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Sample records for nuclear envelope remodeling

  1. Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

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    Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

    2016-04-22

    Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

  2. Plant nuclear envelope proteins.

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    Rose, Annkatrin; Patel, Shalaka; Meier, Iris

    2004-01-01

    Compared to research in the animal field, the plant NE has been clearly under-investigated. The available data so far indicate similarities as well as striking differences that raise interesting questions about the function and evolution of the NE in different kingdoms. Despite a seemingly similar structure and organization of the NE, many of the proteins that are integral components of the animal NE appear to lack homologues in plant cells. The sequencing of the Arabidopsis genome has not led to the identification of homologues of animal NE components, but has indicated that the plant NE must have a distinct protein composition different from that found in metazoan cells. Besides providing a selective barrier between the nucleoplasm and the cytoplasm, the plant NE functions as a scaffold for chromatin but the scaffolding components are not identical to those found in animal cells. The NE comprises an MTOC in higher plant cells, a striking difference to the organization of microtubule nucleation in other eukaryotic cells. Nuclear pores are present in the plant NE, but identifiable orthologues of most animal and yeast nucleoporins are presently lacking. The transport pathway through the nuclear pores via the action of karyopherins and the Ran cycle is conserved in plant cells. Interestingly, RanGAP is sequestered to the NE in plant cells and animal cells, yet the targeting domains and mechanisms of attachment are different between the two kingdoms. At present, only a few proteins localized at the plant NE have been identified molecularly. Future research will have to expand the list of known protein components involved in building a functional plant NE.

  3. Function of nuclear membrane proteins in shaping the nuclear envelope integrity during closed mitosis.

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    Yang, Hui-Ju; Iwamoto, Masaaki; Hiraoka, Yasushi; Haraguchi, Tokuko

    2017-06-01

    The nuclear envelope (NE) not only protects the genome from being directly accessed by detrimental agents but also regulates genome organization. Breaches in NE integrity threaten genome stability and impede cellular function. Nonetheless, the NE constantly remodels, and NE integrity is endangered in dividing or differentiating cells. Specifically, in unicellular eukaryotes undergoing closed mitosis, the NE expands instead of breaking down during chromosome segregation. The newly assembling nuclear pore complexes (NPCs) penetrate the existing NE in interphase. A peculiar example of NE remodelling during nuclear differentiation in Tetrahymena involves formation of the redundant NE and clustered NPCs. Even under these conditions, the NE remains intact. Many recent studies on unicellular organisms have revealed that nuclear membrane proteins, such as LEM-domain proteins, play a role in maintaining NE integrity. This review summarizes and discusses how nuclear membrane proteins participate in NE integrity. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  4. Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope

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    Vahbiz Jokhi

    2013-04-01

    Full Text Available A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP granules exit the nucleus is by budding through the nuclear envelope (NE. This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown. Here, we identify Torsin, an AAA-ATPase that in humans is linked to dystonia, as a major mediator of primary megaRNP envelopment during NE budding. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the messenger RNAs contained within fail to reach synaptic sites, preventing normal synaptic protein synthesis and thus proper synaptic bouton development. These studies begin to establish the cellular machinery underlying the exit of megaRNPs via budding, offer an explanation for the “nuclear blebbing” phenotype found in dystonia models, and provide an important link between Torsin and the synaptic phenotypes observed in dystonia.

  5. Relation between nuclear envelope and nuclear lamina in nuclear assembly in vitro

    Institute of Scientific and Technical Information of China (English)

    蔡树涛; 翟中和

    1997-01-01

    Xenopus laevis egg extracts cell-free nuclear assembly system was used as an experimental model to study the process of nuclear lamina assembly in nuclear reconstitution in vitro. The experimental results showed that lamin was involved in the nuclear assembly in vitro. The assembly of nuclear lamina was preceded by the assembly of nuclear matrix, and probably, inner nuclear matrix assembly provided the basis for nuclear lamina assembly. Inhibition of normal assembly of nuclear lamina, by preincubating egg extracts cell-free system with anti-lamin antibodies, resulted in abnormal assembly of nuclear envelope, suggesting that nuclear envelope assembly is closely associated with nuclear lamina assembly.

  6. Variability of mammalian liver nuclear-envelope preparations.

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    Agutter, P S; Gleed, C D

    1980-10-15

    The composition, density and enzymic activities of sheep liver nuclear-envelope preparations were found to vary markedly according to the concentrations of nuclei during the lysis stage. The effect of nuclear concentration on the properties of the purified envelopes could not be attributed to bound Mg2+ or to other ions, and appeared to result from some component of the nucleus which was not eluted during lysis. The implications of these findings for studies on the nuclear envelope are discussed.

  7. Nuclear envelope remnants: fluid membranes enriched in sterols and polyphosphoinositides.

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    Marie Garnier-Lhomme

    Full Text Available BACKGROUND: The cytoplasm of eukaryotic cells is a highly dynamic compartment where membranes readily undergo fission and fusion to reorganize the cytoplasmic architecture, and to import, export and transport various cargos within the cell. The double membrane of the nuclear envelope that surrounds the nucleus, segregates the chromosomes from cytoplasm and regulates nucleocytoplasmic transport through pores. Many details of its formation are still unclear. At fertilization the sperm devoid of nuclear envelope pores enters the egg. Although most of the sperm nuclear envelope disassembles, remnants of the envelope at the acrosomal and centriolar fossae do not and are subsequently incorporated into the newly forming male pronuclear envelope. Remnants are conserved from annelid to mammalian sperm. METHODOLOGY/PRINCIPAL FINDINGS: Using lipid mass spectrometry and a new application of deuterium solid-state NMR spectroscopy we have characterized the lipid composition and membrane dynamics of the sperm nuclear envelope remnants in isolated sperm nuclei. CONCLUSIONS/SIGNIFICANCE: We report nuclear envelope remnants are relatively fluid membranes rich in sterols, devoid of sphingomyelin, and highly enriched in polyphosphoinositides and polyunsaturated phospholipids. The localization of the polybasic effector domain of MARCKS illustrates the non-nuclear aspect of the polyphosphoinositides. Based on their atypical biophysical characteristics and phospholipid composition, we suggest a possible role for nuclear envelope remnants in membrane fusion leading to nuclear envelope assembly.

  8. Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing.

    Science.gov (United States)

    Webster, Brant M; Thaller, David J; Jäger, Jens; Ochmann, Sarah E; Borah, Sapan; Lusk, C Patrick

    2016-11-15

    The integrity of the nuclear envelope barrier relies on membrane remodeling by the ESCRTs, which seal nuclear envelope holes and contribute to the quality control of nuclear pore complexes (NPCs); whether these processes are mechanistically related remains poorly defined. Here, we show that the ESCRT-II/III chimera, Chm7, is recruited to a nuclear envelope subdomain that expands upon inhibition of NPC assembly and is required for the formation of the storage of improperly assembled NPCs (SINC) compartment. Recruitment to sites of NPC assembly is mediated by its ESCRT-II domain and the LAP2-emerin-MAN1 (LEM) family of integral inner nuclear membrane proteins, Heh1 and Heh2. We establish direct binding between Heh2 and the "open" forms of both Chm7 and the ESCRT-III, Snf7, and between Chm7 and Snf7. Interestingly, Chm7 is required for the viability of yeast strains where double membrane seals have been observed over defective NPCs; deletion of CHM7 in these strains leads to a loss of nuclear compartmentalization suggesting that the sealing of defective NPCs and nuclear envelope ruptures could proceed through similar mechanisms.

  9. SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation

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    Kaufmann, Tanja; Kukolj, Eva; Brachner, Andreas; Beltzung, Etienne; Bruno, Melania; Kostrhon, Sebastian; Opravil, Susanne; Hudecz, Otto; Mechtler, Karl; Warren, Graham

    2016-01-01

    ABSTRACT Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases and progeria. Here, we show that SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype to the recently identified regulator of nuclear envelope reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly. The function of SIRT2 therefore extends beyond the regulation of microtubules to include the regulation of nuclear envelope dynamics. PMID:27875273

  10. Structural plasticity of the nuclear envelope and the endoplasmic reticulum

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    Sheval E. V.

    2014-09-01

    Full Text Available The nuclear envelope is a double membrane structure, continuous with endoplasmic reticulum, and the morphological organization of both these structures is quite conservative. However, nuclear envelope and endoplasmic reticulum demonstrate distinct structural plasticity, i. e., based on common organization, cells may form various non-canonical membrane structures that are observed only in specialized types of cells or appear in different pathologies. In this review, we will discuss the mechanisms of the biogenesis of such non-canonical structures, and the possible role of this plasticity in the development of pathological processes.

  11. The dynamic nature of the nuclear envelope: lessons from closed mitosis.

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    Arnone, James T; Walters, Alison D; Cohen-Fix, Orna

    2013-01-01

    In eukaryotes, chromosomes are encased by a dynamic nuclear envelope. In contrast to metazoans, where the nuclear envelope disassembles during mitosis, many fungi including budding yeast undergo "closed mitosis," where the nuclear envelope remains intact throughout the cell cycle. Consequently, during closed mitosis the nuclear envelope must expand to accommodate chromosome segregation to the two daughter cells. A recent study by Witkin et al. in budding yeast showed that if progression through mitosis is delayed, for example due to checkpoint activation, the nuclear envelope continues to expand despite the block to chromosome segregation. Moreover, this expansion occurs at a specific region of the nuclear envelope- adjacent to the nucleolus- forming an extension referred to as a "flare." These observations raise questions regarding the regulation of nuclear envelope expansion both in budding yeast and in higher eukaryotes, the mechanisms confining mitotic nuclear envelope expansion to a particular region and the possible consequences of failing to regulate nuclear envelope expansion during the cell cycle.

  12. Efflux of RNA from resealed nuclear envelope ghosts.

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    Prochnow, D; Thomson, M; Schröder, H C; Müller, W E; Agutter, P S

    1994-08-01

    mRNA translocation across the nuclear envelope and the appropriate signal-receptor interactions have been studied using resealed rat liver nuclear envelope ghosts (RNEG). We compared export kinetics of nonadenylated (tRNAs, histone-2 poly(A)- mRNA), and adenylated RNAs (poly(A)+ tRNAs, synthetic histone-2 poly(A) +mRNA, albumin mRNA, beta-globin poly(A) +mRNA and a total poly(A) + mRNA extract from rat liver cells). ATP-dependent export of mRNAs and of total poly(A)+ RNA was prevented by inhibitors of a nuclear envelope NTPase. All adenylated RNA species competed with each other for export, but nonadenylated RNAs did not. This indicates the existence of different translocation mechanisms for different RNA species with their appropriate nuclear envelope associated RNA receptors involved in export. The attachment of a poly(A)250 sequence at the 3'-end of tRNA or histone messenger masks the intrinsic RNA export signal of nonadenylated RNAs and results in efflux comparable to that of beta-globin poly(A)+ mRNA. The attachment on oligo(A)5 does not have any comparable effect of nonadenylated RNA translocation. Export of all polyadenylated RNAs from RNEGs is blocked by a monoclonal antibody, which is directed against an intranuclear envelope poly(A) binding protein. The results suggest that the pore complexes do not select RNAs for export to the cytoplasm and are therefore not responsible for nuclear restriction of mRNA precursors.

  13. A novel family of plant nuclear envelope-associated proteins.

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    Pawar, Vidya; Poulet, Axel; Détourné, Gwénaëlle; Tatout, Christophe; Vanrobays, Emmanuel; Evans, David E; Graumann, Katja

    2016-10-01

    This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. The epigenetics of nuclear envelope organization and disease

    Energy Technology Data Exchange (ETDEWEB)

    Schirmer, Eric C. [Wellcome Trust Centre for Cell Biology, University of Edinburgh, Kings Buildings, Michael Swann Building, Room 5.22, Edinburgh EH9 3JR (United Kingdom)], E-mail: e.schirmer@ed.ac.uk

    2008-12-01

    Mammalian chromosomes and some specific genes have non-random positions within the nucleus that are tissue-specific and heritable. Work in many organisms has shown that genes at the nuclear periphery tend to be inactive and altering their partitioning to the interior results in their activation. Proteins of the nuclear envelope can recruit chromatin with specific epigenetic marks and can also recruit silencing factors that add new epigenetic modifications to chromatin sequestered at the periphery. Together these findings indicate that the nuclear envelope is a significant epigenetic regulator. The importance of this function is emphasized by observations of aberrant distribution of peripheral heterochromatin in several human diseases linked to mutations in NE proteins. These debilitating inherited diseases range from muscular dystrophies to the premature aging progeroid syndromes and the heterochromatin changes are just one early clue for understanding the molecular details of how they work. The architecture of the nuclear envelope provides a unique environment for epigenetic regulation and as such a great deal of research will be required before we can ascertain the full range of its contributions to epigenetics.

  15. Role of ooplasm in nuclear and nucleolar remodeling of intergeneric somatic cell nuclear transfer embryos during the first cell cycle

    DEFF Research Database (Denmark)

    Østrup, Olga; Strejcek, Frantisek; Petrovicova, Ida

    2011-01-01

    Initially, development of the zygote is under control of the oocyte ooplasm. However, it is presently unknown if and to what extent is the ooplasm able to interact with a transferred somatic cell from another species in the context of interspecies somatic cell nuclear transfer (SCNT). Here, one-cell...... intergeneric SCNT embryos were compared to their parthenogenetic counterparts to assess the effects of the introduced somatic cell. Despite the absence of morphological remodeling (premature chromatin condensation, nuclear envelope breakdown), reconstructed embryos showed nuclear and nucleolar precursor body...... (NPB) morphology similar to the host ooplasm, which, together with detected posttranslational activity of somatic cell introduced into the bovine ooplasm, suggests a universal function of ooplasmic factors. However, the lack of distinct UBF localization in intergeneric embryos indicates failures...

  16. A Single Herpesvirus Protein Can Mediate Vesicle Formation in the Nuclear Envelope*

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    Lorenz, Michael; Vollmer, Benjamin; Unsay, Joseph D.; Klupp, Barbara G.; García-Sáez, Ana J.; Mettenleiter, Thomas C.; Antonin, Wolfram

    2015-01-01

    Herpesviruses assemble capsids in the nucleus and egress by unconventional vesicle-mediated trafficking through the nuclear envelope. Capsids bud at the inner nuclear membrane into the nuclear envelope lumen. The resulting intralumenal vesicles fuse with the outer nuclear membrane, delivering the capsids to the cytoplasm. Two viral proteins are required for vesicle formation, the tail-anchored pUL34 and its soluble interactor, pUL31. Whether cellular proteins are involved is unclear. Using giant unilamellar vesicles, we show that pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is required for pUL31 membrane recruitment but not for membrane remodeling. pUL31 can inwardly deform membranes by oligomerizing on their inner surface to form buds that constrict to vesicles. Therefore, a single viral protein can mediate all events necessary for membrane budding and abscission. PMID:25605719

  17. Nucleolar remodeling in nuclear transfer embryos

    DEFF Research Database (Denmark)

    Laurincik, Jozef; Maddox-Hyttel, Poul

    2007-01-01

    the developmental potential of embryos originating from varied nuclear transfer protocols. In bovine in vivo developed embryos, functional ribosome-synthesizing nucleoli become structurally distinct toward the end of the 4th post-fertilization cell cycle. In embryonic cell nuclear transfer embryos, fully developed...... nucleoli are not apparent until the 5th cell cycle, whereas in somatic cell nuclear transfer embryos the functional nucleoli emerge already during the 3rd cell cycle. Intergeneric reconstructed embryos produced by the fusion of bovine differentiated somatic cell to a nonactivated ovine cytoplast fail...... is completed toward the end of the 4th cell cycle. A substantial proportion of bovine embryos produced by nuclear transfer of embryonic or somatic cells to bovine ooplasts display aberrations in protein localization in one or more blastomers. This information is indicative of underlying aberrations in genomic...

  18. Nucleolar remodeling in nuclear transfer embryos

    DEFF Research Database (Denmark)

    Laurincik, Jozef; Maddox-Hyttel, Poul

    2007-01-01

    nucleoli are not apparent until the 5th cell cycle, whereas in somatic cell nuclear transfer embryos the functional nucleoli emerge already during the 3rd cell cycle. Intergeneric reconstructed embryos produced by the fusion of bovine differentiated somatic cell to a nonactivated ovine cytoplast fail...... the developmental potential of embryos originating from varied nuclear transfer protocols. In bovine in vivo developed embryos, functional ribosome-synthesizing nucleoli become structurally distinct toward the end of the 4th post-fertilization cell cycle. In embryonic cell nuclear transfer embryos, fully developed...... is completed toward the end of the 4th cell cycle. A substantial proportion of bovine embryos produced by nuclear transfer of embryonic or somatic cells to bovine ooplasts display aberrations in protein localization in one or more blastomers. This information is indicative of underlying aberrations in genomic...

  19. Nucleolar remodeling in nuclear transfer embryos

    DEFF Research Database (Denmark)

    Laurincik, Jozef; Maddox-Hyttel, Poul

    2007-01-01

    nucleoli are not apparent until the 5th cell cycle, whereas in somatic cell nuclear transfer embryos the functional nucleoli emerge already during the 3rd cell cycle. Intergeneric reconstructed embryos produced by the fusion of bovine differentiated somatic cell to a nonactivated ovine cytoplast fail...... the developmental potential of embryos originating from varied nuclear transfer protocols. In bovine in vivo developed embryos, functional ribosome-synthesizing nucleoli become structurally distinct toward the end of the 4th post-fertilization cell cycle. In embryonic cell nuclear transfer embryos, fully developed...... is completed toward the end of the 4th cell cycle. A substantial proportion of bovine embryos produced by nuclear transfer of embryonic or somatic cells to bovine ooplasts display aberrations in protein localization in one or more blastomers. This information is indicative of underlying aberrations in genomic...

  20. Nuclear envelope rupture and repair during cancer cell migration

    Science.gov (United States)

    Denais, Celine M.; Gilbert, Rachel M.; Isermann, Philipp; McGregor, Alexandra L.; te Lindert, Mariska; Weigelin, Bettina; Davidson, Patricia M.; Friedl, Peter; Wolf, Katarina; Lammerding, Jan

    2016-01-01

    During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, requiring extensive deformation of the cell and its nucleus. Here, we investigated tumor cell migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport-III (ESCRT-III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content, requiring efficient NE and DNA damage repair for survival. PMID:27013428

  1. Ribonucleic acid stimulation of mammalian liver nuclear-envelope nucleoside triphosphatase. A possible enzymic marker for the nuclear envelope.

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    Agutter, P S; Harris, J R; Stevenson, I

    1977-03-15

    1. The specific activity of rat and pig liver nuclear-envelope nucleoside triphosphatase (EC 3.6.1.3) decreases when the system is depleted of RNA. The activity can be restored by adding high concentrations of yeast RNA to the assay medium. 2. Exogenous RNA also increases the activity of the enzyme in control envelopes (not RNA-depleted). The effect appears to be largely specific for poly(A) and poly(G); it is not stimulated by rRNA or tRNA preparations, ribonuclease-hydrolysed RNA, AMP, or double- or single-stranded DNA. 3. Inhibitors of the enzyme, in concentrations at which half-maximal inhibition of the enzyme is achieved, do not affect the percentage stimulation of the enzyme by yeast RNA. 4. The simulation is abolished by the inclusion of 150 mM-KCl or -NaCl in the assay medium, but not by increasing the assay pH to 8.5. 5. The results are discussed in the light of the possible role of the nucleoside triphosphatase in vivo in nucleo-cytoplasmic ribonucleoprotein translocation. 6. It is proposed that poly(G)-stimulated Mg2+-activated adenosine triphosphatase activity should be adopted as an enzymic marker for the nuclear envelope.

  2. The Use of Polyacrylamide Hydrogels to Study the Effects of Matrix Stiffness on Nuclear Envelope Properties.

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    Minaisah, Rose-Marie; Cox, Susan; Warren, Derek T

    2016-01-01

    Matrix-derived mechanical cues influence cell proliferation, motility, and differentiation. Recent findings clearly demonstrate that the nuclear envelope (NE) adapts and remodels in response to mechanical signals, including matrix stiffness, yet a plethora of studies have been performed on tissue culture plastic or glass that have a similar stiffness to cortical bone. Using methods that allow modulation of matrix stiffness will provide further insight into the role of the NE in physiological conditions and the impact of changes in stiffness observed during ageing and disease on cellular function. In this chapter, we describe the polyacrylamide hydrogel system, which allows fabrication of hydrogels with variable stiffness to better mimic the environment experienced by cells in most tissues of the body.

  3. Cytosol-dependent membrane fusion in ER, nuclear envelope and nuclear pore assembly: biological implications.

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    Rafikova, Elvira R; Melikov, Kamran; Chernomordik, Leonid V

    2010-01-01

    Endoplasmic reticulum and nuclear envelope rearrangements after mitosis are often studied in the reconstitution system based on Xenopus egg extract. In our recent work we partially replaced the membrane vesicles in the reconstitution mix with protein-free liposomes to explore the relative contributions of cytosolic and transmembrane proteins. Here we discuss our finding that cytosolic proteins mediate fusion between membranes lacking functional transmembrane proteins and the role of membrane fusion in endoplasmic reticulum and nuclear envelope reorganization. Cytosol-dependent liposome fusion has allowed us to restore, without adding transmembrane nucleoporins, functionality of nuclear pores, their spatial distribution and chromatin decondensation in nuclei formed at insufficient amounts of membrane material and characterized by only partial decondensation of chromatin and lack of nuclear transport. Both the mechanisms and the biological implications of the discovered coupling between spatial distribution of nuclear pores, chromatin decondensation and nuclear transport are discussed.

  4. Properties of mammalian nuclear-envelope nucleoside triphosphatase.

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    Agutter, P S; Cockrill, J B; Lavine, J E; McCaldin, B; Sim, R B

    1979-09-01

    The nucleoside triphosphatase activities of the nuclear envelopes from rat liver, pig liver and simian-virus-40-transformed mouse-embryo 3T3 cells were shown to exhibit similar parperties. All three preparations hydrolyse ATP, 2'-dATP, 3'-dATP, GTP, CTP and UTP in the presence of Mg2+, Ca2+, Mn2+ and Co2+ with a pH optimum of 8.0, are sensitive to inhibition by mercurials, arsenicals, quercetin, proflavin and adenosine 5'-[gamma-thio]triphosphate and are partially inactivated by exposure to high ionic strength. The kinetic behaviour is similar for all substrates irrespective of the source of material. The typical Eadie-Hofstee plot, which is concave upwards at pH 8.0 when the ionic strength is 20mM, becomes linear when the pH is increased to 8.5 or the ionic strength to 160mM. The overall evidence, particularly the labelling of only one polypeptide by [gamma-32P]ATP, suggests that under the conditions of preparation and assay used only one class of nucleoside triphosphatase active sites is detectable in nuclear envelopes. The importance of these results for an understanding of the role of the enzyme in vivo is discussed.

  5. NET23/STING promotes chromatin compaction from the nuclear envelope.

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    Poonam Malik

    Full Text Available Changes in the peripheral distribution and amount of condensed chromatin are observed in a number of diseases linked to mutations in the lamin A protein of the nuclear envelope. We postulated that lamin A interactions with nuclear envelope transmembrane proteins (NETs that affect chromatin structure might be altered in these diseases and so screened thirty-one NETs for those that promote chromatin compaction as determined by an increase in the number of chromatin clusters of high pixel intensity. One of these, NET23 (also called STING, MITA, MPYS, ERIS, Tmem173, strongly promoted chromatin compaction. A correlation between chromatin compaction and endogenous levels of NET23/STING was observed for a number of human cell lines, suggesting that NET23/STING may contribute generally to chromatin condensation. NET23/STING has separately been found to be involved in innate immune response signaling. Upon infection cells make a choice to either apoptose or to alter chromatin architecture to support focused expression of interferon genes and other response factors. We postulate that the chromatin compaction induced by NET23/STING may contribute to this choice because the cells expressing NET23/STING eventually apoptose, but the chromatin compaction effect is separate from this as the condensation was still observed when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced compacted chromatin revealed changes in epigenetic marks including changes in histone methylation and acetylation. This indicates a previously uncharacterized nuclear role for NET23/STING potentially in both innate immune signaling and general chromatin architecture.

  6. Microtubules as key coordinators of nuclear envelope and endoplasmic reticulum dynamics during mitosis.

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    Schlaitz, Anne-Lore

    2014-07-01

    During mitosis, cells comprehensively restructure their interior to promote the faithful inheritance of DNA and cytoplasmic contents. In metazoans, this restructuring entails disassembly of the nuclear envelope, redistribution of its components into the endoplasmic reticulum (ER) and eventually nuclear envelope reassembly around the segregated chromosomes. The microtubule cytoskeleton has recently emerged as a critical regulator of mitotic nuclear envelope and ER dynamics. Microtubules and associated molecular motors tear open the nuclear envelope in prophase and remove nuclear envelope remnants from chromatin. Additionally, two distinct mechanisms of microtubule-based regulation of ER dynamics operate later in mitosis. First, association of the ER with microtubules is reduced, preventing invasion of ER into the spindle area, and second, organelle membrane is actively cleared from metaphase chromosomes. However, we are only beginning to understand the role of microtubules in shaping and distributing ER and other organelles during mitosis. © 2014 WILEY Periodicals, Inc.

  7. Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope.

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    Otsuka, Shotaro; Bui, Khanh Huy; Schorb, Martin; Hossain, M Julius; Politi, Antonio Z; Koch, Birgit; Eltsov, Mikhail; Beck, Martin; Ellenberg, Jan

    2016-09-15

    The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the nuclear envelope. How the NPC assembles into this double membrane boundary has remained enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence microscopy revealed the molecular maturation of the intermediates, which initially contained the nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament component Nup358. EM particle averaging showed that the evagination base was surrounded by an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroom-shaped density was continuously associated with the deforming membrane. Quantitative structural analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of the INM.

  8. Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly.

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    Webster, Micah; Witkin, Keren L; Cohen-Fix, Orna

    2009-05-15

    The nucleus is one of the most prominent cellular organelles, yet surprisingly little is known about how it is formed, what determines its shape and what defines its size. As the nuclear envelope (NE) disassembles in each and every cell cycle in metazoans, the process of rebuilding the nucleus is crucial for proper development and cell proliferation. In this Commentary, we summarize what is known about the regulation of nuclear shape and size, and highlight recent findings that shed light on the process of building a nucleus, including new discoveries related to NE assembly and the relationship between the NE and the endoplasmic reticulum (ER). Throughout our discussion, we note interesting aspects of nuclear structure that have yet to be resolved. Finally, we present an idea - which we refer to as ;the limited flat membrane hypothesis' - to explain the formation of a single nucleus that encompasses of all of the cell's chromosomes following mitosis.

