mRNA were detected in equine cumulus cells before and after maturation. Their level did not vary during in vivo or in vitro maturation and was influenced neither by FSH nor by precursors for hyaluronic acid synthesis. Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms.

  7. Immunohistochemistry of connexin 43 throughout anterior pituitary gland in a transgenic rat with green fluorescent protein-expressing folliculo-stellate cells.

    Science.gov (United States)

    Horiguchi, Kotaro; Fujiwara, Ken; Kouki, Tom; Kikuchi, Motoshi; Yashiro, Takashi

    2008-12-01

    Folliculo-stellate (FS) cells in the anterior pituitary gland have been speculated to possess multifunctional properties. Because gap junctions (GJ) have been identified between FS cells, FS cells may be interconnected electrophysiologically by GJ and serve as signal transmission networks to modulate hormone release in the anterior pituitary gland. But whether GJ are localized among FS cells from the pars tuberalis through the pars distalis is unclear. The S100b-GFP transgenic rat has recently been generated, which expresses green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary. This model is expected to be a powerful tool for studies of FS cells. The purpose of the present paper was therefore to examine the localization of GJ on connexin 43 immunohistochemistry throughout the anterior pituitary gland of S100b-GFP rats under confocal laser microscopy. The localization patterns of FS cells was also observed in primary culture of anterior pituitary cells and the question of whether GJ between FS cells are reconstructed in vitro was investigated. In vivo studies showed that GJ were present specifically between FS cells from the pars tuberalis to the pars distalis in the anterior pituitary gland. The appearance of FS cells was distinguished into two types, with localization of GJ differing between types. In vitro, it was observed for the first time that FS cells in primary culture could be categorized into two types. In vivo localization of GJ between FS cells was reconstructed in vitro. These morphological observations are consistent with the hypothesis that FS cells form an electrophysiological network throughout the anterior pituitary for signal transmission.

  8. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    Science.gov (United States)

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r 2  = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  9. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  10. Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

    Science.gov (United States)

    Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

    2013-01-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

  11. Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion.

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    Strale, Pierre-Olivier; Clarhaut, Jonathan; Lamiche, Coralie; Cronier, Laurent; Mesnil, Marc; Defamie, Norah

    2012-11-01

    Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap-junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin-1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo- and heterocellular gap junctional communications (respectively between U251 cells, or between U251 cells and astrocytes). Moreover, the adhesive and invasive capacities are not dependent, in our model, on Cav-1 expression level. Our results tend to show that heterocellular gap junctional communication between cancer and stroma cells may affect the behavior of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor phenotype of glioblastoma U251 cells and in particular, invasion capacity, through its localization in lipid rafts containing Cav-1. Copyright © 2011 Wiley Periodicals, Inc.

  12. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

    Science.gov (United States)

    Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

    2016-12-01

    We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

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    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Aschner, Michael [Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Luo, Wen-Jing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jing-Yuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2016-04-15

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  14. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

    International Nuclear Information System (INIS)

    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua; Aschner, Michael; Luo, Wen-Jing; Chen, Jing-Yuan

    2016-01-01

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  15. Susceptibility of rats with altered thyroid status to malignant arrhythmias is primarily related to myocardial levels of connexin-43 and can be partially ameliorated by supplementation with red palm oil

    Czech Academy of Sciences Publication Activity Database

    Bačová, B.; Vinczenzová, C.; Žurmanová, J.; Kašparová, Dita; Knezl, V.; Radošinská, J.; Beňová, T.; Pavelka, Stanislav; Soukup, Tomáš; Tribulová, N.

    2013-01-01

    Roč. 18, Suppl A (2013), 41A-46A ISSN 1205-6626 R&D Projects: GA MŠk(CZ) 7AMB12SK158; GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GAP304/12/0259 Grant - others:Univerzita Karlova(CZ) 628412 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * connexin-43 * PKC.epsilon * red palm oil Subject RIV: ED - Physiology Impact factor: 0.758, year: 2013

  16. Disruption of gap junctional intercellular communication by antibiotic gentamicin is associated with aberrant localization of occludin, N-cadherin, connexin 43, and vimentin in SerW3 Sertoli cells in vitro.

    Science.gov (United States)

    Bekheet, Souad H M; Stahlmann, Ralf

    2009-09-01

    Spermatogenesis is a very complex process by which male germ cells differentiate into mature spermatozoa. The sophisticated communication network that controls spermatogenesis can be derailed so that dysfunction of one cell type propagates to all types as a cascade. This accounts for the particular vulnerability of the testis to environmental factors such as drugs and xenobiotics. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. In this study, cells from the rat Sertoli line (SerW3) were incubated for 3, 6 and 9 subsequent days in serum free DMEM (SFDM) composed of DMEM supplemented with three different concentrations of antibiotic gentamicin (10, 30, and 100 μg). The effect of the three different concentrations of this antibiotic was determined on Sertoli cell-cell interaction through impaired expression of their constitutive tight junction proteins as early targets for different toxicants in vitro by immunochemistry analysis. The Sertoli SerW3 cell line illustrated the cytotoxicity of GS, as the intercellular junction proteins such as occludin, N-cadherin, connexin 43, and vimentin were delocalized from the membrane to the cytoplasmic compartment during exposure to the antibiotic. This study underlines the potential deleterious effects of the routine use of antibiotics during continuous cell culture.

  17. Bone morphogenetic protein-2 (BMP-2 and transforming growth factor-β1 (TGF-β1 alter connexin 43 phosphorylation in MC3T3-E1 Cells

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    Rudkin George H

    2001-07-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs and transforming growth factor-βs (TGF-βs are important regulators of bone repair and regeneration. BMP-2 and TGF-β1 have been shown to inhibit gap junctional intercellular communication (GJIC in MC3T3-E1 cells. Connexin 43 (Cx43 has been shown to mediate GJIC in osteoblasts and it is the predominant gap junctional protein expressed in these murine osteoblast-like cells. We examined the expression, phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2 or TGF-β1 to investigate a possible mechanism for the inhibition of GJIC. Results Northern blot analysis revealed no detectable change in the expression of Cx43 mRNA. Western blot analysis demonstrated no significant change in the expression of total Cx43 protein. However, significantly higher ratios of unphosphorylated vs. phosphorylated forms of Cx43 were detected after BMP-2 or TGF-β1 treatment. Immunofluorescence and cell protein fractionation revealed no detectable change in the localization of Cx43 between the cytosol and plasma membrane. Conclusions BMP-2 and TGF-β1 do not alter expression of Cx43 at the mRNA or protein level. BMP-2 and TGF-β1 may inhibit GJIC by decreasing the phosphorylated form of Cx43 in MC3T3-E1 cells.

  18. Intercellular communications within the rat anterior pituitary. XVI: postnatal changes of distribution of S-100 protein positive cells, connexin 43 and LH-RH positive sites in the pars tuberalis of the rat pituitary gland. An immunohistochemical and electron microscopic study.

    Science.gov (United States)

    Wada, Ikuo; Sakuma, Eisuke; Shirasawa, Nobuyuki; Wakabayashi, Kenjiro; Otsuka, Takanobu; Hattori, Kazuki; Yashiro, Takashi; Herbert, Damon C; Soji, Tsuyoshi

    2014-02-01

    The architecture of luteinizing hormone-releasing hormone (LH-RH) nerve ends and the S-100 protein containing folliculo-stellate cells forming gap junctions in the pars tuberalis is basically important in understanding the regulation of the hormone producing mechanism of anterior pituitary glands. In this study, intact male rats 5-60 days old were prepared for immunohistochemistry and electron microscopy. From immunostained sections, the S-100 containing cells in pars tuberalis were first detected on day 30 and increased in number to day 60; this was parallel to the immunohistochemical staining of gap junction protein, connexin 43. LH-RH positive sites were clearly observed on just behind the optic chiasm and on the root of pituitary stalk on day 30. On day 60, the width of layer increased, while follicles and gap junctions were frequently observed between agranular cells in 10 or more layers of pars tuberalis. In the present study, we investigated the sexual maturation of the anterior pituitary glands through the postnatal development of S-100 positive cells, connexin 43 and LH-RH nerves. It is suggested that the folliculo-stellate cell system including the LH-RH neurons in the pars tuberalis participates in the control of LH secretion along with the portal vein system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    Science.gov (United States)

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  20. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    International Nuclear Information System (INIS)

    Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

    2013-01-01

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced. • Cx43-mediated gap junction complex assembly correlated with observed changes. • We propose that membranous Cx43 sequesters β-catenin away from the nucleus

  1. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    Energy Technology Data Exchange (ETDEWEB)

    Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

    2013-12-10

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced. • Cx43-mediated gap junction complex assembly correlated with observed changes. • We propose that membranous Cx43 sequesters β-catenin away from the nucleus.

  2. Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status

    Directory of Open Access Journals (Sweden)

    Yuan Chi

    2016-10-01

    Full Text Available Connexin (Cx hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca2+-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43+/+, heterozygous (Cx43+/- and knockout (Cx43-/- littermates showed that Cx43-positive cells (Cx43+/+ exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca2+ depletion, as compared to Cx43-null cells (Cx43-/-. Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH. Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

  3. Connexin 43 Channels are Essential for Normal Bone Structure and Osteocyte Viability

    Science.gov (United States)

    Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A.; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J.; Werner, Sherry L.; Zhao, Hong; Shang, Peng; Johnson, Mark L.; Bonewald, Lynda F.; Jiang, Jean X.

    2014-01-01

    Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks gap junction channel, but not hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to WT and R76W mice. MicroCT analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice which likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption and periosteal apposition, and gap junction communication is involved in the process of bone remodeling. PMID:25270829

  4. Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Katsuhisa Masaki

    Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS: These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.

  5. Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

    Directory of Open Access Journals (Sweden)

    Harissios Vliagoftis

    2014-01-01

    Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

  6. Diabetes and thyroid hormones affect connexin-43 and PKC-ε expression in rat heart atria

    Czech Academy of Sciences Publication Activity Database

    Mitašíková, M.; Lin, H.; Soukup, Tomáš; Imanaga, I.; Tribulová, N.

    2009-01-01

    Roč. 58, č. 2 (2009), s. 211-217 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA304/05/0327; GA ČR(CZ) GA304/08/0256 Grant - others:EC(XE) LSH-CT-2004-511978; VEGA(SK) 2/6064/27; APVV(SK) 51-059505 Institutional research plan: CEZ:AV0Z50110509 Keywords : diabetes * triiodothyronine * atrial fibrillation Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  7. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype.

    NARCIS (Netherlands)

    Paznekas, W.A.; Karczeski, B.; Vermeer, S.; Lowry, R.B.; Delatycki, M.; Laurence, F.; Koivisto, P.A.; Maldergem, L. van; Boyadjiev, S.A.; Bodurtha, J.N.; Jabs, E.W.

    2009-01-01

    The predominantly autosomal dominant disorder, oculodentodigital dysplasia (ODDD) has high penetrance with intra- and interfamilial phenotypic variability. Abnormalities observed in ODDD affect the eye, dentition, and digits of the hands and feet. Patients present with a characteristic facial

  8. Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

    Science.gov (United States)

    Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

    2016-10-01

    Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (PLucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

  9. Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43

    DEFF Research Database (Denmark)

    Morel, Sandrine; Christoffersen, Christina; Axelsen, Lene N

    2016-01-01

    recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce ischemia/reperfusion injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap...

  10. P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    2014-01-01

    Full Text Available Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats. Methods. Twenty-four rats were randomly divided into control group (C, droperidol group (D, or EA group (E. C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg. QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting. Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P0.05. Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

  11. Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.

    NARCIS (Netherlands)

    Paznekas, W.A.; Boyadjiev, S.A.; Shapiro, R.E.; Daniëls, O.; Wollnik, B.; Keegan, C.E.; Innis, J.W.; Dinulos, M.B.; Christian, C.; Hannibal, M.C.; Jabs, E.W.

    2003-01-01

    Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance

  12. Different expressions of connexin 43 and 32 in the fibroblasts of human dental pulp.

    Science.gov (United States)

    Ibuki, N; Yamaoka, Y; Sawa, Y; Kawasaki, T; Yoshida, S

    2002-06-01

    The expression and localization of gap junctional proteins connexin (Cx) 26, 32, and 43 was examined in human dental pulp. Dental pulp tissues were obtained from human third molars immediately after extraction. Some pulp tissues were used for cell culture, and the rest for histological observations. Immunostaining for cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were identified by Western blot analysis. Immunostaining for tissue sections showed that the expression of Cx32 and 43 was observed in the entire region of the pulp and further strong expression of Cx32 was established beneath the cell-rich zone. Considering the close relationship between Cx types and cell functions, the results indicate that DPFs beneath the cell-rich zone may have specific, Cx32-related functions. The cell rich zone is thought to contain progenitor odontoblasts that can be induced to differentiate into mature odontoblasts in response to wounding. Therefore, it may be hypothesized that DPFs just beneath the cell-rich zone produce proteins and induce odontoblast differentiation from the cells in the cell-rich zone.

  13. RXP-E: a connexin43-binding peptide that prevents action potential propagation block

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

    2008-01-01

    . Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20......% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss...... of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2...

  14. Restrictive cardiomyopathy

    Science.gov (United States)

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  15. Restrictive Cardiomyopathy

    Science.gov (United States)

    ... up in the circulatory system. In time, the heart fails. What causes it? Restrictive cardiomyopathy is often caused by diseases in other parts of the body. One known cause is cardiac ... build up in the heart tissue, making the tissue stiff and thickened. Cardiac ...

  16. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    communities and shopping centres through mobility lenses. The article shows how different mobility systems enable and restrict the public access to private-public spaces, and it points out that proprietary communities create an unequal potential for human movement and access in the city. The main argument......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...... and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private/public spaces...

  17. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.

    Science.gov (United States)

    Stehberg, Jimmy; Moraga-Amaro, Rodrigo; Salazar, Christian; Becerra, Alvaro; Echeverría, Cesar; Orellana, Juan A; Bultynck, Geert; Ponsaerts, Raf; Leybaert, Luc; Simon, Felipe; Sáez, Juan C; Retamal, Mauricio A

    2012-09-01

    Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.

  18. Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Yuanyuan Xie

    2017-11-01

    Full Text Available Background/Aims: Cardiomyopathy-associated gene 1 (CMYA1 plays an important role in embryonic cardiac development, postnatal cardiac remodeling and myocardial injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and primary cardiomyopathy. Our study aims to establish the relationship between CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC pathogenesis. Methods: We explored the effects of CMYA1 on connexins (Cx, which contribute to gap junction intercellular communication (GJIC, and the underlying signaling pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co-immunoprecipitation and scrape loading-dye transfer. Results: CMYA1 expression was inversely associated with Cx43 and Cx40 expression, as determined by gap junction PCR array analysis. An increased expression and disordered distribution of CMYA1 at the intercalated discs in LVNC myocardial tissue was also observed. CMYA1 and Cx43 are co-expressed and interact in myocardial cells. CMYA1 expression was positively correlated with p-Cx43 (S368 via the Protein kinase C (PKC signaling pathway in myocardial tissue and HL1 cells. The diffusion distance of Lucifer Yellow in the HL1 cells in which CMYA1 was over-expressed or knocked down was significantly less or more than that of the control group, respectively. Conclusion: Abnormal CMYA1 expression affects the expression and phosphorylation of Cx43 through the PKC signaling pathway, which is involved in the regulation of GJIC. CMYA1 participates in the molecular mechanism of LVNC pathogenesis.

  19. Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma‑associated epileptic discharge (Review).

    Science.gov (United States)

    Dong, Hui; Zhou, Xing-Wang; Wang, Xiang; Yang, Yuan; Luo, Jie-Wen; Liu, Yan-Hui; Mao, Qing

    2017-12-01

    Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment. However, there are still a number of issues concerning this aspect that require further exploration. Cx43, as a potential treatment target against this incurable disease and its common symptom of epilepsy, requires further investigation.

  20. Old cogs, new tricks: a scaffolding role for connexin43 and a junctional role for sodium channels?

    Science.gov (United States)

    Veeraraghavan, Rengasayee; Poelzing, Steven; Gourdie, Robert G

    2014-04-17

    Cardiac conduction is the process by which electrical excitation is communicated from cell to cell within the heart, triggering synchronous contraction of the myocardium. The role of conduction defects in precipitating life-threatening arrhythmias in various disease states has spurred scientific interest in the phenomenon. While the understanding of conduction has evolved greatly over the last century, the process has largely been thought to occur via movement of charge between cells via gap junctions. However, it has long been hypothesized that electrical coupling between cardiac myocytes could also occur ephaptically, without direct transfer of ions between cells. This review will focus on recent insights into cardiac myocyte intercalated disk ultrastructure and their implications for conduction research, particularly the ephaptic coupling hypothesis. Published by Elsevier B.V.

  1. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article discusses three central aspects of the freedoms under European Community law, namely 1) the prohibition against restrictions as an important extension of the prohibition against discrimination, 2) a prohibition against exit restrictions which is just as important as the prohibition...... against host country restrictions, but which is often not recognised to the same extent by national law, and 3) the importance of also identifying and recognising an exit restriction, so that it is possible to achieve the required test of appropriateness and proportionality in relation to the rule...

  2. Restricting wolves risks escape

    Science.gov (United States)

    Mech, L. David; Ballard, Warren; Bangs, Ed; Ream, Bob

    2010-01-01

    Implementing the proposal set forth by Licht and colleagues (BioScience 60: 147–153) requires restricting wolves to tiny "islands," areas that are magnitudes smaller than the ranges of most wolf populations. Wolves naturally have large ranges; restricting their spatial needs increases the risk of wolves escaping, exacerbating public relations and political and legal problems.

  3. Protein restriction and cancer.

    Science.gov (United States)

    Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong

    2018-03-26

    Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-07-01

    Full Text Available It is estimated that the true prevalence of intrauterine growth restriction is 3-10% of all pregnancies, making this fetal condition one of the most frequent obstetric problems, together with premature labor and premature rupture of membranes. The article stresses the importance of early diagnosis because of the associated risks.

  5. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

    Tygesen, Malin Plumhoff; Nielsen, Mette Olaf; Nørgaard, Peder

    2008-01-01

    We investigated the effect of 50% nutrient restriction during the last 6 weeks of gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, ß-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma...

  6. Restricted Variance Interaction Effects

    DEFF Research Database (Denmark)

    Cortina, Jose M.; Köhler, Tine; Keeler, Kathleen R.

    2018-01-01

    Although interaction hypotheses are increasingly common in our field, many recent articles point out that authors often have difficulty justifying them. The purpose of this article is to describe a particular type of interaction: the restricted variance (RV) interaction. The essence of the RV int...

  7. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Directory of Open Access Journals (Sweden)

    Guoqiang Zhong

    2017-05-01

    Full Text Available In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2 is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge of the crossing molecules.

  8. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Science.gov (United States)

    Zhong, Guoqiang; Akoum, Nazem; Appadurai, Daniel A.; Hayrapetyan, Volodya; Ahmed, Osman; Martinez, Agustin D.; Beyer, Eric C.; Moreno, Alonso P.

    2017-01-01

    In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2) is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj) for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge) of the crossing molecules. PMID:28611680

  9. Linoleic Acid Permeabilizes Gastric Epithelial Cells by Increasing Connexin43 Levels in the Cell Membrane Via a GPR40- and Akt-Dependent Mechanism

    Science.gov (United States)

    Puebla, Carlos; Cisterna, Bruno A.; Salas, Daniela P.; Delgado-López, Fernando; Lampe, Paul D.; Sáez, Juan C.

    2016-01-01

    Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintain the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt. PMID:26869446

  10. Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats

    NARCIS (Netherlands)

    Neumann, Elena; Hermanns, Henning; Barthel, Franziska; Werdehausen, Robert; Brandenburger, Timo

    2015-01-01

    MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression

  11. Impaired osteogenic differentiation associated with connexin43/microRNA-206 in steroid-induced avascular necrosis of the femoral head.

    Science.gov (United States)

    Liu, Gang; Luo, Gaobin; Bo, Zhandong; Liang, Xiaonan; Huang, Jie; Li, Donghui

    2016-08-01

    Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/β-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each. Group A was injected intravenously with lipopolysaccharide (10μg/kg body weight, once per day). After 48h, three injections of methylprednisolone (MPS; 20mg/kg body weight) were administered intramuscularly at 24-hour intervals. Group B were fed and housed under identical conditions but received saline injections. All animals were sacrificed at two, four, and eight weeks from the first MPS injection. Typical early osteonecrosis symptoms were observed in Group A. The expression of miR-206 in Group A was significantly higher than that of Group B. The mRNA and protein levels of Cx43, β-catenin, runt-related transcription factor 2, and alkaline phosphatase gradually decreased while Dickkopf-1 (Dkk-1) gradually increased in Group A compared with Group B. These findings indicated that Cx43/miR-206 is involved in the pathogenesis of early stage SANFH and may be associate with Wnt/β-catenin signal pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway.

    Science.gov (United States)

    Morioka, N; Suekama, K; Zhang, F F; Kajitani, N; Hisaoka-Nakashima, K; Takebayashi, M; Nakata, Y

    2014-06-01

    Intercellular communication via gap junctions, comprised of connexin (Cx) proteins, allow for communication between astrocytes, which in turn is crucial for maintaining CNS homeostasis. The expression of Cx43 is decreased in post-mortem brains from patients with major depression. A potentially novel mechanism of tricyclic antidepressants is to increase the expression and functioning of gap junctions in astrocytes. The effect of amitriptyline on the expression of Cx43 and gap junction intercellular communication (GJIC) in rat primary cultured cortical astrocytes was investigated. We also investigated the role of p38 MAPK intracellular signalling pathway in the amitriptyline-induced expression of Cx43 and GJIC. Treatment with amitriptyline for 48 h significantly up-regulated Cx43 mRNA, protein and GJIC. The up-regulation of Cx43 was not monoamine-related since noradrenaline, 5-HT and dopamine did not induce Cx43 expression and pretreatment with α- and β-adrenoceptor antagonists had no effect. Intracellular signalling involved p38 MAPK, as amitriptyline significantly increased p38 MAPK phosphorylation and Cx43 expression and GJIC were significantly blocked by the p38 inhibitor SB 202190. Furthermore, amitriptyline-induced Cx43 expression and GJIC were markedly reduced by transcription factor AP-1 inhibitors (curcumin and tanshinone IIA). The translocation of c-Fos from the cytosol and the nucleus of cortical astrocytes was increased by amitriptyline, and this response was dependent on p38 activity. These findings indicate a novel mechanism of action of amitriptyline through cortical astrocytes, and further suggest that targeting this mechanism could lead to the development of a new class of antidepressants. © 2014 The British Pharmacological Society.

  13. HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

    Science.gov (United States)

    Lin, Pei-Chun; Shen, Chien-Chang; Liao, Chih-Kai; Jow, Guey-Mei; Chiu, Chi-Ting; Chung, Tun-Hui; Wu, Jiahn-Chun

    2013-05-01

    HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression. A confocal microscopic study and scrape-loading/dye transfer analyses demonstrated that HYS-32 (5μM) induced microtubule coiling, accumulation of Cx43 in gap junction plaques, and increased GJIC in astrocytes. The HYS-32-induced microtubule coiling and Cx43 accumulation in gap junction plaques was reversed when HYS-32 was removed. Treatment of astrocytes with cycloheximide resulted in time-dependent degradation of by co-treatment with HYS-32 by increasing the half-life of Cx43. Co-treatment with HYS-32 also prevented the LPS-induced downregulation of Cx43 and inhibition of GJIC in astrocytes. HYS-32 induced activation of PKC, ERK, and JNK, and co-treatment with the PKC inhibitor Go6976 or the ERK inhibitor PD98059, but not the JNK inhibitor SP600125, prevented the HYS-32-induced increase in Cx43 expression and GJIC. Go6976 suppressed the HYS-32-induced PKC phosphorylation and increase in phospho-ERK levels, while PD98059 did not prevent the HYS-32-induced increase in phospho-PKC levels, suggesting that PKC is an upstream effector of ERK. In conclusion, our results show that HYS-32 increases the half-life of Cx43 and enhances Cx43 expression and GJIC in astrocytes via a PKC-ERK signaling cascade. These novel biological effects of HYS-32 on astrocyte gap junctions support its potential for therapeutic use as a protective agent for the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    relies on sampling based approximations of the log-likelihood gradient. I will present an empirical and theoretical analysis of the bias of these approximations and show that the approximation error can lead to a distortion of the learning process. The bias decreases with increasing mixing rate......Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...... of the applied sampling procedure and I will introduce a transition operator that leads to faster mixing. Finally, a different parametrisation of RBMs will be discussed that leads to better learning results and more robustness against changes in the data representation....

  15. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  16. About 'restriction', 'justified' and 'necessary'

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2016-01-01

    The article is an academic fairy tale about why and how all national corporate tax protection legislation should undergo a 3-part test to ensure its consistency with EU law. Each Member State introduce a compulsory 3-step test for each new (corporate) tax provision. The test is simple: (1) Does...... the tax provision constitute a restriction in the sense of EU law? (2) If the answer is yes: Is the restriction justified? (3) If the answer is yes: Is the restriction necessary?"...

  17. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time ...

  18. Aging, adiposity, and calorie restriction.

    Science.gov (United States)

    Fontana, Luigi; Klein, Samuel

    2007-03-07

    Excessive calorie intake and subsequent obesity increases the risk of developing chronic disease and decreases life expectancy. In rodent models, calorie restriction with adequate nutrient intake decreases the risk of developing chronic disease and extends maximum life span. To evaluate the physiological and clinical implications of calorie restriction with adequate nutrient intake. Search of PubMed (1966-December 2006) using terms encompassing various aspects of calorie restriction, dietary restriction, aging, longevity, life span, adiposity, and obesity; hand search of journals that focus on obesity, geriatrics, or aging; and search of reference lists of pertinent research and review articles and books. Reviewed reports (both basic science and clinical) included epidemiologic studies, case-control studies, and randomized controlled trials, with quality of data assessed by taking into account publication in a peer-reviewed journal, number of animals or individuals studied, objectivity of measurements, and techniques used to minimize bias. It is not known whether calorie restriction extends maximum life span or life expectancy in lean humans. However, calorie restriction in adult men and women causes many of the same metabolic adaptations that occur in calorie-restricted rodents and monkeys, including decreased metabolic, hormonal, and inflammatory risk factors for diabetes, cardiovascular disease, and possibly cancer. Excessive calorie restriction causes malnutrition and has adverse clinical effects. Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known. In addition, it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat.

  19. How Harmful are Adaptation Restrictions

    OpenAIRE

    Bruin, de, K.C.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  20. Telomere Restriction Fragment (TRF) Analysis.

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  1. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured ...

  2. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

  3. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli

    2011-02-01

    Full Text Available Two main perspectives of investigation emerge from the study of a territory’s rurality: a geographical approach and a sociological approach. The research examines the sub-regional study case of ‘Nuovo circondario imolese’. The analysis shows that the combination of traditional institutional criteria with detailed informations about the territory, generates more accurate results which determine a better comprehension of the characteristics of restricted areas’ rurality. Over the period 1991-2001, the study highlights an increase in rural areas. This result could be interpreted as an effect of urban sprawl’s intensification, that increases the competition between non-farm residences and agricultural activities.

  4. Parenting and restrictions in childhood epilepsy

    NARCIS (Netherlands)

    Rodenburg, R.; Meijer, A.M.; Scherphof, C.; Carpay, J.A.; Augustijn, P.; Aldenkamp, A.P.; Deković, M.

    2013-01-01

    Purpose: From the overprotection literature, the predictive and interactional (moderation) effects of controlling and indulgent parenting on restrictions in children with epilepsy were examined. Methods: Parents of 73 children with epilepsy completed questionnaires on parenting, restrictions, and

  5. 49 CFR 383.95 - Restrictions.

    Science.gov (United States)

    2010-10-01

    ... the skills test and the restriction, air brakes shall include any braking system operating fully or...; REQUIREMENTS AND PENALTIES Vehicle Groups and Endorsements § 383.95 Restrictions. (a) Air brake restrictions... skills test in a vehicle not equipped with air brakes, the State must indicate on the CDL, if issued...

  6. 9 CFR 92.3 - Movement restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Movement restrictions. 92.3 Section 92... ANIMAL PRODUCTS: PROCEDURES FOR REQUESTING RECOGNITION OF REGIONS § 92.3 Movement restrictions. Whenever... exist and the EC imposes prohibitions or other restrictions on the movement of animals or animal...

  7. 21 CFR 203.20 - Sales restrictions.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sales restrictions. 203.20 Section 203.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Sales Restrictions § 203.20 Sales restrictions. Except as provided in § 203.22 or...

  8. Restricted Predicates for Hypothetical Datalog

    Directory of Open Access Journals (Sweden)

    Fernando Sáenz-Pérez

    2015-12-01

    Full Text Available Hypothetical Datalog is based on an intuitionistic semantics rather than on a classical logic semantics, and embedded implications are allowed in rule bodies. While the usual implication (i.e., the neck of a Horn clause stands for inferring facts, an embedded implication plays the role of assuming its premise for deriving its consequence. A former work introduced both a formal framework and a goal-oriented tabled implementation, allowing negation in rule bodies. While in that work positive assumptions for both facts and rules can occur in the premise, negative assumptions are not allowed. In this work, we cover this subject by introducing a new concept: a restricted predicate, which allows negative assumptions by pruning the usual semantics of a predicate. This new setting has been implemented in the deductive system DES.

  9. A Traffic Restriction Scheme for Enhancing Carpooling

    Directory of Open Access Journals (Sweden)

    Dong Ding

    2017-01-01

    Full Text Available For the purpose of alleviating traffic congestion, this paper proposes a scheme to encourage travelers to carpool by traffic restriction. By a variational inequity we describe travelers’ mode (solo driving and carpooling and route choice under user equilibrium principle in the context of fixed demand and detect the performance of a simple network with various restriction links, restriction proportions, and carpooling costs. Then the optimal traffic restriction scheme aiming at minimal total travel cost is designed through a bilevel program and applied to a Sioux Fall network example with genetic algorithm. According to various requirements, optimal restriction regions and proportions for restricted automobiles are captured. From the results it is found that traffic restriction scheme is possible to enhance carpooling and alleviate congestion. However, higher carpooling demand is not always helpful to the whole network. The topology of network, OD demand, and carpooling cost are included in the factors influencing the performance of the traffic system.

  10. Restricted Interval Valued Neutrosophic Sets and Restricted Interval Valued Neutrosophic Topological Spaces

    Directory of Open Access Journals (Sweden)

    Anjan Mukherjee

    2016-08-01

    Full Text Available In this paper we introduce the concept of restricted interval valued neutrosophic sets (RIVNS in short. Some basic operations and properties of RIVNS are discussed. The concept of restricted interval valued neutrosophic topology is also introduced together with restricted interval valued neutrosophic finer and restricted interval valued neutrosophic coarser topology. We also define restricted interval valued neutrosophic interior and closer of a restricted interval valued neutrosophic set. Some theorems and examples are cites. Restricted interval valued neutrosophic subspace topology is also studied.

  11. Intrauterine growth restriction - part 2.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2016-12-01

    Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

  12. Placental Adaptations in Growth Restriction

    Science.gov (United States)

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  13. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  14. Assessing restrictiveness of national alcohol marketing policies.

    Science.gov (United States)

    Esser, Marissa B; Jernigan, David H

    2014-01-01

    To develop an approach for monitoring national alcohol marketing policies globally, an area of the World Health Organization's (WHO) Global Alcohol Strategy. Data on restrictiveness of alcohol marketing policies came from the 2002 and 2008 WHO Global Surveys on Alcohol and Health. We included four scales in a sensitivity analysis to determine optimal weights to score countries on their marketing policies and applied the selected scale to assess national marketing policy restrictiveness. Nearly, 36% of countries had no marketing restrictions. The overall restrictiveness levels were not significantly different between 2002 and 2008. The number of countries with strict marketing regulations did not differ across years. This method of monitoring alcohol marketing restrictiveness helps track progress towards implementing WHO'S Global Alcohol Strategy. Findings indicate a consistent lack of restrictive policies over time, making this a priority area for national and global action. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  15. Curves of restricted type in euclidean spaces

    Directory of Open Access Journals (Sweden)

    Bengü Kılıç Bayram

    2014-01-01

    Full Text Available Submanifolds of restricted type were introduced in [7]. In the present study we consider restricted type of curves in Em. We give some special examples. We also show that spherical curve in S2(r C E3 is of restricted type if and only if either ƒ(s is constant or a linear function of s of the form ƒ(s = ±s + b and every closed W - curve of rank k and of length 2(r in E2k is of restricted type.

  16. Connexins in the early development of the African clawed frog Xenopus laevis (Amphibia: The role of the connexin43 carboxyl terminal tail in the establishment of the dorso-ventral axis

    Directory of Open Access Journals (Sweden)

    Jaime Cofre

    2007-03-01

    Full Text Available Connexins are a family of related proteins identified in vertebrate forming gap junctions, which mediate cell-to-cell communication in early embryos, with an important role in establishing embryonic asymmetry and ‘communication compartments’. By in situ hybridization, immunocytochemistry, reverse transcriptase PCR (RT-PCR and western blotting we show that a Cx43-like molecule is present in oocytes and embryos of the African clawed frog Xenopus laevis, with specific localization in the animal-vegetal axis. This specific distribution is suggestive for an important role for this protein in the establishment of the dorso-ventral axis. Antisense RNA and antibodies directed against rat carboxyl terminal tail of the Cx43 (CT-Cx43 and injected in 1-cell stage Xenopus embryos, induced pronounced alterations in nervous system development, with a severe ventralization phenotype. Coherently, the overexpression of CT-Cx43 produced a dorsalization of the embryos. In antisense treated embryos, the expression of the beta-catenin gene is eliminated from the Nieuwkoop center, the pattern expression of the Chordin, Xnot and Xbra is modified, with no effect in expression of the Goosecoid gene. In CT-Cx43 mRNA treated embryos the pattern of expression of the beta-catenin, Chordin, Goosecoid, Xnot and engrailed-2 genes is modified. The expression of beta-catenin is increased in the Nieuwkoop center, the expression pattern of Chordin and Goosecoid is expanded to the posterior neural plate and engrailed-2 presents ectopic expression in the ventral region. Taken together our data suggest a role for CT-Cx43 as a maternal determinant with a critical function in the formation of the dorso-ventral axis in Xenopus laevis. The Cx43 may be one of the earliest markers of the dorso-ventral axis in these embryos and could possibly be acting through regionalization of factors responsible for the establishment of this axis.

  17. Silver nanoparticles increase connexin43-mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen-activated protein kinase signal pathway

    DEFF Research Database (Denmark)

    Qin, Yu; Han, Limin; Yang, Di

    2018-01-01

    Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to ...

  18. Universal Cycles of Restricted Classes of Words

    OpenAIRE

    Leitner, Arielle; Godbole, Anant

    2008-01-01

    It is well known that Universal Cycles of $k$-letter words on an $n$-letter alphabet exist for all $k$ and $n$. In this paper, we prove that Universal Cycles exist for restricted classes of words, including: non-bijections, equitable words (under suitable restrictions), ranked permutations, and "passwords".

  19. Freedom and Restrictions in Language Use.

    Science.gov (United States)

    O'Donnell, Roy C.

    Since freedom of thought and expression is essential in a democracy, censorship of language is rightly regarded as a threat to all other freedoms. Still, it is inevitable that certain restrictions will occasionally be imposed on language in America and in other societies. Restrictions on language date back to the Ten Commandments, which condemned…

  20. Protein restriction in chronic renal failure

    NARCIS (Netherlands)

    ECHTEN, JEKT; NAUTA, J; HOP, WCJ; de Jong, MCJ; REITSMABIERENS, WCC; VANAMSTEL, SLBP; VANACKER, KJ; NOORDZIJ, CM; WOLFF, ED

    The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1

  1. Relationship Between Calorie Restriction, Lipid Peroxidation ...

    African Journals Online (AJOL)

    In the brain of the caloric restricted rats, there was little or no change in the tGSH and GSH, although the GSSG and GSSG/GSH% ratio were increased significantly. These results suggest that aging of rats had been decelerated by caloric restriction due to the decrease in the peroxidative damage in the lungs and brain.

  2. Eclampsia despite strict dietary sodium restriction.

    NARCIS (Netherlands)

    Delemarre, F.M.C.; Steegers, E.A.P.; Berendes, J.N.

    2001-01-01

    The classic indication for prescribing dietary sodium restriction in pregnancy has been the prevention of eclampsia. We describe a case of intrapartum eclampsia in a 24-year-old nulliparous woman. A strongly sodium restricted diet was prescribed because of pre-eclampsia. Compliance to the diet was

  3. 7 CFR 3430.205 - Funding restrictions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Funding restrictions. 3430.205 Section 3430.205... Funding restrictions. (a) Prohibition against construction. Funds made available under this subpart shall not be used for the construction of a new building or facility or the acquisition, expansion...

  4. 28 CFR 804.3 - Restrictions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Restrictions. 804.3 Section 804.3 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR THE DISTRICT OF COLUMBIA ACCEPTANCE OF GIFTS § 804.3 Restrictions. (a) The Agency is not authorized to accept gifts of money, stock...

  5. Restricted gravity: Abelian projection of Einstein's theory

    International Nuclear Information System (INIS)

    Cho, Y.M.

    2013-01-01

    Treating Einstein's theory as a gauge theory of Lorentz group, we decompose the gravitational connection Γμ into the restricted connection made of the potential of the maximal Abelian subgroup H of Lorentz group G and the valence connection made of G/H part of the potential which transforms covariantly under Lorentz gauge transformation. With this we show that Einstein's theory can be decomposed into the restricted gravity made of the restricted connection which has the full Lorentz gauge invariance which has the valence connection as gravitational source. The decomposition shows the existence of a restricted theory of gravitation which has the full general invariance but is much simpler than Einstein's theory. Moreover, it tells that the restricted gravity can be written as an Abelian gauge theory,

  6. R Factor-Controlled Restriction and Modification of Deoxyribonucleic Acid: Restriction Mutants

    Science.gov (United States)

    Yoshimori, Robert; Roulland-Dussoix, Daisy; Boyer, Herbert W.

    1972-01-01

    Restriction mutants of two different R factor-controlled host specificities (RI and RII) were isolated. All of the restriction mutants examined had a normal modification phenotype. No complementation was observed between the RI and RII host specificities. It is concluded that for each host specificity no protein subunit is shared by the restriction endonuclease and modification methylase. PMID:4565538

  7. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction

    Science.gov (United States)

    Rauktis, Mary E.; Huefner, Jonathan C.; O'Brien, Kirk; Pecora, Peter J.; Doucette, Ann; Thompson, Ronald W.

    2009-01-01

    The "Restrictiveness of Living Environment Scale" has long been the primary way to conceptualize the "restrictiveness" of a child's living situation. However, changes in systems of care and other factors have created a need to revisit how restrictiveness is conceptualized and measured. A measure was created to assess an environment's level of…

  8. Urban water restrictions: Attitudes and avoidance

    Science.gov (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin

    2011-12-01

    In most urban cities across Australia, water restrictions remain the dominant policy mechanism to restrict urban water consumption. The extensive adoption of water restrictions as a means to limit demand, over several years, means that Australian urban water prices have consistently not reflected the opportunity cost of water. Given the generally strong political support for water restrictions and the likelihood that they will persist for some time, there is value in understanding households' attitudes in this context. More specifically, identifying the welfare gains associated with avoiding urban water restrictions entirely would be a nontrivial contribution to our knowledge and offer insights into the benefits of alternative policy responses. This paper describes the results from a contingent valuation study that investigates consumers' willingness to pay to avoid urban water restrictions. Importantly, the research also investigates the influence of cognitive and exogenous dimensions on the utility gain associated with avoiding water restrictions. The results provide insights into the impact of the current policy mechanism on economic welfare.

  9. Decoding restricted participation in sequential electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Knaut, Andreas; Paschmann, Martin

    2017-06-15

    Restricted participation in sequential markets may cause high price volatility and welfare losses. In this paper we therefore analyze the drivers of restricted participation in the German intraday auction which is a short-term electricity market with quarter-hourly products. Applying a fundamental electricity market model with 15-minute temporal resolution, we identify the lack of sub-hourly market coupling being the most relevant driver of restricted participation. We derive a proxy for price volatility and find that full market coupling may trigger quarter-hourly price volatility to decrease by a factor close to four.

  10. Investigation of restricted baby Skyrme models

    International Nuclear Information System (INIS)

    Adam, C.; Romanczukiewicz, T.; Wereszczynski, A.; Sanchez-Guillen, J.

    2010-01-01

    A restriction of the baby Skyrme model consisting of the quartic and potential terms only is investigated in detail for a wide range of potentials. Further, its properties are compared with those of the corresponding full baby Skyrme models. We find that topological (charge) as well as geometrical (nucleus/shell shape) features of baby Skyrmions are captured already by the soliton solutions of the restricted model. Further, we find a coincidence between the compact or noncompact nature of solitons in the restricted model, on the one hand, and the existence or nonexistence of multi-Skyrmions in the full baby Skyrme model, on the other hand.

  11. distribution, abundance and properties of restriction enzymes

    African Journals Online (AJOL)

    DNA of granule-bound starch synthase (GBSS) I and II with a view to ... properties for manipulation of the genes for production of modified starch. .... procurement, storage and handling of the ..... been made on restriction enzymes of potato,.

  12. Health Benefits of Fasting and Caloric Restriction.

    Science.gov (United States)

    Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

    2017-10-23

    Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

  13. Compensatory mechanisms activated with intermittent energy restriction

    DEFF Research Database (Denmark)

    Coutinho, Sílvia Ribeiro; Halset, Eline Holli; Gåsbakk, Sigrid

    2018-01-01

    Background & aims: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy...... restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. Methods: 35 adults (age......: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting...

  14. Restricted Coherent Risk Measures and Actuarial Solvency

    Directory of Open Access Journals (Sweden)

    Christos E. Kountzakis

    2012-01-01

    Full Text Available We prove a general dual representation form for restricted coherent risk measures, and we apply it to a minimization problem of the required solvency capital for an insurance company.

  15. Evolutionary genomics and HIV restriction factors.

    Science.gov (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

    2015-03-01

    To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

  16. Avoidant/Restrictive Food Intake Disorder

    Science.gov (United States)

    ... Eating Disorder Bulimia Nervosa Pica Rumination Disorder Avoidant/restrictive food intake disorder is characterized by eating very little food and/or avoiding eating certain foods. People with this disorder eat ...

  17. The welfare effects of mobility restrictions

    Czech Academy of Sciences Publication Activity Database

    Jeong, Byeongju

    2003-01-01

    Roč. 6, č. 3 (2003), s. 685-696 ISSN 1094-2025 Institutional research plan: CEZ:AV0Z7085904 Keywords : mobility restriction * partnership * search Subject RIV: AH - Economics Impact factor: 0.600, year: 2003

  18. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Sqd to produce spatially-restricted Egfr activation...

  19. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Squid to produce spatially-restricted EGFR activation...

  20. A topological insight into restricted Boltzmann machines

    NARCIS (Netherlands)

    Mocanu, D.C.; Mocanu, E.; Nguyen, H.P.; Gibescu, M.; Liotta, A.

    Restricted Boltzmann Machines (RBMs) and models derived from them have been successfully used as basic building blocks in deep artificial neural networks for automatic features extraction, unsupervised weights initialization, but also as density estimators. Thus, their generative and discriminative

  1. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  2. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  3. Public Investment, Revenue Shocks, and Borrowing Restrictions

    OpenAIRE

    Büttner, Thiess; Wildasin, David E.

    2010-01-01

    This paper lays out a theory of taxation and public investment in an intertemporal setting under conditions of revenue shocks. Without borrowing restrictions, the optimal policy is characterized by smooth time paths of taxes and public investment. While the introduction of formal borrowing restrictions leads to some precautionary savings, it gives rise to fluctuations in public investment in response to adverse but also favorable revenue shocks. This theoretical result is tested empirically u...

  4. Dietary restriction with and without caloric restriction for healthy aging [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Changhan Lee

    2016-01-01

    Full Text Available Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.

  5. Fasting or caloric restriction for healthy aging.

    Science.gov (United States)

    Anton, Stephen; Leeuwenburgh, Christiaan

    2013-10-01

    Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Cellular Restriction Factors of Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Carsten Münk

    2011-10-01

    Full Text Available Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors or inhibit viral replication (restriction factors. Similar to Human immunodeficiency virus type 1 (HIV-1, the cat lentivirus Feline immunodeficiency virus (FIV is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors.

  7. Cellular Restriction Factors of Feline Immunodeficiency Virus

    Science.gov (United States)

    Zielonka, Jörg; Münk, Carsten

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

  8. Newer antidiabetic drugs and calorie restriction mimicry

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.

  9. Metabolic Regulation of Methionine Restriction in Diabetes.

    Science.gov (United States)

    Yin, Jie; Ren, Wenkai; Chen, Shuai; Li, Yuying; Han, Hui; Gao, Jing; Liu, Gang; Wu, Xin; Li, Tiejun; Kim, Sung Woo; Yin, Yulong

    2018-03-30

    Although the effects of dietary methionine restriction have been investigated in the physiology of aging and diseases related to oxidative stress, the relationship between methionine restriction and the development of metabolic disorders has not been explored extensively. This review summarizes studies of the possible involvement of dietary methionine restriction in improving insulin resistance, glucose homeostasis, oxidative stress, lipid metabolism, the pentose phosphate pathway, and inflammation, with an emphasis on the fibroblast growth factor 21 and protein phosphatase 2A signals and autophagy in diabetes. Diets deficient in methionine may be a useful nutritional strategy in patients with diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Optimizing Restriction Site Placement for Synthetic Genomes

    Science.gov (United States)

    Montes, Pablo; Memelli, Heraldo; Ward, Charles; Kim, Joondong; Mitchell, Joseph S. B.; Skiena, Steven

    Restriction enzymes are the workhorses of molecular biology. We introduce a new problem that arises in the course of our project to design virus variants to serve as potential vaccines: we wish to modify virus-length genomes to introduce large numbers of unique restriction enzyme recognition sites while preserving wild-type function by substitution of synonymous codons. We show that the resulting problem is NP-Complete, give an exponential-time algorithm, and propose effective heuristics, which we show give excellent results for five sample viral genomes. Our resulting modified genomes have several times more unique restriction sites and reduce the maximum gap between adjacent sites by three to nine-fold.

  11. Sight Restrictions in Maghrib Muslim Architecture

    Directory of Open Access Journals (Sweden)

    Mustapha Ben Hamouche

    1999-12-01

    Full Text Available Sight in Islamic culture is subject to legal restrictions that aim at preserving moral consciousness in Muslim societies. These restrictions have a direct impact on architecture in traditional Muslim cities. Details such as placement of doors and windows, the use of balconies and rooftops, and building heights were shaped by legal reasoning based on sight restrictions. The present study aims at highlighting this legal reasoning system by analyzing legal opinions that were continuously advocated by jurists in response to daily practices, and the legal principles on which these opinions were based. This is expected to contribute in developing a new intellectual discourse on Muslim architecture that could go beyond the present design theories.

  12. Predictive factors for intrauterine growth restriction.

    Science.gov (United States)

    Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

    2014-06-15

    Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

  13. Optimal Policy under Restricted Government Spending

    DEFF Research Database (Denmark)

    Sørensen, Anders

    2006-01-01

    Welfare ranking of policy instruments is addressed in a two-sector Ramsey model with monopoly pricing in one sector as the only distortion. When government spending is restricted, i.e. when a government is unable or unwilling to finance the required costs for implementing the optimum policy...... effectiveness canexceed the welfare loss from introducing new distortions. Moreover, it is found that the investment subsidy is gradually phased out of the welfare maximizing policy, which may be a policy combining the two subsidies, when the level of government spending is increased.Keywords: welfare ranking......, indirect and direct policy instruments, restricted government spending JEL: E61, O21, O41...

  14. Effects of restricted and free suckling

    OpenAIRE

    Fröberg, Sofie

    2008-01-01

    The aim of this thesis was to study the effects of restricted and free suckling in comparison with non-suckling on production and behaviour of cow and calf in dairy production systems. In the first and second study cows of Zebu × Holstein (n=24) and Holstein breed (n=27) and their calves were allocated to two treatments, restricted suckling (RS) and artificial rearing (AR) and studied during eight weeks. In the first study calves were present during milking and RS calves suckled after milking...

  15. 47 CFR 64.1200 - Delivery restrictions.

    Science.gov (United States)

    2010-10-01

    ... Advertising § 64.1200 Delivery restrictions. (a) No person or entity may: (1) Initiate any telephone call... telephone service, specialized mobile radio service, or other radio common carrier service, or any service... expect them to be included given the identification of the caller and the product being advertised. (6...

  16. Review: Neuroinflammation in intrauterine growth restriction.

    Science.gov (United States)

    Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey

    2017-06-01

    Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 7 CFR 3430.905 - Funding restrictions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Funding restrictions. 3430.905 Section 3430.905 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE COMPETITIVE AND NONCOMPETITIVE NON-FORMULA FEDERAL...

  18. On restricted context-free grammars

    Czech Academy of Sciences Publication Activity Database

    Dassow, J.; Masopust, Tomáš

    2012-01-01

    Roč. 78, č. 1 (2012), s. 293-304 ISSN 0022-0000 Institutional research plan: CEZ:AV0Z10190503 Keywords : context-free grammars * derivation restriction * normal forms Subject RIV: BA - General Mathematics Impact factor: 1.000, year: 2012 http://www.sciencedirect.com/science/article/pii/S0022000011000572

  19. Determination of genotype differences through restriction ...

    African Journals Online (AJOL)

    Tyrosinase gene or C locus has long been implicated in the coat colour determination. This gene a copper-containing enzyme located on chromosome 11q14.3 is expressed in melanocytes and controls the major steps in pigment production. In camel, C locus a restriction site provoked by the T variant of the mutation was ...

  20. 9 CFR 166.2 - General restrictions.

    Science.gov (United States)

    2010-01-01

    ... of any of the following: Processed products; rendered products; bakery waste; candy waste; eggs... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false General restrictions. 166.2 Section 166.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  1. Epigenetic regulation of caloric restriction in aging

    Directory of Open Access Journals (Sweden)

    Daniel Michael

    2011-08-01

    Full Text Available Abstract The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure, resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetics in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.

  2. A new restriction endonuclease from Citrobacter freundii

    Science.gov (United States)

    Janulaitis, A.A.; Stakenas, P.S.; Lebedenko, E.N.; Berlin, Yu.A.

    1982-01-01

    CfrI, a new restriction endonuclease of unique substrate specificity, has been isolated from a Citrobacter freundii strain. The enzyme recognizes a degenerated sequence PyGGCCPu in double-strand DNA and cleaves it between Py and G residues to yield 5′ -protruding tetranucleotide ends GGCC. Images PMID:6294607

  3. A new restriction endonuclease from Citrobacter freundii

    OpenAIRE

    Janulaitis, A.A.; Stakenas, P.S.; Lebedenko, E.N.; Berlin, Yu.A.

    1982-01-01

    CfrI, a new restriction endonuclease of unique substrate specificity, has been isolated from a Citrobacter freundii strain. The enzyme recognizes a degenerated sequence PyGGCCPu in double-strand DNA and cleaves it between Py and G residues to yield 5′ -protruding tetranucleotide ends GGCC.

  4. Strategies in intrauterine growth restriction at term

    NARCIS (Netherlands)

    Boers, Kim Esther

    2012-01-01

    To establish consensus and to collect evidence on the best management policy in intrauterine growth restriction (IUGR) at term, the DIGITAT-trial (Disproportionate Intrauterine Growth Intervention Trial At Term) was designed. The aim of the DIGITAT study was to compare the effect of induction of

  5. Sleep restriction progress to cardiac autonomic imbalance ...

    African Journals Online (AJOL)

    Since it's more difficult to maintain adequate sleep duration among night watchmen during their working schedule, hence the purpose of our present study was to investigate whether mental stress or fatigue over restricted sleep period in night shift, affects HRV, in order to elucidate on cardiac autonomic modulation among ...

  6. 18 CFR 35.39 - Affiliate restrictions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Affiliate restrictions. 35.39 Section 35.39 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Sales of Electric Energy, Capacity and Ancillary Services at Market-Based Rates § 35.39 Affiliate...

  7. An Adjustment Restriction on Fish Quota

    NARCIS (Netherlands)

    Dijk, van Diana; Hendrix, E.M.T.; Haijema, Rene; Groeneveld, R.A.; Ierland, van E.C.

    2017-01-01

    Management objectives of the European Union for North Sea fish stocks are shifting towards considering both biological sustainability and economic benefits. As part of multiannual management plans, an adjustment restriction on fish quota has been introduced. Its objective is to obtain an

  8. Periodic Solutions for Circular Restricted -Body Problems

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Zhao

    2013-01-01

    Full Text Available For circular restricted -body problems, we study the motion of a sufficiently small mass point (called the zero mass point in the plane of equal masses located at the vertices of a regular polygon. By using variational minimizing methods, for some , we prove the existence of the noncollision periodic solution for the zero mass point with some fixed wingding number.

  9. Sleep restriction progress to cardiac autonomic imbalance

    African Journals Online (AJOL)

    Arbind Kumar Choudhary

    2017-05-31

    May 31, 2017 ... and inadequate sleep is a common feature of night shift work. ... night watchmen during their working schedule, hence the purpose of our ... whether mental stress or fatigue over restricted sleep period in night ... 10 Hence, the variability in heart rate, (with reduced ..... Long-term cardiovascular outcomes.

  10. Nutrigenetics and nutrigenomics of caloric restriction.

    Science.gov (United States)

    Abete, Itziar; Navas-Carretero, Santiago; Marti, Amelia; Martinez, J Alfredo

    2012-01-01

    Obesity is a complex disease resulting from a chronic and long-term positive energy balance in which both genetic and environmental factors are involved. Weight-reduction methods are mainly focused on dietary changes and increased physical activity. However, responses to nutritional intervention programs show a wide range of interindividual variation, which is importantly influenced by genetic determinants. In this sense, subjects carrying several obesity-related single-nucleotide polymorphisms (SNPs) show differences in the response to calorie-restriction programs. Furthermore, there is evidence indicating that dietary components not only fuel the body but also participate in the modulation of gene expression. Thus, the expression pattern and nutritional regulation of several obesity-related genes have been studied, as well as those that are differentially expressed by caloric restriction. The responses to caloric restriction linked to the presence of SNPs in obesity-related genes are reviewed in this chapter. Also, the influence of energy restriction on gene expression pattern in different tissues is addressed. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Rat Neutrophil Phagocytosis Following Feed Restriction

    Czech Academy of Sciences Publication Activity Database

    Slapničková, Martina; Berger, J.

    2002-01-01

    Roč. 11, č. 3 (2002), s. 172-177 ISSN 0938-7714 Institutional research plan: CEZ:AV0Z5052915 Keywords : circulating neutrophil * diet restriction * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.167, year: 2001

  12. Employees, Trade Secrets and Restrictive Covenants

    NARCIS (Netherlands)

    Kamperman Sanders, Anselm; Heath, C.

    2017-01-01

    The book covers the protection of trade secrets and the law on post-contractual non-compete clauses (restrictive covenants) in an employment context. The topic is approached on an international and comparative level (chapters 1–3 and 10), and by way of country reports covering several European and

  13. Restricted Choice in the Management of Change.

    Science.gov (United States)

    North, R. F. J.

    1988-01-01

    Instances from case studies of comprehensive schools in the United Kingdom show that cultural influences restrict possibilities of "rational" action by educational leaders. This article warns against business theory and concludes that we need to know more about how people in schools make choices. (Author/TE)

  14. 32 CFR 701.44 - Restrictions.

    Science.gov (United States)

    2010-07-01

    ... OFFICIAL RECORDS AVAILABILITY OF DEPARTMENT OF THE NAVY RECORDS AND PUBLICATION OF DEPARTMENT OF THE NAVY DOCUMENTS AFFECTING THE PUBLIC FOIA Fees § 701.44 Restrictions. (a) No fees may be charged by any DON activity if the costs of routine collection and processing of the fee are likely to equal or exceed the...

  15. 50 CFR 648.164 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... Atlantic Bluefish Fishery § 648.164 Possession restrictions. (a) No person shall possess more than 15 bluefish in, or harvested from, the EEZ unless that person is the owner or operator of a fishing vessel issued a bluefish commercial permit or is issued a bluefish dealer permit. Persons aboard a vessel that...

  16. 38 CFR 1.462 - Confidentiality restrictions.

    Science.gov (United States)

    2010-07-01

    ... Sickle Cell Anemia § 1.462 Confidentiality restrictions. (a) General. The patient records to which §§ 1..., infection with the HIV, or sickle cell anemia may be acknowledged only if the patient's written consent is... with the HIV, or sickle cell anemia. (2) Any answer to a request for a disclosure of patient records...

  17. Intrauterine growth restriction: screening, diagnosis, and management.

    Science.gov (United States)

    Lausman, Andrea; Kingdom, John

    2013-08-01

    Intrauterine growth restriction (IUGR) is an obstetrical complication, which by definition would screen in 10% of fetuses in the general population. The challenge is to identify the subset of pregnancies affected with pathological growth restriction in order to allow intervention that would decrease morbidity and mortality. The purpose of this guideline is to provide summary statements and recommendations and to establish a framework for screening, diagnosis, and management of pregnancies affected with IUGR. Affected pregnancies are compared with pregnancies in which the fetus is at an appropriate weight for its gestational age. History, physical examination, and laboratory investigations including biochemical markers and ultrasound characteristics of IUGR are reviewed, and a management strategy is suggested. Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in January 2013 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Implementation of the recommendations in this guideline should increase clinician recognition of IUGR and guide intervention where appropriate. Optimal long-term follow-up of neonates diagnosed as IUGR may improve their long-term health.