  9. Early localization of NPA58, a rat nuclear pore-associated protein, to the reforming nuclear envelope during mitosis

    Indian Academy of Sciences (India)

    Radhika Ganeshan; Nandini Rangaraj; Veena K Parnaik

    2001-03-01

    We have studied the mitotic reassembly of the nuclear envelope, using antibodies to nuclear marker proteins and NPA58 in F-111 rat fibroblast cells. In earlier studies we have proposed that NPA58, a 58 kDa rat nuclear protein, is involved in nuclear protein import. In this report, NPA58 is shown to be localized on the cytoplasmic face of the envelope in interphase cells, in close association with nuclear pores. In mitotic cells NPA58 is dispersed in the cytoplasm till anaphase. The targeting of NPA58 to the reforming nuclear envelope in early telophase coincides with the recruitment of a well-characterized class of nuclear pore proteins recognized by the antibody mAb 414, and occurs prior to the incorporation of lamin B1 into the envelope. Significant protein import activity is detectable only after localization of NPA58 in the newly-formed envelope. The early targeting of NPA58 is consistent with its proposed role in nuclear transport.

  10. Effect of donor cell type on nuclear remodelling in rabbit somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Tian, J; Song, J; Li, H; Yang, D; Li, X; Ouyang, H; Lai, L

    2012-08-01

    Cloned rabbits have been produced for many years by somatic cell nuclear transfer (SCNT). The efficiency of cloning by SCNT, however, has remained extremely low. Most cloned embryos degenerate in utero, and the few that develop to term show a high incidence of post-natal death and abnormalities. The cell type used for donor nuclei is an important factor in nuclear transfer (NT). As reported previously, NT embryos reconstructed with fresh cumulus cells (CC-embryos) have better developmental potential than those reconstructed with foetal fibroblasts (FF-embryos) in vivo and in vitro. The reason for this disparity in developmental capacity is still unknown. In this study, we compared active demethylation levels and morphological changes between the nuclei of CC-embryos and FF-embryos shortly after activation. Anti-5-methylcytosine immunofluorescence of in vivo-fertilized and cloned rabbit embryos revealed that there was no detectable active demethylation in rabbit zygotes or NT-embryos derived from either fibroblasts or CC. In the process of nuclear remodelling, however, the proportion of nuclei with abnormal appearance in FF-embryos was significantly higher than that in CC-embryos during the first cell cycle. Our study demonstrates that the nuclear remodelling abnormality of cloned rabbit embryos may be one important factor for the disparity in developmental success between CC-embryos and FF-embryos.

  11. Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins.

    Science.gov (United States)

    Maric, Martina; Haugo, Alison C; Dauer, William; Johnson, David; Roller, Richard J

    2014-07-01

    Herpesvirus infection reorganizes components of the nuclear lamina usually without loss of integrity of the nuclear membranes. We report that wild-type HSV infection can cause dissolution of the nuclear envelope in transformed mouse embryonic fibroblasts that do not express torsinA. Nuclear envelope breakdown is accompanied by an eight-fold inhibition of virus replication. Breakdown of the membrane is much more limited during infection with viruses that lack the gB and gH genes, suggesting that breakdown involves factors that promote fusion at the nuclear membrane. Nuclear envelope breakdown is also inhibited during infection with virus that does not express UL34, but is enhanced when the US3 gene is deleted, suggesting that envelope breakdown may be enhanced by nuclear lamina disruption. Nuclear envelope breakdown cannot compensate for deletion of the UL34 gene suggesting that mixing of nuclear and cytoplasmic contents is insufficient to bypass loss of the normal nuclear egress pathway.

  12. The microtubule aster formation and its role in nuclear envelope assembly around the sperm chromatin in Xenopus egg extracts

    Institute of Scientific and Technical Information of China (English)

    YANG Ning; CHEN Zhongcai; LU Ping; ZHANG Chuanmao; ZHAI Zhonghe; TANG Xiaowei

    2003-01-01

    Nuclear envelope is a dynamic structure in the cell cycle. At the beginning of mitosis, nuclear envelope breaks down and its components disperse into the cytoplasm. At the end of mitosis, nuclear envelope reassembles using the dispersed components. Searching for the mechanisms of the nuclear disassembly and reassembly has for a long time been one of the key projects for cell biologists. In this report we show that microtubules take a role in the nuclear envelope assembly around the sperm chromatin in Xenopus egg extracts. Microtubule cytoskeleton has been demonstrated to take roles in the transport of intracellular membranes such as Golgi and ER vesicles. We found that the nuclear envelope assembly needs functional microtubules. At the beginning of the nuclear assembly, microtubules nucleated to form a microtubule aster around the centrosome at the base of the sperm head. Using the microtubule drug colchicine to disrupt the microtubule nucleation, nuclear envelope reassembly was seriously inhibited. If the microtubules were stabilized by taxol, another microtubule drug, the nuclear envelope reassembly was also interfered, although a significantly large aster formed around the chromatin. Based on these observations, we propose that microtubules play an important role in the nuclear envelope reassembly maybe by transporting the nuclear envelope precursors to the chromatin surfaces.

  13. Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Maric, Martina; Haugo, Alison C. [Department of Microbiology, University of Iowa, Iowa City, IA 52242 (United States); Dauer, William [Department of Neurology, University of Michigan, Ann Arbor, MI 48109 (United States); Johnson, David [Department of Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201 (United States); Roller, Richard J., E-mail: richard-roller@uiowa.edu [Department of Microbiology, University of Iowa, Iowa City, IA 52242 (United States)

    2014-07-15

    Herpesvirus infection reorganizes components of the nuclear lamina usually without loss of integrity of the nuclear membranes. We report that wild-type HSV infection can cause dissolution of the nuclear envelope in transformed mouse embryonic fibroblasts that do not express torsinA. Nuclear envelope breakdown is accompanied by an eight-fold inhibition of virus replication. Breakdown of the membrane is much more limited during infection with viruses that lack the gB and gH genes, suggesting that breakdown involves factors that promote fusion at the nuclear membrane. Nuclear envelope breakdown is also inhibited during infection with virus that does not express UL34, but is enhanced when the US3 gene is deleted, suggesting that envelope breakdown may be enhanced by nuclear lamina disruption. Nuclear envelope breakdown cannot compensate for deletion of the UL34 gene suggesting that mixing of nuclear and cytoplasmic contents is insufficient to bypass loss of the normal nuclear egress pathway. - Highlights: • We show that wild-type HSV can induce breakdown of the nuclear envelope in a specific cell system. • The viral fusion proteins gB and gH are required for induction of nuclear envelope breakdown. • Nuclear envelope breakdown cannot compensate for deletion of the HSV UL34 gene.

  14. Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis.

    Science.gov (United States)

    Porwal, Manvi; Cohen, Sarah; Snoussi, Kenza; Popa-Wagner, Ruth; Anderson, Fenja; Dugot-Senant, Nathalie; Wodrich, Harald; Dinsart, Christiane; Kleinschmidt, Jürgen A; Panté, Nelly; Kann, Michael

    2013-10-01

    Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca⁺⁺ efflux from the lumen between inner and outer nuclear membrane we found that Ca⁺⁺ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis.

  15. Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis.

    Directory of Open Access Journals (Sweden)

    Manvi Porwal

    2013-10-01

    Full Text Available Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca⁺⁺ efflux from the lumen between inner and outer nuclear membrane we found that Ca⁺⁺ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis.

  16. The isolation of nuclear envelopes. Effects of thiol-group oxidation and of calcium ions.

    Science.gov (United States)

    Comerford, S A; McLuckie, I F; Gorman, M; Scott, K A; Agutter, P S

    1985-02-15

    The effects of (a) oxidative cross-linking of protein thiol groups and (b) the presence or absence of Ca2+ ions on rat liver nuclear-envelope isolation were studied. Two envelope-isolation procedures were compared: a well characterized low-ionic-strength method and a recently developed high-ionic-strength method. The latter method seems preferable to the former in respect of lower intranuclear contamination of the envelopes, suppression of endogenous serine proteinase, and maintenance of high specific activities of envelope-associated enzymes. In both procedures, however, the presence of Ca2+ gave rise to a rapid, apparently irreversible, contamination of the envelopes by intranuclear material. This effect was half-maximal at 20 microM-Ca2+. In addition, the envelopes became contaminated with intranuclear material by a Ca2+-independent mechanism, apparently resulting from N-ethylmaleimide-sensitive intermolecular disulphide-bond formation. This oxidative process seemed to have two major kinetic components (half-life, t1/2, approx. 2 min and 10 min). In view of these findings, it is recommended that (i) for most purposes, nuclear envelopes be isolated by the newly developed high-ionic-strength procedure, (ii) irrespective of the method used, Ca2+-chelators be included in all the buffers, (iii) thiol-group oxidation be prevented or reversed during the procedure.

  17. Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application.

    Science.gov (United States)

    Qi, Ying-Xin; Yao, Qing-Ping; Huang, Kai; Shi, Qian; Zhang, Ping; Wang, Guo-Liang; Han, Yue; Bao, Han; Wang, Lu; Li, Hai-Peng; Shen, Bao-Rong; Wang, Yingxiao; Chien, Shu; Jiang, Zong-Lai

    2016-05-10

    Cyclic stretch is an important inducer of vascular smooth muscle cell (VSMC) proliferation, which is crucial in vascular remodeling during hypertension. However, the molecular mechanism remains unclear. We studied the effects of emerin and lamin A/C, two important nuclear envelope proteins, on VSMC proliferation in hypertension and the underlying mechano-mechanisms. In common carotid artery of hypertensive rats in vivo and in cultured cells subjected to high (15%) cyclic stretch in vitro, VSMC proliferation was increased significantly, and the expression of emerin and lamin A/C was repressed compared with normotensive or normal (5%) cyclic stretch controls. Using targeted siRNA to mimic the repressed expression of emerin or lamin A/C induced by 15% stretch, we found that VSMC proliferation was enhanced under static and 5%-stretch conditions. Overexpression of emerin or lamin A/C reversed VSMC proliferation induced by 15% stretch. Hence, emerin and lamin A/C play critical roles in suppressing VSMC hyperproliferation induced by hyperstretch. ChIP-on-chip and MOTIF analyses showed that the DNAs binding with emerin contain three transcription factor motifs: CCNGGA, CCMGCC, and ABTTCCG; DNAs binding with lamin A/C contain the motifs CVGGAA, GCCGCYGC, and DAAGAAA. Protein/DNA array proved that altered emerin or lamin A/C expression modulated the activation of various transcription factors. Furthermore, accelerating local expression of emerin or lamin A/C reversed cell proliferation in the carotid artery of hypertensive rats in vivo. Our findings establish the pathogenetic role of emerin and lamin A/C repression in stretch-induced VSMC proliferation and suggest mechanobiological mechanism underlying this process that involves the sequence-specific binding of emerin and lamin A/C to specific transcription factor motifs.

  18. Prm3p is a pheromone-induced peripheral nuclear envelope protein required for yeast nuclear fusion.

    Science.gov (United States)

    Shen, Shu; Tobery, Cynthia E; Rose, Mark D

    2009-05-01

    Nuclear membrane fusion is the last step in the mating pathway of the yeast Saccharomyces cerevisiae. We adapted a bioinformatics approach to identify putative pheromone-induced membrane proteins potentially required for nuclear membrane fusion. One protein, Prm3p, was found to be required for nuclear membrane fusion; disruption of PRM3 caused a strong bilateral defect, in which nuclear congression was completed but fusion did not occur. Prm3p was localized to the nuclear envelope in pheromone-responding cells, with significant colocalization with the spindle pole body in zygotes. A previous report, using a truncated protein, claimed that Prm3p is localized to the inner nuclear envelope. Based on biochemistry, immunoelectron microscopy and live cell microscopy, we find that functional Prm3p is a peripheral membrane protein exposed on the cytoplasmic face of the outer nuclear envelope. In support of this, mutations in a putative nuclear localization sequence had no effect on full-length protein function or localization. In contrast, point mutations and deletions in the highly conserved hydrophobic carboxy-terminal domain disrupted both protein function and localization. Genetic analysis, colocalization, and biochemical experiments indicate that Prm3p interacts directly with Kar5p, suggesting that nuclear membrane fusion is mediated by a protein complex.

  19. Chromatin Fractal Organization, Textural Patterns, and Circularity of Nuclear Envelope in Adrenal Zona Fasciculata Cells.

    Science.gov (United States)

    Pantic, Igor; Nesic, Dejan; Basailovic, Milos; Cetkovic, Mila; Mazic, Sanja; Suzic-Lazic, Jelena; Popevic, Martin

    2016-12-01

    Despite previous research efforts in the fields of histology and cell physiology, the relationship between chromatin structural organization and nuclear shape remains unclear. The aim of this research was to test the existence and strength of correlations between mathematical parameters of chromatin microarchitecture and roundness of the nuclear envelope. On a sample of 240 nuclei of adrenal zona fasciculata cells stained using the DNA-specific Feulgen method, we quantified fractal parameters such as fractal dimension and lacunarity, as well as textural parameters such as angular second moment (ASM), entropy, inverse difference moment, contrast, and variance. Circularity of the nuclear envelope was determined from the nuclear area and perimeter. The results indicate that there is a statistically significant negative correlation between chromatin ASM and circularity. Moreover, there was a statistically significant positive correlation between chromatin fractal dimension and envelope circularity. This is the first study to demonstrate these relationships in adrenal tissue, and also one of the first studies to test the connection between circularity and fractal and gray-level co-occurrence matrix parameters in DNA-specific Feulgen stain. The results could be useful both as an addition to the current knowledge on chromatin/nuclear envelope interactions, and for design of future computer-assisted research software for evaluation of nuclear morphology.

  20. Remodel the Envelope Around the 21 micrometer PPN IRAS 07134+1005

    CERN Document Server

    Yang, Chun-Hui

    2011-01-01

    Recently, the CO J=3-2 observational result of the envelope of the 21 micrometer PPN IRAS 07134+1005 has been reported. Assuming that the CO J=3-2 line was optically thin, the mass-loss rate of the superwind in this PPN was found to be at least 2 orders of magnitude lower than the typical range. In order to obtain a more accurate mass-loss rate, we reexamine this data and construct a radiative transfer model to compare with the data. Also, in order to better resolve the superwind, we adopt a different weighting on the data to obtain maps at higher resolution. Our result shows that the CO J=3-2 emission is located slightly further away from the central source than the mid-IR emission, probably because that the material is cooler in the outer part and thus better traced by the CO emission. At lower resolution, however, the CO emission appeared to be spatially coincident with the mid-IR emission. Our model has two components, an inner ellipsoidal shell-like superwind with an equatorial density enhancement and an...

  1. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  2. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    Directory of Open Access Journals (Sweden)

    Tzviya Zeev-Ben-Mordehai

    2015-12-01

    Full Text Available Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC, which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.

  3. Poly(A) binding proteins located at the inner surface of resealed nuclear envelopes.

    Science.gov (United States)

    Prochnow, D; Riedel, N; Agutter, P S; Fasold, H

    1990-04-25

    We have used a photoreactive cross-linking reagent, poly(A/8-N3-A) (a poly(A) of average molecular mass of 100 kDa in which 5-10% of the A residues are replaced by 8-N3-A), to label poly(A) binding proteins of rat liver nuclear envelopes. This reagent was prepared by polymerizing a mixture of ADP and 8-N3-ADP with polynucleotide phosphorylase. The purified poly(A) was labeled in the 5'-position with a 32P group. In nuclear envelopes prepared by a low salt DNase I procedure, the poly(A/8-N3-A) labeled a protein-nucleic acid complex of approximately 270 kDa, which on degradation with RNase U2 or NaOH at pH 10 yielded two polypeptides of approximately 50 and 30 kDa. These photoreaction products were markedly decreased when resealed nuclear envelopes or non-nuclear envelope proteins were irradiated in the presence of poly(A/8-N3-A). The affinity labeling was intensified when resealed vesicles were made leaky by freezing or ultrasonication, suggesting that the poly(A) binding proteins are accessible from the nucleoplasmic but not the cytoplasmic face of the envelope. Moreover binding was specific for poly(A). Alternative reagents, random poly(A/8-N3-A,C,G,U) of about 100 kDa and poly(dA) (molecular mass between 350 and 515 kDa), showed a very low affinity for poly(A) recognition proteins in the low salt DNase I-treated nuclear envelopes; the 270-kDa band was labeled only weakly. The binding site was not protected by poly(A,C,G,U), weakly by poly(dA), and distinctly by poly(A).

  4. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective.

    Science.gov (United States)

    Cau, Pierre; Navarro, Claire; Harhouri, Karim; Roll, Patrice; Sigaudy, Sabine; Kaspi, Elise; Perrin, Sophie; De Sandre-Giovannoli, Annachiara; Lévy, Nicolas

    2014-05-01

    Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features

  5. Dynamic Assembly of Brambleberry Mediates Nuclear Envelope Fusion during Early Development

    Science.gov (United States)

    Abrams, Elliott W.; Zhang, Hong; Marlow, Florence L.; Kapp, Lee; Lu, Sumei; Mullins, Mary C.

    2012-01-01

    Summary To accommodate the large cells following zygote formation, early blastomeres employ modified cell divisions. Karyomeres are one such modification, a mitotic intermediate wherein individual chromatin masses are surrounded by nuclear envelope, which then fuse to form a single mononucleus. We identified brambleberry, a maternal-effect zebrafish mutant that disrupts karyomere fusion resulting in formation of multiple micronuclei. brambleberry is a previously unannotated gene homologous to Kar5p, which participates in nuclear fusion in yeast. We demonstrate that Brambleberry is required for pronuclear fusion following fertilization in zebrafish. As karyomeres form, Brambleberry localizes to the nuclear envelope with prominent puncta evident near karyomere-karyomere interfaces corresponding to membrane fusion sites. Our studies identify the first factor acting in karyomere fusion and suggest that specialized proteins are necessary for proper nuclear division in large dividing blastomeres. PMID:22863006

  6. Dynamic assembly of brambleberry mediates nuclear envelope fusion during early development.

    Science.gov (United States)

    Abrams, Elliott W; Zhang, Hong; Marlow, Florence L; Kapp, Lee; Lu, Sumei; Mullins, Mary C

    2012-08-03

    To accommodate the large cells following zygote formation, early blastomeres employ modified cell divisions. Karyomeres are one such modification, mitotic intermediates wherein individual chromatin masses are surrounded by nuclear envelope; the karyomeres then fuse to form a single mononucleus. We identified brambleberry, a maternal-effect zebrafish mutant that disrupts karyomere fusion, resulting in formation of multiple micronuclei. As karyomeres form, Brambleberry protein localizes to the nuclear envelope, with prominent puncta evident near karyomere-karyomere interfaces corresponding to membrane fusion sites. brambleberry corresponds to an unannotated gene with similarity to Kar5p, a protein that participates in nuclear fusion in yeast. We also demonstrate that Brambleberry is required for pronuclear fusion following fertilization in zebrafish. Our studies provide insight into the machinery required for karyomere fusion and suggest that specialized proteins are necessary for proper nuclear division in large dividing blastomeres.

  7. The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell Differentiation

    DEFF Research Database (Denmark)

    Bermeo, Sandra; Al-Saedi, Ahmed; Kassem, Moustapha

    2017-01-01

    Mutations in MAN1, a protein of the nuclear envelope, cause bone phenotypes characterized by hyperostosis. The mechanism of this pro-osteogenic phenotype remains unknown. We increased and decreased MAN1 expression in mesenchymal stem cells (MSC) upon which standard osteogenic and adipogenic...... differentiation were performed. MAN1 knockdown increased osteogenesis and mineralization. In contrast, osteogenesis remained stable upon MAN1 overexpression. Regarding a mechanism, we found that low levels of MAN1 facilitated the nuclear accumulation of regulatory smads and smads-related complexes......, with a concurrently high expression of nuclear β-Catenin. In addition, we found adipogenesis to be decreased in both conditions, although predominantly affected by MAN1 overexpression. Finally, lamin A, a protein of the nuclear envelope that regulates MSC differentiation, was unaffected by changes in MAN1...

  8. The overexpression of nuclear envelope protein Lap2β induces endoplasmic reticulum reorganisation via membrane stacking

    Directory of Open Access Journals (Sweden)

    Ekaterina G. Volkova

    2012-06-01

    Some nuclear envelope proteins are localised to both the nuclear envelope and the endoplasmic reticulum; therefore, it seems plausible that even small amounts of these proteins can influence the organisation of the endoplasmic reticulum. A simple method to study the possible effects of nuclear envelope proteins on endoplasmic reticulum organisation is to analyze nuclear envelope protein overexpression. Here, we demonstrate that Lap2β overexpression can induce the formation of cytoplasmic vesicular structures derived from endoplasmic reticulum membranes. Correlative light and electron microscopy demonstrated that these vesicular structures were composed of a series of closely apposed membranes that were frequently arranged in a circular fashion. Although stacked endoplasmic reticulum cisternae were highly ordered, Lap2β could readily diffuse into and out of these structures into the surrounding reticulum. It appears that low-affinity interactions between cytoplasmic domains of Lap2β can reorganise reticular endoplasmic reticulum into stacked cisternae. Although the effect of one protein may be insignificant at low concentrations, the cumulative effect of many non-specialised proteins may be significant.

  9. Sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope.

    Directory of Open Access Journals (Sweden)

    Jose M González-Granado

    Full Text Available Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6, a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope.

  10. Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes.

    Science.gov (United States)

    Rappa, Germana; Santos, Mark F; Green, Toni M; Karbanová, Jana; Hassler, Justin; Bai, Yongsheng; Barsky, Sanford H; Corbeil, Denis; Lorico, Aurelio

    2017-01-24

    Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication, but how the biomaterials they carry reach the target site in recipient cells is an open question. We report that subdomains of Rab7+ late endosomes and nuclear envelope invaginations come together to create a sub-nuclear compartment, where biomaterials associated with CD9+ EVs are delivered. EV-derived biomaterials were also found in the nuclei of host cells. The inhibition of nuclear import and export pathways abrogated the nuclear localization of EV-derived biomaterials or led to their accumulation therein, respectively, suggesting that their translocation is dependent on nuclear pores. Nuclear envelope invagination-associated late endosomes were observed in ex vivo biopsies in both breast carcinoma and associated stromal cells. The transcriptome of stromal cells exposed to cancer cell-derived CD9+ EVs revealed that the regulation of eleven genes, notably those involved in inflammation, relies on the nuclear translocation of EV-derived biomaterials. Our findings uncover a new cellular pathway used by EVs to reach nuclear compartment.

  11. Effect of colchicine on mammalian liver nuclear envelope and on nucleo-cytoplasmic RNA transport.

    Science.gov (United States)

    Agutter, P S; Suckling, K E

    1982-09-27

    The binding of colchicine to nuclear envelopes was studied in order to elucidate the mechanism whereby this compound inhibits nucleocytoplasmic RNA transport. The results suggest that a single class of colchicine-binding site (dissociation constant=approx. 0.7 mM, concentration=approx. 330 nmol colchicine/mg protein) is localised in the nuclear periphery (pore-lamina) and that binding to these sites effects a constriction of the pore-complexes with concomitant inhibition of RNA egress and disordering of the nuclear membrane phospholipid bilayers.

  12. Till disassembly do us part: a happy marriage of nuclear envelope and chromatin.

    Science.gov (United States)

    Tsuchiya, Yuichi

    2008-02-01

    A characteristic feature of eukaryotic cells is the presence of nuclear envelope (NE) which separates genomic DNA from cytoplasm. NE is composed of inner nuclear membrane (INM), which interacts with chromatin, and outer nuclear membrane, which is connected to endoplasmic reticulum. Nuclear pore complexes are inserted into NE to form transport channels between nucleus and cytoplasm. In metazoan cells, an intermediate filament-based meshwork called as nuclear lamina exists between INM and chromatin. Sophisticated collaboration of these molecular machineries is necessary for the structure and functions of NE. Recent research advances have revealed that NE dynamically communicates with chromatin and cytoskeleton to control multiple nuclear functions. In this mini review, I briefly summarize the basic concepts and current topics of functional relationships between NE and chromatin.

  13. Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication

    Science.gov (United States)

    Lahaye, Xavier; Satoh, Takeshi; Gentili, Matteo; Cerboni, Silvia; Silvin, Aymeric; Conrad, Cécile; Ahmed-Belkacem, Abdelhakim; Rodriguez, Elisa C.; Guichou, Jean-François; Bosquet, Nathalie; Piel, Matthieu; Le Grand, Roger; King, Megan C.; Pawlotsky, Jean-Michel; Manel, Nicolas

    2016-01-01

    Summary During the early phase of replication, HIV reverse transcribes its RNA and crosses the nuclear envelope while escaping host antiviral defenses. The host factor Cyclophilin A (CypA) is essential for these steps and binds the HIV capsid; however, the mechanism underlying this effect remains elusive. Here, we identify related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by CypA. This antiviral restriction of mutated viruses is conserved across species and prevents nuclear import of the viral cDNA. Importantly, the inner nuclear envelope protein SUN2 is required for the antiviral activity of CypA. We show that wild-type HIV exploits SUN2 in primary CD4+ T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. Altogether, these results establish essential CypA-dependent functions of SUN2 in HIV infection at the nuclear envelope. PMID:27149839

  14. Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication

    Directory of Open Access Journals (Sweden)

    Xavier Lahaye

    2016-04-01

    Full Text Available During the early phase of replication, HIV reverse transcribes its RNA and crosses the nuclear envelope while escaping host antiviral defenses. The host factor Cyclophilin A (CypA is essential for these steps and binds the HIV capsid; however, the mechanism underlying this effect remains elusive. Here, we identify related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by CypA. This antiviral restriction of mutated viruses is conserved across species and prevents nuclear import of the viral cDNA. Importantly, the inner nuclear envelope protein SUN2 is required for the antiviral activity of CypA. We show that wild-type HIV exploits SUN2 in primary CD4+ T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. Altogether, these results establish essential CypA-dependent functions of SUN2 in HIV infection at the nuclear envelope.

  15. Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ostlund, Cecilia [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Guan, Tinglu [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Figlewicz, Denise A. [Department of Neurology, University of Michigan, Ann Arbor, MI 48109 (United States); Hays, Arthur P. [Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Worman, Howard J. [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Gerace, Larry [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Schirmer, Eric C., E-mail: e.schirmer@ed.ac.uk [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR (United Kingdom)

    2009-11-13

    Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients with FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.

  16. Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led active random motion, and anomalous diffusion

    Science.gov (United States)

    Marshall, Wallace F.; Fung, Jennifer C.

    2016-04-01

    The recognition and pairing of homologous chromosomes during meiosis is a complex physical and molecular process involving a combination of polymer dynamics and molecular recognition events. Two highly conserved features of meiotic chromosome behavior are the attachment of telomeres to the nuclear envelope and the active random motion of telomeres driven by their interaction with cytoskeletal motor proteins. Both of these features have been proposed to facilitate the process of homolog pairing, but exactly what role these features play in meiosis remains poorly understood. Here we investigate the roles of active motion and nuclear envelope tethering using a Brownian dynamics simulation in which meiotic chromosomes are represented by a Rouse polymer model subjected to tethering and active forces at the telomeres. We find that tethering telomeres to the nuclear envelope slows down pairing relative to the rates achieved by unattached chromosomes, but that randomly directed active forces applied to the telomeres speed up pairing dramatically in a manner that depends on the statistical properties of the telomere force fluctuations. The increased rate of initial pairing cannot be explained by stretching out of the chromosome conformation but instead seems to correlate with anomalous diffusion of sub-telomeric regions.

  17. Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin.