  18. 7 CFR 322.28 - General requirements; restricted articles.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false General requirements; restricted articles. 322.28... EQUIPMENT Importation and Transit of Restricted Articles § 322.28 General requirements; restricted articles. (a) The following articles from any region are restricted articles: (1) Dead bees of any genus; (2...

  19. 7 CFR 319.75-2 - Restricted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Restricted articles. 1 319.75-2 Section 319.75-2... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Khapra Beetle § 319.75-2 Restricted articles. 1 1 The importation of restricted articles may be subject to prohibitions or restrictions under...

  20. Avoidant/Restrictive Food Intake Disorder (ARFID).

    Science.gov (United States)

    Zimmerman, Jacqueline; Fisher, Martin

    2017-04-01

    Avoidant/restrictive food intake disorder (ARFID) is an entirely new diagnosis in the DSM-5. ARFID replaces "feeding disorder of infancy or early childhood," which was a diagnosis in the DSM-IV restricted to children 6 years of age or younger; ARFID has no such age limitations and it is distinct from anorexia nervosa and bulimia nervosa in that there is no body image disturbance. ARFID involves a complex and heterogenous etiology, which is reviewed herein. What is known to date regarding the characteristics and medical and psychiatric comorbidities of this patient population are described and compared to other eating disorders. Evaluation and management strategies are also discussed. No data yet exist regarding ARFID׳s prognosis and prevention; however, recommendations to guide parents in establishing appropriate infant and child feeding practices are provided. Copyright © 2017 Mosby, Inc. All rights reserved.

  1. Sizing of high-pressure restriction orifices

    International Nuclear Information System (INIS)

    Casado Flores, E.

    1995-01-01

    Constant up-grading of power plants sometimes requires the modification of components which form part of suppliers' packages. In order to protect technology they have developed, however, the suppliers do not supply their calculation criteria. In order to reduce the costs of such improvements, and so as to be able to undertake the modification without having to rely on the original supplier, this paper describes the basic criteria applicable to the study of high-pressure restriction orifices, which can be considered to be representative of the components in question. The restriction orifices discussed are: - Insert - Multiplates in series with one perforation in each plate - Multiplates in series with several perforations in each plate For each type, an explanation of their sizing is given, together with the equations relating the corresponding flow and pressure drop. (Author)

  2. Octreotide therapy and restricted fetal growth

    DEFF Research Database (Denmark)

    Geilswijk, Marianne; Andersen, Lise Lotte Torvin; Frost, Morten

    2017-01-01

    that octreotide treatment in pregnancy, as well as hypoglycemia in itself, may pose a risk of fetal growth restriction. During pregnancy, management of blood glucose levels in familial hyperinsulinemic hypoglycemia thus forms a medical dilemma. We report on pregnancy outcomes in a woman with symptomatic familial...... hyperinsulinemic hypoglycemia, type 3. During the patient's first pregnancy with a viable fetus octreotide treatment was instituted in gestational age 23 weeks to prevent severe hypoglycemic incidences. Fetal growth velocity declined, and at 37 weeks of gestation, intrauterine growth retardation was evident...... growth velocity was normal. We conclude that octreotide treatment during pregnancy may pose a risk of fetal growth restriction and warrants careful consideration. In some cases of familial hyperinsulinemic hypoglycemia, blood glucose levels can be successfully managed through diet only, also during...

  3. Investment Restrictions and Contagion in Emerging Markets

    OpenAIRE

    Anna Ilyina

    2005-01-01

    The objectives of this paper are: (1) to analyze an optimal portfolio rebalancing by a fund manager in response to a "volatility shock" in one of the asset markets, under sufficiently realistic assumptions about the fund manager's performance criteria and investment restrictions; and (2) to analyze the sensitivity of the equilibrium price of an asset to shocks originating in other fundamentally unrelated asset markets for a given mix of common investors. The analysis confirms that certain com...

  4. Optimal Detection under the Restricted Bayesian Criterion

    Directory of Open Access Journals (Sweden)

    Shujun Liu

    2017-07-01

    Full Text Available This paper aims to find a suitable decision rule for a binary composite hypothesis-testing problem with a partial or coarse prior distribution. To alleviate the negative impact of the information uncertainty, a constraint is considered that the maximum conditional risk cannot be greater than a predefined value. Therefore, the objective of this paper becomes to find the optimal decision rule to minimize the Bayes risk under the constraint. By applying the Lagrange duality, the constrained optimization problem is transformed to an unconstrained optimization problem. In doing so, the restricted Bayesian decision rule is obtained as a classical Bayesian decision rule corresponding to a modified prior distribution. Based on this transformation, the optimal restricted Bayesian decision rule is analyzed and the corresponding algorithm is developed. Furthermore, the relation between the Bayes risk and the predefined value of the constraint is also discussed. The Bayes risk obtained via the restricted Bayesian decision rule is a strictly decreasing and convex function of the constraint on the maximum conditional risk. Finally, the numerical results including a detection example are presented and agree with the theoretical results.

  5. Meeting licensing restrictions from a regulator's perspective

    International Nuclear Information System (INIS)

    Autry, V.R.; Ragan, F.A.

    1990-01-01

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low level waste has experienced many changes necessitated by technical advancements which led to stricter controls and restrictions for shallow land disposal. Low level waste has evolved from simple contaminated items with minimal radioactivity, to complex waste streams requiring elaborate processing and containment of high quantities of radionuclides. Waste streams also require extensive analysis and qualification to meet many of the restrictions imposed at the burial facility and comply with national standards and regulations for classification. This paper presents a chronological history of many of these restrictions, the rationale for them, and the waste generators' abilities and inabilities to comply. In addition, case histories of some examples are discussed

  6. Emergency building temperature restrictions. Final evaluation

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-11-01

    On July 5, 1979, DOE promulgated final regulations of the Emergency Building Temperature Restrictions program, placing emergency restrictions on thermostat settings for space heating, space cooling, and hot water in commercial, industrial, and nonresidential public buildings. The final regulations restricted space heating to a maximum of 65/sup 0/F, hot water temperature to a maximum of 105/sup 0/F, and cooling temperature to a minimum of 78/sup 0/F. A comprehensive evaluation of the entire EBTF program for a nine-month period from July 16, 1979 is presented. In Chapter 1, an estimate of the population of buildings covered by EBTR is presented. In Chapter 2, EBTR compliance by building type and region is reported. Exemptions are also discussed. In Chapter 3, the simulations of building energy use are explained and the relative impact of various building characteristics and effectiveness of different control strategies are estimated. Finally, in Chapter 4, the methodology for scaling the individual building energy savings to the national level is described, and estimated national energy savings are presented.

  7. Restrictive annuloplasty to treat functional mitral regurgitation: optimize the restriction to improve the results?

    Science.gov (United States)

    Totaro, Pasquale; Adragna, Nicola; Argano, Vincenzo

    2008-03-01

    Today, the 'gold standard' treatment of functional mitral regurgitation (MR) is the subject of much discussion. Although restrictive annuloplasty is currently considered the most reproducible technique, the means by which the degree of annular restriction is optimized remains problematic. The study was designed in order to identify whether the degree of restriction of the mitral annulus could influence early and midterm results following the treatment of functional MR using restrictive annuloplasty. A total of 32 consecutive patients with functional MR grade > or = 3+ was enrolled, among whom the mean anterior-posterior (AP) mitral annulus diameter was 39 +/- 3 mm. Restrictive mitral annuloplasty (combined with coronary artery bypass grafting) was performed in all patients using a Carpentier-Edwards Classic or Physio ring (size 26 or 28). The degree of AP annular restriction was calculated for each patient, and correlated with early and mid-term residual MR and left ventricular (LV) reverse remodeling (in terms of LV end-diastolic diameter (LVEDD) and LV end-diastolic volume (LVEDV) reduction). All surviving patients were examined at a one-year follow up. The mean AP mitral annulus restriction achieved was 48 +/- 4%. Intraoperatively, transesophageal echocardiography showed no residual MR in any patient. Before discharge from hospital, transthoracic echocardiography confirmed an absence of residual MR and showed significant LV reverse remodeling (LVEDV from 121 +/- 25 ml to 97 +/- 26 ml; LVEDD from 55 +/- 6 mm to 47 +/- 8 mm). A significant correlation (r = 0.57, p 40% of preoperative) appears to have a favorable influence on early postoperative LV reverse remodeling, and also allows for complete resolution of functional MR. In addition, 'no tolerance' of early residual MR seems to have a favorable influence on mid-term results, leading to a reduction in the one-year recurrence of significant MR.

  8. [Restricted motion after total knee arthroplasty].

    Science.gov (United States)

    Kucera, T; Urban, K; Karpas, K; Sponer, P

    2007-10-01

    The aim of the study was to ascertain what proportion of patients undergoing total knee arthroplasty (TKA) complain of restricted knee joint motion, and to investigate options for improvement of this situation. Our evaluation included a group of 796 patients treated with TKA at our department in the period from January 1, 1990, to December 31, 2004. In all cases, a condylar implant with preservation of the posterior cruciate ligaments was used. In addition to medical history, the range of motion, knee joint malalignment and radiological findings were assessed before surgery. After THA, the type of implant and complications, if any, were recorded, and improvement in joint motion was followed up. Based on the results of Kim et al., flexion contracture equal to or higher than 15 degrees and/or flexion less than 75 degrees were made the criteria of stiffness after THA. Patients with restricted THA motion who had aseptic or septic implant loosening were not included. Of the 796 evaluated patients, 32 (4.14 %) showed restricted motion after total knee arthroplasty, as assessed by the established criteria. In 16 patients, stiffness defined by these criteria had existed before surgery, and three patients showed an excessive production of adhesions and heterotopic ossifications. In three patients, the implantation procedure resulted in an elevated level of the original joint line and subsequent development of patella infera and increased tension of the posterior cruciate ligament. Four patients declined physical therapy and, in six, the main cause of stiffness could not be found. Seventeen patients did not require surgical therapy for restricted motion; TKA provided significant pain relief and they considered the range of motion achieved to be sufficient. One patient underwent redress 3 months after surgery, but with no success. Repeated releases of adhesions, replacement of a polyethylene liner and revision surgery of the extensor knee structures were performed in 15

  9. Third sound in a restricted geometry

    International Nuclear Information System (INIS)

    Brouwer, P.W.; Draisma, W.A.; Pinkse, P.W.H.; Beelen, H. van; Jochemsen, R.; Frossati, G.

    1992-01-01

    Bergman's general treatment of third sound waves has been extended to a (restricted) parallel plate geometry. In a parallel plate geometry two independent third sound modes can propagate: a symmetric and an antisymmetric one. Calculations show that at temperatures below 1 K the antisymmetric mode carries the most important part of the temperature amplitude. Because of the relatively strong substrate influence the temperature amplitude of the symmetric mode is suppressed. The ΔT/Δh versus T measurements by Laheurte et al. and of the ΔT/Δh versus ω measurements by Ellis et al. are explained. 7 refs., 2 figs

  10. Identifying product order with restricted Boltzmann machines

    Science.gov (United States)

    Rao, Wen-Jia; Li, Zhenyu; Zhu, Qiong; Luo, Mingxing; Wan, Xin

    2018-03-01

    Unsupervised machine learning via a restricted Boltzmann machine is a useful tool in distinguishing an ordered phase from a disordered phase. Here we study its application on the two-dimensional Ashkin-Teller model, which features a partially ordered product phase. We train the neural network with spin configuration data generated by Monte Carlo simulations and show that distinct features of the product phase can be learned from nonergodic samples resulting from symmetry breaking. Careful analysis of the weight matrices inspires us to define a nontrivial machine-learning motivated quantity of the product form, which resembles the conventional product order parameter.

  11. Privacy-Preserving Restricted Boltzmann Machine

    Directory of Open Access Journals (Sweden)

    Yu Li

    2014-01-01

    Full Text Available With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM. The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provide a correctness and efficiency analysis of our algorithms. The comparative experiment shows that the accuracy is very close to the original RBM model.

  12. The Monetary Policy – Restrictive or Expansive?

    Directory of Open Access Journals (Sweden)

    Adam Szafarczyk

    2007-10-01

    Full Text Available The monetary policy plays an important role in macroeconomic policy of government. There is a question concerning type of this policy expansive or restrictive (easy or tidy monetary policy. Unfortunately, we have a lot of criteria. Each of them gives us other answer. So due to equitation of Irving Fisher we have dominantly expansive monetary policy. This same situation exists when we use nominal value of rediscount interest rate of central bank. Opposite result appears when we use real value of this interest rate or level of obligatory reserve. Taking under consideration liquidity on money market we know, that level of interest rate is too high.

  13. A statistical mechanical approach to restricted integer partition functions

    Science.gov (United States)

    Zhou, Chi-Chun; Dai, Wu-Sheng

    2018-05-01

    The main aim of this paper is twofold: (1) suggesting a statistical mechanical approach to the calculation of the generating function of restricted integer partition functions which count the number of partitions—a way of writing an integer as a sum of other integers under certain restrictions. In this approach, the generating function of restricted integer partition functions is constructed from the canonical partition functions of various quantum gases. (2) Introducing a new type of restricted integer partition functions corresponding to general statistics which is a generalization of Gentile statistics in statistical mechanics; many kinds of restricted integer partition functions are special cases of this restricted integer partition function. Moreover, with statistical mechanics as a bridge, we reveal a mathematical fact: the generating function of restricted integer partition function is just the symmetric function which is a class of functions being invariant under the action of permutation groups. Using this approach, we provide some expressions of restricted integer partition functions as examples.

  14. Sales Restriction, Quality Selection and the Mode of Competition

    OpenAIRE

    Boccard, Nicolas; Wauthy, Xavier

    2003-01-01

    A regulator imposing "sales restrictions" on firms competing in oligopolistic markets may enhance quality provision by the firms. Moreover, for most restrictions levels, the impact on quality selection is invariant to the mode of competition.

  15. Restrictive Dermopathy: Molecular diagnosis of restrictive dermopathy in a stillborn fetus from a consanguineous Iranian family

    International Nuclear Information System (INIS)

    Karaminejad, A.; Goodarzi, P.; Huong, Le Thi Thanh; Wehnert, Manfred S.

    2009-01-01

    Restrictive dermopathy (RD) is an autosomal recessive lethal human genetic disorder. It is characterized by intrauterine growth retardation, tight and rigid skin with erosions, multiple joint contractures, lung hypoplasia, prominent superficial vasculature and epidermal hyperkeratosis. In the present report, we describe the first case of restrictive dermopathy in a stillborn fetus of Iranian origin, confirmed by molecular genetic diagnosis. In the index case (G-30159), a homozygous one base insertion in ZMPSTE24exon 9 (c.1085-1086insT) was identified. We believe that by increasing awareness of this disease in clinicians, gynecologists and pathologists, we may be able to help families who have had suspected cases of restrictive dermopathy be diagnosed and offer molecular testing in carriers and prenatal diagnosis to prevent the occurrence of further affected cases. (author)

  16. Can we restrict the health care menu?

    Science.gov (United States)

    Klein, R

    1994-02-01

    The case of Britain's National Health Service is used to illuminate the cross-national debate about whether the availability of health care should be restricted and, if so, how this should be done. Traditionally, the NHS relied on implicit rationing by clinicians within budgetary constraints set by government. However, the logic of the 1989 reforms appeared to require explicit decisions about the packages of health care to be provided to local populations. In practice, purchasers have refused to define such packages. Explicit rationing remains very much the exception. Exploring the reasons for this suggests that defining a restricted menu of health care, by adopting a cost-utility approach and excluding specific procedures or forms of treatment on the Oregon model, is only one of many policy options. There is a large repertory of policy tools for balancing demands and resources, ranging from diluting the intensity of treatment to its earlier termination. Given that health care is characterised by uncertainty, lack of information about outcomes and patient heterogeneity, it may therefore be more 'rational' to diffuse decision-making among clinicians and managers than to try to move towards a centrally determined menu of entitlements.

  17. Cardiorespiratory effects of inelastic chest wall restriction.

    Science.gov (United States)

    Miller, Jordan D; Beck, Kenneth C; Joyner, Michael J; Brice, A Glenn; Johnson, Bruce D

    2002-06-01

    We examined the effects of chest wall restriction (CWR) on cardiorespiratory function at rest and during exercise in healthy subjects in an attempt to approximate the cardiorespiratory interactions observed in clinical conditions that result in restrictive lung and/or chest wall changes and a reduced intrathoracic space. Canvas straps were applied around the thorax and abdomen so that vital capacity was reduced by >35%. Data were acquired at rest and during cycle ergometry at 25 and 45% of peak workloads. CWR elicited significant increases in the flow-resistive work performed on the lung (160%) and the gastric pressure-time integral (>400%) at the higher workload, but it resulted in a decrease in the elastic work performed on the lung (56%) compared with control conditions. With CWR, heart rate increased and stroke volume (SV) fell, resulting in >10% fall in cardiac output at rest and during exercise at matched workloads (P < 0.05). Blood pressure and catecholamines were significantly elevated during CWR exercise conditions (P < 0.05). We conclude that CWR significantly impairs SV during exercise and that a compensatory increase in heart rate does not prevent a significant reduction in cardiac output. O(2) consumption appears to be maintained via increased extraction and a redistribution of blood flow via sympathetic activation.

  18. Restricted Interval Guelph permeameter: Theory and application

    International Nuclear Information System (INIS)

    Freifeld, Barry M.; Oldenburg, Curtis M.

    2003-01-01

    A constant head permeameter system has been developed for use in small diameter boreholes with any orientation. It is based upon the original Guelph permeameter concept of using a Mariotte siphon reservoir to control the applied head. The new tool, called a Restricted Interval Guelph (RIG) permeameter uses either a single pneumatic packer or straddle packer to restrict the area through which water is allowed to flow so that the borehole wetted area is independent of the applied head. The RIG permeameter has been used at Yucca Mountain, Nevada, in the nonwelded rhyolitic Paintbrush Tuff. Analysis of the acquired data is based upon saturated-unsaturated flow theory that relies upon the quasi-linear approximation to estimate field-saturated hydraulic conductivity (Kfs) and the a parameter (sorptive number) of the exponential relative hydraulic conductivity pressure head relationship. These results are compared with a numerical model based upon the solution of the Richards equation using a van Genuchten capillary pressure-saturation formulation. The numerical model incorporates laboratory capillary pressure versus saturation functions measured from cores taken from nearby boreholes. Comparison between the analytical and numerical approaches shows that the simple analytic model is valid for analyzing the data collected. Sensitivity analysis performed with the numerical model shows that the RIG permeameter is an effective tool for estimating permeability and sorptive number for the nonwelded Paintbrush Tuff

  19. 36 CFR 1275.58 - Deletion of restricted portions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Deletion of restricted... HISTORICAL MATERIALS OF THE NIXON ADMINISTRATION Access by the Public § 1275.58 Deletion of restricted... materials after the deletion of the portions which are restricted under this § 1275.50 or § 1275.52. ...

  20. Intermittent′ restrictive ventricular septal defect in Tetralogy of Fallot

    Directory of Open Access Journals (Sweden)

    Sudhir S Shetkar

    2015-01-01

    Full Text Available Ventricular septal defect (VSD in Tetralogy of Fallot (TOF is usually large and non-restrictive with equalization of right and left ventricular pressures. Restrictive VSD in TOF is rare. We present an unusual case of TOF with restriction to VSD caused by accessory tricuspid valve tissue that varied with respiration.

  1. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...

  2. 36 CFR 13.1174 - Whale water restrictions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Whale water restrictions. 13... Vessel Operating Restrictions § 13.1174 Whale water restrictions. (a) May 15 through September 30, the following waters are designated as whale waters. (1) Waters north of a line drawn from Point Carolus to...

  3. 48 CFR 552.203-71 - Restriction on Advertising.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

  4. 50 CFR 697.23 - Restricted gear areas.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Restricted gear areas. 697.23 Section 697... Measures § 697.23 Restricted gear areas. (a) Resolution of lobster gear conflicts with fisheries managed...) Restricted Gear Area I—(1) Duration—(i) Mobile Gear. From October 1 through June 15 of each fishing year, no...

  5. 49 CFR 215.303 - Stenciling of restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

  6. 5 CFR 1304.4605 - Post-employment restrictions.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Post-employment restrictions. 1304.4605 Section 1304.4605 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE PROCEDURES POST EMPLOYMENT CONFLICT OF INTEREST § 1304.4605 Post-employment restrictions. (a) General Restrictions Applicable...

  7. Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations.

    Science.gov (United States)

    Dai, Yun; Thamotharan, Shanthie; Garg, Meena; Shin, Bo-Chul; Devaskar, Sherin U

    2012-09-01

    Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

  8. Membrane barriers for radon gas flow restrictions

    International Nuclear Information System (INIS)

    Archibald, J.F.

    1984-08-01

    Research was performed to assess the feasibility of barrier membrane substances, for use within mining or associated high risk environments, in restricting the diffusion transport of radon gas quantities. Specific tests were conducted to determine permeability parameters of a variety of membrane materials with reference to radon flow capabilities. Tests were conducted both within laboratory and in-situ emanation environments where concentrations and diffusion flows of radon gas were known to exist. Equilibrium radon gas concentrations were monitored in initially radon-free chambers adjacent to gas sources, but separated by specified membrane substances. Membrane barrier effectiveness was demonstrated to result in reduced emanation concentrations of radon gas within the sampling chamber atmosphere. Minimum gas concentrations were evidenced where the barrier membrane material was shown to exhibit lowest radon permeability characteristics

  9. Restricted fish feeding reduces cod otolith opacity

    DEFF Research Database (Denmark)

    Høie, H.; Folkvord, A.; Mosegaard, Henrik

    2008-01-01

    The purpose of this work was to examine the effect of reduced feeding and constant temperature on cod otolith opacity. Three groups of juvenile cod were given restricted food rations at different times for 4 months, resulting in depressed somatic growth. Otolith opacity was measured on pictures...... in otolith opacity were found between individual fish both within groups and between groups. In two of the three groups significantly more translucent otolith material was deposited in response to reduced feeding. Our results show that variations in feeding and hence fish growth resulted in variation...... in otolith opacity, but the effect was minor compared to that of variations in ambient temperature. The combined influence of these effects, which both act on fish metabolism, are most likely controlling the seasonal opacity changes observed in wild fish. Our results help explain the variations seen in fish...

  10. Restrictions on the transnational movement of uranium

    International Nuclear Information System (INIS)

    Rowden, M.A.; Kraemer, J.R.

    1988-01-01

    This paper analyses the United States policy on uranium imports. Recently, the US has moved closer to placing legislative restrictions on enrichment by DOE of foreign-origin uranium and has imposed a ban on the import of South African uranium ore and uranium oxide. American uranium producers have also sought relief in the courts against competition from abroad. The impetus for these events comes from a glut of uranium on world markets coupled with the existence of uranium mines outside the US with significant cost advantages over US producers. The remedies sought by the latter, if adopted, hold the potential for broad disruption of significant commercial interests in international trade in nuclear materials and could adversely affect US nonproliferation objectives (NEA) [fr

  11. Nonequilibrium thermodynamics of restricted Boltzmann machines

    Science.gov (United States)

    Salazar, Domingos S. P.

    2017-08-01

    In this work, we analyze the nonequilibrium thermodynamics of a class of neural networks known as restricted Boltzmann machines (RBMs) in the context of unsupervised learning. We show how the network is described as a discrete Markov process and how the detailed balance condition and the Maxwell-Boltzmann equilibrium distribution are sufficient conditions for a complete thermodynamics description, including nonequilibrium fluctuation theorems. Numerical simulations in a fully trained RBM are performed and the heat exchange fluctuation theorem is verified with excellent agreement to the theory. We observe how the contrastive divergence functional, mostly used in unsupervised learning of RBMs, is closely related to nonequilibrium thermodynamic quantities. We also use the framework to interpret the estimation of the partition function of RBMs with the annealed importance sampling method from a thermodynamics standpoint. Finally, we argue that unsupervised learning of RBMs is equivalent to a work protocol in a system driven by the laws of thermodynamics in the absence of labeled data.

  12. Epitaxial growth by monolayer restricted galvanic displacement

    Directory of Open Access Journals (Sweden)

    Vasilić Rastko

    2012-01-01

    Full Text Available The development of a new method for epitaxial growth of metals in solution by galvanic displacement of layers pre-deposited by underpotential deposition (UPD was discussed and experimentally illustrated throughout the lecture. Cyclic voltammetry (CV and scanning tunneling microscopy (STM are employed to carry out and monitor a “quasi-perfect”, two-dimensional growth of Ag on Au(111, Cu on Ag(111, and Cu on Au(111 by repetitive galvanic displacement of underpotentially deposited monolayers. A comparative study emphasizes the displacement stoichiometry as an efficient tool for thickness control during the deposition process and as a key parameter that affects the deposit morphology. The excellent quality of layers deposited by monolayer-restricted galvanic displacement is manifested by a steady UPD voltammetry and ascertained by a flat and uniform surface morphology maintained during the entire growth process.

  13. Nonequilibrium thermodynamics of restricted Boltzmann machines.

    Science.gov (United States)

    Salazar, Domingos S P

    2017-08-01

    In this work, we analyze the nonequilibrium thermodynamics of a class of neural networks known as restricted Boltzmann machines (RBMs) in the context of unsupervised learning. We show how the network is described as a discrete Markov process and how the detailed balance condition and the Maxwell-Boltzmann equilibrium distribution are sufficient conditions for a complete thermodynamics description, including nonequilibrium fluctuation theorems. Numerical simulations in a fully trained RBM are performed and the heat exchange fluctuation theorem is verified with excellent agreement to the theory. We observe how the contrastive divergence functional, mostly used in unsupervised learning of RBMs, is closely related to nonequilibrium thermodynamic quantities. We also use the framework to interpret the estimation of the partition function of RBMs with the annealed importance sampling method from a thermodynamics standpoint. Finally, we argue that unsupervised learning of RBMs is equivalent to a work protocol in a system driven by the laws of thermodynamics in the absence of labeled data.

  14. Botulinum toxin for treatment of restrictive strabismus.

    Science.gov (United States)

    Merino, Pilar S; Vera, Rebeca E; Mariñas, Laura G; Gómez de Liaño, Pilar S; Escribano, Jose V

    To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  15. The resurgence of selective contracting restrictions.

    Science.gov (United States)

    Marsteller, J A; Bovbjerg, R R; Nichols, L M; Verrilli, D K

    1997-10-01

    As managed care has spread, so has legislation to force plans to contract with any willing provider (AWP) and give patients freedom of choice (FOC). Managed care organizations' selective networks and provider integration reduce patient access to providers, along with provider access to paying patients, so many providers have lobbied for AWP-FOC laws. In opposition are managed care organizations (MCOs), which want full freedom to contract selectively to control prices and utilization. This article comprehensively describes laws in all fifty-one jurisdictions, classifies their relative strength, and assesses the implications of the laws. Most are relatively weak forms and all are limited in application by ERISA and the federal HMO Act. The article also uses an associative multivariate analysis to relate the selective contracting environments to HMO penetration rates, rural population, physician density, and other variables. States with weak laws also have higher HMO penetration and higher physician density, but smaller rural populations. We conclude that the strongest laws overly restrict the management of care, to the likely detriment of cost control. But where market power is rapidly concentrating, not restricting selective contracting could diminish long-term competition and patient access to care. In the face of uncertainty about the impact of these laws, an intermediate approach may be better than all or nothing. States should consider mandating that plans offer point-of-service options, for a separate premium. This option expands patient choice of plans at the time of enrollment and of providers at the time of care, yet maintains plans' ability to control core providers.

  16. Molecular mechanisms of intrauterine growth restriction.

    Science.gov (United States)

    Gurugubelli Krishna, Rao; Vishnu Bhat, B

    2017-07-10

    Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

  17. Intrauterine Growth Restriction: Hungry for an Answer

    Science.gov (United States)

    Chu, Alison

    2016-01-01

    Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

  18. Estimation of fluctuation in restricted energy loss

    International Nuclear Information System (INIS)

    Doke, T.; Hayashi, T.; Nagata, K.