    Science.gov (United States)

    Illner, Doris; Zinner, Roman; Handtke, Violet; Rouquette, Jacques; Strickfaden, Hilmar; Lanctôt, Christian; Conrad, Marcus; Seiler, Alexander; Imhof, Axel; Cremer, Thomas; Cremer, Marion

    2010-06-10

    Extensive changes of higher order chromatin arrangements can be observed during prometaphase, terminal cell differentiation and cellular senescence. Experimental systems where major reorganization of nuclear architecture can be induced under defined conditions, may help to better understand the functional implications of such changes. Here, we report on profound chromatin reorganization in fibroblast nuclei by chaetocin, a thiodioxopiperazine metabolite. Chaetocin induces strong condensation of chromosome territories separated by a wide interchromatin space largely void of DNA. Cell viability is maintained irrespective of this peculiar chromatin phenotype. Cell cycle markers, histone signatures, and tests for cellular senescence and for oxidative stress indicate that chaetocin induced chromatin condensation/clustering (CICC) represents a distinct entity among nuclear phenotypes associated with condensed chromatin. The territorial organization of entire chromosomes is maintained in CICC nuclei; however, the conventional nuclear architecture harboring gene-dense chromatin in the nuclear interior and gene-poor chromatin at the nuclear periphery is lost. Instead gene-dense and transcriptionally active chromatin is shifted to the periphery of individual condensed chromosome territories where nascent RNA becomes highly enriched around their outer surface. This chromatin reorganization makes CICC nuclei an attractive model system to study this border zone as a distinct compartment for transcription. Induction of CICC is fully inhibited by thiol-dependent antioxidants, but is not related to the production of reactive oxygen species. Our results suggest that chaetocin functionally impairs the thioredoxin (Trx) system, which is essential for deoxynucleotide synthesis, but in addition involved in a wide range of cellular functions. The mechanisms involved in CICC formation remain to be fully explored.

  18. Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin

    Energy Technology Data Exchange (ETDEWEB)

    Illner, Doris; Zinner, Roman; Handtke, Violet; Rouquette, Jacques; Strickfaden, Hilmar [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Lanctot, Christian [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Institute of Cellular Biology and Pathology, Charles University Prague (Czech Republic); Conrad, Marcus; Seiler, Alexander [Helmholtz Zentrum Munich, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistr. 25, 81377 Munich (Germany); Imhof, Axel [Adolf Butenandt Institute, Department of Molecular Biology (Germany); Munich Center for Integrated Protein Sciences (CIPSM), 81377 Munich (Germany); Cremer, Thomas [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Munich Center for Integrated Protein Sciences (CIPSM), 81377 Munich (Germany); Cremer, Marion, E-mail: Marion.Cremer@lrz.uni-muenchen.de [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany)

    2010-06-10

    Extensive changes of higher order chromatin arrangements can be observed during prometaphase, terminal cell differentiation and cellular senescence. Experimental systems where major reorganization of nuclear architecture can be induced under defined conditions, may help to better understand the functional implications of such changes. Here, we report on profound chromatin reorganization in fibroblast nuclei by chaetocin, a thiodioxopiperazine metabolite. Chaetocin induces strong condensation of chromosome territories separated by a wide interchromatin space largely void of DNA. Cell viability is maintained irrespective of this peculiar chromatin phenotype. Cell cycle markers, histone signatures, and tests for cellular senescence and for oxidative stress indicate that chaetocin induced chromatin condensation/clustering (CICC) represents a distinct entity among nuclear phenotypes associated with condensed chromatin. The territorial organization of entire chromosomes is maintained in CICC nuclei; however, the conventional nuclear architecture harboring gene-dense chromatin in the nuclear interior and gene-poor chromatin at the nuclear periphery is lost. Instead gene-dense and transcriptionally active chromatin is shifted to the periphery of individual condensed chromosome territories where nascent RNA becomes highly enriched around their outer surface. This chromatin reorganization makes CICC nuclei an attractive model system to study this border zone as a distinct compartment for transcription. Induction of CICC is fully inhibited by thiol-dependent antioxidants, but is not related to the production of reactive oxygen species. Our results suggest that chaetocin functionally impairs the thioredoxin (Trx) system, which is essential for deoxynucleotide synthesis, but in addition involved in a wide range of cellular functions. The mechanisms involved in CICC formation remain to be fully explored.

  19. A unique mechanism of nuclear division in Giardia lamblia involves components of the ventral disk and the nuclear envelope.

    Science.gov (United States)

    Solari, Alberto J; Rahn, Monica I; Saura, Alicia; Lujan, Hugo D

    2003-12-01

    The fine structure of the binucleate, parasitic protist Giardia lamblia during interphase and divisional stages was studied by serial thin sectioning and three-dimensional reconstructions. The earlier sign of nuclear division is the development of a few peripheral areas of densely packed chromatin directly attached to the inner nuclear envelope. An intracytoplasmic sheet of ventral disk components grows from the cell periphery towards one of the nuclei, apparently constricting this nucleus, which becomes located at a ventral bulge. After the basal bodies become duplicated, a full nuclear division occurs in trophozoites, giving two pairs of parent-daughter nuclei. This full division occurs in a dorsal-ventral direction, with the resulting nuclear pairs located at the sides of the two sets of basal bodies. A new ventral disk is formed from the disk-derived sheets in the cell harboring the four nuclei. Cytokinesis is polymorphic, but at early stages is dorsal-to-dorsal. Encysting trophozoites show the development of Golgi cisternae stacks and dense, specific secretory granules. 3-D reconstructions show that cysts contain a single pair of incompletely strangled nuclei. The dividing Giardia lacks a typical, microtubular spindle either inside or outside the nuclei. The nuclear envelope seems to be the only structure involved in the final division of the parent-daughter nuclei.

  20. Virtual nuclear envelope breakdown and its regulators in fission yeast meiosis

    Directory of Open Access Journals (Sweden)

    Haruhiko eAsakawa

    2016-02-01

    Full Text Available Ran, a small GTPase, is required for the spindle formation and nuclear envelope (NE formation. After NE breakdown (NEBD during mitosis in metazoan cells, the Ran-GTP gradient across the NE is lost and Ran-GTP becomes concentrated around chromatin, thus affecting the stability of microtubules and promoting the assembly of spindle microtubules and segregation of chromosomes. Mitosis in which chromosomes are segregated subsequent to NEBD is called open mitosis. In contrast, many fungi undergo a process termed closed mitosis in which chromosome segregation and spindle formation occur without NEBD. Although the fission yeast Schizosaccharomyces pombe undergoes a closed mitosis, it exhibits a short period during meiosis (anaphase of the second meiosis; called anaphase II when nuclear and cytoplasmic proteins are mixed in the presence of intact NE and nuclear pore complexes (NPC. This virtual nuclear envelope breakdown (vNEBD involves changes in the localization of RanGAP1, an activator of Ran-GTP hydrolysis. Recently, Nup132, a component of the structural core Nup107-160 subcomplex of the NPC, has been shown to be involved in the maintenance of the nuclear cytoplasmic barrier in yeast meiosis. In this review, we highlight the possible roles of RanGAP1 and Nup132 in vNEBD and discuss the biological significance of vNEBD in S. pombe meiosis.

  1. Lipid quantification and structure determination of nuclear envelope precursor membranes in the sea urchin.

    Science.gov (United States)

    Garnier-Lhomme, Marie; Dufourc, Erick J; Larijani, Banafshé; Poccia, Dominic

    2009-01-01

    Nuclear envelope assembly is a fundamental cellular process normally taking place once in every cell cycle in eukaryotes. The timing of fusion of nuclear membrane precursors to form the complete double membrane surrounding the chromosomes is tightly controlled, but much remains unclear concerning its regulation. Small amounts of material available and the high background of irrelevant cellular membranes have limited detailed analysis. We have employed several sensitive and high-resolution techniques to analyze the nuclear membrane structure, composition, and dynamics using purified membrane fractions and a cell-free system that results in nuclear envelope formation. We discuss the application of cholesterol and phospholipid colorimetric assays, fluorescent filipin labeling, electrospray ionization tandem mass spectrometry coupled to HPLC (HPLC-ESI/MS/MS), electron microscopy (EM), and solid-state nuclear magnetic resonance (NMR) spectroscopy. Colorimetric assays determine the amounts of inorganic phosphates from phospholipids and cholesterol/ cholesteryl esters present in membrane-containing fractions. Filipin staining of natural membranes allows the localization and relative quantification of cholesterol. HPLC-ESI/MS/MS determines the quantitative composition of membrane phospholipid species from small amounts of membranes. Cryosectioning of cryoprotected sperm cells facilitates EM verification of membrane domains existing in vivo. Deuterium solid-state NMR provides information about membrane rigidity and lipid-phase behavior. The sensitivity, quantification, and structural determinations provided by these techniques should prove useful in studying membrane dynamics in a variety of systems exhibiting membrane fusion.

  2. Chromatin remodeling regulated by steroid and nuclear receptors

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    Coactivators and corepressors regulate transcription by controlling interactions between sequence-specific transcription factors,the basal transcriptional machinery and the chromatin environment,This review consider the access of nuclear and steroid receptors to chromatin,their use of corepressors and coactivators to modify chromatin structure and the implications for transcriptional control.The assembly of specific nucleoprotein architectures and targeted histone modification emerge as central controlling elements for gene expression.

  3. Isolation of chromatin DNA tightly bound to the nuclear envelope of HeLa cells.

    Science.gov (United States)

    Kuvichkin, Vasily Vladimirovich

    2012-11-01

    Recent discovery of the role of nuclear pores in transcription, predicted by our early DNA-membrane complex (DMC) model, makes membrane-bound DNA (MBD) isolation from the cell nucleus and analysis of the MBD actual. The method of MBD isolation proposed by us retains DMC integrity during isolation. We used HeLa cells for DMC extraction. Changing the ionic composition of the isolation medium and replacing DNase I, used commonly for chromatin destruction, with a set of restriction enzymes allowed us to isolate the MBD. Treatment of a nuclear membrane with proteinase K and ultrasound has been used to increase the yield of MBD. Electron microscopic analysis of the purified fraction of isolated DMC supports our previous model of nuclear envelope lipid-chromatin interaction in the nuclear pore assembly.

  4. Three-Dimensional Reconstruction of Nuclear Envelope Architecture Using Dual-Color Metal-Induced Energy Transfer Imaging.

    Science.gov (United States)

    Chizhik, Anna M; Ruhlandt, Daja; Pfaff, Janine; Karedla, Narain; Chizhik, Alexey I; Gregor, Ingo; Kehlenbach, Ralph H; Enderlein, Jörg

    2017-09-20

    The nuclear envelope, comprising the inner and the outer nuclear membrane, separates the nucleus from the cytoplasm and plays a key role in cellular functions. Nuclear pore complexes (NPCs), which are embedded in the nuclear envelope, control transport of macromolecules between the two compartments. Here, using dual-color metal-induced energy transfer (MIET), we determine the axial distance between Lap2β and Nup358 as markers for the inner nuclear membrane and the cytoplasmic side of the NPC, respectively. Using MIET imaging, we reconstruct the 3D profile of the nuclear envelope over the whole basal area, with an axial resolution of a few nanometers. This result demonstrates that optical microscopy can achieve nanometer axial resolution in biological samples and without recourse to complex interferometric approaches.

  5. Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ganjei-Azar Parvin

    2011-03-01

    Full Text Available Abstract Background Despite our substantial understanding of molecular mechanisms and gene mutations involved in cancer, the technical approaches for diagnosis and prognosis of cancer are limited. In routine clinical diagnosis of cancer, the procedure is very basic: nuclear morphology is used as a common assessment of the degree of malignancy, and hence acts as a prognostic and predictive indicator of the disease. Furthermore, though the atypical nuclear morphology of cancer cells is believed to be a consequence of oncogenic signaling, the molecular basis remains unclear. Another common characteristic of human cancer is aneuploidy, but the causes and its role in carcinogenesis are not well established. Methods We investigated the expression of the nuclear envelope proteins lamin A/C in ovarian cancer by immunohistochemistry and studied the consequence of lamin A/C suppression using siRNA in primary human ovarian surface epithelial cells in culture. We used immunofluorescence microscopy to analyze nuclear morphology, flow cytometry to analyze cellular DNA content, and fluorescence in situ hybridization to examine cell ploidy of the lamin A/C-suppressed cells. Results We found that nuclear lamina proteins lamin A/C are often absent (47% in ovarian cancer cells and tissues. Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer cell lines, a significant fraction of the lamin A/C-negative population was observed to intermix with the lamin A/C-positive cells. Down regulation of lamin A/C in non-cancerous primary ovarian surface epithelial cells led to morphological deformation and development of aneuploidy. The aneuploid cells became growth retarded due to a p53-dependent induction of the cell cycle inhibitor p21. Conclusions We conclude that the loss of nuclear envelope structural proteins, such as lamin A/C, may underlie two of the hallmarks of cancer - aberrations in nuclear

  6. Chromatin remodeling complexes in the assembly of long noncoding RNA-dependent nuclear bodies.

    Science.gov (United States)

    Kawaguchi, Tetsuya; Hirose, Tetsuro

    2015-01-01

    Paraspeckles are subnuclear structures that assemble on nuclear paraspeckle assembly transcript 1 (NEAT1) long noncoding (lnc)RNA. Paraspeckle formation requires appropriate NEAT1 biogenesis and subsequent assembly with multiple prion-like domain (PLD) containing RNA-binding proteins. We found that SWI/SNF chromatin remodeling complexes function as paraspeckle components that interact with paraspeckle proteins (PSPs) and NEAT1. SWI/SNF complexes play an essential role in paraspeckle formation that does not require their ATP-dependent chromatin remodeling activity. Instead, SWI/SNF complexes facilitate organization of the PSP interaction network required for intact paraspeckle assembly. SWI/SNF complexes may collectively bind multiple PSPs to recruit them onto NEAT1. SWI/SNF complexes are also required for Sat III (Satellite III) lncRNA-dependent formation of nuclear stress bodies under heat shock conditions. Organization of the lncRNA-dependent omega speckle in Drosophila also depends on the chromatin remodeling complex. These findings raise the possibility that a common mechanism controls the formation of lncRNA-dependent nuclear body architecture.

  7. AFM visualization of sub-50nm polyplex disposition to the nuclear pore complex without compromising the integrity of the nuclear envelope

    DEFF Research Database (Denmark)

    Andersen, Helene; Parhamifar, Ladan; Hunter, A Christy

    2016-01-01

    It has been questioned as to whether polyplexes in the cytoplasm can reach the nuclear compartment and if so in what form. By applying atomic force microscopy (AFM) to the nuclear envelope and the nuclear pore complexes, we demonstrate that disposition of polyethylenimine (PEI)/DNA polyplexes...

  8. Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.

    Science.gov (United States)

    Takemoto, Ai; Kawashima, Shigehiro A; Li, Juan-Juan; Jeffery, Linda; Yamatsugu, Kenzo; Elemento, Olivier; Nurse, Paul

    2016-03-15

    Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation.

  9. Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae.

    Science.gov (United States)

    Rogers, Jason V; Rose, Mark D

    2014-12-02

    During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p's functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion.

  10. Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Arantxa Cebrián-Silla

    2017-07-01

    Full Text Available Neural stem cells (B1 astrocytes; NSCs in the adult ventricular-subventricular-zone (V-SVZ originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS, reported in certain lymphocytes and some cancer cells. Using molecular markers, [3H]thymidine birth-dating, and Ara-C, we found that B1 cells with ELCS correspond to quiescent NSCs. ELCS begin forming in embryonic radial glia cells and represent a specific nuclear compartment containing particular epigenetic modifications and telomeres. These results reveal a unique nuclear compartment in quiescent NSCs, which is useful for identifying these primary progenitors and study their gene regulation.

  11. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

    Science.gov (United States)

    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells.

  12. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber.

    Science.gov (United States)

    Dahl, Kris Noel; Kahn, Samuel M; Wilson, Katherine L; Discher, Dennis E

    2004-09-15

    Mechanical properties of the nuclear envelope have implications for cell and nuclear architecture as well as gene regulation. Using isolated Xenopus oocyte nuclei, we have established swelling conditions that separate the intact nuclear envelope (membranes, pore complexes and underlying lamin filament network) from nucleoplasm and the majority of chromatin. Swelling proves reversible with addition of high molecular mass dextrans. Micropipette aspiration of swollen and unswollen nuclear envelopes is also reversible and yields a network elastic modulus, unaffected by nucleoplasm, that averages 25 mN/m. Compared to plasma membranes of cells, the nuclear envelope is much stiffer and more resilient. Our results suggest that the nuclear lamina forms a compressed network shell of interconnected rods that is extensible but limited in compressibility from the native state, thus acting as a 'molecular shock absorber'. In light of the conservation of B-type lamins in metazoan evolution, the mechanical properties determined in this investigation suggest physical mechanisms by which mutated lamins can either destabilize nuclear architecture or influence nuclear responses to mechanical signals in Emery-Dreifuss muscular dystrophy, cardiomyopathy, progeria syndromes (premature 'aging') and other laminopathies.

  13. Nuclear envelope dynamics during plant cell division suggest common mechanisms between kingdoms.

    Science.gov (United States)

    Graumann, Katja; Evans, David E

    2011-05-01

    Behaviour of the NE (nuclear envelope) during open mitosis has been explored extensively in metazoans, but lack of native markers has limited similar investigations in plants. In the present study, carried out using living synchronized tobacco BY-2 suspension cultures, the non-functional NE marker LBR (lamin B receptor)-GFP (green fluorescent protein) and two native, functional NE proteins, AtSUN1 [Arapidopsis thaliana SUN (Sad1/UNC84) 1] and AtSUN2, we provide evidence that the ER (endoplasmic reticulum)-retention theory for NE membranes is applicable in plants. We also observe two apparently unique plant features: location of the NE-membrane components in close proximity to chromatin throughout division, and spatially distinct reformation of the NE commencing at the chromatin surface facing the spindle poles and concluding at the surface facing the cell plate. Mobility of the proteins was investigated in the interphase NE, during NE breakdown and reformation, in the spindle membranes and the cell plate. A role for AtSUN2 in nuclear envelope breakdown is suggested.

  14. GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Rösner, Heike Ilona; Pedersen, Christina Bøg

    2012-01-01

    GAGE proteins are highly similar, primate-specific molecules with unique primary structure and undefined cellular roles. They are restricted to cells of the germ line in adult healthy individuals, but are broadly expressed in a wide range of cancers. In a yeast two-hybrid screen we identified the...... different dsDNA fragments, suggesting sequence-nonspecific binding. Dual association of GAGE family members with GCL at the nuclear envelope inner membrane in cells, and with dsDNA in vitro, implicate GAGE proteins in chromatin regulation in germ cells and cancer cells....... the metazoan transcriptional regulator, Germ cell-less (GCL), as an interaction partner of GAGE12I. GCL directly binds LEM-domain proteins (LAP2β, emerin, MAN1) at the nuclear envelope, and we found that GAGE proteins were recruited to the nuclear envelope inner membrane by GCL. Based on yeast two...

  15. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    Directory of Open Access Journals (Sweden)

    Birthe Fahrenkrog

    Full Text Available Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML. In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE, in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α. Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  16. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Callinice D. Capo-chichi; Kathy Q. Car; Jennifer Smedberg; Parvin Ganjei-Azar; Andrew K. Godwin; Xiang-Xi Xu

    2011-01-01

    Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C-positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as nonnuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/Cnegative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.

  17. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    Science.gov (United States)

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  18. Human Cytomegalovirus Nuclear Egress Proteins Ectopically Expressed in the Heterologous Environment of Plant Cells are Strictly Targeted to the Nuclear Envelope.

    Science.gov (United States)

    Lamm, Christian E; Link, Katrin; Wagner, Sabrina; Milbradt, Jens; Marschall, Manfred; Sonnewald, Uwe

    2016-03-10

    In all eukaryotic cells, the nucleus forms a prominent cellular compartment containing the cell's nuclear genome. Although structurally similar, animal and plant nuclei differ substantially in details of their architecture. One example is the nuclear lamina, a layer of tightly interconnected filament proteins (lamins) underlying the nuclear envelope of metazoans. So far no orthologous lamin genes could be detected in plant genomes and putative lamin-like proteins are only poorly described in plants. To probe for potentially conserved features of metazoan and plant nuclear envelopes, we ectopically expressed the core nuclear egress proteins of human cytomegalovirus pUL50 and pUL53 in plant cells. pUL50 localizes to the inner envelope of metazoan nuclei and recruits the nuclear localized pUL53 to it, forming heterodimers. Upon expression in plant cells, a very similar localization pattern of both proteins could be determined. Notably, pUL50 is specifically targeted to the plant nuclear envelope in a rim-like fashion, a location to which coexpressed pUL53 becomes strictly corecruited from its initial nucleoplasmic distribution. Using pUL50 as bait in a yeast two-hybrid screening, the cytoplasmic re-initiation supporting protein RISP could be identified. Interaction of pUL50 and RISP could be confirmed by coexpression and coimmunoprecipitation in mammalian cells and by confocal laser scanning microscopy in plant cells, demonstrating partial pUL50-RISP colocalization in areas of the nuclear rim and other intracellular compartments. Thus, our study provides strong evidence for conserved structural features of plant and metazoan nuclear envelops and identifies RISP as a potential pUL50-interacting plant protein.

  19. The budding yeast nuclear envelope adjacent to the nucleolus serves as a membrane sink during mitotic delay.

    Science.gov (United States)

    Witkin, Keren L; Chong, Yolanda; Shao, Sichen; Webster, Micah T; Lahiri, Sujoy; Walters, Alison D; Lee, Brandon; Koh, Judice L Y; Prinz, William A; Andrews, Brenda J; Cohen-Fix, Orna

    2012-06-19

    The mechanisms that dictate nuclear shape are largely unknown. Here we screened the budding yeast deletion collection for mutants with abnormal nuclear shape. A common phenotype was the appearance of a nuclear extension, particularly in mutants in DNA repair and chromosome segregation genes. Our data suggest that these mutations led to the abnormal nuclear morphology indirectly, by causing a checkpoint-induced cell-cycle delay. Indeed, delaying cells in mitosis by other means also led to the appearance of nuclear extensions, whereas inactivating the DNA damage checkpoint pathway in a DNA repair mutant reduced the fraction of cells with nuclear extensions. Formation of a nuclear extension was specific to a mitotic delay, because cells arrested in S or G2 had round nuclei. Moreover, the nuclear extension always coincided with the nucleolus, while the morphology of the DNA mass remained largely unchanged. Finally, we found that phospholipid synthesis continued unperturbed when cells delayed in mitosis, and inhibiting phospholipid synthesis abolished the formation of nuclear extensions. Our data suggest a mechanism that promotes nuclear envelope expansion during mitosis. When mitotic progression is delayed, cells sequester the added membrane to the nuclear envelope associated with the nucleolus, possibly to avoid disruption of intranuclear organization.

  20. The Malleable Nature of the Budding Yeast Nuclear Envelope: Flares, Fusion, and Fenestrations.

    Science.gov (United States)

    Meseroll, Rebecca A; Cohen-Fix, Orna

    2016-11-01

    In eukaryotes, the nuclear envelope (NE) physically separates nuclear components and activities from rest of the cell. The NE also provides rigidity to the nucleus and contributes to chromosome organization. At the same time, the NE is highly dynamic; it must change shape and rearrange its components during development and throughout the cell cycle, and its morphology can be altered in response to mutation and disease. Here we focus on the NE of budding yeast, Saccharomyces cerevisiae, which has several unique features: it remains intact throughout the cell cycle, expands symmetrically during interphase, elongates during mitosis and, expands asymmetrically during mitotic delay. Moreover, its NE is safely breached during mating and when large structures, such as nuclear pore complexes and the spindle pole body, are embedded into its double membrane. The budding yeast NE lacks lamins and yet the nucleus is capable of maintaining a spherical shape throughout interphase. Despite these eccentricities, studies of the budding yeast NE have uncovered interesting, and likely conserved, processes that contribute to NE dynamics. In particular, we discuss the processes that drive and enable NE expansion and the dramatic changes in the NE that lead to extensions and fenestrations. J. Cell. Physiol. 231: 2353-2360, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  1. Release of chromosomes from the nuclear envelope: a universal mechanism for eukaryotic mitosis?

    Science.gov (United States)

    Kanoh, Junko

    2013-01-01

    Multiple domains of chromosomes are associated with the nuclear envelope (NE) in interphase. The association between chromosomes and the NE is involved in a variety of chromosomal reactions, such as gene expression and DNA repair. However, efficient chromosome movements are required for the fidelity of chromosome segregation in mitosis. Most higher eukaryotes perform open mitosis, in which the NE is broken down, enabling chromosomes to be released from the NE as well as spindle microtubules to access to kinetochores. By contrast, lower eukaryotes, such as Schizosaccharomyces pombe, perform closed mitosis, during which NE breakdown does not occur. In S. pombe, telomeres are tethered to the NE in interphase. Phosphorylation of the telomere-binding protein Rap1 at M phase promotes transient dissociation of telomeres from the NE, facilitating the faithful chromosome segregation. These findings imply a common mechanism for genome stability via the dissociation of chromosomes from the NE in eukaryotic mitosis.

  2. Isoforms of the nuclear envelope protein Nurim are differentially expressed during heart development in mice.

    Science.gov (United States)

    Zhang, Wan; Bai, Tianyu; Zhang, Shuai; Xu, Shiqiang; Chen, Hengling; Li, Chenhong

    2017-09-05

    To date, transcript variants of the nuclear envelope protein Nurim and their expression profiles in mice have never been elucidated. In this study, we determined that the primary Nurim variant a was abundantly expressed in mouse heart, liver, spleen and kidney. The protein level of isoform a is initiated at an early stage of heart formation and demonstrated a significant increase in expression throughout embryonic heart development. Interestingly, Nurim b is also up-regulated from E12.5 to E18.5 in different individuals. Our research represents the first report on alternative splicing variants of mouse Nurim and their differential expression profile during embryonic development. These studies suggest a potential role for Nurim in early heart morphogenesis and should help further elucidate the function of Nurim. Copyright © 2017. Published by Elsevier B.V.

  3. Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins.

    Science.gov (United States)

    Agutter, P S; McCaldin, B; McArdle, H J

    1979-09-15

    The nucleoside triphosphate-stimulated efflux of RNA from isolated nuclei was studied under a range of conditions, and the effects of these conditions on the process were compared with the properties of the nucleoside triphosphatase located in the pore complex. A marked similarity between the rate of efflux and the rate of nucleoside triphosphate hydrolysis was apparent, in terms of substrate specificity, sensitivity to treatment with insolubilized trypsin, kinetics and the effects of increased ionic strength and of many inhibitors. These results are taken, in view of earlier evidence, to suggest that the activity of the nucleoside triphosphatase is a prerequisite for nucleo-cytoplasmic RNA transport in vivo. There are some indications that the nuclear-envelope lipid is also involved in regulating the efflux process.

  4. LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.

    Science.gov (United States)

    Gu, Mingyu; LaJoie, Dollie; Chen, Opal S; von Appen, Alexander; Ladinsky, Mark S; Redd, Michael J; Nikolova, Linda; Bjorkman, Pamela J; Sundquist, Wesley I; Ullman, Katharine S; Frost, Adam

    2017-03-14

    Endosomal sorting complexes required for transport III (ESCRT-III) proteins have been implicated in sealing the nuclear envelope in mammals, spindle pole body dynamics in fission yeast, and surveillance of defective nuclear pore complexes in budding yeast. Here, we report that Lem2p (LEM2), a member of the LEM (Lap2-Emerin-Man1) family of inner nuclear membrane proteins, and the ESCRT-II/ESCRT-III hybrid protein Cmp7p (CHMP7), work together to recruit additional ESCRT-III proteins to holes in the nuclear membrane. In Schizosaccharomyces pombe, deletion of the ATPase vps4 leads to severe defects in nuclear morphology and integrity. These phenotypes are suppressed by loss-of-function mutations that arise spontaneously in lem2 or cmp7, implying that these proteins may function upstream in the same pathway. Building on these genetic interactions, we explored the role of LEM2 during nuclear envelope reformation in human cells. We found that CHMP7 and LEM2 enrich at the same region of the chromatin disk periphery during this window of cell division and that CHMP7 can bind directly to the C-terminal domain of LEM2 in vitro. We further found that, during nuclear envelope formation, recruitment of the ESCRT factors CHMP7, CHMP2A, and IST1/CHMP8 all depend on LEM2 in human cells. We conclude that Lem2p/LEM2 is a conserved nuclear site-specific adaptor that recruits Cmp7p/CHMP7 and downstream ESCRT factors to the nuclear envelope.

  5. AFM visualization of sub-50nm polyplex disposition to the nuclear pore complex without compromising the integrity of the nuclear envelope.

    Science.gov (United States)

    Andersen, Helene; Parhamifar, Ladan; Hunter, A Christy; Shahin, Victor; Moghimi, S Moein

    2016-12-28

    It has been questioned as to whether polyplexes in the cytoplasm can reach the nuclear compartment and if so in what form. By applying atomic force microscopy (AFM) to the nuclear envelope and the nuclear pore complexes, we demonstrate that disposition of polyethylenimine (PEI)/DNA polyplexes that were microinjected into the oocytes of Xenopus laevis, as an example of a non-dividing cell, is exclusive to the nuclear pore complex (NPC). AFM images show NPCs clogged only with sub-50nm polyplexes. This mode of disposition neither altered the morphology/integrity of the nuclear membrane nor the NPC. AFM images further show polyplexes on the nucleoplasmic side of the envelope, presumably indicating species in transit. Transmission electron microscopy studies of ruptured nuclei from transfected human cell lines demonstrate the presence of sub-50nm particles resembling polyplexes in morphology compared with control preparations.

  6. Permeabilization of the nuclear envelope following nanosecond pulsed electric field exposure.

    Science.gov (United States)

    Thompson, Gary L; Roth, Caleb C; Kuipers, Marjorie A; Tolstykh, Gleb P; Beier, Hope T; Ibey, Bennett L

    2016-01-29

    Permeabilization of cell membranes occurs upon exposure to a threshold absorbed dose (AD) of nanosecond pulsed electric fields (nsPEF). The ultimate, physiological bioeffect of this exposure depends on the type of cultured cell and environment, indicating that cell-specific pathways and structures are stimulated. Here we investigate 10 and 600 ns duration PEF effects on Chinese hamster ovary (CHO) cell nuclei, where our hypothesis is that pulse disruption of the nuclear envelope membrane leads to observed cell death and decreased viability 24 h post-exposure. To observe short-term responses to nsPEF exposure, CHO cells have been stably transfected with two fluorescently-labeled proteins known to be sequestered for cellular chromosomal function within the nucleus - histone-2b (H2B) and proliferating cell nuclear antigen (PCNA). H2B remains associated with chromatin after nsPEF exposure, whereas PCNA leaks out of nuclei permeabilized by a threshold AD of 10 and 600 ns PEF. A downturn in 24 h viability, measured by MTT assay, is observed at the number of pulses required to induce permeabilization of the nucleus.

  7. Nuclear envelope defects impede a proper response to micronuclear DNA lesions

    Energy Technology Data Exchange (ETDEWEB)

    Terradas, Mariona; Martin, Marta; Hernandez, Laia; Tusell, Laura [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Genesca, Anna, E-mail: anna.genesca@uab.cat [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2012-01-03

    When damage is inflicted in nuclear DNA, cells activate a hierarchical plethora of proteins that constitute the DNA damage response machinery. In contrast to the cell nucleus, the ability of micronuclear DNA lesions to activate this complex network is controversial. In order to determine whether the DNA contained in micronuclei is protected by the cellular damage response system, we studied the recruitment of excision repair factors to photolesions inflicted in the DNA of radiation-induced micronuclei. To perform this analysis, primary human dermal fibroblasts were exposed to UV-C light to induce photolesions in nuclear and micronuclear DNA. By means of immunofluorescence techniques, we observed that most micronuclei were devoid of NER factors. We conclude that UV photoproducts in micronuclei are mostly unable to generate an effective DNA damage response. We observed that the micronuclear envelope structure is a determinant factor that influences the repair of the DNA lesions inside micronuclei. Therefore, our results allow us to conclude that photolesions in radiation-induced micronuclei are poorly processed because the repair factors are unable to reach the micronuclear chromatin when a micronucleus is formed or after a genotoxic insult.

  8. The spindle pole bodies facilitate nuclear envelope division during closed mitosis in fission yeast.

    Science.gov (United States)

    Zheng, Liling; Schwartz, Cindi; Magidson, Valentin; Khodjakov, Alexey; Oliferenko, Snezhana

    2007-07-01

    Many organisms divide chromosomes within the confines of the nuclear envelope (NE) in a process known as closed mitosis. Thus, they must ensure coordination between segregation of the genetic material and division of the NE itself. Although many years of work have led to a reasonably clear understanding of mitotic spindle function in chromosome segregation, the NE division mechanism remains obscure. Here, we show that fission yeast cells overexpressing the transforming acid coiled coil (TACC)-related protein, Mia1p/Alp7p, failed to separate the spindle pole bodies (SPBs) at the onset of mitosis, but could assemble acentrosomal bipolar and antiparallel spindle structures. Most of these cells arrested in anaphase with fully extended spindles and nonsegregated chromosomes. Spindle poles that lacked the SPBs did not lead the division of the NE during spindle elongation, but deformed it, trapping the chromosomes within. When the SPBs were severed by laser microsurgery in wild-type cells, we observed analogous deformations of the NE by elongating spindle remnants, resulting in NE division failure. Analysis of dis1Delta cells that elongate spindles despite unattached kinetochores indicated that the SPBs were required for maintaining nuclear shape at anaphase onset. Strikingly, when the NE was disassembled by utilizing a temperature-sensitive allele of the Ran GEF, Pim1p, the abnormal spindles induced by Mia1p overexpression were capable of segregating sister chromatids to daughter cells, suggesting that the failure to divide the NE prevents chromosome partitioning. Our results imply that the SPBs preclude deformation of the NE during spindle elongation and thus serve as specialized structures enabling nuclear division during closed mitosis in fission yeast.

  9. The spindle pole bodies facilitate nuclear envelope division during closed mitosis in fission yeast.

    Directory of Open Access Journals (Sweden)

    Liling Zheng

    2007-07-01

    Full Text Available Many organisms divide chromosomes within the confines of the nuclear envelope (NE in a process known as closed mitosis. Thus, they must ensure coordination between segregation of the genetic material and division of the NE itself. Although many years of work have led to a reasonably clear understanding of mitotic spindle function in chromosome segregation, the NE division mechanism remains obscure. Here, we show that fission yeast cells overexpressing the transforming acid coiled coil (TACC-related protein, Mia1p/Alp7p, failed to separate the spindle pole bodies (SPBs at the onset of mitosis, but could assemble acentrosomal bipolar and antiparallel spindle structures. Most of these cells arrested in anaphase with fully extended spindles and nonsegregated chromosomes. Spindle poles that lacked the SPBs did not lead the division of the NE during spindle elongation, but deformed it, trapping the chromosomes within. When the SPBs were severed by laser microsurgery in wild-type cells, we observed analogous deformations of the NE by elongating spindle remnants, resulting in NE division failure. Analysis of dis1Delta cells that elongate spindles despite unattached kinetochores indicated that the SPBs were required for maintaining nuclear shape at anaphase onset. Strikingly, when the NE was disassembled by utilizing a temperature-sensitive allele of the Ran GEF, Pim1p, the abnormal spindles induced by Mia1p overexpression were capable of segregating sister chromatids to daughter cells, suggesting that the failure to divide the NE prevents chromosome partitioning. Our results imply that the SPBs preclude deformation of the NE during spindle elongation and thus serve as specialized structures enabling nuclear division during closed mitosis in fission yeast.

  10. Integrating complex functions: coordination of nuclear pore complex assembly and membrane expansion of the nuclear envelope requires a family of integral membrane proteins.

    Science.gov (United States)

    Schneiter, Roger; Cole, Charles N

    2010-01-01

    The nuclear envelope harbors numerous large proteinaceous channels, the nuclear pore complexes (NPCs), through which macromolecular exchange between the cytosol and the nucleoplasm occurs. This double-membrane nuclear envelope is continuous with the endoplasmic reticulum and thus functionally connected to such diverse processes as vesicular transport, protein maturation and lipid synthesis. Recent results obtained from studies in Saccharomyces cerevisiae indicate that assembly of the nuclear pore complex is functionally dependent upon maintenance of lipid homeostasis of the ER membrane. Previous work from one of our laboratories has revealed that an integral membrane protein Apq12 is important for the assembly of functional nuclear pores. Cells lacking APQ12 are viable but cannot grow at low temperatures, have aberrant NPCs and a defect in mRNA export. Remarkably, these defects in NPC assembly can be overcome by supplementing cells with a membrane fluidizing agent, benzyl alcohol, suggesting that Apq12 impacts the flexibility of the nuclear membrane, possibly by adjusting its lipid composition when cells are shifted to a reduced temperature. Our new study now expands these findings and reveals that an essential membrane protein, Brr6, shares at least partially overlapping functions with Apq12 and is also required for assembly of functional NPCs. A third nuclear envelope membrane protein, Brl1, is related to Brr6, and is also required for NPC assembly. Because maintenance of membrane homeostasis is essential for cellular survival, the fact that these three proteins are conserved in fungi that undergo closed mitoses, but are not found in metazoans or plants, may indicate that their functions are performed by proteins unrelated at the primary sequence level to Brr6, Brl1 and Apq12 in cells that disassemble their nuclear envelopes during mitosis.

  11. Structural insights into SUN-KASH complexes across the nuclear envelope

    Institute of Scientific and Technical Information of China (English)

    Wenjia Wang; Zhaocai Zhou; Zhubing Shi; Shi Jiao; Cuicui Chen; Huizhen Wang; Guoguang Liu; Qiang Wang; Yun Zhao; Mark I Greene

    2012-01-01

    Linker of the nucleoskeleton and the cytoskeleton (LINC) complexes are composed of SUN and KASH domaincontaining proteins and bridge the inner and outer membranes of the nuclear envelope.LINC complexes play critical roles in nuclear positioning,cell polarization and cellular stiffness.Previously,we reported the homotrimeric structure of human SUN2.We have now determined the crystal structure of the human SUN2-KASH complex.In the complex structure,the SUN domain homotrimer binds to three independent "hook"-like KASH peptides.The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state.A major conformational change involves the AA'-loop of KASH-bound SUN domain,which rearranges to form a mini β-sheet that interacts with the KASH peptide.The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain,which we termed the BI-pocket.Moreover,two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding.Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro.In addition,transfection of wild-type,but not mutant,SUN2 promotes cell migration in Ovcar-3 cells.These results provide a structural model of the LINC complex,which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.

  12. The fluidity of the nuclear envelope lipid does not affect the rate of nucleocytoplasmic RNA transport in mammalian liver.

    Science.gov (United States)

    Agutter, P S; Suckling, K E

    1982-03-29

    The effects of in vitro and in vivo modifications of nuclear envelope lipid on DNa leakage and on ATP-stimulated RNA release from isolated rat liver nuclei were investigated. The modifications included corn-oil feeding of the animals to alter the fatty acid composition of the lipids, phospholipase treatment of the isolated nuclei, and extraction of the total lipid with Triton X-100. Significant changes in lipid composition and approximate order parameter values of the spin-label 5-doxylstearate resulted, but there was no significant effect on RNA transport rate. It was concluded that the nuclear envelope lipid does not play any important part in nucleocytoplasmic RNA transport in mammalian liver.

  13. GAGE cancer-germline antigens bind DNA and are recruited to the nuclear envelope by Germ cell-less

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Rösner, Heike; Pedersen, Christina Bøg

    GAGE genes encode a highly similar, primate-specific protein family with unique primary structure and undefined roles in germ cells, various fetal cells and cancer cells. We report that GAGE proteins are intrinsically disordered proteins that provide novel interfaces between chromatin and the nuc......GAGE genes encode a highly similar, primate-specific protein family with unique primary structure and undefined roles in germ cells, various fetal cells and cancer cells. We report that GAGE proteins are intrinsically disordered proteins that provide novel interfaces between chromatin...... and the nuclear envelope. Structural analysis by NMR and CD spectroscopy showed GAGE proteins lack distinct secondary or tertiary structure and are therefore intrinsically disordered. In normal cells and cancer cells GAGE proteins localize predominantly in the nucleus; we found GAGE proteins formed stable......) at the nuclear envelope. Furthermore, exogenous and endogenous GAGE proteins were recruited to the nuclear envelope in GCL-overexpressing cells. Gene expression analysis and immunohistochemical staining suggest GAGE proteins and GCL interact physiologically in human cells that express both, including male germ...

  14. Effects of cholesterol on the properties of the membranes of isolated sheep liver nuclei and nuclear envelopes.

    Science.gov (United States)

    Agutter, P S; Suckling, K E

    1981-04-22

    The exchangeability of cholesterol between sheep liver nuclear membranes and liposomes, and the effect of cholesterol on the fluidity of the membrane lipid were studied. In intact nuclei, the cholesterol/phospholipid ratio increased from 0.102 to 0.145 mol/mol on incubation with cholesterol-rich liposomes, with a time for half-maximal uptake of 4.2 h. In isolated envelopes under the same conditions, the ratio increased from 0.110 to 0.266 mol/mol with a time for half-maximal uptake of about 1.9 h. Moreover, the approximate order parameter of the spin label 5-(N-oxyl-4',4'-dimethyloxazolidino)-stearic acid was 0.677 in intact nuclei and 0.723 in isolated envelopes prior to exchange; after exchange, these values increased to 0.717 and 0.756, respectively. These differences between the preparations could not be attributed to differences in the capacity for cholesterol uptake between the two nuclear membranes, or to a slow rate of exchange between them; the presence of an intact nuclear matrix appeared both to disorder the lipid partially and to inhibit cholesterol uptake. The differences indicate that conclusions based on physical studies of the membrane lipid in isolated envelopes are not necessarily applicable to the intact nucleus.

  15. Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress.

    Science.gov (United States)

    Han, Yue; Wang, Lu; Yao, Qing-Ping; Zhang, Ping; Liu, Bo; Wang, Guo-Liang; Shen, Bao-Rong; Cheng, Binbin; Wang, Yingxiao; Jiang, Zong-Lai; Qi, Ying-Xin

    2015-05-01

    The dysfunction of vascular endothelial cells (ECs) influenced by flow shear stress is crucial for vascular remodeling. However, the roles of nuclear envelope (NE) proteins in shear stress-induced EC dysfunction are still unknown. Our results indicated that, compared with normal shear stress (NSS), low shear stress (LowSS) suppressed the expression of two types of NE proteins, Nesprin2 and LaminA, and increased the proliferation and apoptosis of ECs. Targeted small interfering RNA (siRNA) and gene overexpression plasmid transfection revealed that Nesprin2 and LaminA participate in the regulation of EC proliferation and apoptosis. A protein/DNA array was further used to detect the activation of transcription factors in ECs following transfection with target siRNAs and overexpression plasmids. The regulation of AP-2 and TFIID mediated by Nesprin2 and the activation of Stat-1, Stat-3, Stat-5 and Stat-6 by LaminA were verified under shear stress. Furthermore, using Ingenuity Pathway Analysis software and real-time RT-PCR, the effects of Nesprin2 or LaminA on the downstream target genes of AP-2, TFIID, and Stat-1, Stat-3, Stat-5 and Stat-6, respectively, were investigated under LowSS. Our study has revealed that NE proteins are novel mechano-sensitive molecules in ECs. LowSS suppresses the expression of Nesprin2 and LaminA, which may subsequently modulate the activation of important transcription factors and eventually lead to EC dysfunction.

  16. Functional dissection of nuclear envelope mRNA translocation system: effects of phorbol ester and a monoclonal antibody recognizing cytoskeletal structures.

    Science.gov (United States)

    Schröder, H C; Diehl-Seifert, B; Rottmann, M; Messer, R; Bryson, B A; Agutter, P S; Müller, W E

    1988-03-01

    Unidirectional transport of poly(A)-containing mRNA [poly(A)+ mRNA] through the nuclear envelope pore complex is thought to be an energy (ATP or GTP)-dependent process which involves a nuclear envelope nucleoside triphosphatase (NTPase). In the intact envelope, this enzyme is regulatable by poly(A) binding and by poly(A)-dependent phosphorylation/dephosphorylation of other components of the mRNA translocation system, which are as yet unidentified. Monoclonal antibodies (mAbs) were elicited against the poly(A) binding nuclear envelope fraction isolated from rat liver. The mAbs were screened for their modulatory effects on mRNA transport in vitro. One stable clone decreased the efflux of rapidly labeled RNA and of one specific mRNA (ovalbumin) from isolated nuclei. It increased the binding of poly(A) to the envelope and increased the maximal catalytic rate of the NTPase, but it did not alter the apparent Km of the enzyme or the extent of its stimulation by poly(A). The nuclear envelope-associated protein kinase that down-regulates the NTPase was inhibited by the antibody, while other protein kinases were not affected. Because both the NTPase and mRNA efflux were inhibited by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, the sensitive kinase is probably protein kinase C. Protein kinase C was found to be associated with the isolated nuclear envelope. The antibody reacted with both a Mr 83,000 and a Mr 65,000 nuclear envelope polypeptide from rat liver and other tissues. By immunofluorescence microscopy in CV-1 cells, the antibody localized to the nuclear envelope and, in addition, to cytoplasmic filaments which show some superposition with the microfilament network.

  17. Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes.

    Science.gov (United States)

    Kinney, Nicholas Allen; Onufriev, Alexey V; Sharakhov, Igor V

    2015-01-01

    We use a combined experimental and computational approach to study the effects of chromosome-nuclear envelope (Chr-NE) attachments on the 3D genome organization of Drosophila melanogaster (fruit fly) salivary gland nuclei. We consider 3 distinct models: a Null model - without specific Chr-NE attachments, a 15-attachment model - with 15 previously known Chr-NE attachments, and a 48-attachment model - with 15 original and 33 recently identified Chr-NE attachments. The radial densities of chromosomes in the models are compared to the densities observed in 100 experimental images of optically sectioned salivary gland nuclei forming "z-stacks." Most of the experimental z-stacks support the Chr-NE 48-attachment model suggesting that as many as 48 chromosome loci with appreciable affinity for the NE are necessary to reproduce the experimentally observed distribution of chromosome density in fruit fly nuclei. Next, we investigate if and how the presence and the number of Chr-NE attachments affect several key characteristics of 3D genome organization: chromosome territories and gene-gene contacts. This analysis leads to novel insight about the possible role of Chr-NE attachments in regulating the genome architecture. Specifically, we find that model nuclei with more numerous Chr-NE attachments form more distinct chromosome territories and their chromosomes intertwine less frequently. Intra-chromosome and intra-arm contacts are more common in model nuclei with Chr-NE attachments compared to the Null model (no specific attachments), while inter-chromosome and inter-arm contacts are less common in nuclei with Chr-NE attachments. We demonstrate that Chr-NE attachments increase the specificity of long-range inter-chromosome and inter-arm contacts. The predicted effects of Chr-NE attachments are rationalized by intuitive volume vs. surface accessibility arguments.

  18. Myopathy in Marinesco-Sjögren syndrome links endoplasmic reticulum chaperone dysfunction to nuclear envelope pathology.

    Science.gov (United States)

    Roos, Andreas; Buchkremer, Stephan; Kollipara, Laxmikanth; Labisch, Thomas; Gatz, Christian; Zitzelsberger, Manuela; Brauers, Eva; Nolte, Kay; Schröder, J Michael; Kirschner, Janbernd; Jesse, Christopher Marvin; Goebel, Hans Hilmar; Goswami, Anand; Zimmermann, Richard; Zahedi, René Peiman; Senderek, Jan; Weis, Joachim

    2014-05-01

    Marinesco-Sjögren syndrome (MSS) features cerebellar ataxia, mental retardation, cataracts, and progressive vacuolar myopathy with peculiar myonuclear alterations. Most MSS patients carry homozygous or compound heterozygous SIL1 mutations. SIL1 is a nucleotide exchange factor for the endoplasmic reticulum resident chaperone BiP which controls a plethora of essential processes in the endoplasmic reticulum. In this study we made use of the spontaneous Sil1 mouse mutant woozy to explore pathomechanisms leading to Sil1 deficiency-related skeletal muscle pathology. We found severe, progressive myopathy characterized by alterations of the sarcoplasmic reticulum, accumulation of autophagic vacuoles, mitochondrial changes, and prominent myonuclear pathology including nuclear envelope and nuclear lamina alterations. These abnormalities were remarkably similar to the myopathy in human patients with MSS. In particular, the presence of perinuclear membranous structures which have been reported as an ultrastructural hallmark of MSS-related myopathy could be confirmed in woozy muscles. We found that these structures are derived from the nuclear envelope and nuclear lamina and associate with proliferations of the sarcoplasmic reticulum. In line with impaired function of BiP secondary to loss of its nucleotide exchange factor Sil1, we observed activation of the unfolded protein response and the endoplasmic-reticulum-associated protein degradation-pathway. Despite initiation of the autophagy-lysosomal system, autophagic clearance was found ineffective which is in agreement with the formation of autophagic vacuoles. This report identifies woozy muscle as a faithful phenocopy of the MSS myopathy. Moreover, we provide a link between two well-established disease mechanisms in skeletal muscle, dysfunction of chaperones and nuclear envelope pathology.

  19. Effect of Nuclear Factor-κB on Airway Remodeling in Asthmatic Rats

    Institute of Scientific and Technical Information of China (English)

    许淑云; 徐永健; 张珍祥; 倪望; 陈士新

    2004-01-01

    Summary: In order to investigate the effect of nuclear factor-κB (NF-κB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF-κB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF-κB activity and the expression of inhibitory protein κBa (I-κBα) in airway were detected by electrophoretic mobility shift assay (EMSA), Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up-regulation of airway NF-κB activity in asthmatic group, the number of goblet cells (3.08 ±0.86/100μm basement membrane (BM)), the area of collagen (24.71 ± 4. 24 μm2/μm BM) and smooth muscle (13.81 ± 2.11 μm2/μm BM) in airway were significantly increased (P<0.05) as compared with control group (0.14±0. 05/100μm BM, 14.31 ±3.16 μm2/μm BM and 7.67±2.35 μm2/μm BM respectively) and PDTC group (0. 33±0. 14/100 μm BM, 18. 16±2.85 μm2/μm BM and 8.95±2.16 μm2/μm BM respectively). However, there was no significant difference between PDTC group and control group (P>0.05). It was concluded that the activity of NF-κB is increased in airway of asthmatic rats. Inhibition of NF-κB activation can attenuate constructional changes in asthma airway, suggesting NF-κB may contribute to asthmatic airway remodeling.

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

    Science.gov (United States)

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

    2013-09-01

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

  1. Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane.

    Science.gov (United States)

    Farnsworth, Aaron; Wisner, Todd W; Webb, Michael; Roller, Richard; Cohen, Gary; Eisenberg, Roselyn; Johnson, David C

    2007-06-12

    Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and the unenveloped capsids then acquire a second envelope in the trans-Golgi network. Little is known about the process by which herpesviruses virions fuse with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking both the two putative fusion glycoproteins gB and gH failed to cross the nuclear envelope. Enveloped virions accumulated in the perinuclear space or in membrane vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants lacking just gB or gH showed only minor or no defects in nuclear egress. We concluded that either HSV gB or gH can promote fusion between the virion envelope and the outer NM. It is noteworthy that fusion associated with HSV entry requires the cooperative action of both gB and gH, suggesting that the two types of fusion (egress versus entry) are dissimilar processes.

  2. Analysis of the documents about the core envelopment of nuclear reactor at the Laguna Verde U-1 power plant; Analisis de documentos de los materiales de la envolvente del nucleo del reactor nuclear de la CLV U-1

    Energy Technology Data Exchange (ETDEWEB)

    Zamora R, L.; Medina F, A. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1999-07-01

    The degradation of internal components at BWR type reactors is an important subject to consider in the performance availability of the power plant. The Wuergassen nuclear reactor license was confiscated due to the presence of cracking in the core envelopment. In consequence it is necessary carrying out a detailed study with the purpose to avoid these problems in the future. This report presents a review and analysis of documents and technical information referring to the core envelopment of a BWR/5/6 and the Laguna Verde Unit 1 nuclear reactor in Mexico. In this document are presented design data, documents about fabrication processes, and manufacturing of core envelopment. (Author)

  3. Nuclear pore complex remodeling by p75NTR cleavage controls TGF-β signaling and astrocyte functions

    Science.gov (United States)

    Schachtrup, Christian; Ryu, Jae Kyu; Mammadzada, Könül; Khan, Abdullah S.; Carlton, Peter M.; Perez, Alex; Christian, Frank; Le Moan, Natacha; Vagena, Eirini; Baeza-Raja, Bernat; Rafalski, Victoria; Chan, Justin P.; Nitschke, Roland; Houslay, Miles D.; Ellisman, Mark H.; Wyss-Coray, Tony; Palop, Jorge J.; Akassoglou, Katerina

    2016-01-01

    Astrocytes play critical roles in neuronal activity and inhibition of regeneration. Here we show that the cleaved p75 neurotrophin receptor (p75NTR) is a component of the nuclear pore complex (NPC) required for glial scar formation and reduced gamma oscillations in mice via regulation of TGF-β signaling. The cleaved p75NTR interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling. Thus, NPC remodeling by regulated intramembrane cleavage of p75NTR controls astrocyte-neuronal communication in response to profibrotic factors. PMID:26120963

  4. Chromatin remodelling initiation during human spermiogenesis

    Directory of Open Access Journals (Sweden)

    Marieke De Vries

    2012-03-01

    During the last phase of spermatogenesis, spermiogenesis, haploid round spermatids metamorphose towards spermatozoa. Extensive cytoplasmic reduction and chromatin remodelling together allow a dramatic decrease of cellular, notably nuclear volume. DNA packing by a nucleosome based chromatin structure is largely replaced by a protamine based one. At the cytoplasmic level among others the acrosome and perinuclear theca (PNT are formed. In this study we describe the onset of chromatin remodelling to occur concomitantly with acrosome and PNT development. In spread human round spermatid nuclei, we show development of a DAPI-intense doughnut-like structure co-localizing with the acrosomal sac and sub acrosomal PNT. At this structure we observe the first gradual decrease of nucleosomes and several histones. Histone post-translational modifications linked to chromatin remodelling such as H4K8ac and H4K16ac also delineate the doughnut, that is furthermore marked by H3K9me2. During the capping phase of acrosome development, the size of the doughnut-like chromatin domain increases, and this area often is marked by uniform nucleosome loss and the first appearance of transition protein 2 and protamine 1. In the acrosome phase at nuclear elongation, chromatin remodelling follows the downward movement of the marginal ring of the acrosome. Our results indicate that acrosome development and chromatin remodelling are interacting processes. In the discussion we relate chromatin remodelling to the available data on the nuclear envelope and the linker of nucleoskeleton and cytoskeleton (LINC complex of spermatids, suggesting a signalling route for triggering chromatin remodelling.