    1983-01-01

    Restricted Energy Loss (REL) is defined as an energy loss [(dE/dX)/sub E//sub delta/<ν/] that produced the delta-rays of energies less than some specified energy ν and is often used as a simple measure of track structure. For example, REL is a measure of track formation threshold in plastic track detector and the growth rate of track in chemical etching solution is considered to depend only on REL given along the track. Using a stack of elastic sheets, recently, it became possible to identify isotopes of incident particles. In that case, the limit of mass resolution is determined by fluctuation of REL in the length of etch pit produced along the path of particle. A computer program was developed to calculate the probability distribution for energy deposition in absorber allowing for electron escape. In this calculation, it is assumed that all electrons with energies greater than a certain value epsilon/sub d/ escape. This means that this calculation directly gives the fluctuation of REL. Therefore, we tried to use the computer program to estimate the ultimate mass resolution in plastic detector. In this paper, we show firstly the comparison of ASB's calculation with the experimental results obtained by a gas counter and next the results of estimation of ultimate mass resolution in plastic detectors

  19. Restriction-modification systems in Mycoplasma spp

    Directory of Open Access Journals (Sweden)

    Marcelo Brocchi

    2007-01-01

    Full Text Available Restriction and Modification (R-M systems are present in all Mycoplasma species sequenced so far. The presence of these genes poses barriers to gene transfer and could protect the cell against phage infections. The number and types of R-M genes between different Mycoplasma species are variable, which is characteristic of a polymorphism. The majority of the CDSs code for Type III R-M systems and particularly for methyltransferase enzymes, which suggests that functions other than the protection against the invasion of heterologous DNA may exist. A possible function of these enzymes could be the protection against the invasion of other but similar R-M systems. In Mycoplasma hyopneumoniae strain J, three of the putative methyltransferase genes were clustered in a region forming a genomic island. Many R-M CDSs were mapped in the vicinity of transposable elements suggesting an association between these genes and reinforcing the idea of R-M systems as mobile selfish DNA. Also, many R-M genes present repeats within their coding sequences, indicating that their expression is under the control of phase variation mechanisms. Altogether, these data suggest that R-M systems are a remarkable characteristic of Mycoplasma species and are probably involved in the adaptation of these bacteria to different environmental conditions.

  20. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  1. [Sodium restriction during pregnancy: an outdated advice].

    Science.gov (United States)

    de Leeuw, P W; Peeters, L L

    1999-10-23

    Even in an early phase of pregnancy marked haemodynamic changes occur, including a fall in vascular resistance and blood pressure and a rise in cardiac output. To compensate for the increased intravascular capacity the kidney retains more sodium and water. Apparently, the set point of sodium homeostasis shifts to a higher level at the expense of an expansion of extracellular volume. Studies during the normal menstrual cycle have shown that these changes, albeit smaller, also occur during the luteal phase. These fluctuations with the menstrual cycle are less apparent if salt intake is low, suggesting that a high salt intake is needed to facilitate the process of sodium retention. In pregnancies complicated by hypertension and/or pre-eclampsia body fluid volumes are low with an enhanced tendency to retain sodium after a volume challenge. These data, together with the lack of an apparent benefit of sodium restriction, suggest that the practice of prescribing a low-salt diet to hypertensive pregnant women should be abandoned.

  2. An ontology for major histocompatibility restriction.

    Science.gov (United States)

    Vita, Randi; Overton, James A; Seymour, Emily; Sidney, John; Kaufman, Jim; Tallmadge, Rebecca L; Ellis, Shirley; Hammond, John; Butcher, Geoff W; Sette, Alessandro; Peters, Bjoern

    2016-01-01

    MHC molecules are a highly diverse family of proteins that play a key role in cellular immune recognition. Over time, different techniques and terminologies have been developed to identify the specific type(s) of MHC molecule involved in a specific immune recognition context. No consistent nomenclature exists across different vertebrate species. To correctly represent MHC related data in The Immune Epitope Database (IEDB), we built upon a previously established MHC ontology and created an ontology to represent MHC molecules as they relate to immunological experiments. This ontology models MHC protein chains from 16 species, deals with different approaches used to identify MHC, such as direct sequencing verses serotyping, relates engineered MHC molecules to naturally occurring ones, connects genetic loci, alleles, protein chains and multi-chain proteins, and establishes evidence codes for MHC restriction. Where available, this work is based on existing ontologies from the OBO foundry. Overall, representing MHC molecules provides a challenging and practically important test case for ontology building, and could serve as an example of how to integrate other ontology building efforts into web resources.

  3. Calorie Restriction, Stem Cells, and Rejuvenation Approach

    Directory of Open Access Journals (Sweden)

    Taufiqurrachman Nasihun

    2017-03-01

    Full Text Available Aging may be defined as the time-dependent deterioration in function of an organism associated with or responsible for the increase in susceptibility to disease and probability of death with advancing age (Harman, 1981; Cefalu, 2011. Generally, the aging organisms are characterized by both biochemical and functional declines. Declining of basal metabolism rates, protein turnover, glucose tolerance, reproductive capacity, telomere shortening, and oxidative phosphorylation are related to the biochemical. Whilst, lung expansion volume, renal glomerular and tubular capacities, cardiovascular performance, musculoskeletal system, nerve conduction velocity, endocrine and exocrine systems, immunological defenses, and sensory systems are associated with the physiological declining (Baynes and Dominiczak, 2015. Some evidences indicated that, although members of a species develop into adults in the same way, even genetically similar or identical individuals, raised in identical conditions and eating identical food, but they may age differently (Baynes and Dominiczak, 2015. These aging differences are attributable to the life style particularly calorie and dietary restriction intakes, reactive oxygen species (ROS production, and thus its implication on severity of damage, repair capacity, and error accumulation in cellular genetic material (Baynes and Dominiczak, 2015; Mihaylova et al., 2014; Mazzoccoli et al., 2014. Therefore, in molecular terms, aging can be defined as a decline of the homeostatic mechanisms that ensure the function of cells, tissues, and organs systems (Mazzoccoli et al., 2014. Accordingly, if the homeostatic mechanism can be repaired, the result is rejuvenation.

  4. Calorie restriction in rodents: Caveats to consider.

    Science.gov (United States)

    Ingram, Donald K; de Cabo, Rafael

    2017-10-01

    The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward. Published by Elsevier B.V.

  5. Effect on Caries of Restricting Sugars Intake

    Science.gov (United States)

    Moynihan, P.J.; Kelly, S.A.M.

    2014-01-01

    A systematic review of studies in humans was conducted to update evidence on the association between the amount of sugars intake and dental caries and on the effect of restricting sugars intake to caries to inform the updating of World Health Organization guidelines on sugars consumption. Data sources included MEDLINE, EMBASE, Cochrane Database, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences, China National Knowledge Infrastructure, Wanfang, and South African Department of Health. Eligible studies reported the absolute amount of sugars and dental caries, measured as prevalence, incidence, or severity. The review was conducted and reported in accordance with the PRISMA statement, and the evidence was assessed according to GRADE Working Group guidelines. From 5,990 papers identified, 55 studies were eligible – 3 intervention, 8 cohort, 20 population, and 24 cross-sectional. Data variability limited meta-analysis. Of the studies, 42 out of 50 of those in children and 5 out of 5 in adults reported at least one positive association between sugars and caries. There is evidence of moderate quality showing that caries is lower when free-sugars intake is caries risk throughout the life course. PMID:24323509

  6. Origins and Consequences of Religious Restrictions: A Global Overview

    Science.gov (United States)

    Finke, Roger

    2014-01-01

    Despite the international controversies surrounding religious restrictions and freedoms, the topic has only recently received substantial research attention. Drawing on this new body of research, and multiple research projects in progress, this address explores both the origins and consequences of religious restrictions in the global arena. To understand the motives for restrictions, I propose hypotheses in three areas: the relationship or lack of relationship between institutional religion and the state, the willingness and capacity of the state to ensure freedoms, and the larger social and cultural pressures restricting freedoms, including social and political movements targeting minority religions. Turning to the consequences of religious restrictions, I explore how and why restrictions alter the religious economy (i.e., formation, supply and operation of religions) and are associated with higher levels of religious persecution, religious violence and intrastate conflict in general. Finally, I review additional areas where research is needed. PMID:25364225

  7. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas

    2015-01-01

    activity restriction more often than obstetricians in five of the nine scenarios, in women with preterm premature rupture of membranes, preterm labour, cervical ripening, total placenta praevia, and intrauterine growth restriction, whereas no differences were found in the remaining scenarios. Compared...... to the obstetricians, the midwives also reported that they expected the recommendation to be more effective. Most midwives and obstetricians reported that they thought strict activity restriction was associated with severe or moderate adverse effect, and recommended antithrombotic prophylaxis. Conclusions: Danish...... obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....

  8. Host Specificity of Salmonella typhimurium Deoxyribonucleic Acid Restriction and Modification

    Science.gov (United States)

    Slocum, Harvey; Boyer, Herbert W.

    1973-01-01

    The restriction and modification genes of Salmonella typhimurium which lie near the thr locus were transferred to a restrictionless mutant of Escherichia coli. These genes were found to be allelic to the E. coli K, B, and A restriction and modification genes. E. coli recombinants with the restriction and modification host specificity of S. typhimurium restricted phage λ that had been modified by each of the seven known host specificities of E. coli at efficiency of plating levels of about 10−2. Phage λ modified with the S. typhimurium host specificity was restricted by six of the seven E. coli host specificities but not by the RII (fi− R-factor controlled) host specificity. It is proposed that the restriction and modification enzymes of this S. typhimurium host specificity have two substrates, one of which is a substrate for the RII host specificity enzymes. PMID:4570605

  9. Consequences in Infants That Were Intrauterine Growth Restricted

    Directory of Open Access Journals (Sweden)

    Erich Cosmi

    2011-01-01

    Full Text Available Intrauterine growth restriction is a condition fetus does not reach its growth potential and associated with perinatal mobility and mortality. Intrauterine growth restriction is caused by placental insufficiency, which determines cardiovascular abnormalities in the fetus. This condition, moreover, should prompt intensive antenatal surveillance of the fetus as well as follow-up of infants that had intrauterine growth restriction as short and long-term sequele should be considered.

  10. Maternal serum copeptin as a marker for fetal growth restriction

    Directory of Open Access Journals (Sweden)

    Ashraf A. Foda

    2013-09-01

    Conclusion: Maternal serum copeptin level can differentiate between the normal sized and small for gestational age fetuses. Also, it can differentiate between constitutionally small and growth restricted fetuses.

  11. Activity restriction among women with a short cervix.

    Science.gov (United States)

    Grobman, William A; Gilbert, Sharon A; Iams, Jay D; Spong, Catherine Y; Saade, George; Mercer, Brian M; Tita, Alan T N; Rouse, Dwight J; Sorokin, Yoram; Leveno, Kenneth J; Tolosa, Jorge E; Thorp, John M; Caritis, Steve N; Van Dorsten, J Peter

    2013-06-01

    To estimate determinants of and outcomes associated with activity restriction among women with a short cervix. This was a secondary analysis of a randomized trial of 17-α hydroxyprogesterone caproate for prevention of preterm birth among nulliparous women with singleton gestations and cervices less than 30 mm by midtrimester ultrasonography. Women were asked weekly whether they had been placed on pelvic, work, or nonwork rest. "Any activity restriction" was defined as being placed on any type of rest. Factors associated with any activity restriction were determined and the association between preterm birth and activity restriction was estimated with multivariable logistic regression. Of the 657 women in the trial, 646 (98%) responded to questions regarding activity restriction. Two hundred fifty-two (39.0%) were placed on any activity restriction at a median of 23.9 weeks (interquartile range 22.6-27.9 weeks). Women on activity restriction were older, more likely to have private insurance, less likely to be Hispanic, had a shorter cervical length, and were more likely to have funneling and intra-amniotic debris. Preterm birth at less than 37 weeks of gestation was more common among women placed on activity restriction (37% compared with 17%, Prestriction (adjusted odds ratio 2.37, 95% confidence interval 1.60-3.53). Results were similar for preterm birth at less than 34 weeks of gestation. Activity restriction did not reduce the rate of preterm birth in asymptomatic nulliparous women with a short cervix.

  12. Can early protein restriction induce the development of binge eating?

    Science.gov (United States)

    Fechine, Madge Farias; Borba, Tássia Karin; Cabral-Filho, José Eulálio; Bolaños-Jiménez, Francisco; Lopes-de-Souza, Sandra; Manhães-de-Castro, Raul

    2016-04-01

    We tested the hypothesis that perinatal undernourishment is a factor for binge eating. At 52 days rats born from dams fed on 17% protein (Control) or 8% protein (Undernourished) were distributed into four groups, two of which continued to be fed ad libitum chow and two were submitted to three consecutive Restricted/Refeeding (R/R) cycles. According to the following schedule: Control Naïve (from mothers fed 17% protein/no restriction phase); Control Restricted (from mothers fed 17% protein/restriction phase); Undernourished Naïve (from mothers fed 8% protein/no restriction phase); and Undernourished Restricted (from mothers fed 8% protein/restriction phase). Each cycle consisted of a restriction phase (in the first four days 40% of the mean daily individual chow intake was offered for consumption), followed by a refeeding phase (4 days of chow ad libitum). After the three cycles, all animals were subjected to a feeding test (chow diet and palatable food ad libitum for 24h). During the feeding test, the Undernourished Restricted demonstrated rebound hyperphagia during 2, 4 and 6h. These results suggest the perinatal undernourishment cannot contribute to a binge eating phenotype. Copyright © 2016. Published by Elsevier B.V.

  13. Restricted mass energy absorption coefficients for use in dosimetry

    International Nuclear Information System (INIS)

    Brahme, A.

    1977-02-01

    When matter is irradiated by a photon beam the fraction of energy absorbed locally in some region Rsub(Δ) (where the size of the region Rsub(Δ) is related to the range of secondary electrons of some restriction energy Δ) is expressed by the restricted mass energy absorption coefficient. In this paper an example is given of how restricted mass energy absorption coefficients can be calculated from existing differential photon interaction cross sections. Some applications of restricted mass absorption coefficients in dosimetry are also given. (B.D.)

  14. 33 CFR 106.265 - Security measures for restricted areas.

    Science.gov (United States)

    2010-07-01

    ...) Protect stores and industrial supplies from tampering. (b) Designation of restricted areas. The OCS... stores and industrial supplies; and (vii) Areas containing hazardous materials. (c) The OCS facility...

  15. Resource implications of adopting a restrictive neonatal blood ...

    African Journals Online (AJOL)

    Resource implications of adopting a restrictive neonatal blood transfusion policy. ... Objective. To determine whether adopting a restrictive BTF policy results in fewer transfusions. Methods. Data were retrospectively collected on all infants who received BTFs in the GSH nursery over a 6-month period following adoption of a ...

  16. Acute sleep restriction reduces insulin sensitivity in adolescent boys

    DEFF Research Database (Denmark)

    Klingenberg, Lars; Chaput, Jean-Philippe; Holmbäck, Ulf

    2013-01-01

    Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction.......Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction....

  17. 30 CFR 57.4461 - Gasoline use restrictions underground.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Gasoline use restrictions underground. 57.4461... Prevention and Control Flammable and Combustible Liquids and Gases § 57.4461 Gasoline use restrictions underground. If gasoline is used underground to power internal combustion engines— (a) The mine shall be...

  18. 32 CFR 1903.16 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Restriction on animals. 1903.16 Section 1903.16... AGENCY INSTALLATIONS § 1903.16 Restriction on animals. Animals, except for those animals used for the assistance of persons with disabilities, or animals under the charge and control of the Central Intelligence...

  19. 32 CFR 234.12 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Restriction on animals. 234.12 Section 234.12 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS CONDUCT ON THE PENTAGON RESERVATION § 234.12 Restriction on animals. Animals, except guide dogs...

  20. 32 CFR 228.15 - Restriction regarding animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Restriction regarding animals. 228.15 Section 228.15 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS SECURITY PROTECTIVE FORCE § 228.15 Restriction regarding animals. No animals except...

  1. 25 CFR 141.14 - Trade in livestock restricted.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Trade in livestock restricted. 141.14 Section 141.14... livestock restricted. (a) No person other than an enrolled member of the tribe or any association... livestock from tribal members without a special permit issued by the Commissioner. (b) The Commissioner...

  2. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA

    DEFF Research Database (Denmark)

    Nielsen, P.E.; Egholm, M.; Berg, R.H.

    1993-01-01

    Plasmids containing double-stranded 10-mer PNA (peptide nucleic acid chimera) targets proximally flanked by two restriction enzyme sites were challenged with the complementary PNA or PNAs having one or two mismatches, and the effect on the restriction enzyme cleavage of the flanking sites was ass...

  3. Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

    Science.gov (United States)

    Rodriguez-Guerineau, Luciana; Perez-Cruz, Miriam; Gomez Roig, María D; Cambra, Francisco J; Carretero, Juan; Prada, Fredy; Gómez, Olga; Crispi, Fátima; Bartrons, Joaquim

    2018-02-01

    Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

  4. Consequences of intrauterine growth restriction for the kidney

    NARCIS (Netherlands)

    M.F. Schreuder; A. van Wijk (Ans); H.A. Delemarre-van de Waal (Henriette)

    2006-01-01

    textabstractLow birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. The purpose of this review is to describe the effects of intrauterine growth restriction

  5. 49 CFR 236.813a - State, most restrictive.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false State, most restrictive. 236.813a Section 236.813a Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... State, most restrictive. The mode of an electric or electronic device that is equivalent to a track...

  6. ECO-generation for some restricted classes of compositions

    Directory of Open Access Journals (Sweden)

    Jean-Luc Baril

    2013-04-01

    Full Text Available We study several restricted classes of compositions by giving one-to-one maps between them and different classes of restricted binary strings or pattern avoiding permutations. Inspired by the ECO method \\cite{BDPP99}, new succession rules for these classes are presented. Finally, we obtain generating algorithms in Constant Amortized Time (CAT for theses classes.

  7. 30 CFR 77.1502 - Auger holes; restriction against entering.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auger holes; restriction against entering. 77... UNDERGROUND COAL MINES Auger Mining § 77.1502 Auger holes; restriction against entering. No person shall be permitted to enter an auger hole except with the approval of the MSHA Coal Mine Safety and Health District...

  8. Synthesis of conformationally restricted beta-turn mimics

    NARCIS (Netherlands)

    IJsselstijn, M.

    2006-01-01

    This thesis aims at developing methods for introducing conformational restriction in Beta-turns, the turn elements present in Beta-sheets. A conformationally restricted peptide might either be formed via incorporation of a bridging diamino acids in a growing peptide chain, or via covalent bond

  9. Reduced Automatic Motivational Orientation Towards Food in Restricting Anorexia Nervosa

    NARCIS (Netherlands)

    Veenstra, Esther M.; de Jong, Peter J.

    A striking and characteristic feature of the restricting subtype of anorexia nervosa (AN) is that they are extremely successful in regulating their food intake in a destructive manner. A possible explanation for the persistent character of their restricted food intake could be a loss of the

  10. 7 CFR 301.92 - Restrictions on interstate movement.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement. 301.92 Section... Restrictions on interstate movement. (a) No person may move interstate from any quarantined area any regulated... plant that was found infected with Phytophthora ramorum, unless such movement is in accordance with part...

  11. Growth throughout childhood of children born growth restricted

    NARCIS (Netherlands)

    Beukers, Fenny; Rotteveel, Joost; van Weissenbruch, Mirjam M.; Ganzevoort, Wessel; van Goudoever, Johannes B.; van Wassenaer-Leemhuis, Aleid G.

    2017-01-01

    Many studies that examine growth in growth-restricted children at birth do not discriminate between fetal growth restriction (FGR) and small for gestational age (SGA). These terms however are not synonymous. In SGA, stunting and increased weight gain have been reported. We do not know if this holds

  12. The growth performance of growing pigs during feed restriction and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-19

    Jan 19, 2009 ... Available online at http://www.academicjournals.org/AJB ... the best feed cost/kg gain values at restriction and re-alimentation. It is concluded that restricting growing pigs at 80% of the ad libitum intake of the control yields best performance and ... largely proved not to be very effective due to availability.

  13. Symmetrical and asymmetrical growth restriction in preterm-born children

    NARCIS (Netherlands)

    Bocca-Tjeertes, Inger; Bos, Arend; Kerstjens, Jorien; de Winter, Andrea; Reijneveld, Sijmen

    OBJECTIVE: To determine how symmetric (proportionate; SGR) and asymmetric (disproportionate; AGR) growth restriction influence growth and development in preterms from birth to 4 years. METHODS: This community-based cohort study of 810 children comprised 86 SGR, 61 AGR, and 663 non-growth restricted

  14. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study

    NARCIS (Netherlands)

    Hecher, K.; Bilardo, C. M.; Stigter, R. H.; Ville, Y.; Hackelöer, B. J.; Kok, H. J.; Senat, M. V.; Visser, G. H.

    2001-01-01

    To describe the time sequence of changes in fetal monitoring variables in intrauterine growth restriction and to correlate these findings with fetal outcome at delivery. This was a prospective longitudinal observational multicenter study on 110 singleton pregnancies with growth-restricted fetuses

  15. Effect Of Feed Restriction On Growth Performance And Economy Of ...

    African Journals Online (AJOL)

    The dietary treatments consisted of providing feed ad libitum (ull fed) and two feed restriction treatments restrictingeedng 80 % of ad libitum ... A cost – benefit analysis was utilized for the economy of production. ... Feed efficiency was improved by restriction followed with re-alimentation. ... AJOL African Journals Online.

  16. Qualitative versus quantitative feed restriction in Pekin breeder ...

    African Journals Online (AJOL)

    titative (60% of a group fed ad lib) feed restriction during the rearing period with a ... restriction to reduce growth rate and delay sexual maturity. Since the amount of .... ing in the cost of feed when compared to the more expensive ad lib diet.

  17. 75 FR 11620 - Waiver of Restriction on Assistance to Cambodia

    Science.gov (United States)

    2010-03-11

    ... DEPARTMENT OF STATE [Public Notice 6918] Waiver of Restriction on Assistance to Cambodia Pursuant to section 7086(c)(2) of the Department of State, Foreign Operations, and Related Programs... Cambodia, and I hereby waive such restriction. This determination shall be reported to the Congress, and...

  18. 48 CFR 1403.570 - Restrictions on contractor advertising.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

  19. 12 CFR 615.5462 - Restrictive endorsement of bearer securities.

    Science.gov (United States)

    2010-01-01

    ... Credit Securities § 615.5462 Restrictive endorsement of bearer securities. When consolidated and... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Restrictive endorsement of bearer securities. 615.5462 Section 615.5462 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND...

  20. 9 CFR 590.800 - Identification of restricted eggs.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Identification of restricted eggs. 590... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Identification of Restricted Eggs Or Egg Products Not Intended for Human Consumption § 590.800 Identification of...

  1. 50 CFR 635.21 - Gear operation and deployment restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear operation and deployment restrictions....21 Gear operation and deployment restrictions. Link to an amendment published at 75 FR 57701, Sept. 22, 2010. The green-stick gear authorization requirements under paragraphs (c)(2)(v)(A), (c)(2)(v)(B...

  2. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be taken only with the following allowable gear and methods: (1) Hand harvest; (2) Spear; (3) Slurp gun; (4...

  3. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be taken only with the following allowable gear and methods: (1) Hand harvest; (2) Spear; (3) Slurp gun; (4...

  4. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken only with the following allowable gear and methods: (1) Hand harvest; (2) Spear; (3) Slurp gun; (4...

  5. 50 CFR 640.22 - Gear and diving restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear and diving restrictions. 640.22... ATLANTIC Management Measures § 640.22 Gear and diving restrictions. (a) Prohibited gear and methods. (1) A spiny lobster may not be taken in the EEZ with a spear, hook, or similar device, or gear containing such...

  6. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may be taken only with the following allowable gear and methods: (1) Hand harvest; (2) Spear; (3) Slurp...

  7. 37 CFR 1.144 - Petition from requirement for restriction.

    Science.gov (United States)

    2010-07-01

    ... Inventions in One Application; Restriction § 1.144 Petition from requirement for restriction. After a final..., may petition the Director to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A...

  8. 37 CFR 1.142 - Requirement for restriction.

    Science.gov (United States)

    2010-07-01

    ... at any time before final action. (b) Claims to the invention or inventions not elected, if not... Inventions in One Application; Restriction § 1.142 Requirement for restriction. (a) If two or more independent and distinct inventions are claimed in a single application, the examiner in an Office action will...

  9. 21 CFR 1314.20 - Restrictions on sales quantity.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Restrictions on sales quantity. 1314.20 Section 1314.20 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RETAIL SALE OF SCHEDULED LISTED CHEMICAL PRODUCTS Sales by Regulated Sellers § 1314.20 Restrictions on sales quantity. (a) Without...

  10. Electricity system planning under the CO2 emission restriction

    International Nuclear Information System (INIS)

    Lim, Chae Young; Lee, Man Ki; Roh, Jae Hyung; Kim, Eun Hwan

    2004-01-01

    Objective of this study is to analyze how the restriction of CO 2 emission from power generation will affect the national electricity supply system. The role of nuclear power is investigated under the restriction of CO 2 emission in Korea. A simplified electricity system was modeled for the analysis. To analyze the impact of CO 2 emission restriction, 2 different scenarios were established and compared with the base scenario. The first scenario was 'CO 2 emission restriction with new nuclear power installation'. In this scenario, a CO 2 emission restriction of 0.11kg-C/kWh was imposed and there was no restriction on the nuclear power construction. While, in the second scenario, 'CO 2 emission restriction without new nuclear power installation' the same amount of CO 2 restriction was imposed with no consideration of nuclear power installation. It is found out that the current national emission target(0.11kg- C/kWh) in the electricity sector can not be achieved without nuclear and renewable(wind power) options considered

  11. [Restrictions for ICD patients in daily life].

    Science.gov (United States)

    Köbe, Julia; Gradaus, Rainer; Zumhagen, Sven; Böcker, Dirk

    2005-11-01

    Patients with an implantable cardioverter defibrillator (ICD) may experience loss of consciousness. Electromagnetic interference (EMI) may trigger undesired or inhibit necessary therapy in patients with an ICD. Therefore, questions about personal or professional activities for ICD patients arise. Restricting driving or other personal activities has adverse effects on the patient's quality of life. The national Societies of Cardiology provide recommendations for ICD patients concerning driving of motor vehicles. Patients with an ICD that is implanted prophylactically do not have to refrain from driving after recovery from the implantation procedure. Patients with arrhythmias are classified into different groups depending on the risk of recurrence of tachycardias and symptoms. Commercial driving is not allowed for patients with an ICD in Germany except for those with a prophylactic indication without a history of arrhythmias. Those patients may drive small cars but no trucks or busses. Guidelines for medical fitness in commercial or military flying are regulated by the Joint Aviation Authorities (JAA) and ventricular tachycardias are a contraindication for both. Fortunately, loss of consciousness is not dangerous in most jobs. Strong sources of EMI can occur at special workplaces. Patients have to be advised and tested individually concerning their risk for EMI at their employment site before returning safely. Modern life exposes to an increasing amount of EMI. Intact household devices usually do not interfere with ICDs. Mobile phones may interfere with implanted devices. Interaction can be minimized by special precautions like maintaining a distance of minimum 10 cm between mobile phone and ICD. Electronic surveillance systems work differently and have the potential to interact with devices. Patients should be advised to pass those systems with avoiding longer exposure. The presence of an ICD is presently a contraindication for undergoing magnetic resonance imaging

  12. Restrictions in Availability of Drugs Used for Suicide

    DEFF Research Database (Denmark)

    Nordentoft, Merete

    2007-01-01

    Availability of drugs with high lethality has been hypothesized to increase the risk of self-poisoning suicides. A literature search concerning deliberate self-poisoning and the effect of restricting access to drugs was conducted, and the effect of restrictions in availability of barbiturates, tr...... in availability of drugs with high case fatality should be a part of suicide prevention strategies.......Availability of drugs with high lethality has been hypothesized to increase the risk of self-poisoning suicides. A literature search concerning deliberate self-poisoning and the effect of restricting access to drugs was conducted, and the effect of restrictions in availability of barbiturates......, tricyclic antidepressants, dextropropoxyphene, and weak analgesics was reviewed. The correlations between method-specific and overall suicide rates and sales figures for barbiturates, dextropropoxyphene, weak analgesics, and tricyclic antidepressants were reviewed. It is concluded that restriction...

  13. Retroviral restriction and dependency factors in primates and carnivores

    Science.gov (United States)

    Fadel, Hind J.; Poeschla, Eric M.

    2014-01-01

    Recent studies have extended the rapidly developing retroviral restriction factor field to cells of carnivore species. Carnivoran genomes, and the domestic cat genome in particular, are revealing intriguing properties vis-à;-vis the primate and feline lentiviruses, not only with respect to their repertoires of virus-blocking restriction factors but also replication-enabling dependency factors. Therapeutic application of restriction factors is envisioned for human immunodeficiency virus (HIV) disease and the feline immunodeficiency virus (FIV) model has promise for testing important hypotheses at the basic and translational level. Feline cell-tropic HIV-1 clones have also been generated by a strategy of restriction factor evasion. We review progress in this area in the context of what is known about retroviral restriction factors such as TRIM5alpha, TRIMCyp, APOBEC3 proteins and BST-2/Tetherin. PMID:21715018

  14. 7 CFR 57.905 - Importation of restricted eggs or eggs containing more restricted eggs than permitted in the...

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Importation of restricted eggs or eggs containing more restricted eggs than permitted in the official standards for U.S. Consumer Grade B. 57.905 Section 57.905... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG...

  15. 9 CFR 590.905 - Importation of restricted eggs or eggs containing more restricted eggs than permitted in the...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Importation of restricted eggs or eggs containing more restricted eggs than permitted in the official standards for U.S. Consumer Grade B. 590.905... EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Imports...

  16. Effect of dietary protein restriction on renal ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Guo, Hui; Verlander, Jill W.

    2015-01-01

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

  17. Controlling pandemic flu: the value of international air travel restrictions.

    Directory of Open Access Journals (Sweden)

    Joshua M Epstein

    2007-05-01

    Full Text Available Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration.A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects of travel restrictions and vaccination. Economic costs of intervention are also considered. The distribution of First Passage Times (FPT to the United States and the numbers of infected persons in metropolitan areas worldwide are studied assuming various times and locations of the initial outbreak. International air travel restrictions alone provide a small delay in FPT to the U.S. When other containment measures are applied at the source in conjunction with travel restrictions, delays could be much longer. If in addition, control measures are instituted worldwide, there is a significant reduction in cases worldwide and specifically in the U.S. However, if travel restrictions are not combined with other measures, local epidemic severity may increase, because restriction-induced delays can push local outbreaks into high epidemic season. The per annum cost to the U.S. economy of international and major domestic air passenger travel restrictions is minimal: on the order of 0.8% of Gross National Product.International air travel restrictions may provide a small but important delay in the spread of a pandemic, especially if other disease control measures are implemented during the afforded time. However, if other measures are not instituted, delays may worsen regional epidemics by pushing the outbreak into high epidemic season. This important interaction between policy and seasonality is only evident with a global-scale model. Since the benefit of travel restrictions can be substantial while

  18. HIV-related travel restrictions: trends and country characteristics.

    Science.gov (United States)

    Chang, Felicia; Prytherch, Helen; Nesbitt, Robin C; Wilder-Smith, Annelies

    2013-06-03

    Increasingly, HIV-seropositive individuals cross international borders. HIV-related restrictions on entry, stay, and residence imposed by countries have important consequences for this mobile population. Our aim was to describe the geographical distribution of countries with travel restrictions and to examine the trends and characteristics of countries with such restrictions. In 2011, data presented to UNAIDS were used to establish a list of countries with and without HIV restrictions on entry, stay, and residence and to describe their geographical distribution. The following indicators were investigated to describe the country characteristics: population at mid-year, international migrants as a percentage of the population, Human Development Index, estimated HIV prevalence (age: 15-49), presence of a policy prohibiting HIV screening for general employment purposes, government and civil society responses to having non-discrimination laws/regulations which specify migrants/mobile populations, government and civil society responses to having laws/regulations/policies that present obstacles to effective HIV prevention, treatment, care, and support for migrants/mobile populations, Corruption Perception Index, and gross national income per capita. HIV-related restrictions exist in 45 out of 193 WHO countries (23%) in all regions of the world. We found that the Eastern Mediterranean and Western Pacific Regions have the highest proportions of countries with these restrictions. Our analyses showed that countries that have opted for restrictions have the following characteristics: smaller populations, higher proportions of migrants in the population, lower HIV prevalence rates, and lack of legislation protecting people living with HIV from screening for employment purposes, compared with countries without restrictions. Countries with a high proportion of international migrants tend to have travel restrictions - a finding that is relevant to migrant populations and travel

  19. Human cellular restriction factors that target HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2009-09-01

    Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

  20. Predicting support for restricting food marketing to youth.

    Science.gov (United States)

    Goren, Amir; Harris, Jennifer L; Schwartz, Marlene B; Brownell, Kelly D

    2010-01-01

    To address the obesity crisis, public health experts recommend major reductions in the marketing of unhealthy food to youth. However, policies to restrict food marketing are not currently viewed as politically feasible. This paper examines attitudes and knowledge about food marketing and support for restricting unhealthy food marketing [corrected] among one group of constituents: parents. A survey of 807 parents found that those most likely to support food marketing restrictions were also more likely to have negative views of current food practices. [corrected] These findings suggest that increased public education about the harm caused by food marketing may increase public support for policy interventions.

  1. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  2. Company Law as a Restriction to Free Movement

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2014-01-01

    . There is evidence that non-discriminatory obstacles to free movement found in company law can be restrictions. However, recent cases show that the Court may be willing to apply a more restrictive approach where only non-discriminatory measures that have a qualified deterrent effect may constitute restrictions.......Focusing on recent judgments from the Court of Justice of the European Union, this article investigates how the notion of ‘restriction’ – which is the first step in examining whether there is an infringement of the free movement rights – is used in cases involving company law measures...

  3. Removal of phase transfer agent leads to restricted dynamics of ...

    Indian Academy of Sciences (India)

    Wintec

    has been investigated by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies. The experi- ... gauche defects near the head group for the 3D SAMs similar to 2D ... chain motion is more restricted in hydroxyl termi- nated SAMs.

  4. HCUP State Emergency Department Databases (SEDD) - Restricted Access File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The State Emergency Department Databases (SEDD) contain the universe of emergency department visits in participating States. Restricted access data files are...

  5. Supporting several levels of restriction in the UML

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Damm, Christian Heide; Thomsen, Michael

    2000-01-01

    The emergence of the Unified Modeling Language (UML) has provided software developers with an effective and efficient shared language. However, UML is often too restrictive in initial, informal, and creative modelling, and it is in some cases not restrictive enough, e.g., for code generation. Bas....... This approach potentially increases the usability of the UML, and thus ultimately leads to greater quality and adoption of UML models.......The emergence of the Unified Modeling Language (UML) has provided software developers with an effective and efficient shared language. However, UML is often too restrictive in initial, informal, and creative modelling, and it is in some cases not restrictive enough, e.g., for code generation. Based...

  6. 77 FR 3037 - Proposed Exemptions From Certain Prohibited Transaction Restrictions

    Science.gov (United States)

    2012-01-20

    ... Vol. 77 Friday, No. 13 January 20, 2012 Part II Department of Labor Employee Benefits Security... Employee Benefits Security Administration Proposed Exemptions From Certain Prohibited Transaction Restrictions AGENCY: Employee Benefits Security Administration, Labor. ACTION: Notice of Proposed Exemptions...

  7. 40 CFR 152.168 - Advertising of restricted use products.

    Science.gov (United States)

    2010-07-01

    ... advertising. (5) Billboards and posters. (c) The requirement may be satisfied for printed material by... in the broadcast of the spoken words “Restricted use pesticide,” or a statement of the terms of...

  8. Cuba: U.S. Restrictions on Travel and Legislative Initiatives

    National Research Council Canada - National Science Library

    Sullivan, Mark P

    2003-01-01

    .... In March 2003, the Administration eased restrictions on those visiting close family members in Cuba, while at the same time it eliminated travel for people-to-people educational exchanges unrelated...

  9. Drought Tip: Keeping Plants Alive under Drought or Water Restrictions

    OpenAIRE

    Hartin, Janet; Oki, Loren; Fujino, Dave; Faber, Ben

    2015-01-01

    Plants that don't receive enough water eventually show signs of water stress. During a drought or under water restrictions aimed at water conservation, keeping plants alive can be particularly difficult.

  10. Grout Treatment Facility Land Disposal Restriction Management Plan

    International Nuclear Information System (INIS)

    Hendrickson, D.W.

    1991-01-01

    This document establishes management plans directed to result in the land disposal of grouted wastes at the Hanford Grout Facilities in compliance with Federal, State of Washington, and Department of Energy land disposal restrictions. 9 refs., 1 fig

  11. 76 FR 14083 - Proposed Exemptions From Certain Prohibited Transaction Restrictions

    Science.gov (United States)

    2011-03-15

    ... firms that litigate securities fraud cases on a contingency fee basis. Finally, IFS stated that the... DEPARTMENT OF LABOR Employee Benefits Security Administration Proposed Exemptions From Certain Prohibited Transaction Restrictions AGENCY: Employee Benefits Security Administration, Labor. ACTION: Notice...

  12. Prenatal smoking exposure and asymmetric fetal growth restriction

    NARCIS (Netherlands)

    Delpisheh, Ali; Brabin, Loretta; Drummond, Sandra; Brabin, Bernard J.

    2008-01-01

    Background: Prenatal smoking exposure causes intrauterine fetal growth restriction ( IUGR), although its effects on fetal proportionality are less clearly defined. Aim: The present study assessed fetal proportionality in babies with IUGR using maternal salivary cotinine to indicate maternal smoking

  13. Effects of feed forms, levels of quantitative feed restriction on ...

    African Journals Online (AJOL)

    Nigerian Journal of Animal Production ... Data were collected on growth performance, carcass characteristics, and cost benefits were calculated. Data were subjected to ... Keywords: Broilers, carcass, performance, quantitative feed restriction ...

  14. Phenylketonuria : tyrosine supplementation in phenylalanine-restricted diets

    NARCIS (Netherlands)

    van Spronsen, FJ; van Rijn, M; Bekhof, J; Koch, R; Smit, PGA

    Treatment of phenylketonuria (PKU) consists of restriction of natural protein and provision of a protein substitute that lacks phenylalanine but is enriched in tyrosine. Large and unexplained differences exist, however, in the tyrosine enrichment of the protein substitutes. Furthermore, some

  15. Role of HIV-2 envelope in Lv2-mediated restriction

    International Nuclear Information System (INIS)

    Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.; Dittmar, Matthias T.

    2005-01-01

    We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1 (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-AΔenv-GFP, ROD-AΔenv-RFP, or ROD-AΔenv-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E)

  16. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  17. Services trade restrictiveness and manufacturing productivity : the role of institutions

    OpenAIRE

    BEVERELLI, Cosimo; FIORINI, Matteo; HOEKMAN, Bernard M.

    2015-01-01

    We study the effect of services trade restrictiveness on manufacturing productivity for a broad cross-section of countries at different stages of economic development. Decreasing services trade restrictiveness has a positive indirect impact on the manufacturing sectors that use services as intermediate inputs in production. We identify a critical role of local institutions in shaping this effect: countries with high institutional capacity benefit the most from services trade policy reforms in...

  18. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  19. Open superstring field theory on the restricted Hilbert space

    International Nuclear Information System (INIS)

    Konopka, Sebastian; Sachs, Ivo

    2016-01-01

    It appears that the formulation of an action for the Ramond sector of open superstring field theory requires to either restrict the Hilbert space for the Ramond sector or to introduce auxiliary fields with picture −3/2. The purpose of this note is to clarify the relation of the restricted Hilbert space with other approaches and to formulate open superstring field theory entirely in the small Hilbert space.

  20. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

    OpenAIRE

    Longo, Valter D.; Panda, Satchidananda

    2016-01-01

    Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily...

  1. Immediate metabolic consequences of intrauterine growth restriction and low birthweight.

    Science.gov (United States)

    Bhatia, Jatinder; Gates, Amy

    2013-01-01

    Optimal fetal growth resulting in a 'normally grown' term infant is of paramount importance for assuring a healthy start for postnatal growth and development. Fetal, infant and childhood growth restriction is an important clinical problem for obstetricians, neonatologists, pediatricians and globally, for public health. Worldwide, an estimated 20 million infants are born with low birthweight and a substantial proportion are small for gestational age. Many advances have been made in defining growth restriction by prenatal techniques, thus allowing the recognition of intrauterine growth restriction. Distinguishing infants who are small but have appropriate growth potential from those with growth restriction is important in order to apply obstetric surveillance, anticipate neonatal problems and plan for postneonatal guidance. It is clear that the fetus in growth-restricted pregnancies has limited supply of nutrients and oxygen. The resultant changes, if involving the placenta as well, can lead to circulatory and metabolic changes affecting both short- and long-term survival and development. In this paper, the causes and immediate consequence of being born with low birthweight, intrauterine growth restriction or small for gestational age will be discussed. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  2. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier

    2017-12-01

    Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

  3. Napping reverses increased pain sensitivity due to sleep restriction.

    Science.gov (United States)

    Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

    2015-01-01

    To investigate pain sensitivity after sleep restriction and the restorative effect of napping. A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Laboratory-based study. 11 healthy male volunteers. Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

  4. Napping reverses increased pain sensitivity due to sleep restriction.

    Directory of Open Access Journals (Sweden)

    Brice Faraut

    Full Text Available To investigate pain sensitivity after sleep restriction and the restorative effect of napping.A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed.Laboratory-based study.11 healthy male volunteers.Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon.Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area.Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

  5. Screening, diagnosis, and management of intrauterine growth restriction.

    Science.gov (United States)

    Lausman, Andrea; McCarthy, Fergus P; Walker, Melissa; Kingdom, John

    2012-01-01

    To provide comprehensive background knowledge relevant to the SOGC Maternal-Fetal Medicine Committee-approved guideline entitled "Intrauterine Growth Restriction: Screening, Diagnosis, and Management." Publications in English were retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and any key words (fetal growth, restriction, growth retardation, intrauterine growth restriction [IUGR], low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and high-quality prospective and retrospective observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Evidence obtained from at least one properly randomized controlled trial, Cochrane Reviews, and high quality cohort data have been combined to provide clinicians with evidence to optimize their practice for screening, diagnosis, and management of intrauterine growth restriction. Considerable advances have been made to improve clinicians' ability to screen, diagnose, and manage pregnancies with suspected IUGR more effectively, including several properly randomized controlled trials. Pregnancies with late-onset IUGR may be managed equally effectively by early delivery or delayed delivery (with increased surveillance) anticipating favourable outcomes. By contrast, many aspects of the management of early-onset IUGR require further clinical trials.

  6. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

    Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

  7. Perceived need for restrictions on activity for children with epilepsy.

    Science.gov (United States)

    Brna, Paula M; Gordon, Kevin E; Woolridge, Elaine; Dooley, Joseph M; Wood, Ellen

    2017-08-01

    Children and youth with epilepsy have long been subjected to excessive restrictions on extracurricular activities due to concerns over risk of injury. Over time physicians and medical regulatory associations have liberalized the advice given for people with epilepsy to promote independence, self-esteem and general health benefits of physical activity. Current evidence suggests that few restrictions are needed for children with epilepsy beyond water-related precautions and avoidance of very high-risk activities. However, more stringent restrictions on daily activities may be imposed by caregivers. This study was aimed at exploring current perceptions of parents regarding restrictions on activity for children with epilepsy and the child's perspective on restrictions related to the diagnosis. A self-administered questionnaire was offered to a sample of parent-child dyads of children/youth with epilepsy attending summer camp for children with epilepsy age 8-18years. A 10-item validated HARCES Parent Scale of Childhood Epilepsy was completed by the parent/guardian and a modified-HARCES completed by the child. The primary objective was to assess the degree of restrictions placed on children with epilepsy from the perspective of child and parent assessed independently. Agreement of perceived restrictions between parent-child dyads was also determined. 21 parent/guardian-child pairs were recruited with mean age of children/youth 12.7years (range 9-16years). Total HARCES scores for parents and guardians ranged from 11-26 (x=16.5; SD 4.9) while total scores for children with epilepsy similarly ranged from 10-25 (x=15.2; SD 4.9). There were no differences in total parent scores when analyzed by child's age (13years), gender, age of seizure onset, seizure frequency or seizure type. Total HARCES scores showed no agreement between parent and child pairs with correlation of 0.2798 (95% CI -0.173-0.635). Children and youth with epilepsy often face activity restrictions based on

  8. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity.

    Science.gov (United States)

    Hall, Kevin D; Bemis, Thomas; Brychta, Robert; Chen, Kong Y; Courville, Amber; Crayner, Emma J; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Knuth, Nicolas D; Miller, Bernard V; Prado, Carla M; Siervo, Mario; Skarulis, Monica C; Walter, Mary; Walter, Peter J; Yannai, Laura

    2015-09-01

    Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Hypercaloric diet prevents sexual impairment induced by maternal food restriction.

    Science.gov (United States)

    Bernardi, M M; Macrini, D J; Teodorov, E; Bonamin, L V; Dalboni, L C; Coelho, C P; Chaves-Kirsten, G P; Florio, J C; Queiroz-Hazarbassanov, N; Bondan, E F; Kirsten, T B

    2017-05-01

    Prenatal undernutrition impairs copulatory behavior and increases the tendency to become obese/overweight, which also reduces sexual behavior. Re-feeding rats prenatally undernourished with a normocaloric diet can restore their physiological conditions and copulatory behavior. Thus, the present study investigated whether a hypercaloric diet that is administered in rats during the juvenile period prevents sexual impairments that are caused by maternal food restriction and the tendency to become overweight/obese. Female rats were prenatally fed a 40% restricted diet from gestational day 2 to 18. The pups received a hypercaloric diet from postnatal day (PND) 23 to PND65 (food restricted hypercaloric [FRH] group) or laboratory chow (food restricted control [FRC] group). Pups from non-food-restricted dams received laboratory chow during the entire experiment (non-food-restricted [NFR] group). During the juvenile period and adulthood, body weight gain was evaluated weekly. The day of balanopreputial separation, sexual behavior, sexual organ weight, hypodermal adiposity, striatal dopamine and serotonin, serum testosterone, and tumor necrosis factor α (TNF-α) were evaluated. The FRH group exhibited an increase in body weight on PND58 and PND65. The FRC group exhibited an increase in the latency to the first mount and intromission and an increase in serum TNF-α levels but a reduction of dopaminergic activity. The hypercaloric diet reversed all of these effects but increased adiposity. We concluded that the hypercaloric diet administered during the juvenile period attenuated reproductive impairments that were induced by maternal food restriction through increases in the energy expenditure but not the tendency to become overweight/obese. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Influence of traffic restriction on road and construction fugitive dust].

    Science.gov (United States)

    Tian, Gang; Li, Gang; Qin, Jian-Ping; Fan, Shou-Bin; Huang, Yu-Hu; Nie, Lei

    2009-05-15

    By monitoring the road and construction dust fall continuously during the "Good Luck Beijing" sport events, the reduction of road and construction dust fall caused by traffic restriction was studied. The contribution rate of road and construction dust to particulate matter of Beijing atmosphere environment, and the emission ratio of it to total local PM10 emission were analyzed. The results show that the traffic restriction reduces road and construction dust fall significantly. The dust fall average value of ring roads was 0.27 g x (m2 x d)(-1) in the "traffic restriction" period, and the values were 0.81 and 0.59 g x (m2 x d)(-1) 1 month and 7 days before. The dust fall average value of major arterial and minor arterial was 0.21 g x (m2 x d)(-1) in the "traffic restriction" period, and the values were 0.54 and 0.58 g x (m2 x d)(-1) 1 month and 7 days before. The roads emission reduced 60%-70% compared with before traffic restriction. The dust fall average values of civil architecture and utility architecture were 0.61 and 1.06 g x (m2 x d)(-1) in the "traffic restriction" period, and the values were 1.15 and 1.55 g x (m2 x d)(-1) 20 days before. The construction dust reduced 30%-47% compared with 20 days before traffic restriction. Road and construction dust emission are the main source of atmosphere particulate matter in Beijing, and its contribution to ambient PM10 concentration is 21%-36%. PM10 emitted from roads and constructions account for 42%-72% and 30%-51% of local emission while the local PM10 account for 50% and 70% of the total emission.

  11. Parental perceptions of teen driving: Restrictions, worry and influence.

    Science.gov (United States)

    Jewett, Amy; Shults, Ruth A; Bhat, Geeta

    2016-12-01

    Parents play a critical role in preventing crashes among teens. Research of parental perceptions and concerns regarding teen driving safety is limited. We examined results from the 2013 Summer ConsumerStyles survey that queried parents about restrictions placed on their teen drivers, their perceived level of "worry" about their teen driver's safety, and influence of parental restrictions regarding their teen's driving. We produced frequency distributions for the number of restrictions imposed, parental "worry," and influence of rules regarding their teen's driving, reported by teen's driving license status (learning to drive or obtained a driver's license). Response categories were dichotomized because of small cell sizes, and we ran separate log-linear regression models to explore whether imposing all four restrictions on teen drivers was associated with either worry intensity ("a lot" versus "somewhat, not very much or not at all") or perceived influence of parental rules ("a lot" versus "somewhat, not very much or not at all"). Among the 456 parent respondents, 80% reported having restrictions for their teen driver regarding use of safety belts, drinking and driving, cell phones, and text messaging while driving. However, among the 188 parents of licensed teens, only 9% reported having a written parent-teen driving agreement, either currently or in the past. Worrying "a lot" was reported less frequently by parents of newly licensed teens (36%) compared with parents of learning teens (61%). Parents report having rules and restrictions for their teen drivers, but only a small percentage formalize the rules and restrictions in a written parent-teen driving agreement. Parents worry less about their teen driver's safety during the newly licensed phase, when crash risk is high as compared to the learning phase. Further research is needed into how to effectively support parents in supervising and monitoring their teen driver. Published by Elsevier Ltd.

  12. Attitudes towards smoking restrictions and tobacco advertisement bans in Georgia.

    Science.gov (United States)

    Bakhturidze, George D; Mittelmark, Maurice B; Aarø, Leif E; Peikrishvili, Nana T

    2013-11-25

    This study aims to provide data on a public level of support for restricting smoking in public places and banning tobacco advertisements. A nationally representative multistage sampling design, with sampling strata defined by region (sampling quotas proportional to size) and substrata defined by urban/rural and mountainous/lowland settlement, within which census enumeration districts were randomly sampled, within which households were randomly sampled, within which a randomly selected respondent was interviewed. The country of Georgia, population 4.7 million, located in the Caucasus region of Eurasia. One household member aged between 13 and 70 was selected as interviewee. In households with more than one age-eligible person, selection was carried out at random. Of 1588 persons selected, 14 refused to participate and interviews were conducted with 915 women and 659 men. Respondents were interviewed about their level of agreement with eight possible smoking restrictions/bans, used to calculate a single dichotomous (agree/do not agree) opinion indicator. The level of agreement with restrictions was analysed in bivariate and multivariate analyses by age, gender, education, income and tobacco use status. Overall, 84.9% of respondents indicated support for smoking restrictions and tobacco advertisement bans. In all demographic segments, including tobacco users, the majority of respondents indicated agreement with restrictions, ranging from a low of 51% in the 13-25 age group to a high of 98% in the 56-70 age group. Logistic regression with all demographic variables entered showed that agreement with restrictions was higher with age, and was significantly higher among never smokers as compared to daily smokers. Georgian public opinion is normatively supportive of more stringent tobacco-control measures in the form of smoking restrictions and tobacco advertisement bans.

  13. Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.

    Science.gov (United States)

    White, Matthew J; Beaver, Charlotte M; Goodier, Martin R; Bottomley, Christian; Nielsen, Carolyn M; Wolf, Asia-Sophia F M; Boldrin, Luisa; Whitmore, Charlotte; Morgan, Jennifer; Pearce, Daniel J; Riley, Eleanor M

    2016-01-01

    Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a - CD44 lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b - CD27 + cells and correspondingly lower proportions of highly differentiated CD11b + CD27 - NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

  14. Alteration of placental haemostatic mechanisms in idiopathic intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Jaime Eduardo Bernal Villegas

    2012-08-01

    Full Text Available Intrauterine growth restriction is a complication of pregnancy with a high probability of perinatal morbidity and mortality. It appears tobe caused by abnormal development of placental vasculature. Haemostatic processes are important for the development of the placenta,and an imbalance between procoagulant and anticoagulant factors has been associated with risk of intrauterine growth restriction.Objective. To evaluate coagulation abnormalities in placenta of pregnancies complicated with idiopathic intrauterine growth restriction.Materials and methods. Five placentas from pregnancies with idiopathic intrauterine growth restriction were compared to 19 controls.We performed gross and histological examination of the placenta. Analysis was made of both mRNA expression by real-time PCRand protein by ELISA of tissue factor and thrombomodulin in placental tissue. Results. Results based on histological evaluation wereconsistent with an increased prothrombotic state in placentas from pregnancies with idiopathic intrauterine growth restriction, andthrombosis of chorionic vessels was the most important finding. The study showed an increased expression of tissue factor protein(p=0.0411 and an increase in the ratio of tissue factor/thrombomodulin mRNA (p=0.0411 and protein (p=0.0215 in placentas frompregnancies with idiopathic intrauterine growth restriction. There were no statistically significant differences neither between cases andcontrols in the mRNA levels of tissue factor or thrombomodulin nor at the protein level of thrombomodulin. Conclusion. Evidence ofalteration of local haemostatic mechanisms at the level of the placenta, including abnormal expression of tissue factor and tissue factor/thrombomodulin ratio, in pregnancies that occur with idiopathic intrauterine growth restriction is presented.

  15. HIV restriction by APOBEC3 in humanized mice.

    Directory of Open Access Journals (Sweden)

    John F Krisko

    2013-03-01

    Full Text Available Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3 family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV, Hepatitis B virus (HBV, Human Papilloma virus (HPV, and Human T Cell Leukemia virus (HTLV. The best characterized members of this family are APOBEC3G (A3G and APOBEC3F (A3F and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif. Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.

  16. Restricted Social Engagement among Adults Living with Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Kayla P. Meek

    2018-01-01

    Full Text Available Background: Social engagement is key to health and quality of life. Little is known about social engagement patterns of middle-aged and older adults who live with one or more chronic illnesses. This study investigated social engagement restrictions among middle-aged and older adults with chronic conditions and factors associated with these restrictions. Methods: Cross-sectional representative data from the National Council on Aging Chronic Care Survey were examined for relationships between social engagement restrictions and chronic conditions, health status, support, quality of life implications, self-care barriers, caregiving, and demographics. Associations were tested using bivariate analyses and binary logistic regression. Results: Participants were 793 middle-aged (age 44–64 and older adults (age 65+ with one or more chronic conditions. Factors associated with social engagement restrictions included having higher education, receiving care, having more physician visits and hospitalizations, being disabled, being unemployed, and having higher Emotional and Physical Problems Scale scores. Conclusions: Findings reveal the prevalence of social engagement restrictions among middle-aged and older adults with chronic conditions. Results highlight the importance of promoting research, assessments, and interventions to increase social engagement among this aging population.

  17. Evaluation of placenta in foetal demise and foetal growth restriction.

    Science.gov (United States)

    Ch, Ujwala; Guruvare, Shyamala; Bhat, Sudha S; Rai, Lavanya; Rao, Sugandhi

    2013-11-01

    The study objective was to evaluate the pathological changes of the placenta in foetal death and foetal growth restriction and to find correlation of the findings with clinical causes. Prospective study at a tertiary care hospital. Gross and histopathological examinations of the placentae were carried out in pregnancies with foetal demise (IUD) and Foetal Growth Restriction (FGR). SPSS, version 11.5. Placentae of twenty seven women with foetal demise and of equal number of women with foetal growth restriction were studied. Placental weight was less than 10(th) percentile in 61.5% women in IUD group and in 93% women in the FGR group. Gross examination of placentae showed abnormalities in 12 (44%) women of IUD group and in 16 (59%) women of FGR group. Histopathological abnormalities were observed in 74.1% women of the IUD group and in 66.7% women of FGR group. Placental histopathology correlated with clinical risk factors in 60% women of IUD group and in 40% women of FGR group. Among the women with no clinically explainable cause for IUD and FGR, 86% and 57% had placental histopathological abnormalities respectively. The histopathological abnormalities of the placenta can be used to document the clinical causes of foetal demise and growth restriction; it may explain the causes in cases of clinically unexplained foetal demise and foetal growth restriction.

  18. Restrictions on Software for Personal and Professional Use

    CERN Multimedia

    2004-01-01

    A growing number of computer security incidents detected at CERN are due to additional software installed for personal and professional use. As a consequence, the smooth operation of CERN is put at risk and often many hours are lost solving the problems. To reduce this security risk, installation and/or use of software on CERN's computing and network infrastructure needs to be restricted. Therefore: Do NOT install software for personal use Do NOT install 'free' or other software unless you have the expertise to configure and maintain it securely. Please comply to these rules to keep our computer systems safe. Further explanation of these restrictions is at http://cern.ch/security/software-restrictions Restricted software, known to cause security and/or network problems (e.g. KaZaA and other P2P/Peer-to-Peer file sharing applications, Skype P2P telephony software, ICQ, VNC, ...), is listed at: http://cern.ch/security/software-restrictions/list

  19. The Effects of Calorie Restriction in Depression and Potential Mechanisms.

    Science.gov (United States)

    Zhang, Yifan; Liu, Changhong; Zhao, Yinghao; Zhang, Xingyi; Li, Bingjin; Cui, Ranji

    2015-01-01

    Depression, also called major depressive disorder, is a neuropsychiatric disorder jeopardizing an increasing number of the population worldwide. To date, a large number of studies have devoted great attention to this problematic condition and raised several hypotheses of depression. Based on these theories, many antidepressant drugs were developed for the treatment of depression. Yet, the depressed patients are often refractory to the antidepressant therapies. Recently, increasing experimental evidences demonstrated the effects of calorie restriction in neuroendocrine system and in depression. Both basic and clinical investigations indicated that short-term calorie restriction might induce an antidepressant efficacy in depression, providing a novel avenue for treatment. Molecular basis underlying the antidepressant actions of calorie restriction might involve multiple physiological processes, primarily including orexin signaling activation, increased CREB phosphorylation and neurotrophic effects, release of endorphin and ketone production. However, the effects of chronic calorie restriction were quite controversial, in the cases that it often resulted in the long-term detrimental effects via inhibiting the function of 5-HT system and decreasing leptin levels. Here we review such dual effects of calorie restriction in depression and potential molecular basis behind these effects, especially focusing on antidepressant effects.