  5. Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach.

    Directory of Open Access Journals (Sweden)

    Nicholas Allen Kinney

    Full Text Available Three dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope (Chr-NE attachments of polytene (giant chromosomes in Drosophila melanogaster salivary glands. The model represents chromosomes as self-avoiding polymer chains confined within the nucleus; parameters of the model are taken directly from experiment, no fitting parameters are introduced. Methods are developed to objectively quantify chromosome territories and intertwining, which are discussed in the context of corresponding experimental observations. In particular, a mathematically rigorous definition of a territory based on convex hull is proposed. The self-avoiding polymer model is used to re-analyze previous experimental data; the analysis suggests 33 additional Chr-NE attachments in addition to the 15 already explored Chr-NE attachments. Most of these new Chr-NE attachments correspond to intercalary heterochromatin--gene poor, dark staining, late replicating regions of the genome; however, three correspond to euchromatin--gene rich, light staining, early replicating regions of the genome. The analysis also suggests 5 regions of anti-contact, characterized by aversion for the NE, only two of these correspond to euchromatin. This composition of chromatin suggests that heterochromatin may not be necessary or sufficient for the formation of a Chr-NE attachment. To the extent that the proposed model represents reality, the confinement of the polytene chromosomes in a spherical nucleus alone does not favor the positioning of specific chromosome regions at the NE as seen in experiment; consequently, the 15 experimentally known Chr-NE attachment positions do not

  6. A flow cytometry-based screen of nuclear envelope transmembrane proteins identifies NET4/Tmem53 as involved in stress-dependent cell cycle withdrawal.

    Directory of Open Access Journals (Sweden)

    Nadia Korfali

    Full Text Available Disruption of cell cycle regulation is one mechanism proposed for how nuclear envelope protein mutation can cause disease. Thus far only a few nuclear envelope proteins have been tested/found to affect cell cycle progression: to identify others, 39 novel nuclear envelope transmembrane proteins were screened for their ability to alter flow cytometry cell cycle/DNA content profiles when exogenously expressed. Eight had notable effects with seven increasing and one decreasing the 4N:2N ratio. We subsequently focused on NET4/Tmem53 that lost its effects in p53(-/- cells and retinoblastoma protein-deficient cells. NET4/TMEM53 knockdown by siRNA altered flow cytometry cell cycle/DNA content profiles in a similar way as overexpression. NET4/TMEM53 knockdown did not affect total retinoblastoma protein levels, unlike nuclear envelope-associated proteins Lamin A and LAP2α. However, a decrease in phosphorylated retinoblastoma protein was observed along with a doubling of p53 levels and a 7-fold increase in p21. Consequently cells withdrew from the cell cycle, which was confirmed in MRC5 cells by a drop in the percentage of cells expressing Ki-67 antigen and an increase in the number of cells stained for ß-galactosidase. The ß-galactosidase upregulation suggests that cells become prematurely senescent. Finally, the changes in retinoblastoma protein, p53, and p21 resulting from loss of NET4/Tmem53 were dependent upon active p38 MAP kinase. The finding that roughly a fifth of nuclear envelope transmembrane proteins screened yielded alterations in flow cytometry cell cycle/DNA content profiles suggests a much greater influence of the nuclear envelope on the cell cycle than is widely held.

  7. NSF- and SNARE-mediated membrane fusion is required for nuclear envelope formation and completion of nuclear pore complex assembly in Xenopus laevis egg extracts.

    Science.gov (United States)

    Baur, Tina; Ramadan, Kristijan; Schlundt, Andreas; Kartenbeck, Jürgen; Meyer, Hemmo H

    2007-08-15

    Despite the progress in understanding nuclear envelope (NE) reformation after mitosis, it has remained unclear what drives the required membrane fusion and how exactly this is coordinated with nuclear pore complex (NPC) assembly. Here, we show that, like other intracellular fusion reactions, NE fusion in Xenopus laevis egg extracts is mediated by SNARE proteins that require activation by NSF. Antibodies against Xenopus NSF, depletion of NSF or the dominant-negative NSF(E329Q) variant specifically inhibited NE formation. Staging experiments further revealed that NSF was required until sealing of the envelope was completed. Moreover, excess exogenous alpha-SNAP that blocks SNARE function prevented membrane fusion and caused accumulation of non-flattened vesicles on the chromatin surface. Under these conditions, the nucleoporins Nup107 and gp210 were fully recruited, whereas assembly of FxFG-repeat-containing nucleoporins was blocked. Together, we define NSF- and SNARE-mediated membrane fusion events as essential steps during NE formation downstream of Nup107 recruitment, and upstream of membrane flattening and completion of NPC assembly.

  8. Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase.

    Science.gov (United States)

    Wisner, Todd W; Wright, Catherine C; Kato, Akihisa; Kawaguchi, Yasushi; Mou, Fan; Baines, Joel D; Roller, Richard J; Johnson, David C

    2009-04-01

    Herpesvirus capsids collect along the inner surface of the nuclear envelope and bud into the perinuclear space. Enveloped virions then fuse with the outer nuclear membrane (NM). We previously showed that herpes simplex virus (HSV) glycoproteins gB and gH act in a redundant fashion to promote fusion between the virion envelope and the outer NM. HSV mutants lacking both gB and gH accumulate enveloped virions in herniations, vesicles that bulge into the nucleoplasm. Earlier studies had shown that HSV mutants lacking the viral serine/threonine kinase US3 also accumulate herniations. Here, we demonstrate that HSV gB is phosphorylated in a US3-dependent manner in HSV-infected cells, especially in a crude nuclear fraction. Moreover, US3 directly phosphorylated the gB cytoplasmic (CT) domain in in vitro assays. Deletion of gB in the context of a US3-null virus did not add substantially to defects in nuclear egress. The majority of the US3-dependent phosphorylation of gB involved the CT domain and amino acid T887, a residue present in a motif similar to that recognized by US3 in other proteins. HSV recombinants lacking gH and expressing either gB substitution mutation T887A or a gB truncated at residue 886 displayed substantial defects in nuclear egress. We concluded that phosphorylation of the gB CT domain is important for gB-mediated fusion with the outer NM. This suggested a model in which the US3 kinase is incorporated into the tegument layer (between the capsid and envelope) in HSV virions present in the perinuclear space. By this packaging, US3 might be brought close to the gB CT tail, leading to phosphorylation and triggering fusion between the virion envelope and the outer NM.

  9. Inhibition of the host translation shutoff response by herpes simplex virus 1 triggers nuclear envelope-derived autophagy.

    Science.gov (United States)

    Radtke, Kerstin; English, Luc; Rondeau, Christiane; Leib, David; Lippé, Roger; Desjardins, Michel

    2013-04-01

    Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the viral protein γ34.5, which can inhibit macroautophagy via binding to beclin-1. Using mutant viruses, we were able to show that binding of beclin-1 by γ34.5 had no effect on NEDA, demonstrating that NEDA is regulated differently than macroautophagy. Instead, NEDA was triggered in response to γ34.5 binding to protein phosphatase 1α, an interaction used by the virus to prevent host cells from shutting off protein translation. NEDA was not triggered when late viral protein production was inhibited with acyclovir or hippuristanol, indicating that the accumulation of these proteins might stress infected cells. Interestingly, expression of the late viral protein gH was sufficient to rescue NEDA in the context of infection with a virus that otherwise does not support strong late viral protein expression. We argue that NEDA is a cellular stress response triggered late during HSV-1 infection and might compensate for the viral alteration of the macroautophagic response.

  10. Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion.

    Science.gov (United States)

    Bosse, Jens B; Hogue, Ian B; Feric, Marina; Thiberge, Stephan Y; Sodeik, Beate; Brangwynne, Clifford P; Enquist, Lynn W

    2015-10-20

    The nuclear chromatin structure confines the movement of large macromolecular complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm assemble in the nucleoplasm and must reach the nuclear membranes for egress. Previous studies concluded that nuclear herpesvirus capsid motility is active, directed, and based on nuclear filamentous actin, suggesting that large nuclear complexes need metabolic energy to escape nuclear entrapment. However, this hypothesis has recently been challenged. Commonly used microscopy techniques do not allow the imaging of rapid nuclear particle motility with sufficient spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we dubbed a ring-sheet, to image and track viral capsids with high temporal and spatial resolution. We do not find any evidence for directed transport. Instead, infection with different herpesviruses induced an enlargement of interchromatin domains and allowed particles to diffuse unrestricted over longer distances, thereby facilitating nuclear egress for a larger fraction of capsids.

  11. Nanoscale invaginations of the nuclear envelope: Shedding new light on wormholes with elusive function.

    Science.gov (United States)

    Schoen, Ingmar; Aires, Lina; Ries, Jonas; Vogel, Viola

    2017-07-07

    Recent advances in fluorescence microscopy have opened up new possibilities to investigate chromosomal and nuclear 3D organization on the nanoscale. We here discuss their potential for elucidating topographical details of the nuclear lamina. Single molecule localization microscopy (SMLM) in combination with immunostainings of lamina proteins readily reveals tube-like invaginations with a diameter of 100-500 nm. Although these invaginations have been established as a frequent and general feature of interphase nuclei across different cell types, their formation mechanism and function have remained largely elusive. We critically review the current state of research, propose possible connections to lamina associated domains (LADs), and revisit the discussion about the potential role of these invaginations for accelerating mRNA nuclear export. Illustrative studies using 3D super-resolution imaging are shown and will be instrumental to decipher the physiological role of these nanoscale invaginations.

  12. Chromatin-bound NLS proteins recruit membrane vesicles and nucleoporins for nuclear envelope assembly via importin-α/β

    Institute of Scientific and Technical Information of China (English)

    Quanlong Lu; Zhigang Lu; Qinying Liu; Li Guo; He Ren; Jingyan Fu; Qing Jiang; Paul R Clarke; Chuanmao Zhang

    2012-01-01

    The mechanism for nuclear envelope (NE) assembly is not fully understood.Importin-β and the small GTPase Ran have been implicated in the spatial regulation of NE assembly process.Here we report that chromatin-bound NLS (nuclear localization sequence) proteins provide docking sites for the NE precursor membrane vesicles and nucleoporins via importin-α and -β during NE assembly in Xenopus egg extracts.We show that along with the fast recruitment of the abundant NLS proteins such as nucleoplasmin and histones to the demembranated sperm chromatin in the extracts,importin-α binds the chromatin NLS proteins rapidly.Meanwhile,importin-β binds cytoplasmic NE precursor membrane vesicles and nucleoporins.Through interacting with importin-α on the chromatin NLS proteins,importin-β targets the membrane vesicles and nucleoporins to the chromatin surface.Once encountering RanGTP on the chromatin generated by RCC1,importin-β preferentially binds Ran-GTP and releases the membrane vesicles and nucleoporins for NE assembly.NE assembly is disrupted by blocking the interaction between importin-α and NLS proteins with excess soluble NLS proteins or by depletion of importin-β from the extract.Our findings reveal a novel molecular mechanism for NE assembly in Xenopus egg extracts.

  13. Transcription profiling of Epstein-Barr virus nuclear antigen (EBNA-1 expressing cells suggests targeting of chromatin remodeling complexes.

    Directory of Open Access Journals (Sweden)

    Ramakrishna Sompallae

    Full Text Available The Epstein-Barr virus (EBV encoded nuclear antigen (EBNA-1 regulates virus replication and transcription, and participates in the remodeling of the cellular environment that accompanies EBV induced B-cell immortalization and malignant transformation. The putative cellular targets of these effects of EBNA-1 are largely unknown. To address this issue we have profiled the transcriptional changes induced by short- and long-term expression of EBNA-1 in the EBV negative B-cell lymphoma BJAB. Three hundred and nineteen cellular genes were regulated in a conditional transfectant shortly after EBNA-1 induction while a ten fold higher number of genes was regulated upon continuous EBNA-1 expression. Promoter analysis of the differentially regulated genes demonstrated a significant enrichment of putative EBNA-1 binding sites suggesting that EBNA-1 may directly influence the transcription of a subset of genes. Gene ontology analysis of forty seven genes that were consistently regulated independently on the time of EBNA-1 expression revealed an unexpected enrichment of genes involved in the maintenance of chromatin architecture. The interaction network of the affected gene products suggests that EBNA-1 may promote a broad rearrangement of the cellular transcription landscape by altering the expression of key components of chromatin remodeling complexes.

  14. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    DEFF Research Database (Denmark)

    Østrup, Olga; Hyttel, Poul; Klærke, Dan Arne;

    2011-01-01

    . This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling...... complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract......Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression...

  15. Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation.

    Science.gov (United States)

    Raaijmakers, Jonne A; van Heesbeen, Roy G H P; Meaders, Johnathan L; Geers, Erica F; Fernandez-Garcia, Belen; Medema, René H; Tanenbaum, Marvin E

    2012-11-05

    The microtubule motor protein kinesin-5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti-cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5-independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)-associated dynein that drives centrosome separation in prophase. This NE-dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5-dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin-5 inhibitors.

  16. Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation.

    Science.gov (United States)

    González-Granado, José M; Silvestre-Roig, Carlos; Rocha-Perugini, Vera; Trigueros-Motos, Laia; Cibrián, Danay; Morlino, Giulia; Blanco-Berrocal, Marta; Osorio, Fernando G; Freije, José M P; López-Otín, Carlos; Sánchez-Madrid, Francisco; Andrés, Vicente

    2014-04-22

    In many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naïve T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A-dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response.

  17. SAFEGUARDS ENVELOPE

    Energy Technology Data Exchange (ETDEWEB)

    Duc Cao; Richard Metcalf

    2010-07-01

    The Safeguards Envelope is a strategy to determine a set of specific operating parameters within which nuclear facilities may operate to maximize safeguards effectiveness without sacrificing safety or plant efficiency. This paper details advanced statistical techniques that will be applied to real plant process monitoring (PM) data from the Idaho Chemical Processing Plant (ICPP). In a simulation based on this data, multi-tank and multi-attribute correlations were tested against synthetic diversion scenarios. Kernel regression smoothing was used to fit a curve to the historical data, and multivariable, residual analysis and cumulative sum techniques set parameters for operating conditions. Diversion scenarios were created and tested, showing improved results when compared with a previous study utilizing only one-variable Z-testing. A brief analysis of the impact of the safeguards optimization on the rest of plant efficiency, criticality concerns, and overall requirements is presented.

  18. SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells.

    Directory of Open Access Journals (Sweden)

    Chung-Hsin Yeh

    Full Text Available Male infertility affects approximately 50% of all infertile couples. The male-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile or immature sperm, and sperm with structural defects such as those caused by premature chromosomal condensation and DNA damage. Our previous studies based on a knockout mice model indicated that SEPT12 proteins are critical for the terminal morphological formation of sperm. SEPT12 mutations in men result in teratozospermia and oligozospermia. In addition, the spermatozoa exhibit morphological defects of the head and tail, premature chromosomal condensation, and nuclear damage. However, the molecular functions of SEPT12 during spermatogenesis remain unclear. To determine the molecular functions of SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Seven proteins that interact with SEPT12 were identified: SEPT family proteins (SEPT4 and SEPT6, nuclear or nuclear membrane proteins (protamine 2, sperm-associated antigen 4, and NDC1 transmembrane nucleoproine, and sperm-related structural proteins (pericentriolar material 1 and obscurin-like 1. Sperm-associated antigen 4 (SPAG4; also known as SUN4 belongs to the SUN family of proteins and acts as a linker protein between nucleoskeleton and cytoskeleton proteins and localizes in the nuclear membrane. We determined that SEPT12 interacts with SPAG4 in a male germ cell line through coimmunoprecipitation. During human spermiogenesis, SEPT12 is colocalized with SPAG4 near the nuclear periphery in round spermatids and in the centrosome region in elongating spermatids. Furthermore, we observed that SEPT12/SPAG4/LAMINB1 formed complexes and were coexpressed in the nuclear periphery of round spermatids. In addition, mutated SEPT12, which was screened from an infertile man, affected the integration of these nuclear envelope complexes through coimmunoprecipitation. This was the first study that suggested that SEPT

  19. Immunological evidence for the localization of a 110 kDa poly(A) binding protein from rat liver in nuclear envelopes and its phosphorylation by protein kinase C.

    Science.gov (United States)

    Schäfer, P; Aitken, S J; Bachmann, M; Agutter, P S; Müller, W E; Prochnow, D

    1993-11-01

    We have purified a 110 kDa poly(A) binding protein (P110) from rat liver which is thought to be involved in mRNA translocation through the nuclear pores and have demonstrated its localisation in the nuclear envelope using polyclonal antibodies and confocal laser scanning microscopy. Although P110 was prepared from highly purified nuclear envelopes, the polyclonal antibodies raised against them bind to nucleo- and cytoplasmic structures to a minor extent, but not to nucleolar structures. P110 decays spontaneously into several fragments which are also recognized by the polyclonal antibodies. The 110 kDa polypeptide and its fragments were phosphorylated by a nuclear envelope kinase and this phosphorylation was inhibited by a monoclonal antibody against protein kinase C and by a specific protein kinase C inhibitor obtained from bovine brain. Scatchard analysis was used to determine the influence of protein kinase C activators and inhibitors on nuclear envelope protein phosphorylation and RNA binding. The data indicate a close association between the RNA translocation machinery (the 110 kDa protein) and protein kinase C within the nuclear envelope. We suggest that the fragmentation of P110 is triggered before or during mRNA export and is not due to nonspecific proteolysis.

  20. Proteins from rat liver cytosol which stimulate mRNA transport. Purification and interactions with the nuclear envelope mRNA translocation system.

    Science.gov (United States)

    Schröder, H C; Rottmann, M; Bachmann, M; Müller, W E; McDonald, A R; Agutter, P S

    1986-08-15

    Two polysome-associated proteins with particular affinities for poly(A) have been purified from rat liver. These proteins stimulate the efflux of mRNA from isolated nuclei in conditions under which such efflux closely stimulates mRNA transport in vivo, and they are therefore considered as mRNA-transport-stimulatory proteins. Their interaction with the mRNA-translocation system in isolated nuclear envelopes has been studied. The results are generally consistent with the most recently proposed kinetic model of mRNA translocation. One protein, P58, has not been described previously. It inhibits the protein kinase that down-regulates the NTPase, it enhances the NTPase activity in both the presence and the absence of poly(A) and it seems to increase poly(A) binding in unphosphorylated, but not in phosphorylated, envelopes. The other protein, P31, which probably corresponds to the 35,000-Mr factor described by Webb and his colleagues, enhances the binding of poly(A) to the mRNA-binding site in the envelope, thus stimulating the phosphoprotein phosphatase and, in consequence, the NTPase. The possible physiological significance of these two proteins is discussed.

  1. Microprocessor-Controlled Pulsed NQR Spectrometer for Automatic Acquisition of Zeeman Perturbed Nuclear Quadrupole Spin Echo Envelope Modulations (ZSEEM )

    Science.gov (United States)

    Reddy, Narsimha; Bhavsar, Arun; Narasimhan, P. T.

    1986-02-01

    A simple microprocessor-controlled pulsed NQR spectrometer system has been developed with the capability to acquire Zeeman perturbed spin echo envelope modulations (ZSEEM). The CPU of the system is based on the Intel Corporation 8085 A microprocessor. The performance of the spectrometer is illustrated with the presentation of ZSEEM spectra of NaClO3 and KClO3.

  2. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    Energy Technology Data Exchange (ETDEWEB)

    Ostrup, Olga, E-mail: osvarcova@gmail.com [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway); Hyttel, Poul; Klaerke, Dan A. [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Collas, Philippe, E-mail: philc@medisin.uio.no [Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway)

    2011-09-02

    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  3. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome.

    Science.gov (United States)

    Kitagawa, Hirochika; Fujiki, Ryoji; Yoshimura, Kimihiro; Mezaki, Yoshihiro; Uematsu, Yoshikatsu; Matsui, Daisuke; Ogawa, Satoko; Unno, Kiyoe; Okubo, Mataichi; Tokita, Akifumi; Nakagawa, Takeya; Ito, Takashi; Ishimi, Yukio; Nagasawa, Hiromichi; Matsumoto, Toshio; Yanagisawa, Junn; Kato, Shigeaki

    2003-06-27

    We identified a human multiprotein complex (WINAC) that directly interacts with the vitamin D receptor (VDR) through the Williams syndrome transcription factor (WSTF). WINAC has ATP-dependent chromatin-remodeling activity and contains both SWI/SNF components and DNA replication-related factors. The latter might explain a WINAC requirement for normal S phase progression. WINAC mediates the recruitment of unliganded VDR to VDR target sites in promoters, while subsequent binding of coregulators requires ligand binding. This recruitment order exemplifies that an interaction of a sequence-specific regulator with a chromatin-remodeling complex can organize nucleosomal arrays at specific local sites in order to make promoters accessible for coregulators. Furthermore, overexpression of WSTF could restore the impaired recruitment of VDR to vitamin D regulated promoters in fibroblasts from Williams syndrome patients. This suggests that WINAC dysfunction contributes to Williams syndrome, which could therefore be considered, at least in part, a chromatin-remodeling factor disease.

  4. Building envelope

    CSIR Research Space (South Africa)

    Gibberd, Jeremy T

    2009-01-01

    Full Text Available This chapter describes the way building envelopes can contribute to developing green buildings and sets out some objectives that could be aimed for. It also proposes a number of approaches that can be used to help design green building envelopes...

  5. Lycopene attenuates inflammation and apoptosis in post-myocardial infarction remodeling by inhibiting the nuclear factor-κB signaling pathway.

    Science.gov (United States)

    He, Qin; Zhou, Wei; Xiong, Caijin; Tan, Gang; Chen, Manhua

    2015-01-01

    Inflammatory response and cardiomyocyte apoptosis are important processes in ventricular remodeling post-myocardial infarction (MI) and may form the basic mechanisms in the development of chronic heart failure. The nuclear factor κB (NF-κB) signaling pathway could promote inflammation and apoptosis and it has been demonstrated that lycopene inhibits cigarette smoke extract-mediated NF-κB activation. Therefore, it was hypothesized that the NF-κB signaling pathway may be a key target of lycopene in the reversal of ventricular remodeling post MI. An MI model was established by left anterior descending coronary artery ligation in mice. Following ligation, the mice were administered with lycopene (10 mg/kg/day) or saline. The mice underwent echocardiography and were sacrificed after 4 weeks. The mRNA expression of fibrosis markers transforming growth factor-β1 (TGF-β1), collagen I and III and inflammatory markers tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were examined by quantitative polymerase chain reaction. The protein expression of apoptotic markers, including caspase-3, -8, -9 and activation of the NF-κB signaling pathway were analyzed by western blotting. Lycopene reduced the expression of TGF-β1, collagen I, collagen III, TNF-α, IL-1β, caspase-3, -8 and -9 and inhibited the activation of the NF-κB signaling pathway. The level of ventricular remodeling post-MI was also attenuated following treatment with lycopene. Lycopene may inhibit the NF-κB signaling pathway thereby reducing the inflammatory response and cardiomyocyte apoptosis post-MI, which could be a key mechanism of lycopene in attenuating ventricular remodeling.

  6. Lysine 242 within helix 10 of the pseudorabies virus nuclear egress complex pUL31 component is critical for primary envelopment of nucleocapsids.

    Science.gov (United States)

    Rönfeldt, Sebastian; Klupp, Barbara G; Franzke, Kati; Mettenleiter, Thomas C

    2017-09-06

    Newly assembled herpesvirus nucleocapsids are translocated from the nucleus to the cytosol by a vesicle-mediated process engaging the nuclear membranes. This transport is governed by the conserved nuclear egress complex (NEC), consisting of the alphaherpesviral pUL34 and pUL31 homologs. The NEC is not only required for efficient nuclear egress but also sufficient for vesicle formation from the inner nuclear membrane (INM) as well as from synthetic lipid bilayers. The recently solved crystal structures for the NECs from different herpesviruses revealed molecular details of this membrane deformation and scission machinery uncovering the interfaces involved in complex and coat formation. However, the interaction domain with the nucleocapsid remained undefined. Since the NEC assembles a curved hexagonal coat on the nucleoplasmic side of the INM consisting of tightly interwoven pUL31/pUL34 heterodimers arranged in hexamers, only the membrane-distal end of the NEC formed by pUL31 residues appears accessible for interaction with the nucleocapsid cargo. To identify the amino acids involved in capsid incorporation we mutated the corresponding regions in the alphaherpesvirus pseudorabies virus (PrV). Site-specifically mutated pUL31 were tested for localization, interaction with pUL34 and complementation of PrV-ΔUL31. Here, we identify a conserved lysine residue at amino acid position 242 in PrV pUL31 located in the alpha-helical domain H10 exposed on the membrane-distal end of the NEC as a key residue for nucleocapsid incorporation into the nascent primary particle.IMPORTANCE Vesicular transport through the nuclear envelope is a focus of research but still not well understood. Herpesviruses pioneered this mechanism for translocation of the newly assembled nucleocapsid from the nucleus into the cytosol via vesicles derived from the inner nuclear membrane which fuse in a well-tuned process with the outer nuclear membrane to release their content. The structure of the viral

  7. Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins.

    NARCIS (Netherlands)

    Vos, W.H. De; Houben, F.; Hoebe, R.A.; Hennekam, R.; Engelen, B.G.M. van; Manders, E.M.; Ramaekers, F.C.S.; Broers, J.L.; Oostveldt, P. Van

    2010-01-01

    BACKGROUND: The nuclear lamina provides structural support to the nucleus and has a central role in defining nuclear organization. Defects in its filamentous constituents, the lamins, lead to a class of diseases collectively referred to as laminopathies. On the cellular level, lamin mutations affect

  8. Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins.

    NARCIS (Netherlands)

    Vos, W.H. De; Houben, F.; Hoebe, R.A.; Hennekam, R.; Engelen, B.G.M. van; Manders, E.M.; Ramaekers, F.C.S.; Broers, J.L.; Oostveldt, P. Van

    2010-01-01

    BACKGROUND: The nuclear lamina provides structural support to the nucleus and has a central role in defining nuclear organization. Defects in its filamentous constituents, the lamins, lead to a class of diseases collectively referred to as laminopathies. On the cellular level, lamin mutations affect

  9. Cytoplasmic capes are nuclear envelope intrusions that are enriched in endosomal proteins and depend upon βH-spectrin and Annexin B9.