  20. Restrictions of process machine retooling at machine-building enterprises

    Directory of Open Access Journals (Sweden)

    Kuznetsova Elena

    2017-01-01

    Full Text Available The competitiveness of the national economy depends on the technological level of the machine-building enterprises production equipment. Today in Russia there are objective and subjective restrictions for the optimum policy formation of the manufacturing equipment renewal. The analysis of the manufacturing equipment age structure dynamics in the Russian machine-building complex indicates the negative tendencies intensification: increase in the equipment service life, reduction in the share of up-to-date equipment, and drop in its use efficiency. The article investigates and classifies the main restrictions of the manufacturing equipment renewal process, such as regulatory and legislative, financial, organizational, competency-based. The economic consequences of the revealed restrictions influence on the machine-building enterprises activity are shown.

  1. Almost-Quantum Correlations Violate the No-Restriction Hypothesis.

    Science.gov (United States)

    Sainz, Ana Belén; Guryanova, Yelena; Acín, Antonio; Navascués, Miguel

    2018-05-18

    To identify which principles characterize quantum correlations, it is essential to understand in which sense this set of correlations differs from that of almost-quantum correlations. We solve this problem by invoking the so-called no-restriction hypothesis, an explicit and natural axiom in many reconstructions of quantum theory stating that the set of possible measurements is the dual of the set of states. We prove that, contrary to quantum correlations, no generalized probabilistic theory satisfying the no-restriction hypothesis is able to reproduce the set of almost-quantum correlations. Therefore, any theory whose correlations are exactly, or very close to, the almost-quantum correlations necessarily requires a rule limiting the possible measurements. Our results suggest that the no-restriction hypothesis may play a fundamental role in singling out the set of quantum correlations among other nonsignaling ones.

  2. The ability of multimerized cyclophilin A to restrict retrovirus infection

    International Nuclear Information System (INIS)

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan Wen; Yeung, Darwin F.; Li Xing; Song Byeongwoon; Sodroski, Joseph

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection

  3. Affective neural response to restricted interests in autism spectrum disorders.

    Science.gov (United States)

    Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2014-01-01

    Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

  4. [Suplemented restricted diet in old patients with chronic renal disease].

    Science.gov (United States)

    Teplan, Vladimír

    2016-01-01

    In last decades was confirmed remarkable increase in number of old patients with chronic kidney disease. Despide of developments in dialysis technology and kidney transplantation there is a growing number of old patients who are not suitable for these methods. Recently were published data showing long-term effect of protein restricted diet supplemented with keto amino acids in elderly. Based on our results obtained in re-analysis of 3 000 patients we can confirm also good compliance and low risk of malnutrition.Key words: chronic kidney disease - keto amino acids - old age - restricted diet.

  5. Restriction genes for retroviruses influence the risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Hansen, Bettina; Nissen, Kari K

    2013-01-01

    known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22...... and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement....

  6. Site-specific DNA transesterification catalyzed by a restriction enzyme

    OpenAIRE

    Sasnauskas, Giedrius; Connolly, Bernard A.; Halford, Stephen E.; Siksnys, Virginijus

    2007-01-01

    Most restriction endonucleases use Mg2+ to hydrolyze phosphodiester bonds at specific DNA sites. We show here that BfiI, a metal-independent restriction enzyme from the phospholipase D superfamily, catalyzes both DNA hydrolysis and transesterification reactions at its recognition site. In the presence of alcohols such as ethanol or glycerol, it attaches the alcohol covalently to the 5′ terminus of the cleaved DNA. Under certain conditions, the terminal 3′-OH of one DNA strand can attack the t...

  7. Semiparametric regression for restricted mean residual life under right censoring

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben; Scheike, Thomas H.

    2015-01-01

    is not observed, the restricted mean residual life must be considered. In this paper, we propose the proportional restricted mean residual life model for fitting survival data under right censoring. For inference on the model parameters, martingale estimating equations are developed, and the asymptotic properties...... of the proposed estimators are established. In addition, a class of goodness-of-fit test is presented to assess the adequacy of the model. The finite sample behavior of the proposed estimators is evaluated through simulation studies, and the approach is applied to a set of real life data collected from...

  8. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS

    2016-02-01

    Full Text Available ABSTRACT Objective: To analyze the growth rate of premature infants in the first weeks of life and factors associated with extrauterine growth restriction. Methods: This is a cross-sectional study of 254 premature infants in a neonatal intensive care unit conducted from January 1, 2008 to December 31, 2010. Infants who died or had malformations incompatible with life were excluded. Median weight curves according to gestational age were constructed for the first four weeks of life. The Fenton growth chart calculations provided the weight Z-scores. Extrauterine growth restriction was defined as corrected weight-for-age Z-score ≤-2. Perinatal, morbidity, and health care variables were analyzed. The Poisson regression model yielded the prevalenceratios . Associations between extrauterine growth restriction and the perinatal, morbidity, and care variables were investigated. Poisson regression controlled possible confounding factors. Results: The frequency of extrauterine growth restriction was 24.0%. Most (85.0% small-for-gestational-age infants developed extrauterine growth restriction; 55.3% of extrauterine growth restriction cases involved small-for-gestational-age infants. Premature infants with gestational age >32 weeks did not recover the median birth weight until the third week of life and had a higher frequency of small-for-gestational-age. The Z-scores of non-small-for-gestational-age infants decreased more after birth than those of small-for-gestational-age infants. extrauterine growth restriction was associated with small-for-gestational-age (PR=6.14; 95%CI=3.33-11.33;p <0.001 and time without enteral diet (PR=1.08; 95%CI=1.04-1.13; p =0.010. Conclusion: Extrauterine growth restriction occurs in premature infants of all gestational age. The participation of small-for-gestational-age and nutritional practices in its genesis is noteworthy. We suggest prospective studies of all premature infants. The implementation of best care practices

  9. Restricted use of antibiotics in organic pig farming

    DEFF Research Database (Denmark)

    Aabo, Søren; Jensen, Annette Nygaard

    2013-01-01

    Can the restricted use of antibiotics in organic pig farming be documented to provide a safer, high quality meat product with less antibiotic resistant bacteria? The project SafeOrganic aims to document that the restricted use of antimicrobials in organic pig production leads to lower levels...... of antibiotic resistant bacteria compared with the level in conventional pigs. However, the project will also address the risk of losing this quality parameter, due to a widespread practice of slaughtering organic pigs together with conventional pigs, implying a risk of cross-contamination....

  10. Restriction Theorem for Principal bundles in Arbitrary Characteristic

    DEFF Research Database (Denmark)

    Gurjar, Sudarshan

    2015-01-01

    The aim of this paper is to prove two basic restriction theorem for principal bundles on smooth projective varieties in arbitrary characteristic generalizing the analogues theorems of Mehta-Ramanathan for vector bundles. More precisely, let G be a reductive algebraic group over an algebraically...... closed field k and let X be a smooth, projective variety over k together with a very ample line bundle O(1). The main result of the paper is that if E is a semistable (resp. stable) principal G-bundle on X w.r.t O(1), then the restriction of E to a general, high multi-degree, complete-intersection curve...

  11. Partial digestion with restriction enzymes of ultraviolet-irradiated human genomic DNA: a method for identifying restriction site polymorphisms

    International Nuclear Information System (INIS)

    Nobile, C.; Romeo, G.

    1988-01-01

    A method for partial digestion of total human DNA with restriction enzymes has been developed on the basis of a principle already utilized by P.A. Whittaker and E. Southern for the analysis of phage lambda recombinants. Total human DNA irradiated with uv light of 254 nm is partially digested by restriction enzymes that recognize sequences containing adjacent thymidines because of TT dimer formation. The products resulting from partial digestion of specific genomic regions are detected in Southern blots by genomic-unique DNA probes with high reproducibility. This procedure is rapid and simple to perform because the same conditions of uv irradiation are used for different enzymes and probes. It is shown that restriction site polymorphisms occurring in the genomic regions analyzed are recognized by the allelic partial digest patterns they determine

  12. Incremental Effect of the Addition of Prescriber Restrictions on a State Medicaid's Pharmacy-Only Patient Review and Restriction Program.

    Science.gov (United States)

    Keast, Shellie L; Pham, Timothy; Teel, Ashley; Nesser, Nancy J

    2017-08-01

    Patient review and restriction programs (PRRPs), used by state Medicaid programs to limit potential abuse and misuse of opioids and related controlled medications, often restrict members to a single pharmacy for controlled medications. While most states use a restricted pharmacy access model, not all states include restricted prescriber access. Oklahoma Medicaid (MOK) added a restricted prescriber access feature to its PRRP in July 2014. To evaluate the incremental effect that the addition of a prescriber restriction to MOK's pharmacy-only PRRP had on the pharmacy and resource utilization of the enrolled members. MOK members with at least 6 months of enrollment in the pharmacy-only PRRP were restricted to a maximum of 3 prescribers for controlled substances in July 2014 and were identified as "cases." Using a propensity score method, cases were matched to controls from the MOK non-PRRP enrolled population based on demographics and baseline health care utilization. Data from January 1, 2014, through December 31, 2014, were evaluated. Each member's monthly health care resource utilization, defined in terms of medical and pharmacy costs, prescription counts, and opioid use per member per month (PMPM), was analyzed. A difference-indifferences (DID) regression estimated the change in resource utilization following the July 2014 policy change. This study included 378 controls and 126 cases after propensity matching. No differences were noted for daily morphine equivalents, benzodiazepine prescriptions, or maintenance prescriptions. There were decreases in mean PMPM use for both groups for short-acting opioid (SAO) claims (P evidence that overall opioid claims were affected, the addition of prescriber restrictions may have resulted in an incremental change to SAO, prescriber, and pharmacy use in the PRPP population. Use of PRRPs may be an effective tool in reducing inappropriate use of prescription opioids within payer systems. The question remains whether these changes

  13. 45 CFR 1226.10 - Hatch Act restrictions.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Hatch Act restrictions. 1226.10 Section 1226.10 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY... candidates on canvassing or speaking tours. (12) Participation in or organizing a political parade. (13...

  14. 4 CFR 201.9 - Restrictions on charging fees.

    Science.gov (United States)

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Restrictions on charging fees. 201.9 Section 201.9 Accounts RECOVERY ACCOUNTABILITY AND TRANSPARENCY BOARD PUBLIC INFORMATION AND REQUESTS § 201.9... the news media. (2) The Board shall provide without charge to all but commercial users: (i) The first...

  15. Effectiveness of electro-fencing for restricting the ranging behaviour ...

    African Journals Online (AJOL)

    Here, we assessed the effectiveness of electro-fencing for restricting movement patterns of several wild ungulates in Akagera National Park (NP), Rwanda. Following the turmoil of the Rwandan genocide and civil war (1991–1995), large numbers of returning war refugees brought about an increasing pressure on land use, ...

  16. DOPING AND OTHER RESTRICTED METHODS IN SPORTS SUMMARY

    Directory of Open Access Journals (Sweden)

    Duško Bjelica

    2007-05-01

    Full Text Available Since sport has become an industry, it has lost all its elements of tolerance and chivalry and become an arena which is made for making profi t. Under those conditions everyone wanted to succeed by no means. The stocks such as: power, speed and endurance were of immeasurable value on the market. The level of the biomothoric dimensions could be raised as a matter of course or, unfortunately, by using restricted substances where the science was abused. Many private laboratories have started with the production of the restricted substances whose aim was to raise the level of power, strength and endurance, but only temporary, because the harmful effects lasted much longer and even caused lethal consequences. The natives from the South Africa used to use a kind of alcohol drink which was called “dop”. That word came to Europe by the Dutchmen, where it has become a “doping” in English. These restricted substances can be classifi ed into the groups with a specifi c effect. These substances are called restricted substances and methods in sports. These are the substances such as: stimulants, narcotics, canabiodies, anabolic steroids, peptide hormones, beta-2 agonists, anti-estrogen agenses, covered agenses and glycocorticoids.

  17. Classifying images using restricted Boltzmann machines and convolutional neural networks

    Science.gov (United States)

    Zhao, Zhijun; Xu, Tongde; Dai, Chenyu

    2017-07-01

    To improve the feature recognition ability of deep model transfer learning, we propose a hybrid deep transfer learning method for image classification based on restricted Boltzmann machines (RBM) and convolutional neural networks (CNNs). It integrates learning abilities of two models, which conducts subject classification by exacting structural higher-order statistics features of images. While the method transfers the trained convolutional neural networks to the target datasets, fully-connected layers can be replaced by restricted Boltzmann machine layers; then the restricted Boltzmann machine layers and Softmax classifier are retrained, and BP neural network can be used to fine-tuned the hybrid model. The restricted Boltzmann machine layers has not only fully integrated the whole feature maps, but also learns the statistical features of target datasets in the view of the biggest logarithmic likelihood, thus removing the effects caused by the content differences between datasets. The experimental results show that the proposed method has improved the accuracy of image classification, outperforming other methods on Pascal VOC2007 and Caltech101 datasets.

  18. Fetal Growth Restriction at the Limits of Viability

    NARCIS (Netherlands)

    Visser, G. H. A.; Bilardo, Caterina M.; Lees, Christopher

    2014-01-01

    The outcome of early small-for-gestational age and/or intrauterine growth-restricted fetuses is reviewed. In these fetuses the outcome appears to be considerably poorer than that of appropriately grown fetuses and this seems mainly to be caused by intrauterine malnutrition rather than by hypoxemia.

  19. 13 CFR 120.383 - Restrictions on loan processing.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Restrictions on loan processing. 120.383 Section 120.383 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS.... Since greater risk may be associated with a loan to an applicant under this program, a Certified Lender...

  20. 17 CFR 1.22 - Use of customer funds restricted.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Use of customer funds... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.22 Use of customer funds restricted. No futures commission merchant shall use, or permit the use of, the customer funds of...

  1. On some special cases of the restricted assignment problem

    NARCIS (Netherlands)

    Wang, C. (Chao); R.A. Sitters (René)

    2016-01-01

    textabstractWe consider some special cases of the restricted assignment problem. In this scheduling problem on parallel machines, any job j can only be assigned to one of the machines in its given subset Mj of machines. We give an LP-formulation for the problem with two job sizes and show that it

  2. First order normalization in the perturbed restricted three–body ...

    African Journals Online (AJOL)

    This paper performs the first order normalization that will be employed in the study of the nonlinear stability of triangular points of the perturbed restricted three – body problem with variable mass. The problem is perturbed in the sense that small perturbations are given in the coriolis and centrifugal forces. It is with variable ...

  3. Longitudinal study of computerized cardiotocography in early fetal growth restriction

    NARCIS (Netherlands)

    Wolf, H.; Arabin, B.; Lees, Christoph C.; Oepkes, D.; Prefumo, Federico; Thilaganathan, B.; Todros, T.; Visser, G.H.A.; Bilardo, Caterina M.; Derks, J. B.; Diemert, A.; Duvekot, Johannes J.; Ferrazzi, E.; Frusca, T.; Hecher, K.; Marlow, N.; Martinelli, P.; Ostermayer, E.; Papageorghiou, Aris T.; Scheepers, Hubertina C. J.; Schlembach, D.; Schneider, K. T M; Valcamonico, A.; van Wassenaer-Leemhuis, A.; Ganzevoort, W.; Aktas, Ayse; Borgione, Silvia; Brezinka, Christoph; Calvert, Sandra; Chaoui, Rabih; Cornette, Jerome M J; Diehl, Thilo; van Eyck, Jim; Fratelli, Nicola; van Haastert, Inge Lot; Johnson, Samantha; Lobmaier, Silvia; Lopriore, Enrico; Mansi, Giuseppina; Missfelder-Lobos, Hannah; Martelli, Paola; Maso, Gianpaolo; Maurer-Fellbaum, Ute; Van Charante, Nico Mensing; De Tollenaer, Susanne Mulder; Moore, Tamanna; Napolitano, Raffaele; Oberto, Manuela; Ogge, Giovanna; van der Post, Joris Am; Preston, Lucy; Raimondi, Francesco; Reiss, Irwin K M; Rigano, Serena; Schuit, Ewoud; Skabar, Aldo; Spaanderman, Marc E.; Weisglas-Kuperus, Nynke; Zimmermann, Andrea

    2017-01-01

    Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. Methods: The

  4. Partial sleep restriction decreases insulin sensitivity in type 1 diabetes

    NARCIS (Netherlands)

    Donga, Esther; van Dijk, Marieke [Leiden Univ., LUMC; van Dijk, J. Gert; Biermasz, Nienke R.; Lammers, Gert-Jan; van Kralingen, Klaas; Hoogma, Roel P. L. M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

    2010-01-01

    Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. We studied seven patients (three men, four women) with type 1 diabetes: mean age 44

  5. Moment Restriction-based Econometric Methods: An Overview

    NARCIS (Netherlands)

    N. Kunitomo (Naoto); M.J. McAleer (Michael); Y. Nishiyama (Yoshihiko)

    2010-01-01

    textabstractMoment restriction-based econometric modelling is a broad class which includes the parametric, semiparametric and nonparametric approaches. Moments and conditional moments themselves are nonparametric quantities. If a model is specified in part up to some finite dimensional parameters,

  6. 29 CFR 15.23 - Restrictions on certain claims.

    Science.gov (United States)

    2010-07-01

    ... restrictions noted: (a) Money or currency. Claims may be allowed for loss of money or currency (which includes... currency is limited to an amount which is determined to have been reasonable for the claimant to have had... motor vehicles were required to be used for official Government business (official Government business...

  7. 22 CFR 513.225 - Failure to adhere to restrictions.

    Science.gov (United States)

    2010-04-01

    ... shall not knowingly do business under a covered transaction with a person who is— (1) Debarred or... excluded from the covered transaction. (b) Violation of the restriction under paragraph (a) of this section may result in disallowance of costs, annulment or termination of award, issuance of a stop work order...

  8. Distribution Learning in Evolutionary Strategies and Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Krause, Oswin

    The thesis is concerned with learning distributions in the two settings of Evolutionary Strategies (ESs) and Restricted Boltzmann Machines (RBMs). In both cases, the distributions are learned from samples, albeit with different goals. Evolutionary Strategies are concerned with finding an optimum ...

  9. Airflow-Restricting Mask Reduces Acute Performance in Resistance Exercise

    Directory of Open Access Journals (Sweden)

    Yuri L. Motoyama

    2016-09-01

    Full Text Available Background: The aim of this study was to compare the number of repetitions to volitional failure, the blood lactate concentration, and the perceived exertion to resistance training with and without an airflow-restricting mask. Methods: Eight participants participated in a randomized, counterbalanced, crossover study. Participants were assigned to an airflow-restricting mask group (MASK or a control group (CONT and completed five sets of chest presses and parallel squats until failure at 75% one-repetition-maximum test (1RM with 60 s of rest between sets. Ratings of perceived exertion (RPEs, blood lactate concentrations (Lac−, and total repetitions were taken after the training session. Results: MASK total repetitions were lower than those of the CONT, and (Lac− and MASK RPEs were higher than those of the CONT in both exercises. Conclusions: We conclude that an airflow-restricting mask in combination with resistance training increase perceptions of exertion and decrease muscular performance and lactate concentrations when compared to resistance training without this accessory. This evidence shows that the airflow-restricting mask may change the central nervous system and stop the exercise beforehand to prevent some biological damage.

  10. The Historical Foundations of Religious Restrictions in Contemporary China

    Directory of Open Access Journals (Sweden)

    Yu Tao

    2017-12-01

    Full Text Available The ruling Chinese Communist Party (CCP abolished its total ban on religious activities in 1982. However, the distrust that the CCP feels for religions remains obvious today, and the religious restrictions in contemporary China remain tight. Conventional wisdom tells us that the official atheist ideology of Marxism-Leninism is the main reason behind the CCP’s distrust for, and restriction of, religion. However, taking a historical institutionalist perspective, this paper argues that the religious restrictions in contemporary China are in fact rooted in the fierce political struggles of the country’s two major revolutions in the first half of the twentieth century. Without the support of religious groups, the Nationalist Republicans would have found it difficult to survive and succeed in overthrowing the Qing Dynasty during the Chinese Republican Revolution in the first decade of the twentieth century. Likewise, without cooperating with a wide range of religious groups, the CCP would have struggled to defeat the Nationalist regime and the Japanese invaders in the Chinese Communist Revolution between 1920s and 1940s. Thanks to the collaborations and struggles with various religious groups during the two revolutions which lead to its eventual ascent to power, the CCP thoroughly understands the organisational strength and mobilising capability embedded within religious groups. The tight restrictions on religious affairs in contemporary China is therefore likely to stem from the CCP’s worry that prospective competitors could mobilise religious groups to challenge its rule through launching, supporting, or sponsoring collective actions.

  11. Drunkorexia: Calorie Restriction Prior to Alcohol Consumption among College Freshman

    Science.gov (United States)

    Burke, Sloane C.; Cremeens, Jennifer; Vail-Smith, Karen; Woolsey, Conrad

    2010-01-01

    Using a sample of 692 freshmen at a southeastern university, this study examined caloric restriction among students prior to planned alcohol consumption. Participants were surveyed for self-reported alcohol consumption, binge drinking, and caloric intake habits prior to drinking episodes. Results indicated that 99 of 695 (14%) of first year…

  12. Patterns of endemicity and range restriction among southern African ...

    African Journals Online (AJOL)

    Patterns of endemicity and range restriction among southern African coastal marine invertebrates. RJ Scott, CL Griffiths, TB Robinson. Abstract. Southern Africa supports a rich marine biota of 12 734 currently described marine species. Although the distribution and overall species-richness patterns of several component ...

  13. 12 CFR 5.65 - Restrictions on undercapitalized institutions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Restrictions on undercapitalized institutions. 5.65 Section 5.65 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY RULES... defined in 12 CFR part 6. ...

  14. Quantitative feed restriction of Pekin breeder ducks during the ...

    African Journals Online (AJOL)

    hatchability of incubated duck eggs owing to restricted feed intake. ... Egg numbers, infertile eggs, fertile eggs, dead embryos, and duck- lings hatched were recorded for each of the 12 pens. At the same time as the six male and 24 female ducks were ..... treatment but thereafter there was a drop, even lower than the.

  15. 78 FR 51696 - Restrictions on Legal Assistance to Aliens

    Science.gov (United States)

    2013-08-21

    ... LEGAL SERVICES CORPORATION 45 CFR Part 1626 Restrictions on Legal Assistance to Aliens AGENCY... assistance to aliens. The revisions are intended to implement three statutory changes on aliens eligible for... provided to aliens, were enacted in 1996 and have been reincorporated annually with amendments. Section 504...

  16. 31 CFR 360.48 - Restrictions on reissue; denominational exchange.

    Science.gov (United States)

    2010-07-01

    ...; denominational exchange. 360.48 Section 360.48 Money and Finance: Treasury Regulations Relating to Money and... GOVERNING DEFINITIVE UNITED STATES SAVINGS BONDS, SERIES I Reissue and Denominational Exchange § 360.48 Restrictions on reissue; denominational exchange. Reissue is not permitted solely to change denominations. ...

  17. Use of qualitative feed restriction as a management strategy for ...

    African Journals Online (AJOL)

    A 5-week experiment was conducted to investigate the effects of qualitative feed restriction through the use low-quality diet on finisher broiler performance, and to determine if sufficient compensatory growth can be achieved at that phase of broiler production. Seventytwo (72) 4 weeks old broiler chicks of Anak strain ...

  18. 38 CFR 36.4362 - Rights and restrictions.

    Science.gov (United States)

    2010-07-01

    ... parking areas or facilities. (ii) Any contract or lease, including franchises and licenses, to which a declarant is a party. (iii) The requirements of paragraphs (a)(2)(i) and (ii) of this section do not apply... restrictions are acceptable: (i) A requirement that leases have a minimum initial term of up to 1 year; or (ii...

  19. Stability analysis of nonlinear systems with slope restricted nonlinearities.

    Science.gov (United States)

    Liu, Xian; Du, Jiajia; Gao, Qing

    2014-01-01

    The problem of absolute stability of Lur'e systems with sector and slope restricted nonlinearities is revisited. Novel time-domain and frequency-domain criteria are established by using the Lyapunov method and the well-known Kalman-Yakubovich-Popov (KYP) lemma. The criteria strengthen some existing results. Simulations are given to illustrate the efficiency of the results.

  20. Stability Analysis of Nonlinear Systems with Slope Restricted Nonlinearities

    Directory of Open Access Journals (Sweden)

    Xian Liu

    2014-01-01

    Full Text Available The problem of absolute stability of Lur’e systems with sector and slope restricted nonlinearities is revisited. Novel time-domain and frequency-domain criteria are established by using the Lyapunov method and the well-known Kalman-Yakubovich-Popov (KYP lemma. The criteria strengthen some existing results. Simulations are given to illustrate the efficiency of the results.

  1. 28 CFR 549.13 - Programming, duty, and housing restrictions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Programming, duty, and housing... INSTITUTIONAL MANAGEMENT MEDICAL SERVICES Infectious Disease Management § 549.13 Programming, duty, and housing restrictions. (a) The CD will assess any inmate with an infectious disease for appropriateness for programming...

  2. Restriction Inhibition Assay: A Qualitative and Quantitative Method to ...

    African Journals Online (AJOL)

    rich fractions (PRFs) with high affinity for EcoRI and HindIII restriction sequences and correlate their interaction to an anticancer activity. Methods: pBR322 linear plasmid DNA was used as a template to screen the sequence-selective inhibition of ...

  3. Restricted Interests and Anxiety in Children with Autism

    Science.gov (United States)

    Spiker, Michael A.; Lin, C. Enjey; Van Dyke, Marilyn; Wood, Jeffrey J.

    2012-01-01

    A preoccupation with restricted interests (RI) is a core symptom of autism spectrum disorders (ASD). Engagement in RI is commonly observed in this population and impacts social, adaptive, and emotional functioning. The presence of anxiety disorders and overlap in symptom expression with RI, such as obsessive compulsive disorder (OCD), in children…

  4. 50 CFR 648.88 - Multispecies open access permit restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Multispecies open access permit... Management Measures for the NE Multispecies and Monkfish Fisheries § 648.88 Multispecies open access permit restrictions. (a) Handgear permit. A vessel issued a valid open access NE multispecies Handgear permit is...

  5. Proposal of Realization Restricted Quantum Game with Linear Optic Method

    International Nuclear Information System (INIS)

    Zhao Haijun; Fang Ximing

    2006-01-01

    We present a quantum game with the restricted strategic space and its realization with linear optical system, which can be played by two players who are separated remotely. This game can also be realized on any other quantum computers. We find that the constraint brings some interesting properties that are useful for making game models.

  6. 76 FR 50535 - Waiver of Restriction on Assistance to Lebanon

    Science.gov (United States)

    2011-08-15

    ... DEPARTMENT OF STATE [Public Notice: 7555] Waiver of Restriction on Assistance to Lebanon Pursuant to Section 7086(c)(2) of the Department of State, Foreign Operations, and Related Programs... States to waive the requirements of Section 7086(c)(1) of the Act with respect to Lebanon and I hereby...

  7. 7 CFR 1786.167 - Restrictions to additional RUS financing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Restrictions to additional RUS financing. 1786.167... additional RUS financing. (a) No borrower that prepays an electric loan at a discount as provided under this... borrower is unable to obtain financing at reasonable terms to restore the system from non-RUS sources...

  8. 31 CFR 315.6 - Restrictions on registration.

    Science.gov (United States)

    2010-07-01

    ... purchased as a gift to a minor under a gifts-to-minors statute must be registered as prescribed by the... States but only if the bonds are purchased on a payroll deduction plan and the owner provides a taxpayer... resident of any restricted area. (c) Minors. (1) Minors may purchase with their wages, earnings, or other...

  9. Kamm on Inviolability and Agent-Relative Restrictions

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2009-01-01

    Abstract  Agent-relative restrictions prohibit minimizing violations: that is, they require us not to minimize the total number of their violations by violating them ourselves. Frances Kamm has explained this prohibition in terms of the moral worth of persons, which, in turn, she explains in term...