    Directory of Open Access Journals (Sweden)

    Juan Wu

    Full Text Available It is increasingly recognized that non-erythroid spectrins have roles remote from the plasma membrane, notably in endomembrane trafficking. The large spectrin isoform, βH, partners with Annexin B9 to modulate endosomal processing of internalized proteins. This modulation is focused on the early endosome through multivesicular body steps of endocytic processing and loss of either protein appears to cause a traffic jam before removal of ubiquitin at the multivesicular body. We previously reported that βH/Annexin B9 influenced EGF receptor signaling. While investigating this effect we noticed that mSptiz, the membrane bound precursor of the secreted EGF receptor ligand sSpitz, is located in striking intrusions of the nuclear membrane. Here we characterize these structures and identify them as 'cytoplasmic capes', which were previously identified in old ultrastructural studies and probably coincide with recently recognized sites of non-nuclear-pore RNA export. We show that cytoplasmic capes contain multiple endosomal markers and that their existence is dependent upon βH and Annexin B9. Diminution of these structures does not lead to a change in mSpitz processing. These results extend the endosomal influence of βH and its partner Annexin B9 to this unusual compartment at the nuclear envelope.

  10. The Use of Two-Photon FRET-FLIM to Study Protein Interactions During Nuclear Envelope Fusion In Vivo and In Vitro.

    Science.gov (United States)

    Byrne, Richard D; Larijani, Banafshé; Poccia, Dominic L

    2016-01-01

    FRET-FLIM techniques have wide application in the study of protein and protein-lipid interactions in cells. We have pioneered an imaging platform for accurate detection of functional states of proteins and their interactions in fixed cells. This platform, two-site-amplified Förster resonance energy transfer (a-FRET), allows greater signal generation while retaining minimal noise thus enabling application of fluorescence lifetime imaging microscopy (FLIM) to be routinely deployed in different types of cells and tissue. We have used the method described here, time-resolved FRET monitored by two-photon FLIM, to demonstrate the direct interaction of Phospholipase Cγ (PLCγ) by Src Family Kinase 1 (SFK1) during nuclear envelope formation and during male and female pronuclear membrane fusion in fertilized sea urchin eggs. We describe here a generic method that can be applied to monitor any proteins of interest.

  11. Lamin b1 polymorphism influences morphology of the nuclear envelope, cell cycle progression, and risk of neural tube defects in mice.

    Directory of Open Access Journals (Sweden)

    Sandra C P De Castro

    in maintaining integrity of the nuclear envelope and ensuring normal cell cycle progression.

  12. The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies

    OpenAIRE

    Xue, Yutong; Gibbons, Richard; Yan, Zhijiang; Yang, Dafeng; McDowell, Tarra L.; Sechi, Salvatore; QIN Jun; Zhou, Sharleen; Higgs, Doug; Wang, Weidong

    2003-01-01

    ATRX syndrome is characterized by X-linked mental retardation associated with α-thalassemia. The gene mutated in this disease, ATRX, encodes a plant homeodomain-like finger and a SWI2/SNF2-like ATPase motif, both of which are often found in chromatin-remodeling enzymes, but ATRX has not been characterized biochemically. By immunoprecipitation from HeLa extract, we found that ATRX is in a complex with transcription cofactor Daxx. The following evidence supports that ATRX and Daxx are component...

  13. Inhibition of TGF-β Signaling at the Nuclear Envelope: Characterization of Interactions between MAN1, Smad2 and 3, and PPM1A

    Science.gov (United States)

    Bourgeois, Benjamin; Gilquin, Bernard; Tellier-Lebègue, Carine; Östlund, Cecilia; Wu, Wei; Pérez, Javier; El Hage, Perla; Lallemand, François; Worman, Howard J.; Zinn-Justin, Sophie

    2013-01-01

    Signaling by transforming growth factor–β (TGF-β) is critical for various developmental processes and culminates in the activation of the transcription factors Smad2 and Smad3. MAN1, an integral protein of the inner nuclear membrane, inhibits TGF-β signalling by binding to Smad2 and Smad3. Depletion of the gene LEMD3 encoding MAN1 leads to developmental anomalies in mice, and heterozygous loss-of-function mutations in LEMD3 in humans cause sclerosing bone dysplasia. We modeled the three-dimensional structure of the MAN1-Smad2 complex from nuclear magnetic resonance and small angle x-ray scattering data. As predicted by this model, we found that MAN1 competed in vitro and in cells with the transcription factor FAST1 (forkhead activin signal transducer 1) for binding to Smad2. The model further predicted that MAN1 bound to activated Smad2-Smad4 or Smad3-Smad4 complexes, which was confirmed by in vitro experiments; however, in cells, MAN1 bound only to Smad2 and Smad3, and not to the Smad4-containing complexes. Overexpression of MAN1 led to dephosphorylation of Smad2 and Smad3, thus hindering their recognition by Smad4, and MAN1 bound directly in vitro to the phosphatase PPM1A, which catalyzes the dephosphorylation of Smad2/3. These results demonstrate a nuclear envelope-localized mechanism of inactivating TGF-β signaling in which MAN1 competes with transcription factors for binding to Smad2 and Smad3 and facilitates their dephosphorylation by PPM1A. PMID:23779087

  14. The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation.

    Science.gov (United States)

    Li, Ping; Stumpf, Maria; Müller, Rolf; Eichinger, Ludwig; Glöckner, Gernot; Noegel, Angelika A

    2017-08-22

    SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.

  15. Meiosis, egg activation, and nuclear envelope breakdown are differentially reliant on Ca2+, whereas germinal vesicle breakdown is Ca2+ independent in the mouse oocyte

    Science.gov (United States)

    Tombes, R. M.; Simerly, C.; Borisy, G. G.; Schatten, G.

    1992-01-01

    During early development, intracellular Ca2+ mobilization is not only essential for fertilization, but has also been implicated during other meiotic and mitotic events, such as germinal vesicle breakdown (GVBD) and nuclear envelope breakdown (NEBD). In this study, the roles of intracellular and extracellular Ca2+ were examined during meiotic maturation and reinitiation at parthenogenetic activation and during first mitosis in a single species using the same methodologies. Cumulus-free metaphase II mouse oocytes immediately resumed anaphase upon the induction of a large, transient Ca2+ elevation. This resumption of meiosis and associated events, such as cortical granule discharge, were not sensitive to extracellular Ca2+ removal, but were blocked by intracellular Ca2+ chelators. In contrast, meiosis I was dependent on external Ca2+; in its absence, the formation and function of the first meiotic spindle was delayed, the first polar body did not form and an interphase-like state was induced. GVBD was not dependent on external Ca2+ and showed no associated Ca2+ changes. NEBD at first mitosis in fertilized eggs, on the other hand, was frequently, but not always associated with a brief Ca2+ transient and was dependent on Ca2+ mobilization. We conclude that GVBD is Ca2+ independent, but that the dependence of NEBD on Ca2+ suggests regulation by more than one pathway. As cells develop from Ca(2+)-independent germinal vesicle oocytes to internal Ca(2+)-dependent pronuclear eggs, internal Ca2+ pools increase by approximately fourfold.

  16. The Nuclear Factor kappaB Inhibitor Pyrrolidine Dithiocarbamate Prevents Cardiac Remodelling and Matrix Metalloproteinase-2 Up-Regulation in Renovascular Hypertension.

    Science.gov (United States)

    Cau, Stefany B A; Guimaraes, Danielle A; Rizzi, Elen; Ceron, Carla S; Gerlach, Raquel F; Tanus-Santos, Jose E

    2015-10-01

    Imbalanced matrix metalloproteinase (MMP) activity is involved in hypertensive cardiac hypertrophy. Pharmacological inhibition of nuclear factor kappaB (NF-кB) with pyrrolidine dithiocarbamate (PDTC) can prevent MMP up-regulation. We suggested that treatment with PDTC could prevent 2-kidney, 1-clip (2K1C) hypertension-induced left ventricular remodelling. Sham-operated controls or 2K1C rats with hypertension received either vehicle or PDTC (100 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure was monitored every week. Histological assessment of left ventricles was carried out with haematoxylin/eosin sections, and fibrosis was quantified in picrosirius red-stained sections. Oxidative stress was evaluated in heart samples with the dihydroethidium probe. Cardiac MMP activity was determined by in situ zymography, and cardiac MMP-2 was assessed by immunofluorescence. 2K1C surgery significantly increased systolic blood pressure in the 2K1C vehicle. PDTC exerted antihypertensive effects after 2 weeks of treatment. Histology revealed increased left ventricular and septum wall thickness associated with augmented myocyte diameter in hypertensive rats, which were reversed by treatment with PDTC. Hypertensive rats developed pronounced cardiac fibrosis with increased interstitial collagen area, increased cardiac reactive oxygen species levels, gelatinase activity and MMP-2 expression. PDTC treatment decreased these alterations. These findings show that PDTC modulates myocardial MMP-2 expression and ameliorates cardiac remodelling in renovascular hypertension. These results suggest that interfering with MMP expression at transcriptional level may be an interesting strategy in the therapy of organ damage associated with hypertension.

  17. Immunoregulation of bone remodelling.

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-05-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also.

  18. The KASH protein Kms2 coordinates mitotic remodeling of the spindle pole body.

    Science.gov (United States)

    Wälde, Sarah; King, Megan C

    2014-08-15

    Defects in the biogenesis of the spindle pole body (SPB), the yeast centrosome equivalent, can lead to monopolar spindles and mitotic catastrophe. The KASH domain protein Kms2 and the SUN domain protein Sad1 colocalize within the nuclear envelope at the site of SPB attachment during interphase and at the spindle poles during mitosis in Schizosaccharomyces pombe. We show that Kms2 interacts with the essential SPB components Cut12 and Pcp1 and the Polo kinase Plo1. Depletion of Kms2 delays mitotic entry and leads to defects in the insertion of the SPB into the nuclear envelope, disrupting stable bipolar spindle formation. These effects are mediated in part by a delay in the recruitment of Plo1 to the SPB at mitotic entry. Plo1 activity supports mitotic SPB remodeling by driving a burst of incorporation of Cut12 and Pcp1. Thus, a fission yeast SUN-KASH complex plays an important role in supporting the remodeling of the SPB at mitotic entry.

  19. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling......-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope...

  20. Relatively Flat Envelopes

    Institute of Scientific and Technical Information of China (English)

    丁南庆

    1994-01-01

    The aim of this paper is to investigate relatively flat envelopes. A necessary and sufficient condition is given for a relatively-finitely presented module to have a (mono-morphic or epic) relatively flat envelope. Then those rings are characterized whose every relatively-finitely presented module has a relatively flat envelope which coincides with its in-jective envelope. Some known results are obtained as corollaries.

  1. Reprogramming of fibroblast nuclei in cloned bovine embryos involves major structural remodeling with both striking similarities and differences to nuclear phenotypes of in vitro fertilized embryos.

    Science.gov (United States)

    Popken, Jens; Brero, Alessandro; Koehler, Daniela; Schmid, Volker J; Strauss, Axel; Wuensch, Annegret; Guengoer, Tuna; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Zakhartchenko, Valeri; Wolf, Eckhard; Cremer, Thomas

    2014-01-01

    Nuclear landscapes were studied during preimplantation development of bovine embryos, generated either by in vitro fertilization (IVF), or generated as cloned embryos by somatic cell nuclear transfer (SCNT) of bovine fetal fibroblasts, using 3-dimensional confocal laser scanning microscopy (3D-CLSM) and structured illumination microscopy (3D-SIM). Nuclear landscapes of IVF and SCNT embryonic nuclei were compared with each other and with fibroblast nuclei. We demonstrate that reprogramming of fibroblast nuclei in cloned embryos requires changes of their landscapes similar to nuclei of IVF embryos. On the way toward the 8-cell stage, where major genome activation occurs, a major lacuna, enriched with splicing factors, was formed in the nuclear interior and chromosome territories (CTs) were shifted toward the nuclear periphery. During further development the major lacuna disappeared and CTs were redistributed throughout the nuclear interior forming a contiguous higher order chromatin network. At all stages of development CTs of IVF and SCNT embryonic nuclei were built up from chromatin domain clusters (CDCs) pervaded by interchromatin compartment (IC) channels. Quantitative analyses revealed a highly significant enrichment of RNA polymerase II and H3K4me3, a marker for transcriptionally competent chromatin, at the periphery of CDCs. In contrast, H3K9me3, a marker for silent chromatin, was enriched in the more compacted interior of CDCs. Despite these striking similarities, we also detected major differences between nuclear landscapes of IVF and cloned embryos. Possible implications of these differences for the developmental potential of cloned animals remain to be investigated. We present a model, which integrates generally applicable structural and functional features of the nuclear landscape.

  2. Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates.

    Science.gov (United States)

    Ning, Jue; Otto, Thomas D; Pfander, Claudia; Schwach, Frank; Brochet, Mathieu; Bushell, Ellen; Goulding, David; Sanders, Mandy; Lefebvre, Paul A; Pei, Jimin; Grishin, Nick V; Vanderlaan, Gary; Billker, Oliver; Snell, William J

    2013-05-15

    Fertilization is a crucial yet poorly characterized event in eukaryotes. Our previous discovery that the broadly conserved protein HAP2 (GCS1) functioned in gamete membrane fusion in the unicellular green alga Chlamydomonas and the malaria pathogen Plasmodium led us to exploit the rare biological phenomenon of isogamy in Chlamydomonas in a comparative transcriptomics strategy to uncover additional conserved sexual reproduction genes. All previously identified Chlamydomonas fertilization-essential genes fell into related clusters based on their expression patterns. Out of several conserved genes in a minus gamete cluster, we focused on Cre06.g280600, an ortholog of the fertilization-related Arabidopsis GEX1. Gene disruption, cell biological, and immunolocalization studies show that CrGEX1 functions in nuclear fusion in Chlamydomonas. Moreover, CrGEX1 and its Plasmodium ortholog, PBANKA_113980, are essential for production of viable meiotic progeny in both organisms and thus for mosquito transmission of malaria. Remarkably, we discovered that the genes are members of a large, previously unrecognized family whose first-characterized member, KAR5, is essential for nuclear fusion during yeast sexual reproduction. Our comparative transcriptomics approach provides a new resource for studying sexual development and demonstrates that exploiting the data can lead to the discovery of novel biology that is conserved across distant taxa.

  3. Envelopes of Commutative Rings

    Institute of Scientific and Technical Information of China (English)

    Rafael PARRA; Manuel SAOR(I)N

    2012-01-01

    Given a significative class F of commutative rings,we study the precise conditions under which a commutative ring R has an F-envelope.A full answer is obtained when.F is the class of fields,semisimple commutative rings or integral domains.When F is the class of Noetherian rings,we give a full answer when the Krull dimension of R is zero and when the envelope is required to be epimorphic.The general problem is reduced to identifying the class of non-Noetherian rings having a monomorphic Noetherian envelope,which we conjecture is the empty class.

  4. Nuclear Egress of Herpesviruses

    Institute of Scientific and Technical Information of China (English)

    Richard J.Roller

    2008-01-01

    Herpesviruses assemble and fill their capsids in the infected cell nucleus,and must then move this enormous macromolecular assembly across the nuclear membrane and into the cytoplasm.Doing so is a complex,multi-step process that involves envelopment of the capsid at the inner nuclear membrane and de-envelopment by fusion with the outer nuclear membrane.This process is orchestrated by viral proteins,but requires the modification of cellular structures and mechanisms including the nuclear lamina.In this review I summarize recent research on the mechanism of nuclear envelopment and the viral and cellular systems involved in its execution.

  5. Prevalencia de anticuerpos anti envoltura nuclear y sus isotipos en sueros positivos para anticuerpos antinucleares Prevalence of antinuclear envelope antibodies and their isotypes in sera positive for antinuclear antibodies

    Directory of Open Access Journals (Sweden)

    Miriam Arcavi

    2006-08-01

    Full Text Available Los anticuerpos antinucleares detectados por inmunofluorescencia indirecta en células HEp-2 presentan una gran variedad de imágenes, entre ellas el patrón de envoltura nuclear que suele ser un hallazgo poco frecuente. Se procesaron 2594 sueros en los cuales se detectó un 37.6% de anticuerpos antinucleares. La prevalencia de anticuerpos anti-envoltura nuclear (ANEA fue del 1.2% presentando una alta asociación con hepatopatías autoinmunes (83% y baja con lupus eritematoso sistémico. En los 21 sueros de los pacientes que presentaron ANEA no se detectaron anticuerpos anti-ADNn hallándose 28.6% de anticuerpos anti-músculo liso y 19% de anticuerpos anti-mitocondriales. El corte triple de tejido de rata mostró ser un sustrato menos sensible que HEp-2 para la detección de ANEA. Al utilizar conjugados dirigidos contra diferentes isotipos de anticuerpos para la detección de ANEA, se encontró: 90.5% de IgG, 66.6% de IgA y 9.5% de IgM. Dos de los pacientes presentaron ANEA-IgA a altos títulos (³1:160 en ausencia de ANEA-IgG. En este trabajo se destaca la importancia de realizar pruebas complementarias que detecten anticuerpos anti-músculo liso, anti-mitocondriales y anti-ADNn, para orientar el diagnóstico clínico de los pacientes que presentan ANEA. Además, sostiene la postura de utilizar como conjugado para IFI-HEp2 anticuerpos anti-inmunoglobulinas totales en lugar de anti-IgG hasta tanto se clarifique el rol que juegan los anticuerpos IgA en estas enfermedades autoimunes.Antinuclear antibodies detected in HEp-2 cells by indirect immunofluorescence assay display a great variety of images, including the nuclear envelope pattern. This is quite a less frequent finding. Two thousand five hundred and ninety-four sera were processed, and 37.6% of ANA were detected. The prevalence of anti-nuclear envelope antibodies (ANEA was of 1.2%, with a high association with autoimmune liver diseases (83% and a low association with systemic lupus

  6. The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors.

    Science.gov (United States)

    Zhang, Yiguo; Lucocq, John M; Hayes, John D

    2009-03-01

    In rat liver RL-34 cells, endogenous Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is localized in the ER (endoplasmic reticulum) where it exists as a glycosylated protein. Electron microscopy has demonstrated that ectopic Nrf1 in COS-1 cells is located in the ER and the NE (nuclear envelope). Subcellular fractionation, together with a membrane proteinase protection assay, revealed that Nrf1 is an integral membrane protein with both luminal and cytoplasmic domains. The N-terminal 65 residues of Nrf1 direct its integration into the ER and NE membranes and tether it to a Triton X-100-resistant membrane microdomain that is associated with lipid rafts. The activity of Nrf1 was increased by the electrophile tBHQ (t-butyl hydroquinone) probably through an N-terminal domain-dependent process. We found that the NST (Asn/Ser/Thr-rich) domain, along with AD1 (acidic domain 1), contributes positively to the transactivation activity of full-length Nrf1. Furthermore, the NST domain contains seven putative -Asn-Xaa-Ser/Thr- glycosylation sites and, when glycosylation was prevented by replacing all of the seven asparagine residues with either glutamine (Nrf1(1-7xN/Q)) or aspartic acid (Nrf1(1-7xN/D)), the former multiple point mutant possessed less activity than the wild-type factor, whereas the latter mutant exhibited substantially greater activity. Lastly, the ER stressors tunicamycin, thapsigargin and Brefeldin A were found to inhibit basal Nrf1 activity by approximately 25%, and almost completely prevented induction of Nrf1-mediated transactivation by tBHQ. Collectively, these results suggest that the activity of Nrf1 critically depends on its topology within the ER, and that this is modulated by redox stressors, as well as by its glycosylation status.

  7. Drug design from the cryptic inhibitor envelope.

    Science.gov (United States)

    Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J; Zhou, Pei

    2016-02-25

    Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC--an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target--access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics.

  8. Drug design from the cryptic inhibitor envelope

    Science.gov (United States)

    Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J.; Zhou, Pei

    2016-01-01

    Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC—an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target—access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics. PMID:26912110

  9. Safeguards Envelope Progress FY10

    Energy Technology Data Exchange (ETDEWEB)

    Richard Metcalf

    2010-10-01

    The Safeguards Envelope is a strategy to determine a set of specific operating parameters within which nuclear facilities may operate to maximize safeguards effectiveness without sacrificing safety or plant efficiency. This paper details the additions to the advanced operating techniques that will be applied to real plant process monitoring (PM) data from the Idaho Chemical Processing Plant (ICPP). Research this year focused on combining disparate pieces of data together to maximize operating time with minimal downtime due to safeguards. A Chi-Square and Croiser's cumulative sum were both included as part of the new analysis. Because of a major issue with the original data, the implementation of the two new tests did not add to the existing set of tests, though limited one-variable optimization made a small increase in detection probability. Additional analysis was performed to determine if prior analysis would have caused a major security or safety operating envelope issue. It was determined that a safety issue would have resulted from the prior research, but that the security may have been increased under certain conditions.

  10. Nuclear inclusion bodies of mutant and wild-type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodeling by p53 aggregation.

    Science.gov (United States)

    De Smet, Frederik; Saiz Rubio, Mirian; Hompes, Daphne; Naus, Evelyne; De Baets, Greet; Langenberg, Tobias; Hipp, Mark S; Houben, Bert; Claes, Filip; Charbonneau, Sarah; Blanco, Javier Delgado; Plaisance, Stephane; Ramkissoon, Shakti; Ramkissoon, Lori; Simons, Colinda; van den Brandt, Piet; Weijenberg, Matty; Van England, Manon; Lambrechts, Sandrina; Amant, Frederic; D'Hoore, André; Ligon, Keith L; Sagaert, Xavier; Schymkowitz, Joost; Rousseau, Frederic

    2016-12-30

    Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild-type p53 as the most frequent aggregation-like phenotype across six different cancer types. p53-positive nIBs co-stained with nuclear aggregation markers and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour-associated stress was a strong inducer of p53 aggregation and nuclear inclusion body formation. This was most prominent for mutant p53, but could also be observed in wild-type p53 cell lines for which nIB formation correlated to the loss of p53s transcriptional activity. Importantly, protein aggregation also fueled the dysregulation of the proteostasis network in the tumour cell by inducing a hyper-activated, oncogenic heat-shock response to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients exhibiting tumours with p53-positive nIBs suffered from a poor clinical outcome similar to loss-of-p53-expression, and tumour biopsies displayed a differential proteostatic expression profile associated to p53-nIBs. p53-positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (i) the functional inactivation of p53 through mutation and/or aggregation and (ii) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration.

  11. Structure and membrane remodeling activity of ESCRT-III helical polymers

    Science.gov (United States)

    McCullough, John; Clippinger, Amy K.; Talledge, Nathaniel; Skowyra, Michael L.; Saunders, Marissa G.; Naismith, Teresa V.; Colf, Leremy A.; Afonine, Pavel; Arthur, Christopher; Sundquist, Wesley I.; Hanson, Phyllis I.; Frost, Adam

    2015-01-01

    The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 Å resolution cryo-EM reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, CHMP1B and IST1. The inner strand comprises “open” CHMP1B subunits that interlock in an elaborate domain-swapped architecture, and is encircled by an outer strand of “closed” IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively-curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature. PMID:26634441

  12. Linac Envelope Optics

    CERN Document Server

    Baartman, Rick

    2015-01-01

    I develop the formalism that allows calculation of beam envelopes through a linear accelerator given its on-axis electric field. Space charge can naturally be added using Sacherer formalism. A complicating feature is that the reference particle's energy-time coordinates are not known a priori. Since first order matrix formalism applies to deviations from the reference particle, this means the reference particle's time and energy must be calculated simultaneously with the beam envelope and transfer matrix. The code TRANSOPTR is used to track envelopes for general elements whose infinitesimal transfer matrices are known, and in the presence of space charge. Incorporation of the linac algorithm into TRANSOPTR is described, and some examples given.

  13. Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells.

    Science.gov (United States)

    Therizols, Pierre; Illingworth, Robert S; Courilleau, Celine; Boyle, Shelagh; Wood, Andrew J; Bickmore, Wendy A

    2014-12-05

    During differentiation, thousands of genes are repositioned toward or away from the nuclear envelope. These movements correlate with changes in transcription and replication timing. Using synthetic (TALE) transcription factors, we found that transcriptional activation of endogenous genes by a viral trans-activator is sufficient to induce gene repositioning toward the nuclear interior in embryonic stem cells. However, gene relocation was also induced by recruitment of an acidic peptide that decondenses chromatin without affecting transcription, indicating that nuclear reorganization is driven by chromatin remodeling rather than transcription. We identified an epigenetic inheritance of chromatin decondensation that maintained central nuclear positioning through mitosis even after the TALE transcription factor was lost. Our results also demonstrate that transcriptional activation, but not chromatin decondensation, is sufficient to change replication timing.

  14. HIV-1 envelope glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Caulfield, Michael; Cupo, Albert; Dean, Hansi; Hoffenberg, Simon; King, C. Richter; Klasse, P. J.; Marozsan, Andre; Moore, John P.; Sanders, Rogier W.; Ward, Andrew; Wilson, Ian; Julien, Jean-Philippe

    2017-08-22

    The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

  15. Remodeling A School Shop?

    Science.gov (United States)

    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  16. Different TP53 mutations are associated with specific chromosomal rearrangements, telomere length changes, and remodeling of the nuclear architecture of telomeres.

    Science.gov (United States)

    Samassekou, Oumar; Bastien, Nathalie; Lichtensztejn, Daniel; Yan, Ju; Mai, Sabine; Drouin, Régen

    2014-11-01

    TP53 mutations are the most common mutations in human cancers, and TP53-R175H and TP53-R273H are the most frequent. The impact of these mutations on genomic instability after tumor initiation is still uncovered. To gain insight into this, we studied the effects of three specific TP53 mutants (TP53-V143A, TP53-R175H, and TP53-R273H) on genomic instability using four isogenic lines of LoVo cells. Multicolor fluorescence in situ hybridization (FISH), three-dimensional (3D) quantitative FISH (Q-FISH) on interphase and Q-FISH on metaphases were used to investigate genomic instability. We found that LoVo cells expressing mutant TP53-R175H displayed the highest level of chromosomal instability among the LoVo cell lines. Furthermore, we observed that mutant TP53-R175H and TP53-V143A showed more alterations in their 3D nuclear architecture of telomeres than the mutant TP53-R273H and the wild type. Moreover, we noted an association between some chromosomal abnormalities and telomere elongation in the mutant TP53-R175H. Taken together, our results indicate that the mutation TP53-R175H is more likely to cause higher levels of genomic instability than the other TP53 mutations. We proposed that the type of TP53 mutations and the genetic background of a cancer cell are major determinants of the TP53-dependent genomic instability.

  17. Data envelopment analysis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This review introduces the history and present status of data envelopment analysis (DEA) research, particularly the evaluation process. And extensions of some DEA models are also described. It is pointed out that mathematics, economics and management science are the main forces in the DEA development, optimization provides the fundamental method for the DEA research, and the wide range of applications enforces the rapid development of DEA.

  18. Internal mail envelopes

    CERN Multimedia

    2003-01-01

    Internal mail envelopes often finish up in large piles in certain offices, thus creating a shortage for other users of the mail service, who would be grateful if everyone with an unusual stock could deposit them in their mail box, after attaching them together with an elastic band or piece of string. The messengers will then collect them so that the Mail Office can put them back in circulation. Thank you for your understanding and collaboration. Mail Office

  19. URGENT - Internal Mail Envelopes

    CERN Multimedia

    2007-01-01

    Internal mail envelopes often finish up in large piles in certain offices, thus creating a shortage for other users of the mail service, who would be grateful if everyone with an unused stock could deposit them in their mail box, after attaching them together with an elastic band or piece of string. The messengers will then collect them so that the Mail Office can put them back in circulation. Thank you for your understanding and collaboration. Mail Office

  20. Thermal Activated Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Pasold, Anke

    2015-01-01

    search procedure, the combination of materials and their bonding temperature is found in relation to the envelope effect on a thermal environment inside a defined space. This allows the designer to articulate dynamic composites with time-based thermal functionality, related to the material dynamics......, environmental dynamics and occupancy dynamics. Lastly, a physical prototype is created, which illustrates the physical expression of the bi-materials and the problems related to manufacturing of these composite structures....

  1. Conservation of proteo-lipid nuclear membrane fusion machinery during early embryogenesis.

    Science.gov (United States)

    Byrne, Richard D; Veeriah, Selvaraju; Applebee, Christopher J; Larijani, Banafshé

    2014-01-01

    The fusogenic lipid diacylglycerol is essential for remodeling gamete and zygote nuclear envelopes (NE) during early embryogenesis. It is unclear whether upstream signaling molecules are likewise conserved. Here we demonstrate PLCγ and its activator SFK1, which co-operate during male pronuclear envelope formation, also promote the subsequent male and female pronuclear fusion. PLCγ and SFK1 interact directly at the fusion site leading to PLCγ activation. This is accompanied by a spatially restricted reduction of PtdIns(4,5)P2. Consequently, pronuclear fusion is blocked by PLCγ or SFK1 inhibition. These findings identify new regulators of events in the early embryo and suggest a conserved "toolkit" of fusion machinery drives successive NE fusion events during embryogenesis.

  2. Cofilin Regulates Nuclear Architecture through a Myosin-II Dependent Mechanotransduction Module

    Science.gov (United States)

    Wiggan, O’Neil; Schroder, Bryce; Krapf, Diego; Bamburg, James R.; DeLuca, Jennifer G.

    2017-01-01

    Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking. Here we identify that Cofilin/ADF-family F-actin remodeling proteins are essential for normal nuclear structure in different cell types. siRNA mediated silencing of Cofilin/ADF provokes striking nuclear defects including aberrant shapes, nuclear lamina disruption and reductions to peripheral heterochromatin. We provide evidence that these anomalies are primarily due to Rho kinase (ROCK) controlled excessive contractile myosin-II activity and not to elevated F-actin polymerization. Furthermore, we demonstrate a requirement for nuclear envelope LINC (linker of nucleoskeleton and cytoskeleton) complex proteins together with lamin A/C for nuclear aberrations induced by Cofilin/ADF loss. Our study elucidates a pivotal regulatory mechanism responsible for normal nuclear structure and which is expected to fundamentally influence nuclear function. PMID:28102353

  3. Uncertain data envelopment analysis

    CERN Document Server

    Wen, Meilin

    2014-01-01

    This book is intended to present the milestones in the progression of uncertain Data envelopment analysis (DEA). Chapter 1 gives some basic introduction to uncertain theories, including probability theory, credibility theory, uncertainty theory and chance theory. Chapter 2 presents a comprehensive review and discussion of basic DEA models. The stochastic DEA is introduced in Chapter 3, in which the inputs and outputs are assumed to be random variables. To obtain the probability distribution of a random variable, a lot of samples are needed to apply the statistics inference approach. Chapter 4

  4. Application of FMEA-DEA (Failure Modes and Effect Analysis - Data Envelopment Analysis) to the air conditioning system of the control room a nuclear power plant; Aplicacao de FMEA-DEA ao sistema de ar condicionado da sala de controle de uma usina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa Junior, Gilberto Varanda

    2007-03-15

    This dissertation presents the FMEA-DEA analysis application to the air conditioning system of the control room of a nuclear power plant. After obtaining the failure modes, the index associated to the occurrence probability, the severity of the effects and the potential of detention, a priority order is established for the failure modes or deviations. This number is obtained by multiplying the three mentioned index that vary in a natural scale from 1 to 10, where the higher the index, the more critical the situation will be. In this work, it is intended to use a model based on the data envelopment analysis, DEA jointly with the FMEA, to identify the current efficiency of the system and which failure modes or deviations are considered more critical, and by means of the weights attributed for the mathematical modeling to identify which index are contributing more for these deviations. From this identification, improvements can be set, which may consider administrative changes, operator training and so on, thus adding value to the final product. (author)

  5. Thermal Responsive Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Pasold, Anke

    2015-01-01

    The paper presents an architectural computational method and model, which, through additive and subtractive processes, create composite elements with bending behaviour based on thermal variations in the surrounding climatic environment. The present effort is focused on the manipulation of assembly...... composite layers and their relative layer lengths thereby embedding the merged material effect to create a responsive behavioural architectural envelope. Copper and polypropylene are used as base materials for the composite structure due to their high differences in thermal expansion, surface emissivity...... alterations, their respective durability and copper’s architectural (visual and transformative) aesthetic qualities. Through the use of an evolutionary solver, the composite structure of the elements are organised to find the bending behaviour specified by and for the thermal environments. The entire model...

  6. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up concept......Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or two...

  7. Categories with envelopes and imprints

    CERN Document Server

    Akbarov, Sergei

    2011-01-01

    An envelope in a category is a construction generalizing operations of "exterior completion", like completion of a locally convex space. Dually, an imprint generalizes operations of "interior enrichment", like saturation of a locally convex space. We give abstract definition for envelopes and imprints, prove existence of these objects in the categories of stereotype spaces and of stereotype algebras, and give some examples.

  8. Thermal testing of building envelopes

    Science.gov (United States)

    Lebedev, O.; Kirzhanov, D.; Avramenko, V.; Budadin, O.

    2006-04-01

    Averaged heat transfer resistance of the building envelope is the primary parameter that determines the energy saving characteristics of the building. At the phase of the building design it is usually taken into account that building must preserve heat effectively. It is mostly important in northern countries where cold seasons last for more than a half of year. Usually infrared methods are used to find mechanical defects of the building envelope. In this article an alternative way to describe the building envelope using infrared camera is presented. The method includes the determination of local heat engineering characteristics of the envelope using contact measurements and the determination of averaged heat transfer resistance of the buildings envelope using its infrared image.

  9. Fast Moreau envelope computation I

    Science.gov (United States)

    Lucet, Yves

    2006-11-01

    The present article summarizes the state of the art algorithms to compute the discrete Moreau envelope, and presents a new linear-time algorithm, named NEP for NonExpansive Proximal mapping. Numerical comparisons between the NEP and two existing algorithms: The Linear-time Legendre Transform (LLT) and the Parabolic Envelope (PE) algorithms are performed. Worst-case time complexity, convergence results, and examples are included. The fast Moreau envelope algorithms first factor the Moreau envelope as several one-dimensional transforms and then reduce the brute force quadratic worst-case time complexity to linear time by using either the equivalence with Fast Legendre Transform algorithms, the computation of a lower envelope of parabolas, or, in the convex case, the non expansiveness of the proximal mapping.

  10. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  11. Masonry building envelope analysis

    Science.gov (United States)

    McMullan, Phillip C.

    1993-04-01

    Over the past five years, infrared thermography has proven an effective tool to assist in required inspections on new masonry construction. However, with more thermographers providing this inspection service, establishing a standard for conducting these inspections is imperative. To attempt to standardize these inspections, it is important to understand the nature of the inspection as well as the context in which the inspection is typically conducted. The inspection focuses on evaluating masonry construction for compliance with the design specifications with regard to structural components and thermal performance of the building envelope. The thermal performance of the building includes both the thermal resistance of the material as well as infiltration/exfiltration characteristics. Given that the inspections occur in the 'field' rather than the controlled environment of a laboratory, there are numerous variables to be considered when undertaking this type of inspection. Both weather and site conditions at the time of the inspection can vary greatly. In this paper we will look at the variables encountered during recent inspections. Additionally, the author will present the standard which was employed in collecting this field data. This method is being incorporated into a new standard to be included in the revised version of 'Guidelines for Specifying and Performing Infrared Inspections' developed by the Infraspection Institute.

  12. Envelope glycoprotein of arenaviruses.

    Science.gov (United States)

    Burri, Dominique J; da Palma, Joel Ramos; Kunz, Stefan; Pasquato, Antonella

    2012-10-17

    Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC) by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP). GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.

  13. Envelope Glycoprotein of Arenaviruses

    Directory of Open Access Journals (Sweden)

    Antonella Pasquato

    2012-10-01

    Full Text Available Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1/Site-1 Protease (S1P yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP. GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.

  14. Multifamily Envelope Leakage Model

    Energy Technology Data Exchange (ETDEWEB)

    Faakye, Omari [Consortium for Advanced Residential Buildings, Norwalk, CT (United States); Griffiths, Dianne [Consortium for Advanced Residential Buildings, Norwalk, CT (United States)

    2015-05-08

    “The cost for blower testing is high, because it is labor intensive, and it may disrupt occupants in multiple units. This high cost and disruption deter program participants, and dissuade them from pursuing energy improvements that would trigger air leakage testing, such as improvements to the building envelope.” This statement found in a 2012 report by Heschong Mahone Group for several California interests emphasizes the importance of reducing the cost and complexity of blower testing in multifamily buildings. Energy efficiency opportunities are being bypassed. The cost of single blower testing is on the order of $300. The cost for guarded blower door testing—the more appropriate test for assessing energy savings opportunities—could easily be six times that, and that’s only if you have the equipment and simultaneous access to multiple apartments. Thus, the proper test is simply not performed. This research seeks to provide an algorithm for predicting the guarded blower door test result based upon a single, total blower door test.

  15. Remodeling with the sun

    Energy Technology Data Exchange (ETDEWEB)

    Bodzin, S. [ed.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  16. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  17. Tissue Remodelling following Resection of Porcine Liver

    Directory of Open Access Journals (Sweden)

    Ingvild Engdal Nygård

    2015-01-01

    Full Text Available Aim. To study genes regulating the extracellular matrix (ECM and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx- induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC and collagen 1, alpha 2 (COL1A2 were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson’s Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.

  18. Physical principles of membrane remodelling during cell mechanoadaptation.

    Science.gov (United States)

    Kosmalska, Anita Joanna; Casares, Laura; Elosegui-Artola, Alberto; Thottacherry, Joseph Jose; Moreno-Vicente, Roberto; González-Tarragó, Víctor; del Pozo, Miguel Ángel; Mayor, Satyajit; Arroyo, Marino; Navajas, Daniel; Trepat, Xavier; Gauthier, Nils C; Roca-Cusachs, Pere

    2015-06-15

    Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope--the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.

  19. Nuclear shape changes are induced by knockdown of the SWI/SNF ATPase BRG1 and are independent of cytoskeletal connections.

    Directory of Open Access Journals (Sweden)

    Karen M Imbalzano

    Full Text Available Changes in nuclear morphology occur during normal development and have been observed during the progression of several diseases. The shape of a nucleus is governed by the balance of forces exerted by nuclear-cytoskeletal contacts and internal forces created by the structure of the chromatin and nuclear envelope. However, factors that regulate the balance of these forces and determine nuclear shape are poorly understood. The SWI/SNF chromatin remodeling enzyme ATPase, BRG1, has been shown to contribute to the regulation of overall cell size and shape. Here we document that immortalized mammary epithelial cells show BRG1-dependent nuclear shape changes. Specifically, knockdown of BRG1 induced grooves in the nuclear periphery that could be documented by cytological and ultrastructural methods. To test the hypothesis that the observed changes in nuclear morphology resulted from altered tension exerted by the cytoskeleton, we disrupted the major cytoskeletal networks and quantified the frequency of BRG1-dependent changes in nuclear morphology. The results demonstrated that disruption of cytoskeletal networks did not change the frequency of BRG1-induced nuclear shape changes. These findings suggest that BRG1 mediates control of nuclear shape by internal nuclear mechanisms that likely control chromatin dynamics.

  20. Adverse Remodeling and Reverse Remodeling After Myocardial Infarction.

    Science.gov (United States)

    Bhatt, Ankeet S; Ambrosy, Andrew P; Velazquez, Eric J

    2017-08-01

    The purpose of this review it to summarize the current literature on remodeling after myocardial infarction, inclusive of pathophysiological considerations, imaging modalities, treatment strategies, and future directions. As patients continue to live longer after myocardial infarction (MI), the prevalence of post-MI heart failure continues to rise. Changes in the left ventricle (LV) after MI involve complex interactions between cellular and extracellular components, under neurohormonal regulation. Treatments to prevent adverse LV remodeling and promote reverse remodeling in the post-MI setting include early revascularization, pharmacotherapy aimed at neurohormonal blockade, and device-based therapies that address ventricular dyssynchrony. Despite varying definitions of adverse LV remodeling examined across multiple imaging modalities, the presence of an enlarged LV cavity and/or reduced ejection fraction is consistently associated with poor clinical outcomes. Advances in our knowledge of the neurohormonal regulation of adverse cardiac remodeling have been instrumental in generating therapies aimed at arresting adverse remodeling and promoting reserve remodeling. Further investigation into other specific mechanisms of adverse LV remodeling and pathways to disrupt these mechanisms is ongoing and may provide incremental benefit to current evidence-based therapies.

  1. Chromatin dynamics: interplay between remodeling enzymes and histone modifications.

    Science.gov (United States)

    Swygert, Sarah G; Peterson, Craig L

    2014-08-01

    Chromatin dynamics play an essential role in regulating the accessibility of genomic DNA for a variety of nuclear processes, including gene transcription and DNA repair. The posttranslational modification of the core histones and the action of ATP-dependent chromatin remodeling enzymes represent two primary mechanisms by which chromatin dynamics are controlled and linked to nuclear events. Although there are examples in which a histone modification or a remodeling enzyme may be sufficient to drive a chromatin transition, these mechanisms typically work in concert to integrate regulatory inputs, leading to a coordinated alteration in chromatin structure and function. Indeed, site-specific histone modifications can facilitate the recruitment of chromatin remodeling enzymes to particular genomic regions, or they can regulate the efficiency or the outcome of a chromatin remodeling reaction. Conversely, chromatin remodeling enzymes can also influence, and sometimes directly modulate, the modification state of histones. These functional interactions are generally complex, frequently transient, and often require the association of myriad additional factors. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The LHC on an envelope

    CERN Multimedia

    2007-01-01

    The series of envelopes featuring CERN issued this summer was a huge success. The French postal services of the Pays de Gex will shortly be launching the second set of pre-paid envelopes issued in collaboration with the Laboratory this year, this time highlighting the LHC. Five thousand envelopes describing the accelerator’s capabilities will go on sale on 12 November, and some of the packs will even contain a small sample of the cables from the heart of the LHC magnets. The sets of ten pre-paid envelopes will tell you everything about CERN’s flagship accelerator, from its astounding technical capabilities to its spin-offs in the fields of technology and human resources. Each envelope will feature a different attribute or spin-off of the LHC. People will be invited to consult CERN’s public website for more detailed explanations if they want to know more. The new envelopes will be available from five post offices in the Pays ...

  3. The LHC in an envelope

    CERN Multimedia

    2007-01-01

    The series of envelopes featuring CERN issued this summer was a huge success. The French postal services of the Pays de Gex will shortly be launching the second set of pre-paid envelopes issued in collaboration with the Laboratory this year, this time highlighting the LHC. Five thousand envelopes describing the accelerator’s capabilities will go on sale on 12 November, and some of the packs will even contain a small sample of the cables from the heart of the LHC magnets. The sets of ten pre-paid envelopes will tell you everything about CERN’s flagship accelerator, from its astounding technical capabilities to its spin-offs in the fields of technology and human resources. Each envelope will feature a different attribute or spin-off of the LHC. People will be invited to consult CERN’s public website for more detailed explanations if they want to know more. The new envelopes will be available from five post offices in the Pays de Gex (Ferney-Voltaire, Prévessin...

  4. To Remodel or To Build?

    Science.gov (United States)

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  5. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  6. Design stars: how small DNA viruses remodel the host nucleus.

    Science.gov (United States)

    Jiang, Mengxi; Imperiale, Michael J

    2012-05-01

    Numerous host components are encountered by viruses during the infection process. While some of these host structures are left unchanged, others may go through dramatic remodeling processes. In this review, we summarize these host changes that occur during small DNA virus infections, with a focus on host nuclear components and pathways. Although these viruses differ significantly in their genome structures and infectious pathways, there are common nuclear targets that are altered by various viral factors. Accumulating evidence suggests that these nuclear remodeling processes are often essential for productive viral infections and/or viral-induced transformation. Understanding the complex interactions between viruses and these host structures and pathways will help to build a more integrated network of how the virus completes its life cycle and point toward the design of novel therapeutic regimens that either prevent harmful viral infections or employ viruses as nontraditional treatment options or molecular tools.

  7. Parasitic Events in Envelope Analysis

    Directory of Open Access Journals (Sweden)

    J. Doubek

    2001-01-01

    Full Text Available Envelope analysis allows fast fault location of individual gearboxes and parts of bearings by repetition frequency determination of the mechanical catch of an amplitude-modulated signal. Systematic faults arise when using envelope analysis on a signal with strong changes. The source of these events is the range of function definition of used in convolution integral definition. This integral is used for Hilbert image calculation of analyzed signal. Overshoots (almost similar to Gibbs events on a synthetic signal using the Fourier series are result from these faults. Overshoots are caused by parasitic spectral lines in the frequency domain, which can produce faulty diagnostic analysis.This paper describes systematic arising during faults rising by signal numerical calculation using envelope analysis with Hilbert transform. It goes on to offer a mathematical analysis of these systematic faults.

  8. Moisture dynamics in building envelopes

    Energy Technology Data Exchange (ETDEWEB)

    Peuhkuri, R.

    2003-07-01

    The overall scope of this Thesis 'Moisture dynamics in building envelopes' has been to characterise how the various porous insulation materials investigated performed hygro thermally under conditions similar to those in a typical building envelope. As a result of the changing temperature and moisture conditions in the exterior weather and indoor climate the materials dynamically absorb and release moisture. The complexity of the impact of these conditions on the resulting moisture transport and content of the materials has been studied in this Thesis with controlled laboratory tests. (au)

  9. Perforating the nuclear boundary - how nuclear pore complexes assemble.

    Science.gov (United States)

    Weberruss, Marion; Antonin, Wolfram

    2016-12-15

    The nucleus is enclosed by the nuclear envelope, a double membrane which creates a selective barrier between the cytoplasm and the nuclear interior. Its barrier and transport characteristics are determined by nuclear pore complexes (NPCs) that are embedded within the nuclear envelope, and control molecular exchange between the cytoplasm and nucleoplasm. In this Commentary, we discuss the biogenesis of these huge protein assemblies from approximately one thousand individual proteins. We will summarize current knowledge about distinct assembly modes in animal cells that are characteristic for different cell cycle phases and their regulation.

  10. Understanding the chromatin remodeling code.

    Science.gov (United States)

    Ha, Misook

    2013-10-01

    Remodeling a chromatin structure enables the genetic elements stored in a genome to function in a condition-specific manner and predisposes the interactions between cis-regulatory elements and trans-acting factors. A chromatin signature can be an indicator of the activity of the underlying genetic elements. This paper reviews recent studies showing that the combination and arrangements of chromatin remodeling marks play roles as chromatin code affecting the activity of genetic elements. This paper also reviews recent studies inferring the primary DNA sequence contexts associated with chromatin remodeling that suggest interactions between genetic and epigenetic factors. We conclude that chromatin remodeling, which provides accurate models of gene expression and morphological variations, may help to find the biological marks that cannot be detected by genome-wide association study or genetic study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Effective envelope method for Stewart platform workspace

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The workspace of Stewart platform is the intersection of 6 son workspaces of 6 loop chains, so it is important to determine the boundary of the son workspace when locating the boundary of the son workspace. An effectivc envelope method is proposed in this paper. Firstly the envelope theory of a family of singular parameter curve surfaces is used to find the envelope surfaces of the son workspace. Then the numerical method is applied to determine the effective envelope surface. And after that the full boundary of the son workspace, which is the envelope of the effective envelope surfaces, is determined. Finally the workspace can be obtained with a section plane method.

  12. Handbook on data envelopment analysis

    CERN Document Server

    Cooper, William W; Zhu, Joe

    2011-01-01

    Focusing on extensively used Data Envelopment Analysis topics, this volume aims to both describe the state of the field and extend the frontier of DEA research. New chapters include DEA models for DMUs, network DEA, models for supply chain operations and applications, and new developments.

  13. Energy efficiency of building envelope

    OpenAIRE

    2014-01-01

    November, 12-13th, in Saint-Petersburg the 7th International congress "Energy efficiency. XXI century" took place. The reports were done in breakuo groups according to the various aspects of energy efficiency challenge: HVAC systems, water supply and sewerage systems, gas supply, energy metering. One of the grourps was devoted to thermophysics of buildings and energy effective design of building envelope.

  14. Structure of the Enveloping Algebras

    Directory of Open Access Journals (Sweden)

    Č. Burdík

    2007-01-01

    Full Text Available The adjoint representations of several small dimensional Lie algebras  on their universal enveloping algebras  are explicitly decomposed. It is shown that commutants of raising operators are generated as polynomials in several basic elements. The explicit form of these elements is given and the general method for obtaining  these elements is described. 

  15. Envelope Inflation or Stellar Wind?

    Science.gov (United States)

    Ro, S.; Matzner, C. D.

    We an optically-thick, transonic, steady wind model for a H-free Wolf-Rayet star. A bifurcation is found across a critical mass loss rate Mb. Slower winds M interest for extended envelopes and winds, radiative hydrodynamic instabilities (eg. wind stagnation, clumping, etc.), and NLTE atmospheric models.

  16. Moisture Dynamics in Building Envelopes

    DEFF Research Database (Denmark)

    Peuhkuri, Ruut Hannele

    2003-01-01

    The overall scope of this Thesis "Moisture dynamics in building envelopes" has been to characterise how the various porous insulation materials investigated performed hygrothermally under conditions similar to those in a typical building envelope. As a result of the changing temperature and moist......The overall scope of this Thesis "Moisture dynamics in building envelopes" has been to characterise how the various porous insulation materials investigated performed hygrothermally under conditions similar to those in a typical building envelope. As a result of the changing temperature...... and moisture conditions in the exterior weather and indoor climate the materials dynamically absorb and release moisture. The complexity of the impact of these conditions on the resulting moisture transport and content of the materials has been studied in this Thesis with controlled laboratory tests. The first...... part of the Thesis consists of a theory and literature review on the moisture storage and transport processes (Chapter 2), on the non-Fickian moisture transport (Chapter 3)and on the methods for determining the moisture properties (Chapter 4). In the second part, the conducted experimental work...

  17. 重大环境事件与当代国际社会的重塑——福岛核泄漏事件的环境社会学反思%On Major Environmental Pollution Accidents and Remodeling of Contemporary International Society:The Sociological Reflection on Fukushima Nuclear Accident

    Institute of Scientific and Technical Information of China (English)

    王书明; 徐文涛

    2012-01-01

    In Fukushima nuclear accident, various social activists re-constructed themselves in response to the nuclear risks, which triggered interaction among them. The risk interaction caused by Fukushima nuclear acci- dent has become a great driving force to remodel the international society. Fukushima nuclear accident stimulated strong safety needs in well-off society and reflective modernization. It shows that the risk event can not only be the enemy to human security, but also be an important mechanism for safety re-construction. Reflection and gov- ernance on risk events will bring us closer towards a future with greater security.%在福岛核泄漏事件中,各种各样的社会行动者纷纷建构自身以应对核风险,这些建构自身的活动产生了行动主体间的交互影响。福岛核泄漏事件产生的风险互动成为重塑国际社会的重要力量,激发了富裕社会以及自反性现代化对安全的强烈需求。福岛核泄漏事件表明,风险事件既是人类安全需求的对立物,也是安全建构的重要机遇,风险事件的反思和治理会使未来社会更加安全。

  18. Residential Building Envelope Alternatives with Equivalent Cost

    OpenAIRE

    2011-01-01

    Selecting the optimum envelope alternative in buildings is one of the most important factors in ensuring thermal comfort. This study calculated the heating costs, construction and lifecycle costs for a residential building in Istanbul with different envelope alternatives created by changing the type and thickness of the body and insulation materials used in the walls and roof, which are the structural components forming the building envelope. Envelope alternatives with equivalent costs were d...

  19. Assaying chromatin structure and remodeling by restriction enzyme accessibility

    OpenAIRE

    Trotter, Kevin W.; Archer, Trevor K.

    2012-01-01

    The packaging of eukaryotic DNA into nucleosomes, the fundamental unit of chromatin, creates a barrier to nuclear processes, such as transcription, DNA replication, recombination, and repair(1). This obstructive nature of chromatin can be overcome by the enzymatic activity of chromatin remodeling complexes which creates a more favorable environment for the association of essential factors and regulators to sequences within target genes. Here we describe a detailed approach for analyzing chrom...

  20. Transcriptional regulation of bone and joint remodeling by NFAT

    OpenAIRE

    2010-01-01

    Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particula...

  1. microRNAs and Cardiovascular Remodeling.

    Science.gov (United States)

    Ono, Koh

    2015-01-01

    Heart failure (HF) is associated with significant morbidity and mortality attributable largely to structural changes in the heart and with associated cardiac dysfunction. Remodeling is defined as alteration of the mass, dimensions, or shape of the heart (termed cardiac or ventricular remodeling) and vessels (vascular remodeling) in response to hemodynamic load and/or cardiovascular injury in association with neurohormonal activation. Remodeling may be described as physiologic or pathologic; alternatively, remodeling may be classified as adaptive or maladaptive. The importance of remodeling as a pathogenic mechanism has been controversial because factors leading to remodeling as well as the remodeling itself may be major determinants of patients' prognosis. The basic mechanisms of cardiovascular remodeling, and especially the roles of microRNAs in HF progression and vascular diseases, will be reviewed here.

  2. Moisture Dynamics in Building Envelopes

    DEFF Research Database (Denmark)

    Peuhkuri, Ruut Hannele

    2003-01-01

    The overall scope of this Thesis "Moisture dynamics in building envelopes" has been to characterise how the various porous insulation materials investigated performed hygrothermally under conditions similar to those in a typical building envelope. As a result of the changing temperature...... and moisture conditions in the exterior weather and indoor climate the materials dynamically absorb and release moisture. The complexity of the impact of these conditions on the resulting moisture transport and content of the materials has been studied in this Thesis with controlled laboratory tests. The first......, results, and analysis are presented (Chapters 5-7). The major findings are discussed (Chapter 8), before the final conclusion (Chapter 9). The Appendices include the material parameters used, some additional results and the description of the simulation models....