  10. Restrictions in social participation of young adults with spina bifida

    NARCIS (Netherlands)

    Barf, H. A.; Post, M. W. M.; Verhoef, M.; Jennekens-Schinkel, A.; Gooskens, R. H. J. M.; Prevo, A. J. H.

    2009-01-01

    Purpose. To determine participation restrictions of young adults with spina bifida (SB) in relation to health condition and activity limitations. Method. A total of 179 persons aged 16-25 years and born with SB participated in a cross-sectional study. The main outcome on four domains of

  11. Growth restriction and gender influence cerebral oxygenation in preterm neonates

    NARCIS (Netherlands)

    Cohen, Emily; Baerts, Willem; Alderliesten, Thomas; Derks, Jan; Lemmers, Petra; van Bel, Frank

    2016-01-01

    OBJECTIVE: To investigate the effect of fetal growth restriction and gender on cerebral oxygenation in preterm neonates during the first 3 days of life. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS: 68 (41 males)

  12. Influence of Maternal Nutrient Restriction during the Period of ...

    African Journals Online (AJOL)

    Influence of Maternal Nutrient Restriction during the Period of Embryonic and Maximal Placental Growth on Organ Development in the Adult Sheep. ... Objective: It is apparent that maternal under nutrition at specific period during pregnancy has differential effects on placental and fetal development, such that the resulting ...

  13. 47 CFR 64.1505 - Restrictions on collect telephone calls.

    Science.gov (United States)

    2010-10-01

    ... SERVICES (CONTINUED) MISCELLANEOUS RULES RELATING TO COMMON CARRIERS Interstate Pay-Per-Call and Other Information Services § 64.1505 Restrictions on collect telephone calls. (a) No common carrier shall provide interstate transmission or billing and collection services to an entity offering any service within the scope...

  14. 40 CFR 152.175 - Pesticides classified for restricted use.

    Science.gov (United States)

    2010-07-01

    ...% and less All uses (domestic and nondomestic) Unclassified Paraquat (dichloride) and paraquat bis... subsoil ......do Do. ......do All subsoil uses Unclassified Sulfotepp Sprays and smoke generators All uses Restricted Inhalation hazard to humans. Zinc Phosphide All formulations 2% and less All domestic uses and non...

  15. Restrictive Language Policy in Practice: English Learners in Arizona

    Science.gov (United States)

    Heineke, Amy J.

    2016-01-01

    As the most restrictive language policy context in the United States, Arizona's monolingual and prescriptive approach to teaching English learners continues to capture international attention. More than five school years after initial implementation, this study uses qualitative data from the individuals doing the policy work to provide a holistic…

  16. Effect of quantitative feed restriction on pullet development and ...

    African Journals Online (AJOL)

    Hen-day and hen-housed production levels as well as cost of feed per unit weight or dozen eggs, were not significantly affected by the treatments. These studies showed that when growing birds are restricted in quantity of feed fed, they respond with a reduction in mature weight, but the laying phase is unaffected.

  17. 49 CFR 591.7 - Restrictions on importations.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) IMPORTATION OF VEHICLES AND EQUIPMENT SUBJECT TO FEDERAL SAFETY, BUMPER AND THEFT PREVENTION STANDARDS § 591.7 Restrictions on importations. (a) A vehicle or... a vehicle or equipment item under § 591.5(j) does not intend to export or destroy the vehicle or...

  18. 24 CFR 888.315 - Restrictions on retroactive payments.

    Science.gov (United States)

    2010-04-01

    ... PROGRAM, SECTION 202 SUPPORTIVE HOUSING FOR THE ELDERLY PROGRAM AND SECTION 811 SUPPORTIVE HOUSING FOR PERSONS WITH DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM-FAIR MARKET RENTS AND... Elderly or Handicapped, and Special Allocations Projects § 888.315 Restrictions on retroactive payments...

  19. Removing the Restrictions Imposed on Finite State Machines ...

    African Journals Online (AJOL)

    This study determines an effective method of removing the fixed and finite state amount of memory that restricts finite state machines from carrying out compilation jobs that require larger amount of memory. The study is ... The conclusion reviewed the various steps followed and made projections for further reading. Keyword: ...

  20. Restrictive partially blind signature for resource-constrained information systems

    NARCIS (Netherlands)

    Qiu, Weidong; Gong, Zheng; Liu, Bozhong; Long, Yu; Chen, Kefei

    2010-01-01

    Restrictive partially blind signature, which is designed for privacy oriented information systems, allows a user to obtain a blind signature from a signer whilst the blind message must obey some certain rules. In order to reduce storage and communication costs, several public-key cryptosystems are

  1. 15 CFR 2008.15 - General restrictions on access.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false General restrictions on access. 2008.15 Section 2008.15 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE REGULATIONS TO IMPLEMENT E.O. 12065; OFFICE OF THE UNITED...

  2. Calvin's Restrictions on Interest : Guidelines for the Credit Crisis

    NARCIS (Netherlands)

    Graafland, J.J.

    2009-01-01

    Calvin’s view on the legitimacy of interest has had a great impact on the economic development of Western society. Although Calvin took a fundamentally positive attitude to interest, he also proposed several restrictions on the charging of interest. In this article, we investigate the relevance of

  3. The reno-protective effects of dietary caloric restriction against ...

    African Journals Online (AJOL)

    Studies have shown that dietary caloric restriction (CR) without malnutrition can increase longevity. This study aims to evaluate the protective effects of CR on oxidative stress, lipid peroxidation and inflammatory cytokines in the kidney of streptozotocin-induced diabetic rats. Forty 12-week old male Wistar rats, weighing ...

  4. 7 CFR 57.800 - Identification of restricted eggs.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Identification of restricted eggs. 57.800 Section 57... AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing the Inspection of Eggs...

  5. Guiding IEP Teams on Meeting the Least Restrictive Environment Mandate

    Science.gov (United States)

    Marx, Teri A.; Hart, Jennifer L.; Nelson, Leslie; Love, Jessica; Baxter, Christine M.; Gartin, Barbara; Schaefer Whitby, Peggy J.

    2014-01-01

    Two diametrically opposed beliefs are held concerning the meaning of the least restrictive environment (LRE) when determining the class placements of students with disabilities. One group adheres to the placement philosophy that the LRE is always the general education setting. The other group believes that the LRE is where the students' needs may…

  6. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  7. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery

    DEFF Research Database (Denmark)

    Mazer, C David; Whitlock, Richard P; Fergusson, Dean A

    2017-01-01

    BACKGROUND: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a E...

  8. 7 CFR 982.41 - Free and restricted percentages.

    Science.gov (United States)

    2010-01-01

    ... percentages in effect at the end of the previous marketing year shall be applicable. [51 FR 29548, Aug. 19... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... WASHINGTON Order Regulating Handling Marketing Policy § 982.41 Free and restricted percentages. The free and...

  9. Data Input and Content Exploration in Scenarios with Restrictions

    NARCIS (Netherlands)

    D.C. Pedrosa

    2014-01-01

    htmlabstractAs technology evolves, new devices and interaction techniques are developed. These transformations create several challenges in terms of usability and user experience. Our research faces some challenges for data input or content exploration in scenarios with restrictions. It is not our

  10. A topological insight into restricted Boltzmann machines (extented abstract)

    NARCIS (Netherlands)

    Mocanu, D.C.; Mocanu, E.; Nguyen, H.P.; Gibescu, M.; Liotta, A.

    2016-01-01

    Restricted Boltzmann Machines (RBMs) and models derived from them have been successfully used as basic building blocks in deep neural networks for automatic features extraction, unsupervised weights initialization, but also as standalone models for density estimation, activity recognition and so on.

  11. The non-isospectral AKNS hierarchy with reality conditions restriction

    International Nuclear Information System (INIS)

    Zhou Lingjun

    2008-01-01

    In this paper, we will prove the existence of the non-isospectral AKNS hierarchy with reality conditions restriction and construct the matrix form Darboux transformation. Using this Darboux transformation, the solutions of the relevant nonlinear equations can be expressed explicitly

  12. 77 FR 65840 - Chrysanthemum White Rust Regulatory Status and Restrictions

    Science.gov (United States)

    2012-10-31

    ... Regulatory Status and Restrictions AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Advance... for our advance notice of proposed rulemaking that solicits public comment on whether and how we... importation of plant material that is a host of CWR. This action will allow interested persons additional time...

  13. Evaluation of Feeding Torerance in Intrauterine Growth Restricted Preterm Infants

    NARCIS (Netherlands)

    Bozzetti, V.

    2016-01-01

    Intra Uterine Growth Restriction (IUGR) is an important and common problem in obstetrics. The purpose of the present thesis was to investigate: 1. Feeding issues in IUGR preterm infants; 2. Clinical and strumental parameters as predictors of feeding tolerance in IUGR preterm infants; 3. Splanchnic

  14. Deep Restricted Kernel Machines Using Conjugate Feature Duality.

    Science.gov (United States)

    Suykens, Johan A K

    2017-08-01

    The aim of this letter is to propose a theory of deep restricted kernel machines offering new foundations for deep learning with kernel machines. From the viewpoint of deep learning, it is partially related to restricted Boltzmann machines, which are characterized by visible and hidden units in a bipartite graph without hidden-to-hidden connections and deep learning extensions as deep belief networks and deep Boltzmann machines. From the viewpoint of kernel machines, it includes least squares support vector machines for classification and regression, kernel principal component analysis (PCA), matrix singular value decomposition, and Parzen-type models. A key element is to first characterize these kernel machines in terms of so-called conjugate feature duality, yielding a representation with visible and hidden units. It is shown how this is related to the energy form in restricted Boltzmann machines, with continuous variables in a nonprobabilistic setting. In this new framework of so-called restricted kernel machine (RKM) representations, the dual variables correspond to hidden features. Deep RKM are obtained by coupling the RKMs. The method is illustrated for deep RKM, consisting of three levels with a least squares support vector machine regression level and two kernel PCA levels. In its primal form also deep feedforward neural networks can be trained within this framework.

  15. Consensus Based Definition of Growth Restriction in the Newborn.

    Science.gov (United States)

    Beune, Irene M; Bloomfield, Frank H; Ganzevoort, Wessel; Embleton, Nicholas D; Rozance, Paul J; van Wassenaer-Leemhuis, Aleid G; Wynia, Klaske; Gordijn, Sanne J

    2018-05-01

    To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard. An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm. In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight definition for growth restriction in the newborn. This definition recognizes that infants with birth weights 10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Endogenous technology in dairy farming under environmental restrictions

    NARCIS (Netherlands)

    Peerlings, J.H.M.; Komen, M.H.C.

    2001-01-01

    In this paper an applied general equilibrium AGE model written in mixed-complementarity format is used to analyse the effects of an increase in milk quota in the Netherlands when nitrogen emissions in agriculture are restricted. The model combines the strengths of AGE models and mathematical

  17. Kamm on Inviolability and Agent-Relative Restrictions

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2009-01-01

    Abstract  Agent-relative restrictions prohibit minimizing violations: that is, they require us not to minimize the total number of their violations by violating them ourselves. Frances Kamm has explained this prohibition in terms of the moral worth of persons, which, in turn, she explains in terms...

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

    Science.gov (United States)

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

    2016-12-01

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

  19. Parental perceptions of teen driving: Restrictions, worry and influence☆

    Science.gov (United States)

    Jewett, Amy; Shults, Ruth A.; Bhat, Geeta

    2016-01-01

    Introduction Parents play a critical role in preventing crashes among teens. Research of parental perceptions and concerns regarding teen driving safety is limited. We examined results from the 2013 Summer ConsumerStyles survey that queried parents about restrictions placed on their teen drivers, their perceived level of “worry” about their teen driver’s safety, and influence of parental restrictions regarding their teen’s driving. Methods We produced frequency distributions for the number of restrictions imposed, parental “worry,” and influence of rules regarding their teen’s driving, reported by teen’s driving license status (learning to drive or obtained a driver’s license). Response categories were dichotomized because of small cell sizes, and we ran separate log-linear regression models to explore whether imposing all four restrictions on teen drivers was associated with either worry intensity (“a lot” versus “somewhat, not very much or not at all”) or perceived influence of parental rules (“a lot” versus “somewhat, not very much or not at all”). Results Among the 456 parent respondents, 80% reported having restrictions for their teen driver regarding use of safety belts, drinking and driving, cell phones, and text messaging while driving. However, among the 188 parents of licensed teens, only 9% reported having a written parent-teen driving agreement, either currently or in the past. Worrying “a lot” was reported less frequently by parents of newly licensed teens (36%) compared with parents of learning teens (61%). Conclusions and Practical Applications Parents report having rules and restrictions for their teen drivers, but only a small percentage formalize the rules and restrictions in a written parent-teen driving agreement. Parents worry less about their teen driver’s safety during the newly licensed phase, when crash risk is high as compared to the learning phase. Further research is needed into how to effectively

  20. GENETIC CONTROL OF RESTRICTION AND MODIFICATION IN ESCHERICHIA COLI1

    Science.gov (United States)

    Boyer, Herbert

    1964-01-01

    Boyer, Herbert (Yale University, New Haven, Conn.). Genetic control of restriction and modification in Escherichia coli. J. Bacteriol. 88:1652–1660. 1964.—Bacterial crosses with K-12 strains of Escherichia coli as Hfr donors (Hfr Hayes, Hfr Cavalli, and Hfr P4X-6) and B/r strains of E. coli as F− recipients were found to differ from crosses between K-12 Hfr donors and K-12 F− recipients in two ways: (i) recombinants (leu, pro, lac, and gal) did not appear at discrete time intervals but did appear simultaneously 30 min after matings were initiated, and (ii) the linkage of unselected markers to selected markers was reduced. Integration of a genetic region linked to the threonine locus of K-12 into the B/r genome resulted in a hybrid which no longer gave anomalous results in conjugation experiments. A similar region of the B strain was introduced into the K-12 strain, which then behaved as a typical B F− recipient. These observations are interpreted as the manifestation of host-controlled modification and restriction on the E. coli chromosome. This was verified by experiments on the restriction and modification of the bacteriophage lambda, F-lac, F-gal, and sex-factor, F1. It was found that the genetic region that controlled the mating responses of the K-12 and B/r strains also controlled the modification and restriction properties of these two strains. The genes responsible for the restricting and modifying properties of the K-12 and B strains of E. coli were found to be allelic, linked to each other, and linked to the threonine locus. PMID:14240953

  1. Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

    Directory of Open Access Journals (Sweden)

    Mariângela Alves Souza

    Full Text Available OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65 and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162 placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022 and dichorionic (p<0.001 twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36 or dichorionic (p=0.68 twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

  2. 10 CFR 2.903 - Protection of restricted data and national security information.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Protection of restricted data and national security... Restricted Data and/or National Security Information § 2.903 Protection of restricted data and national security information. Nothing in this subpart shall relieve any person from safeguarding Restricted Data or...

  3. 10 CFR 1045.33 - Appointment of restricted data management official.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Appointment of restricted data management official. 1045... DECLASSIFICATION Generation and Review of Documents Containing Restricted Data and Formerly Restricted Data § 1045.33 Appointment of restricted data management official. (a) Each agency with access to RD or FRD shall...

  4. 78 FR 40958 - Amendment of Restricted Areas R-2504A & R-2504B; Camp Roberts, CA, and Restricted Area R-2530...

    Science.gov (United States)

    2013-07-09

    ...-0515; Airspace Docket No. 13-AWP-8] RIN 2120-AA66 Amendment of Restricted Areas R-2504A & R-2504B; Camp Roberts, CA, and Restricted Area R-2530; Sierra Army Depot, CA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends the descriptions of restricted areas R...

  5. Unaccompanied adolescents seeking asylum - Poorer mental health under a restrictive reception : poorer mental health under a restrictive reception

    NARCIS (Netherlands)

    Reijneveld, S.A.; de Boer, J.B.; Bean, T.; Korfker, D.G.

    2005-01-01

    We assessed the effects of a stringent reception policy on the mental health of unaccompanied adolescent asylum seekers by comparing the mental health of adolescents in a restricted campus reception setting and in a setting offering more autonomy (numbers [response rates]: 69 [93%] and 53 [69%],

  6. Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout

    Directory of Open Access Journals (Sweden)

    Birkedal Rikke

    2009-12-01

    Full Text Available Abstract Background Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss, which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20°C in the absence and presence of creatine. Results Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria. Conclusions The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that

  7. Avoidant restrictive food intake disorder: an illustrative case example.

    Science.gov (United States)

    Bryant-Waugh, Rachel

    2013-07-01

    Avoidant/restrictive food intake disorder (ARFID) is a new diagnostic category in DSM-5. Although replacing Feeding Disorder of Infancy or Early Childhood, it is not restricted to childhood presentations. In keeping with the broader aim of revising and updating criteria and text to better reflect lifespan issues and clinical expression across the age range, ARFID is a diagnosis relevant to children, adolescents, and adults. This case example of a 13-year old boy with ARFID illustrates key issues in diagnosis and treatment planning. The issues discussed are not exhaustive, but serve as a guide for central diagnostic and treatment issues to be considered by the clinician. It is anticipated that the inclusion of specific criteria for ARFID as a category within Feeding and Eating Disorders in DSM-5 will stimulate research into its typology, prevalence, and incidence in different populations and facilitate the development of effective, evidence-based interventions for this patient group. Copyright © 2013 Wiley Periodicals, Inc.

  8. Focusing and restricting: two aspects of motivational selectivity in adulthood.

    Science.gov (United States)

    Riediger, Michaela; Freund, Alexandra M

    2006-03-01

    Using a short-term longitudinal design, the authors investigated implications of 2 facets of motivational selectivity--restricting (to few goals) and focusing (on central and similar goals)--for goal-pursuit investment. Participants were 20-69 years old (Time 1, N = 177; Time 2, N = 160). Results show that motivational selectivity in terms of focusing (but not in terms of restricting) is associated with an enhanced involvement in goal pursuit (assessed 3 months later), irrespective of age. Structural equation models demonstrated that this association is completely mediated by the degree of mutual facilitation among goals. Furthermore, motivational selectivity increases from middle to older adulthood. This contributes to the maintenance of high goal involvement into later adulthood, despite aging-related increases in resource limitations. ((c) 2006 APA, all rights reserved).

  9. Performance of a New Restricted Biased Estimator in Logistic Regression

    Directory of Open Access Journals (Sweden)

    Yasin ASAR

    2017-12-01

    Full Text Available It is known that the variance of the maximum likelihood estimator (MLE inflates when the explanatory variables are correlated. This situation is called the multicollinearity problem. As a result, the estimations of the model may not be trustful. Therefore, this paper introduces a new restricted estimator (RLTE that may be applied to get rid of the multicollinearity when the parameters lie in some linear subspace  in logistic regression. The mean squared errors (MSE and the matrix mean squared errors (MMSE of the estimators considered in this paper are given. A Monte Carlo experiment is designed to evaluate the performances of the proposed estimator, the restricted MLE (RMLE, MLE and Liu-type estimator (LTE. The criterion of performance is chosen to be MSE. Moreover, a real data example is presented. According to the results, proposed estimator has better performance than MLE, RMLE and LTE.

  10. Evaluating the economic cost of natural gas strategic storage restrictions

    International Nuclear Information System (INIS)

    Ejarque, Joao Miguel

    2011-01-01

    The European Commission wants to implement a single market for gas. One of the components of this market is a regulated provision for ''security of supply'' which consists of rules for the implementation and use of a given reserve stock of gas. We investigate the impact of this policy on the profitability of a storage operator, using data from Denmark and Italy. Keeping storage capacity constant, the costs of the strategic stock are around 20% of the value of the storage market for Denmark, and 16% for Italy. This cost is due to the inability to extract arbitrage profits from the captive stock. Furthermore, the strategic storage restriction induces behavior that would virtually never be replicated by a private storage operator in an unconstrained market, in particular in the first 6 months of the year when unconstrained firms empty their reservoirs much faster, suggesting the strategic restriction is unnecessarily distorting the market. (author)

  11. Endocrine responses to water restriction in desert sheep

    International Nuclear Information System (INIS)

    Ahmed, Muna M.M.

    1994-01-01

    For ruminants grazing in semi-arid areas, the maintenance of balanced water and energy metabolism is challenging to productivity.The metabolic effects of water restriction usually stimulate endocrine which control metabolic activity depending on the thermal environment.Radioimmunoasay technique was used to determine the level of endocrine hormones, namely thyroid stimulating hormone(TSH),thyroxine(T4) and cortisol in desert sheep.Intermittent watering every 24h, 48h and 72h increased TSH level during the morning but decreased it during the afternoon.T4 level decreased during both morning and afternoon.The cortisol level was depressed by water restriction during the morning and afternoon but showed an overlapping pattern with that of the control during the afternoon. (Author)

  12. Circumvention of MHC class II restriction by genetic immunization.

    Science.gov (United States)

    Schuler, K; Lu, C; Chang, H D; Croft, M; Zanetti, M; Gerloni, M

    2001-11-12

    The fate of T cell responses to peptide-based vaccination is subject to constraints by the major histocompatibility complex (MHC), MHC restriction. Using as a model system of T and B cell epitopes from the circumsporozoite protein of Plasmodium falciparum malaria parasite, we show that vaccination by somatic transgene immunization readily primes Balb/c mice (H-2(d)) a strain previously reported to be non-responder to immunization with a synthetic peptide vaccine encompassing these epitopes. Following genetic vaccination Balb/c mice developed a primary T cell response comparable to that of the responder strain C57Bl/6 (H-2(b)). Following booster immunization on day 45 Balb/c mice responded with a typical T cell memory response. Priming induced the formation of specific antibodies, which rose sharply after booster immunization. These findings suggests that genetic immunization can circumvent MHC class II restriction.

  13. Generating families in the restricted three-body problem

    CERN Document Server

    Hénon, Michel

    The classical restricted three-body problem is of fundamental importance because of its applications in astronomy and space navigation, and also as a simple model of a non-integrable Hamiltonian dynamical system. A central role is played by periodic orbits, of which many have been computed numerically. This is the second volume of an attempt to explain and organize the material through a systematic study of generating families, the limits of families of periodic orbits when the mass ratio of the two main bodies becomes vanishingly small. We use quantitative analysis in the vicinity of bifurcations of types 1 and 2. In most cases the junctions between branches can now be determined. A first-order approximation of families of periodic orbits in the vicinity of a bifurcation is also obtained. This book is intended for scientists and students interested in the restricted problem, in its applications to astronomy and space research, and in the theory of dynamical systems.

  14. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai

    2015-01-01

    OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions. DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: Cochrane central register of controlled...... differences with 95% confidence intervals. RESULTS: 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean...... were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion...

  15. Restricting oral fluid and food intake during labour.

    Science.gov (United States)

    Singata, Mandisa; Tranmer, Joan; Gyte, Gillian M L

    2013-08-22

    Restricting fluids and foods during labour is common practice across many birth settings with some women only being allowed sips of water or ice chips. Restriction of oral intake may be unpleasant for some women, and may adversely influence their experience of labour. To determine the benefits and harms of oral fluid or food restriction during labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013) and reference lists of retrieved studies. Randomised controlled trials (RCTs) and quasi-RCTs of restricting fluids and food for women in labour compared with women free to eat and drink. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We identified 19 studies of which we included five, involving 3130 women. We excluded eight studies, one awaits classification and five are ongoing studies. All the included studies looked at women in active labour and at low risk of potentially requiring a general anaesthetic. One study looked at complete restriction versus giving women the freedom to eat and drink at will; two studies looked at water only versus giving women specific fluids and foods and two studies looked at water only versus giving women carbohydrate drinks.When comparing any restriction of fluids and food versus women given some nutrition in labour, the meta-analysis was dominated by one study undertaken in a highly medicalised environment. There were no statistically significant differences identified in: caesarean section (average risk ratio (RR) 0.89, 95% confidence interval (CI) 0.63 to 1.25, five studies, 3103 women), operative vaginal births (average RR 0.98, 95% CI 0.88 to 1.10, five studies, 3103 women) and Apgar scores less than seven at five minutes (average RR 1.43, 95% CI 0.77 to 2.68, four studies, 2902 infants), nor in any of the other outcomes assessed. Women's views were not assessed. The pooled data were insufficient to assess the

  16. Control of wheeled mobile robot in restricted environment

    Science.gov (United States)

    Ali, Mohammed A. H.; En, Chang Yong

    2018-03-01

    This paper presents a simulation and practical control system for wheeled mobile robot in restricted environment. A wheeled mobile robot with 3 wheels is fabricated and controlled by proportional derivative active force control (PD-AFC) to move in a pre-planned restricted environment to maintain the tracking errors at zero level. A control system with two loops, outer by PD controller and inner loop by Active Force Control, are designed to control the wheeled mobile robot. Fuzzy logic controller is implemented in the Active force Control to estimate the inertia matrix that will be used to calculate the actual torque applied on the wheeled mobile robot. The mobile robot is tested in two different trajectories, namely are circular and straight path. The actual path and desired path are compared.

  17. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai

    2015-01-01

    OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions. DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: Cochrane central register of controlled...... trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials....... TRIAL SELECTION: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size. DATA EXTRACTION: Two authors independently screened...

  18. DOE Land Disposal Restrictions strategy report for radioactive mixed waste

    International Nuclear Information System (INIS)

    1989-09-01

    This report is based on preliminary information available at the time of the Land Disposal Restrictions (LDR) Strategy Workshop in June 1989, and the critical review of the workshop data conducted by the Office Of Defense Programs and the affected Operations Offices in July and August 1989. The purpose of the workshop and this subsequent report is to identify the magnitude and scope of LDR issues and impacts regarding the storage, treatment, and disposal of RMW, and to suggest potential strategies for addressing LDR requirements. This report was prepared under the overall direction and coordination of the Department of Energy (DOE) Headquarters Environmental Guidance Division, RCRA/CERCLA Unit (EH-231). The report is a product of the LDR Strategy Workshop held during the month of June 1989. The workshop was divided into two work groups: a Land Disposal Restriction compliance strategy group and a RMW Best Demonstrated Available Technology and National Capacity Variance group

  19. Restrictive extraocular myopathy: A presenting feature of acromegaly

    Directory of Open Access Journals (Sweden)

    Steven Heireman

    2011-01-01

    Full Text Available A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

  20. Growth assessment in diagnosis of Fetal Growth Restriction. Review.

    Science.gov (United States)

    Albu, A R; Horhoianu, I A; Dumitrascu, M C; Horhoianu, V

    2014-06-15

    The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories.

  1. Work-hour restrictions as an ethical dilemma for residents.

    Science.gov (United States)

    Carpenter, Robert O; Austin, Mary T; Tarpley, John L; Griffin, Marie R; Lomis, Kimberly D

    2006-04-01

    We propose that the standardized work-hour limitations have created an ethical dilemma for residents. A survey tool was designed to assess factors that influence the number of hours residents work and report. The program directors of pediatrics, internal medicine, and general surgery at our institution supported their residents' participation. A voluntary, anonymous survey of these residents was performed. One hundred seventy of 265 eligible residents were surveyed. Eighty-one percent of residents surveyed responded. Eighty percent of respondents reported exceeding work-hour restrictions at least once within the past 6 months. The factor of greatest influence measured was concern for patient care (80%). Forty-nine percent of respondents admitted underreporting their work hours. The Accreditation Council for Graduate Medical Education work-hour restrictions have created an ethical dilemma for residents. Our data show that a significant number of residents feel compelled to exceed work-hour regulations and report those hours falsely.

  2. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

    Science.gov (United States)

    Longo, Valter D.; Panda, Satchidananda

    2016-01-01

    Summary Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily fasting period to last >12 h, thus imparting pleiotropic benefits in multiple organisms. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMD, both basic science and translational research are warranted to develop fasting-associated interventions into effective and inexpensive treatments with the potential to improve healthspan. PMID:27304506

  3. Strong dietary restrictions protect Drosophila against anoxia/reoxygenation injuries.

    Directory of Open Access Journals (Sweden)

    Paul Vigne

    Full Text Available Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2 for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside, an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling

  4. Effect of restriction of working memory on reported paranormal belief.

    Science.gov (United States)

    Dudley, R T

    1999-02-01

    56 college students completed Tobacyk's 1988 Revised Paranormal Belief Scale and Watson, Clark, and Tellegen's 1988 Positive and Negative Affect Scale. Experimental group participants, but not control group participants, rehearsed a five-digit number while completing the Paranormal Belief Scale. Analysis showed higher reported paranormal belief for experimental group participants but no differences on the Positive and Negative Affect Scale. Results are discussed in terms of the effect of restriction in working memory on the critical evaluation of paranormal phenomena.

  5. Ad libitum and restricted day and night sleep architecture.

    Science.gov (United States)

    Korompeli, Anna St; Muurlink, Olav; Gavala, Alexandra; Myrianthefs, Pavlos; Fildissis, Georgios; Baltopoulos, Georgios

    2016-01-01

    This study represents a first controlled comparison of restricted versus unrestricted sleep in both day and night sleep categories. A repeated measures study of a homogenous group of young women without sleep disorders (n=14) found that stage 1, 2, 3 and REM sleep, as well as sleep latency were not statistically different between day ad libitum sleep (DAL) and day interrupted (DI) sleep categories, while night interrupted (NI) and ad libitum (NAL) sleep showed strikingly different architecture.

  6. Restrictions of process machine retooling at machine-building enterprises

    OpenAIRE

    Kuznetsova Elena; Tipner Ludmila; Ershov Alexey

    2017-01-01

    The competitiveness of the national economy depends on the technological level of the machine-building enterprises production equipment. Today in Russia there are objective and subjective restrictions for the optimum policy formation of the manufacturing equipment renewal. The analysis of the manufacturing equipment age structure dynamics in the Russian machine-building complex indicates the negative tendencies intensification: increase in the equipment service life, reduction in the share of...

  7. Entry Restrictions, Corruption and Extortion in the Context of Transition

    OpenAIRE

    Inna Cabelkova

    2001-01-01

    This paper argues that even temporary barriers to entry present at the very beginning of transition may lead to permanent extortion development. Entry restrictions, if binding, lead to excess profits, which create an incentive to extort. The emergence of extortionists reduces the expected profit from production, making producers expect extortion in the future. If, after this adaptation of expectations, the government removes the barriers to entry, only a few new firms will enter the market. H...

  8. Effects of the restriction of hand gestures on disfluency.

    OpenAIRE

    Finlayson, Sheena; Forrest, Victoria; Lickley, Robin; Beck, Janet M

    2003-01-01

    This paper describes an experimental pilot study of disfluency and gesture rates in spontaneous speech where speakers perform a communication task in three conditions: hands free, one arm immobilized, both arms immobilized. Previous work suggests that the restriction of the ability to gesture can have an impact on the fluency of speech. In particular, it has been found that the inability to produce iconic gestures, which depict actions and objects, results in a higher rate of disfluency. Mode...

  9. Restrictions on running IRC (Internet Relay Chat) at CERN

    CERN Multimedia

    2005-01-01

    Due to the large number of computer security incidents at CERN where intruders have used IRC (Internet Relay Chat) software to control computers, IRC connections will be blocked in the CERN firewall from 1st February 2005. Personal use of IRC software is not permitted at CERN. Further details of the restrictions on both personal and professional use of IRC are documented at http://cern.ch/security/IRC.

  10. Smartphone Restriction and its Effect on Subjective Withdrawal Related Scores

    OpenAIRE

    Aarestad, Sarah Helene; Eide, Tine Almenning

    2017-01-01

    Smartphone overuse is associated with a number of negative consequences for the individual and the environment. In the right end of the distribution of smartphone usage, concepts such as smartphone addiction seem warranted. An area that so far lacks research concerns the effect of smartphone restriction generally and specifically on subjective withdrawal related scores across different degrees of smartphone usage. The present study examined withdrawal related scores on the Smartphone Withdraw...

  11. Inherited thrombophilia in pregnant women with intrauterine growth restriction.

    Science.gov (United States)

    Coriu, Letitia; Copaciu, Elena; Tulbure, Dan; Talmaci, Rodica; Secara, Diana; Coriu, Daniel; Cirstoiu, Monica

    2014-12-01

    Intrauterine growth restriction (IUGR) is a major cause of fetal morbidity and mortality during pregnancy. The role of mutation in the factor V gene, prothrombin gene, MTHFR gene, as risk factors for intrauterine growth restriction during pregnancy, is not very well known so far. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: intrauterine growth restriction, preeclampsia, recurrent pregnancy loss or maternal venous thromboembolism, who were admitted in Bucharest Emergency University Hospital, during the period January 2010 to July 2014. Genetic testing was performed for all the cases to detect: factor V Leiden mutation, G20210A mutation in the prothrombin gene, C677T mutation and A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. Blood samples were obtained as soon as the diagnosis of intrauterine growth restriction was established with ultrasonography. The following gene mutations were associated with increased risk of IUGR: G20210A prothrombin gene mutation (OR 4.81, 95% CI 1.05 - 2.22, p= 0.043), G1691A factor V gene mutation (factor V Leiden) (OR 1.58, 95% CI 0.61 - 4.080, p= 0.347), C677T MTHFR gene mutation (OR 1.61, 95% CI 0.79 to 3.26, p= 0.186), compound heterozygous MTHFR C677T and A1298C (OR 1.66, 95% CI 0.81- 3.42, p= 0.169). Particularly, for G20210A prothrombin gene mutation we found statistically significant risk (p≤0.05) of IUGR.

  12. Growth assessment in diagnosis of Fetal Growth Restriction. Review

    OpenAIRE

    Albu, AR; Horhoianu, IA; Dumitrascu, MC; Horhoianu, V

    2014-01-01

    Abstract The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the t...

  13. A database for compliance with land disposal restrictions

    International Nuclear Information System (INIS)

    McCoy, M.W.

    1990-09-01

    The new restrictions on land disposal introduce additional challenges to hazardous waste managers. Laboratory waste streams consisting of small volumes of diverse waste types will be particularly difficult to manage due to the large number of possible treatment standards that could be applied. To help remedy this management problem, a user-friendly database has been developed to provide the regulatory information required for each of the hazardous wastes present in the wastes stream of a large research laboratory. 3 figs., 1 tab

  14. Restricted access: aboriginal women and health care in Canada

    OpenAIRE

    Falcon-Borduas, Amelie

    2010-01-01

    Restricted Access: Aboriginal Women and Health Care in Canada” addresses the barriers faced by indigenous women when accessing health care services in Canada. Using the distinction of practical (or needs-based) and strategic (or equity-based) barriers, it highlights the impact of physical isolation, cultural differences, and socio-economic disparities when using health services. However, the emphasis is placed on strategic challenges and more specifically on the impact of marginalization fro...

  15. Restrictions on SU(5) as a grand unified theory

    International Nuclear Information System (INIS)

    Shellard, R.C.

    1984-01-01

    Some restrictions imposed upon Grand Unified Theories by dynamical symetry breakdown are examined. They are shown that, in particular, theories SU(5) as symmetry group, with 3 or more fermion families undergo dynamical symmetry breakdown, and some of the fermions will acquire mass at the Grand Unified scale. On the other hand, the SO(10) group, with 3 families is free from this problem. (Author) [pt

  16. Essays on Currency Competition, Institutional Restrictions and Exchange Rates

    OpenAIRE

    Bhattacharya, Arghya

    2017-01-01

    This dissertation consists of three essays on currency competition, institutional restrictions and exchange rates. When faced with currency competition, a country's government has two tools at its disposal: reduce the level of inflation or place institutional barriers to the use of foreign currency. In the first chapter, I propose a two-country, two-currency New Monetarist model to study currency competition. I model institutional barriers as a `tax' on the real value of foreign currency hol...

  17. RESTRICTING PESTICIDE USE: THE IMPACT ON PROFITABILITY BY FARM SIZE

    OpenAIRE

    Whittaker, Gerald W.; Lin, Biing-Hwan; Vasavada, Utpal

    1995-01-01

    A sample of 226 cash grain farms in the Lake States-Corn Belt region are analyzed to estimate the impact of restricting pesticide use on profits. These 226 farms are classified into small medium, and large farms according to their sale revenues. The results suggest the existence of pest management practices that could substantially reduce pesticide use without incurring economic losses. The reductions in profit associated with gradual reduction in pesticide expenditure appear to increase with...

  18. Model of adipose tissue cellularity dynamics during food restriction.

    Science.gov (United States)

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-07

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Dietary restriction alters fine motor function in rats.

    Science.gov (United States)

    Smith, Lori K; Metz, Gerlinde A

    2005-08-07

    A number of standard behavioral tasks in animal research utilize food rewards for positive reinforcement. In order to enhance the motivation to participate in these tasks, animals are usually placed on a restricted diet. While dietary restriction (DR) has been shown to have beneficial effects on recovery after brain injury, life span and aging processes, it might also represent a stressor. Since stress can influence a broad range of behaviors, the purpose of this study was to assess whether DR may have similar effects on skilled movement. Adult male Long-Evans rats were trained and tested in a skilled reaching task both prior to and during a mild food restriction regimen that maintained their body weights at 90-95% of baseline weight for eight days. The observations revealed that DR decreased reaching success and increased the number of attempts to grasp a single food pellet. The animals appeared to be more frantic when attempting to reach for food pellets, and the time taken to reach for 20 pellets decreased following the onset of DR. A second experiment investigating behaviors that do not require food rewards, including a ladder rung walking task and an open field test, confirmed that rats on DR display deficits in skilled movements and are hyperactive. These findings suggest that results obtained in motor tasks using food rewards need to be interpreted with caution. The findings are discussed with respect to stress associated with DR.

  20. Hypotrochoids in conformal restriction systems and Virasoro descendants

    International Nuclear Information System (INIS)

    Doyon, Benjamin

    2013-01-01

    A conformal restriction system is a commutative, associative, unital algebra equipped with a representation of the groupoid of univalent conformal maps on connected open sets of the Riemann sphere, along with a family of linear functionals on subalgebras, satisfying a set of properties including conformal invariance and a type of restriction. This embodies some expected properties of expectation values in conformal loop ensembles CLE κ (at least for 8/3 iθ and w. We find that it has an expansion in positive powers of u and u-bar , and that the coefficients of pure u ( u-bar ) powers are holomorphic in w ( w-bar ). We identify these coefficients (the ‘hypotrochoid fields’) with certain Virasoro descendants of the identity field in conformal field theory, thereby showing that they form part of a vertex operator algebraic structure. This largely generalizes works by the author (in CLE), and the author with his collaborators Riva and Cardy (in SLE 8/3 and other restriction measures), where the case of the ellipse, at the order u 2 , led to the stress–energy tensor of CFT. The derivation uses in an essential way the Virasoro vertex operator algebra structure of conformal derivatives established recently by the author. The results suggest in particular the exact evaluation of CLE expectations of products of hypotrochoid fields as well as nontrivial relations amongst them through the vertex operator algebra, and further shed light onto the relationship between CLE and CFT. (paper)

  1. BARRIER MARKET RESTRICTIONS, THEIR ECONOMIC NATURE AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    Maksimova Ekaterina Yurievna

    2018-02-01

    Full Text Available Subject: indicators of modern economic growth in construction, published by the government agencies, reflect individual directions of growth. At the same time, the analysis of the reasons for the unachieved results is conducted by various researchers primarily from the standpoint of the inadequacy of economic and other resources. This article deals with the problem of ensuring the growth of construction enterprises from the viewpoint of systemic barriers, and in this regard, these barriers are defined as the subject of the present research. Research objectives: studying the concept of barrier market restrictions, their impact on the activities of construction companies. Materials and methods: statistical data in the field of housing construction, provided by the Ministry of Construction of the Russian Federation and Rosstat, is examined to solve the given tasks set. The content of state programs and activities of state institutions in the field of support and development of construction activities is considered. Based on investigations of sustainable economic development, an understanding of the constraints and incentives for development is revealed. Results: we have identified the content of barrier market restrictions, which are not possible to overcome only by involving additional economic resources in the turnover. The ways of confronting these restrictions are shown. Conclusions: it was shown that implementation of promising activities is impossible without overcoming various systemic constraints. Their structure is described in sufficient detail. Principles of economic sustainable development are proposed. It was proved that the reserve system can serve as an effective way to overcome market barriers.

  2. Hanford land disposal restrictions plan for mixed wastes

    International Nuclear Information System (INIS)

    1990-10-01

    Since the early 1940s, the Hanford Site has been involved in the production and purification of nuclear defense materials. These production activities have resulted in the generation of large quantities of liquid and solid radioactive mixed waste. This waste is subject to regulation under authority of both the Resource Conservation and Recovery Act of 1976 (RCRA) and the Atomic Energy Act. The State of Washington Department of Ecology (Ecology), the US Environmental Protection Agency (EPA), and the US Department of Energy (DOE) have entered into an agreement, the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) to bring Hanford Site Operations into compliance with dangerous waste regulations. The Tri-Party Agreement was amended to require development of the Hanford Land Disposal Restrictions Plan for Mixed Wastes (this plan) to comply with land disposal restrictions requirements for radioactive mixed waste. The Tri-Party Agreement requires, and the this plan provides, the following sections: Waste Characterization Plan, Storage Report, Treatment Report, Treatment Plan, Waste Minimization Plan, a schedule, depicting the events necessary to achieve full compliance with land disposal restriction requirements, and a process for establishing interim milestones. 34 refs., 28 figs., 35 tabs

  3. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Francine Einstein

    2010-01-01

    Full Text Available Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  4. Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

    Science.gov (United States)

    Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.

    2010-01-01

    Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

  5. Comprehensive tobacco marketing restrictions: promotion, packaging, price and place.

    Science.gov (United States)

    Henriksen, Lisa

    2012-03-01

    Evidence of the causal role of marketing in the tobacco epidemic and the advent of the WHO Framework Convention on Tobacco Control have inspired more than half the countries in the world to ban some forms of tobacco marketing. This paper briefly describes the ways in which cigarette marketing is restricted and the tobacco industry's efforts to subvert restrictions. It reviews what is known about the impact of marketing regulations on smoking by adults and adolescents. It also addresses what little is known about the impact of marketing bans in relation to concurrent population-level interventions, such as price controls, anti-tobacco media campaigns and smoke-free laws. Point of sale is the least regulated channel and research is needed to address the immediate and long-term consequences of policies to ban retail advertising and pack displays. Comprehensive marketing restrictions require a global ban on all forms of promotion, elimination of packaging and price as marketing tools, and limitations on the quantity, type and location of tobacco retailers.

  6. Aging, neurogenesis, and caloric restriction in different model organisms.

    Science.gov (United States)

    Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

    2013-08-01

    Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

  7. Waste management and the land disposal restriction storage prohibition

    International Nuclear Information System (INIS)

    1992-05-01

    RCRA Sect. 3004(j) prohibits storage of wastes that have been prohibited from land disposal, unless that storage is for the purpose of accumulating sufficient quantities of hazardous wastes to facilitate proper recovery, treatment, or disposal. This requirement was incorporated as part of the Land Disposal Restriction (LDR) regulations. Under the LDR storage prohibition, facilities may only store restricted wastes in containers and tanks. As stated in the Third LDR rule, storage of prohibited waste is only allowed in non-land based storage units since land-based storage is a form of disposal. The EPA has recognized that generators and storers of radioactive mixed waste (RMW) may find it impossible to comply with storage prohibition in cases where no available treatment capacity exists. Additionally, under the current regulatory interpretation, there is no provision that would allow for storage of wastes for which treatment capacity and capability are not available, even where capacity is legitimately being developed. Under the LDR program, restricted wastes that are disposed of, or placed into storage before an LDR effective date, are not subject to the LDR requirements. However, if such wastes are removed from a storage or disposal site after the effective date, such wastes would be subject to LDR requirements. The purpose of this information brief is to clarify what waste management practices constitute removal from storage

  8. Weak values in a classical theory with an epistemic restriction

    International Nuclear Information System (INIS)

    Karanjai, Angela; Cavalcanti, Eric G; Bartlett, Stephen D; Rudolph, Terry

    2015-01-01

    Weak measurement of a quantum system followed by postselection based on a subsequent strong measurement gives rise to a quantity called the weak value: a complex number for which the interpretation has long been debated. We analyse the procedure of weak measurement and postselection, and the interpretation of the associated weak value, using a theory of classical mechanics supplemented by an epistemic restriction that is known to be operationally equivalent to a subtheory of quantum mechanics. Both the real and imaginary components of the weak value appear as phase space displacements in the postselected expectation values of the measurement device's position and momentum distributions, and we recover the same displacements as in the quantum case by studying the corresponding evolution in our theory of classical mechanics with an epistemic restriction. By using this epistemically restricted theory, we gain insight into the appearance of the weak value as a result of the statistical effects of post selection, and this provides us with an operational interpretation of the weak value, both its real and imaginary parts. We find that the imaginary part of the weak value is a measure of how much postselection biases the mean phase space distribution for a given amount of measurement disturbance. All such biases proportional to the imaginary part of the weak value vanish in the limit where disturbance due to measurement goes to zero. Our analysis also offers intuitive insight into how measurement disturbance can be minimized and the limits of weak measurement. (paper)

  9. Better understanding flow-restricted environments from hideout return analyses

    International Nuclear Information System (INIS)

    Ollar, Ph.; Viricel-Honorez, L.

    1998-01-01

    Understanding and controlling the chemical phenomena in flow-restricted areas of the secondary side of steam generators (SG) is a key point in fighting against corrosion (IGA) in these areas. Hence, more than 150 hideout returns from French plants are used to assess the chemical environment in flow-restricted areas. The influence of several parameters such as tube support plates design, SG blowdown flowrate and temperature at the end of hideout returns, on returned weights and on flow-restricted environments predicted by modelling are examined. A correlation between different operating and returned chemistry indexes (molar ratios), and IGA is sought: no link is found between IGA and Na/Cl molar ratio at the beginning of hideout returns. However, as IGA extends, the returned weights of sodium and chloride seem to decrease, suggesting a greater hideout and a lower hideout return efficiency, perhaps due to SG fouling, and/or a smaller hideout/hideout return thanks to an improved operating chemistry. Using the pH computed from hideout return data as an index for the presence of IGA is also studied: no correlation is found between the two. Improving plants chemistry is finally proposed, based on an optimization of hideout returns. (authors)

  10. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults

    Directory of Open Access Journals (Sweden)

    Mariana G. Figueiro

    2012-01-01

    Full Text Available Acute and chronic sleep restrictions cause a reduction in leptin and an increase in ghrelin, both of which are associated with hunger. Given that light/dark patterns are closely tied to sleep/wake patterns, we compared, in a within-subjects study, the impact of morning light exposures (60 lux of 633-nm [red], 532-nm [green], or 475-nm [blue] lights to dim light exposures on leptin and ghrelin concentrations after subjects experienced 5 consecutive days of both an 8-hour (baseline and a 5-hour sleep-restricted schedule. In morning dim light, 5-hour sleep restriction significantly reduced leptin concentrations compared to the baseline, 8-hour sleep/dim-light condition (1,32 = 2.9; =0.007. Compared to the 5-hour sleep/dim-light condition, the red, green, and blue morning light exposures significantly increased leptin concentrations (1,32 = 5.7; <0.0001, 1,32 = 3.6; =0.001, and 1,32 = 3.0; =0.005, resp.. Morning red light and green light exposures significantly decreased ghrelin concentrations (1,32 = 3.3; <0.003 and 1,32 = 2.2; =0.04, resp., but morning blue light exposures did not. This study is the first to demonstrate that morning light can modulate leptin and ghrelin concentrations, which could have an impact on reducing hunger that accompanies sleep deprivation.

  11. Hanford land disposal restrictions plan for mixed wastes

    Energy Technology Data Exchange (ETDEWEB)

    1990-10-01

    Since the early 1940s, the Hanford Site has been involved in the production and purification of nuclear defense materials. These production activities have resulted in the generation of large quantities of liquid and solid radioactive mixed waste. This waste is subject to regulation under authority of both the Resource Conservation and Recovery Act of 1976 (RCRA) and the Atomic Energy Act. The State of Washington Department of Ecology (Ecology), the US Environmental Protection Agency (EPA), and the US Department of Energy (DOE) have entered into an agreement, the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) to bring Hanford Site Operations into compliance with dangerous waste regulations. The Tri-Party Agreement was amended to require development of the Hanford Land Disposal Restrictions Plan for Mixed Wastes (this plan) to comply with land disposal restrictions requirements for radioactive mixed waste. The Tri-Party Agreement requires, and the this plan provides, the following sections: Waste Characterization Plan, Storage Report, Treatment Report, Treatment Plan, Waste Minimization Plan, a schedule, depicting the events necessary to achieve full compliance with land disposal restriction requirements, and a process for establishing interim milestones. 34 refs., 28 figs., 35 tabs.

  12. Comprehensive tobacco marketing restrictions: promotion, packaging, price and place

    Science.gov (United States)

    Henriksen, Lisa

    2014-01-01

    Evidence of the causal role of marketing in the tobacco epidemic and the advent of the WHO Framework Convention on Tobacco Control have inspired more than half the countries in the world to ban some forms of tobacco marketing. This paper briefly describes the ways in which cigarette marketing is restricted and the tobacco industry's efforts to subvert restrictions. It reviews what is known about the impact of marketing regulations on smoking by adults and adolescents. It also addresses what little is known about the impact of marketing bans in relation to concurrent population-level interventions, such as price controls, anti-tobacco media campaigns and smoke-free laws. Point of sale is the least regulated channel and research is needed to address the immediate and long-term consequences of policies to ban retail advertising and pack displays. Comprehensive marketing restrictions require a global ban on all forms of promotion, elimination of packaging and price as marketing tools, and limitations on the quantity, type and location of tobacco retailers. PMID:22345238

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

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

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

  14. The influence of food restriction on the small bowel: Does intensive short‑term food restriction lead to weight loss?

    Czech Academy of Sciences Publication Activity Database

    Makovický, Peter; Tůmová, E.; Volek, Z.; Makovický, P.; Arnone, J.M.; Švecová, Ivana; Samasca, G.

    2017-01-01

    Roč. 118, č. 6 (2017), s. 361-365 ISSN 0006-9248 R&D Projects: GA MŠk(CZ) LM2015040; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : experimental medicine * food restriction * rabbit * slimming * small bowel weight loss Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Pathology Impact factor: 0.667, year: 2016

  15. Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

    Science.gov (United States)

    Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

    2014-01-01

    Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

  16. Restriction enzyme body doubles and PCR cloning: on the general use of type IIs restriction enzymes for cloning.

    Science.gov (United States)

    Tóth, Eszter; Huszár, Krisztina; Bencsura, Petra; Kulcsár, Péter István; Vodicska, Barbara; Nyeste, Antal; Welker, Zsombor; Tóth, Szilvia; Welker, Ervin

    2014-01-01

    The procedure described here allows the cloning of PCR fragments containing a recognition site of the restriction endonuclease (Type IIP) used for cloning in the sequence of the insert. A Type IIS endonuclease--a Body Double of the Type IIP enzyme--is used to generate the same protruding palindrome. Thus, the insert can be cloned to the Type IIP site of the vector without digesting the PCR product with the same Type IIP enzyme. We achieve this by incorporating the recognition site of a Type IIS restriction enzyme that cleaves the DNA outside of its recognition site in the PCR primer in such a way that the cutting positions straddle the desired overhang sequence. Digestion of the PCR product by the Body Double generates the required overhang. Hitherto the use of Type IIS restriction enzymes in cloning reactions has only been used for special applications, the approach presented here makes Type IIS enzymes as useful as Type IIP enzymes for general cloning purposes. To assist in finding Body Double enzymes, we summarised the available Type IIS enzymes which are potentially useful for Body Double cloning and created an online program (http://group.szbk.u-szeged.hu/welkergr/body_double/index.html) for the selection of suitable Body Double enzymes and the design of the appropriate primers.

  17. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

    Science.gov (United States)

    Volek, Jeff S; Feinman, Richard D

    2005-11-16

    Metabolic Syndrome (MetS) represents a constellation of markers that indicates a predisposition to diabetes, cardiovascular disease and other pathologic states. The definition and treatment are a matter of current debate and there is not general agreement on a precise definition or, to some extent, whether the designation provides more information than the individual components. We consider here five indicators that are central to most definitions and we provide evidence from the literature that these are precisely the symptoms that respond to reduction in dietary carbohydrate (CHO). Carbohydrate restriction is one of several strategies for reducing body mass but even in the absence of weight loss or in comparison with low fat alternatives, CHO restriction is effective at ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG), low HDL and high blood pressure. In addition, low fat, high CHO diets have long been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen glycemic control. Thus, whereas there are numerous strategies for weight loss, a patient with high BMI and high TAG is likely to benefit most from a regimen that reduces CHO intake. Reviewing the literature, benefits of CHO restriction are seen in normal or overweight individuals, in normal patients who meet the criteria for MetS or in patients with frank diabetes. Moreover, in low fat studies that ameliorate LDL and total cholesterol, controls may do better on the symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful phenomenon and may, in fact, be operationally defined as the set of markers that responds to CHO restriction. Insofar as this is an accurate characterization it is likely the result of the effect of dietary CHO on insulin metabolism. Glucose is the major insulin secretagogue and insulin resistance has been tied to the hyperinsulinemic state or the effect of such a state on lipid metabolism. The conclusion is probably not

  18. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2005-11-01

    Full Text Available Abstract Metabolic Syndrome (MetS represents a constellation of markers that indicates a predisposition to diabetes, cardiovascular disease and other pathologic states. The definition and treatment are a matter of current debate and there is not general agreement on a precise definition or, to some extent, whether the designation provides more information than the individual components. We consider here five indicators that are central to most definitions and we provide evidence from the literature that these are precisely the symptoms that respond to reduction in dietary carbohydrate (CHO. Carbohydrate restriction is one of several strategies for reducing body mass but even in the absence of weight loss or in comparison with low fat alternatives, CHO restriction is effective at ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG, low HDL and high blood pressure. In addition, low fat, high CHO diets have long been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen glycemic control. Thus, whereas there are numerous strategies for weight loss, a patient with high BMI and high TAG is likely to benefit most from a regimen that reduces CHO intake. Reviewing the literature, benefits of CHO restriction are seen in normal or overweight individuals, in normal patients who meet the criteria for MetS or in patients with frank diabetes. Moreover, in low fat studies that ameliorate LDL and total cholesterol, controls may do better on the symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful phenomenon and may, in fact, be operationally defined as the set of markers that responds to CHO restriction. Insofar as this is an accurate characterization it is likely the result of the effect of dietary CHO on insulin metabolism. Glucose is the major insulin secretagogue and insulin resistance has been tied to the hyperinsulinemic state or the effect of such a state on lipid metabolism. The

  19. Sex selection and restricting abortion and sex determination.

    Science.gov (United States)

    Zilberberg, Julie

    2007-11-01

    Sex selection in India and China is fostered by a limiting social structure that disallows women from performing the roles that men perform, and relegates women to a lower status level. Individual parents and individual families benefit concretely from having a son born into the family, while society, and girls and women as a group, are harmed by the widespread practice of sex selection. Sex selection reinforces oppression of women and girls. Sex selection is best addressed by ameliorating the situations of women and girls, increasing their autonomy, and elevating their status in society. One might argue that restricting or prohibiting abortion, prohibiting sex selection, and prohibiting sex determination would eliminate sex selective abortion. But this decreases women's autonomy rather than increases it. Such practices will turn underground. Sex selective infanticide, and slower death by long term neglect, could increase. If abortion is restricted, the burden is placed on women seeking abortions to show that they have a legally acceptable or legitimate reason for a desired abortion, and this seriously limits women's autonomy. Instead of restricting abortion, banning sex selection, and sex determination, it is better to address the practice of sex selection by elevating the status of women and empowering women so that giving birth to a girl is a real and positive option, instead of a detriment to the parents and family as it is currently. But, if a ban on sex selective abortion or a ban on sex determination is indeed instituted, then wider social change promoting women's status in society should be instituted simultaneously.

  20. Calorie restriction increases cigarette use in adult smokers.

    Science.gov (United States)

    Cheskin, Lawrence J; Hess, Judith M; Henningfield, Jack; Gorelick, David A

    2005-05-01

    Cigarette smokers weigh less than nonsmokers, and smokers often gain weight when they quit. This is a major barrier to smoking cessation, especially among women. However, strict dieting is not recommended during smoking cessation out of concern that it might promote relapse. This concern derives, in part, from the observation that calorie restriction increases self-administration of drugs of abuse in animals. This relationship has never been experimentally demonstrated in humans. To evaluate whether calorie restriction increases cigarette smoking in humans. Seventeen (nine males, eight females) healthy, normal-weight smokers not attempting to quit were cycled in partially counterbalanced order, double-blind, through four diets-normal calorie (2,000-2,800 kcal/day), low calorie (700 kcal/day deficit), low-carbohydrate (CHO)/normal-calorie, and low-CHO/low-calorie-for 6 days per diet in an inpatient research ward. Smoking was assessed by cigarette counts, breath carbon monoxide (CO) levels, and cigarette craving. Compared with the normal-calorie diet, while on the low-calorie diet, subjects smoked 8% more cigarettes (Plow-CHO/normal-calorie diet showed no significant effect on either variable, but there was a 15% increase in breath CO levels (Plow-CHO/low-calorie diet. There were no changes in self-reported cigarette craving or mood. Consistent with animal studies, moderate calorie restriction was associated with a small but statistically significant increase in cigarette smoking, with no independent effect of CHO deprivation. These findings suggest that dieting may increase smoking behavior and could impede smoking-cessation attempts.