  3. Safeguards Envelope Progress FY08

    Energy Technology Data Exchange (ETDEWEB)

    Robert Bean; Richard Metcalf; Aaron Bevill

    2008-09-01

    The Safeguards Envelope Project met its milestones by creating a rudimentary safeguards envelope, proving the value of the approach on a small scale, and determining the most appropriate path forward. The Idaho Chemical Processing Plant’s large cache of reprocessing process monitoring data, dubbed UBER Data, was recovered and used in the analysis. A probabilistic Z test was used on a Markov Monte Carlo simulation of expected diversion data when compared with normal operating data. The data regarding a fully transient event in a tank was used to create a simple requirement, representative of a safeguards envelope, whose impact was a decrease in operating efficiency by 1.3% but an increase in material balance period of 26%. This approach is operator, state, and international safeguards friendly and should be applied to future reprocessing plants. Future requirements include tank-to-tank correlations in reprocessing facilities, detailed operations impact studies, simulation inclusion, automated optimization, advanced statistics analysis, and multi-attribute utility analysis.

  4. Modulation of bacterial outer membrane vesicle production by envelope structure and content.

    Science.gov (United States)

    Schwechheimer, Carmen; Kulp, Adam; Kuehn, Meta J

    2014-12-21

    Vesiculation is a ubiquitous secretion process of Gram-negative bacteria, where outer membrane vesicles (OMVs) are small spherical particles on the order of 50 to 250 nm composed of outer membrane (OM) and lumenal periplasmic content. Vesicle functions have been elucidated in some detail, showing their importance in virulence factor secretion, bacterial survival, and biofilm formation in pathogenesis. Furthermore, OMVs serve as an envelope stress response, protecting the secreting bacteria from internal protein misfolding stress, as well as external envelope stressors. Despite their important functional roles very little is known about the regulation and mechanism of vesicle production. Based on the envelope architecture and prior characterization of the hypervesiculation phenotypes for mutants lacking the lipoprotein, Lpp, which is involved in the covalent OM-peptidoglycan (PG) crosslinks, it is expected that an inverse relationship exists between OMV production and PG-crosslinked Lpp. In this study, we found that subtle modifications of PG remodeling and crosslinking modulate OMV production, inversely correlating with bound Lpp levels. However, this inverse relationship was not found in strains in which OMV production is driven by an increase in "periplasmic pressure" resulting from the accumulation of protein, PG fragments, or lipopolysaccharide. In addition, the characterization of an nlpA deletion in backgrounds lacking either Lpp- or OmpA-mediated envelope crosslinks demonstrated a novel role for NlpA in envelope architecture. From this work, we conclude that OMV production can be driven by distinct Lpp concentration-dependent and Lpp concentration-independent pathways.

  5. Introducing the Adaptive Convex Enveloping

    CERN Document Server

    Yu, Sheng

    2011-01-01

    Convexity, though extremely important in mathematical programming, has not drawn enough attention in the field of dynamic programming. This paper gives conditions for verifying convexity of the cost-to-go functions, and introduces an accurate, fast and reliable algorithm for solving convex dynamic programs with multivariate continuous states and actions, called Adaptive Convex Enveloping. This is a short introduction of the core technique created and used in my dissertation, so it is less formal, and misses some parts, such as literature review and reference, compared to a full journal paper.

  6. Flexible Envelope Request Notation (FERN)

    Science.gov (United States)

    Zoch, David R.; Lavallee, David; Weinstein, Stuart

    1991-01-01

    The following topics are presented in view graph form and include the following: scheduling application; the motivation for the Flexible Envelope Request Notation (FERN); characteristics of FERN; types of information needed in requests; where information is stored in requests; FERN structures; generic requests; resource availability for pooled resources; expressive notation; temporal constraints; time formats; changes to FERN; sample FERN requests; the temporal relationship between two steps; maximum activity length to limit step delays; alternative requests; the temporal relationship between two activities; and idle resource usage between steps.

  7. Continuum remodeling revisited : deformation rate driven functional adaptation using a hypoelastic constitutive law.

    Science.gov (United States)

    Negus, Charles H; Impelluso, Thomas J

    2007-07-01

    Recent research effort in bone remodeling has been directed toward describing interstitial fluid flow in the lacuno-canalicular system and its potential as a cellular stimulus. Regardless of the precise contents of the mechanotransduction "black box", it seems clear that the fluid flow on which the remodeling is predicated cannot occur under static loading conditions. In an attempt to help continuum remodeling simulations catch up with cellular and subcellular research, this paper presents a simple, strain rate driven remodeling algorithm for density allocation and principal material direction rotations. An explicit finite element code was written and deployed on a supercomputer which discretizes the remodeling process and uses an objective hypoelastic constitutive law to simulate trabecular realignment. Results indicate that a target strain rate for this dynamic approach is |D ( I )| = 1.7% per second which seems reasonable when compared to observed strain rates. Simulations indicate that a morpho-mechanically realistic three-dimensional bone can be synthesized by applying a few dynamic loads at the envelope of common daily physiological rates, even with no static loading component.

  8. Early Site Permit Demonstration Program: Plant parameters envelope report. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1993-03-01

    The Early Site Permit (ESP) Demonstration Program is the nuclear industry`s initiative for piloting the early resolution of siting-related issues before the detailed design proceedings of the combined operating license review. The ESP Demonstration Program consists of three phases. The plant parameters envelopes task is part of Phase 1, which addresses the generic review of applicable federal regulations and develops criteria for safety and environmental assessment of potential sites. The plant parameters envelopes identify parameters that characterize the interface between an ALWR design and a potential site, and quantify the interface through values selected from the Utility Requirements Documents, vendor design information, or engineering assessments. When augmented with site-specific information, the plant parameters envelopes provide sufficient information to allow ESPs to be granted based on individual ALWR design information or enveloping design information for the evolutionary, passive, or generic ALWR plants. This document is expected to become a living document when used by future applicants.

  9. Adaptive Flight Envelope Estimation and Protection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Impact Technologies, in collaboration with the Georgia Institute of Technology, proposes to develop and demonstrate an innovative flight envelope estimation and...

  10. Building Construction Elements, Building Envelope and Method for Constructing a Building Envelope

    DEFF Research Database (Denmark)

    2009-01-01

    High-strength concrete building system and method of assembly for construction a buiding envelope.......High-strength concrete building system and method of assembly for construction a buiding envelope....

  11. Functional evolution of nuclear structure

    OpenAIRE

    Wilson, Katherine L.; Dawson, Scott C.

    2011-01-01

    The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These compo...

  12. LPS Remodeling Triggers Formation of Outer Membrane Vesicles in Salmonella

    Science.gov (United States)

    Elhenawy, Wael; Bording-Jorgensen, Michael; Valguarnera, Ezequiel; Haurat, M. Florencia; Wine, Eytan

    2016-01-01

    ABSTRACT Outer membrane vesicles (OMV) are proposed to mediate multiple functions during pathogenesis and symbiosis. However, the mechanisms responsible for OMV formation remain poorly understood. It has been shown in eukaryotic membranes that lipids with an inverted-cone shape favor the formation of positive membrane curvatures. Based on these studies, we formulated the hypothesis that lipid A deacylation might impose shape modifications that result in the curvature of the outer membrane (OM) and subsequent OMV formation. We tested the effect of lipid A remodeling on OMV biogenesis employing Salmonella enterica serovar Typhimurium as a model organism. Expression of the lipid A deacylase PagL resulted in increased vesiculation, without inducing an envelope stress response. Mass spectrometry analysis revealed profound differences in the patterns of lipid A in OM and OMV, with accumulation of deacylated lipid A forms exclusively in OMV. OMV biogenesis by intracellular bacteria upon macrophage infection was drastically reduced in a pagL mutant strain. We propose a novel mechanism for OMV biogenesis requiring lipid A deacylation in the context of a multifactorial process that involves the orchestrated remodeling of the outer membrane. PMID:27406567

  13. LPS Remodeling Triggers Formation of Outer Membrane Vesicles in Salmonella

    Directory of Open Access Journals (Sweden)

    Wael Elhenawy

    2016-07-01

    Full Text Available Outer membrane vesicles (OMV are proposed to mediate multiple functions during pathogenesis and symbiosis. However, the mechanisms responsible for OMV formation remain poorly understood. It has been shown in eukaryotic membranes that lipids with an inverted-cone shape favor the formation of positive membrane curvatures. Based on these studies, we formulated the hypothesis that lipid A deacylation might impose shape modifications that result in the curvature of the outer membrane (OM and subsequent OMV formation. We tested the effect of lipid A remodeling on OMV biogenesis employing Salmonella enterica serovar Typhimurium as a model organism. Expression of the lipid A deacylase PagL resulted in increased vesiculation, without inducing an envelope stress response. Mass spectrometry analysis revealed profound differences in the patterns of lipid A in OM and OMV, with accumulation of deacylated lipid A forms exclusively in OMV. OMV biogenesis by intracellular bacteria upon macrophage infection was drastically reduced in a pagL mutant strain. We propose a novel mechanism for OMV biogenesis requiring lipid A deacylation in the context of a multifactorial process that involves the orchestrated remodeling of the outer membrane.

  14. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  15. Reach Envelope of Human Extremities

    Institute of Scientific and Technical Information of China (English)

    YANG Jingzhou(杨景周); ZHANG Yunqing(张云清); CHEN Liping(陈立平); ABDEL-MALEK Karim

    2004-01-01

    Significant attention in recent years has been given to obtain a better understanding of human joint ranges, measurement, and functionality, especially in conjunction with commands issued by the central nervous system. While researchers have studied motor commands needed to drive a limb to follow a path trajectory, various computer algorithms have been reported that provide adequate analysis of limb modeling and motion. This paper uses a rigorous mathematical formulation to model human limbs, understand their reach envelope, delineate barriers therein where a trajectory becomes difficult to control, and help visualize these barriers. Workspaces of a typical forearm with 9 degrees of freedom, a typical finger modeled as a 4- degree-of-freedom system, and a lower extremity with 4 degrees of freedom are discussed. The results show that using the proposed formulation, joint limits play an important role in distinguishing the barriers.

  16. THE COMPLEX ORGANIZATION OF EUKARYOTIC CELL NUCLEUS (III: THE NUCLEAR MATRIX AND THE NUCLEAR LAMINA

    Directory of Open Access Journals (Sweden)

    Cristian S. Cimpeanu

    2013-07-01

    Full Text Available A large variety of nuclear fibrous proteins (such as actin, myosin, lamin B, transcription factors, topoisomerases, etc represent constitutive elements of complex structures present in the eukaryotic nuclei: the nuclear matrix and the nuclear lamina, repectively. These nuclear compartments, with fibrous network-like structure, play crucialroles in structural organization of nuclei, chromatin remodeling, DNA transcription, signals transduction, cell cycle regulation, embryonic development and other nuclear basic processes.

  17. Calcium remodeling in colorectal cancer.

    Science.gov (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2017-06-01

    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin

  18. Comment on "The envelope of projectile trajectories"

    CERN Document Server

    Butikov, E I

    2003-01-01

    Several simple alternative methods to obtain the equation of the envelope of the family of projectile trajectories corresponding to the same initial speed are suggested, including methods in which the boundary of the region occupied by the parabolic trajectories is found as an envelope of a set of circles. Two possible generalizations of the discussed problem are also suggested. (letters and comments)

  19. 14 CFR 23.333 - Flight envelope.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Flight envelope. 23.333 Section 23.333... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Structure Flight Loads § 23.333 Flight envelope. (a) General. Compliance with the strength requirements of this subpart must be shown...

  20. Implementation of an Improved Safe Operating Envelope

    Energy Technology Data Exchange (ETDEWEB)

    Prime, Robyn; McIntyre, Mark [NB Power Nuclear, P.O. Box 600, Lepreau, NB (Canada); Reeves, David [Atlantic Nuclear Services Ltd., PO Box 1268 Fredericton, NB (Canada)

    2008-07-01

    This paper is a continuation of the paper presented at IYNC 2004 on 'The Definition of a Safe Operating Envelope'. The current paper concentrates on the implementation process of the Safe Operating Envelope employed at the Point Lepreau Generating Station. (authors)

  1. Lipid partitioning at the nuclear envelope controls membrane biogenesis

    NARCIS (Netherlands)

    Barbosa, Antonio Daniel; Sembongi, Hiroshi; Su, Wen-Min; Abreu, Susana; Reggiori, Fulvio; Carman, George M.; Siniossoglou, Symeon

    2015-01-01

    Partitioning of lipid precursors between membranes and storage is crucial for cell growth, and its disruption underlies pathologies such as cancer, obesity, and type 2 diabetes. However, the mechanisms and signals that regulate this process are largely unknown. In yeast, lipid precursors are mainly

  2. The remodeling transient and the calcium economy.

    Science.gov (United States)

    Aloia, J F; Arunabh-Talwar, S; Pollack, S; Yeh, J K

    2008-07-01

    The remodeling transient describes a change in bone mass that lasts one remodeling cycle following an intervention that disturbs the calcium economy. We demonstrated the transient in a study of the response of bone density to calcium/vitamin D3 supplementation and show the hazards of misinterpretation if the transient is not considered. The remodeling transient describes a change in bone mass that lasts for one remodeling cycle following an intervention that disturbs the calcium economy. We report an intervention with calcium and vitamin D supplementation in 208 postmenopausal African-American women where the remodeling transient was considered a priori in the study design. Both groups (calcium alone vs. calcium + 20 microg (800 IU) vitamin D3) were ensured a calcium intake in excess of 1200 mg/day. There were no differences between the two groups in changes in BMD over time. These BMD changes were therefore interpreted to reflect increased calcium intake in both groups but not any influence of vitamin D. A transient increase in bone mineral density was observed during the first year of study, followed by a decline. The remodeling period was estimated at about 9 months, which is similar to histomorphometric estimates. It is problematic to draw conclusions concerning interventions that influence the calcium economy without considering the remodeling transient in study design. Studies of agents that effect bone remodeling must be carried out for at least two remodeling cycles and appropriate techniques must be used in data analysis.

  3. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  4. Spectral Envelopes - A Preliminary Report

    CERN Document Server

    Lawton, Wayne

    2012-01-01

    The spectral envelope S(F) of a subset of integers is the set of probability measures on the circle group that are weak star limits of squared moduli of trigonometric polynomials with frequencies in F. Fourier transforms of these measures are positive and supported in F - F but the converse generally fails. The characteristic function chiF of F is a binary sequence whose orbit closure gives a symbolic dynamical system O(F). Analytic properties of S(F) are related to dynamical properties of chiF. The Riemann-Lebesque lemma implies that if chiF is minimal, then S(F) is convex and hence S(F) is the closure of the convex hull of its extreme points Se(F). In this paper we (i) review the relationship between these concepts and the special case of the still open 1959 Kadison-Singer problem called Feichtinger's conjecture for exponential functions, (ii) partially characterize of elements in Se(F), for minimal chiF, in terms of ergodic properties of (O(F),lambda) where lambda is a shift invariant probability measure w...

  5. Circumplanetary disk or circumplanetary envelope?

    CERN Document Server

    Szulágyi, J; Lega, E; Crida, A; Morbidelli, A; Guillot, T

    2016-01-01

    We present three-dimensional simulations with nested meshes of the dynamics of the gas around a Jupiter mass planet with the JUPITER and FARGOCA codes. We implemented a radiative transfer module into the JUPITER code to account for realistic heating and cooling of the gas. We focus on the circumplanetary gas flow, determining its characteristics at very high resolution ($80\\%$ of Jupiter's diameter). In our nominal simulation where the temperature evolves freely by the radiative module and reaches 13000 K at the planet, a circumplanetary envelope was formed filling the entire Roche-lobe. Because of our equation of state is simplified and probably overestimates the temperature, we also performed simulations with limited maximal temperatures in the planet region (1000 K, 1500 K, and 2000 K). In these fixed temperature cases circumplanetary disks (CPDs) were formed. This suggests that the capability to form a circumplanetary disk is not simply linked to the mass of the planet and its ability to open a gap. Inste...

  6. New pharmacological strategies to fight enveloped viruses.

    Science.gov (United States)

    Wisskirchen, Karin; Lucifora, Julie; Michler, Thomas; Protzer, Ulrike

    2014-09-01

    Enveloped viruses pose an important health threat because most of the persistent and many emerging viruses are enveloped. In particular, newly emerging viruses create a need to develop broad-spectrum antivirals, which usually are obtained by targeting host cell factors. Persistent viruses have developed efficient strategies to escape host immune control, and treatment options are limited. Targeting host cell factors essential for virus persistence, or immune-based therapies provide alternative approaches. In this review, we therefore focus on recent developments to generate antivirals targeting host cell factors or immune-based therapeutic approaches to fight infections with enveloped viruses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. On the history of nuclear matrix manifestation

    Institute of Scientific and Technical Information of China (English)

    ZBARSKYIB

    1998-01-01

    The nonchromatin proteinous residue of the cell nucleus was revealed in our laboratory as early as in 1948 and then identified by light and electron microscopy as residual nucleoli,intranuclear network and nuclear envelope before 1960,This structure termed afterwards as "nuclear residue","nuclear skeleton","nuclear cage","nuclear carcass"etc.,was much later(in 1974) isolated,studied and entitled as "nuclear matrix" by Berezney and Coffey,to whom the discovery of this residual structure is often wronly ascribed.The real history of nuclear matrix manifestation is reported in this paper.

  8. Small artery remodelling in diabetes.

    Science.gov (United States)

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-05-01

    The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure.

  9. Non-Nuclear Testing of Space Nuclear Systems at NASA MSFC

    Science.gov (United States)

    Houts, Michael G.; Pearson, Boise J.; Aschenbrenner, Kenneth C.; Bradley, David E.; Dickens, Ricky; Emrich, William J.; Garber, Anne; Godfroy, Thomas J.; Harper, Roger T.; Martin, Jim J.; hide

    2010-01-01

    Highly realistic non-nuclear testing can be used to investigate and resolve potential issues with space nuclear power and propulsion systems. Non-nuclear testing is particularly useful for systems designed with fuels and materials operating within their demonstrated nuclear performance envelope. Non-nuclear testing allows thermal hydraulic, heat transfer, structural, integration, safety, operational, performance, and other potential issues to be investigated and resolved with a greater degree of flexibility and at reduced cost and schedule compared to nuclear testing. The primary limit of non-nuclear testing is that nuclear characteristics and potential nuclear issues cannot be directly investigated. However, non-nuclear testing can be used to augment the potential benefit from any nuclear testing that may be required for space nuclear system design and development. This paper describes previous and ongoing non-nuclear testing related to space nuclear systems at NASA's Marshall Space Flight Center (MSFC).

  10. Enveloping Relief Surfaces of Landslide Terrain

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Two relief surfaces that envelop the rock fall region in a part of Garhwal Himalayas around Chamoli have been identified. Relative relief and absolute relief have been analyzed and the enveloping surfaces recorded at two levels of relief in the landscape. All landslide activity lies within these surfaces. The lower enveloping surface (800 m) dips due south by 7-8 degrees, due to an elevation rise of 100 meters within 12 km from south to north, i.e., a gradient of 8 percent. The nature of the surface is smooth. The upper enveloping surface (> 2500 m) is almost parallel to the lower one but its surface is undulatory due to landslides and denudation. The area has been a seismically active region and has undergone seismic activity up until recently, as evidenced by the Chamoli earthquake of 29th March 1999. The effects of earthquakes are seen at higher levels in the form of landslide imprints on the terrain.

  11. Small carbon chains in circumstellar envelopes

    CERN Document Server

    Hargreaves, R J; Bernath, P F

    2014-01-01

    Observations were made for a number of carbon-rich circumstellar envelopes using the Phoenix spectrograph on the Gemini South telescope to determine the abundance of small carbon chain molecules. Vibration-rotation lines of the $\

  12. Solar envelope concepts: moderate density building applications

    Science.gov (United States)

    Knowles, R. L.; Berry, R. D.

    1980-04-01

    The public policy mechanism for guaranteeing solar access is conceptualized as a solar zoning envelope that allows the largest possible building bulk on a land parcel without shadowing neighboring properties during specified times. Step-by-step methods for generating solar envelopes are described with extensive drawings, showing a variety of urban platting and lot configurations. Development and design possibilities are examined on a selected set of Los Angeles sites with typically diverse urban characteristics. Envelope attributes suitable for encouraging moderate-density commercial and residential building are examined in the context of two hypothetical but realistic development programs: one for speculative office buildings and one for condominium housing. Numerous illustrations of envelope forms and prototypical building designs are provided.

  13. Remodeling, Renovation, & Conversion of Educational Facilities.

    Science.gov (United States)

    Association of Physical Plant Administrators of Universities and Colleges, Washington, DC.

    Based on a series of workshops, this collection of papers provides a framework for thought--emphasizing planning within time, flexibility, and maintenance constraints--as well as a practical guide for actual engineering of remodeling/renovation/conversion projects. Is remodeling always less expensive than new construction? Should high initial…

  14. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  15. The Envelope of Projectile Trajectories in Midair

    CERN Document Server

    Chudinov, P

    2005-01-01

    A classic problem of the motion of a point mass (projectile) thrown at an angle to the horizon is reviewed. The air drag force is taken into account with the drag factor assumed to be constant. Analytic approach is used for investigation. Simple analytical formulas are used for the constructing the envelope of the family of the point mass trajectories. The equation of envelope is applied for determination of maximum range of flight. The motion of a baseball is presented as an example.

  16. Investment Costs of the Building Envelope Reconstructions

    OpenAIRE

    2014-01-01

    The article is aimed at the design of the measurements improving the thermal-technical properties of the building envelope from the point of view of the economic evaluation. The starting point for the evaluation of economic aspects is the quantification of the partial and total costs according to the individual constructions of the building envelope in relation to the earlier requirements. The result is the determination of the minimal thickness of the thermal insulation i.e. the determinatio...

  17. Multi-layered breathing architectural envelope

    DEFF Research Database (Denmark)

    Lund Larsen, Andreas; Foged, Isak Worre; Jensen, Rasmus Lund

    2014-01-01

    A multi layered breathing envelope is developed as a method of natural ventilation. The two main layers consist of mineral wool and air permeable concrete. The mineral wool works as a dynamic insulation and the permeable concrete as a heat recovery system with a high thermal mass for heat storage....... The performance of the envelope is simulated and put through an optimization process. The impact of a design system on the architectural potential of Performance -based design was investigated....

  18. Role of thyroid hormones in ventricular remodeling.

    Science.gov (United States)

    Rajagopalan, Viswanathan; Gerdes, A Martin

    2015-04-01

    Cardiac remodeling includes alterations in molecular, cellular, and interstitial systems contributing to changes in size, shape, and function of the heart. This may be the result of injury, alterations in hemodynamic load, neurohormonal effects, electrical abnormalities, metabolic changes, etc. Thyroid hormones (THs) serve as master regulators for diverse remodeling processes of the cardiovascular system-from the prenatal period to death. THs promote a beneficial cardiomyocyte shape and improve contractility, relaxation, and survival via reversal of molecular remodeling. THs reduce fibrosis by decreasing interstitial collagen and reduce the incidence and duration of arrhythmias via remodeling ion channel expression and function. THs restore metabolic function and also improve blood flow both by direct effects on the vessel architecture and decreasing atherosclerosis. Optimal levels of THs both in the circulation and in cardiac tissues are critical for normal homeostasis. This review highlights TH-based remodeling and clinically translatable strategies for diverse cardiovascular disorders.

  19. Genetic Diversity of Koala Retroviral Envelopes

    Directory of Open Access Journals (Sweden)

    Wenqin Xu

    2015-03-01

    Full Text Available Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process.

  20. Cooling of neutron stars with diffusive envelopes

    CERN Document Server

    Beznogov, M V; Haensel, P; Yakovlev, D G; Zdunik, J L

    2016-01-01

    We study the effects of heat blanketing envelopes of neutron stars on their cooling. To this aim, we perform cooling simulations using newly constructed models of the envelopes composed of binary ion mixtures (H--He, He--C, C--Fe) varying the mass of lighter ions (H, He or C) in the envelope. The results are compared with those calculated using the standard models of the envelopes which contain the layers of lighter (accreted) elements (H, He and C) on top of the Fe layer, varying the mass of accreted elements. The main effect is that the chemical composition of the envelopes influences their thermal conductivity and, hence, thermal insulation of the star. For illustration, we apply these results to estimate the internal temperature of the Vela pulsar and to study the cooling of neutron stars of ages of 0.1 - 1 Myr at the photon cooling stage. The uncertainties of the cooling models associated with our poor knowledge of chemical composition of the heat insulating envelopes strongly complicate theoretical reco...

  1. All the Universe in an envelope

    CERN Document Server

    2007-01-01

    Do you know which force is hidden in an envelope or how many billions of years old are the atoms it contains? You will find the answers to these (curious) questions in a post office in the Pays de Gex. The French postal services of the Pays de Gex are again issuing pre-paid envelopes in collaboration with CERN (see Bulletin No. 24/2006). The new series presents some of the concepts of modern physics in an amazing way by showing what you can learn about the Universe with a single envelope. Packets of ten pre-stamped envelopes, each carrying a statement on fundamental physics, will be on sale from 7 July onwards. To learn more about the physics issues presented on the envelopes, people are invited to go to the CERN Web site where they will find the explanations. Five thousand envelopes will be put on sale in July and five thousand more during the French "Fête de la science" in October. They will be available from five post offices in the Pays de Gex (F...

  2. Genetic Diversity of Koala Retroviral Envelopes

    Science.gov (United States)

    Xu, Wenqin; Gorman, Kristen; Santiago, Jan Clement; Kluska, Kristen; Eiden, Maribeth V.

    2015-01-01

    Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A) were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process. PMID:25789509

  3. The joke envelope: a neglected precursor of the psychic envelope concept in Freud's writing.

    Science.gov (United States)

    Spero, Moshe Halevi

    2009-01-01

    The concepts of the primeval skin ego, psychic envelope, and related pre-ego containing and wrapping functions elaborated respectively by Esther Bick, Didier Anzieu, and Francis Tustin occupy an important position in contemporary psychoanalytic theory and clinical practice. The psychic envelope begins as a virtual mental protostructure ("proto" because it is not yet based on fully symbolized representations) that holds the budding mind together pending further developments. With maturity, the enveloping functions adopt symbolized, metaphoric form (for example, the aesthetic use of cloth, the analytic framework), but can regress to more concrete and pathological forms. The aforementioned authors based their ideas on a cluster of specific allusions to the idea of a psychic covering, barrier, or envelope in Freud's work. Yet they neglected one reference, hidden in Freud's analysis of the structure ofjokes and humor: the 'joke envelope"--die witzige Einkleidung. The present essay explores Freud's use of the term Einkleidung, including his intriguing idea that a joke requires three people whereas a dream does not and the fact that Freud nowhere speaks of a "dream envelope. "I take the "joke envelope" beyond its original context and posit a relationship between laughter and the early, normative traumas of breathing, crying, and loss, and the dawn of rhythmic envelopes that enable mentalization. Jokes and joking symbolically repeat the early rupture and rapture of breathing and self-other differentiation and the internalization of maternal containing and envelopment.

  4. Exercise-induced cardiac remodeling.

    Science.gov (United States)

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  5. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  6. Nuclear and nuclear reprogramming during the first cell cycle in bovine nuclear transfer embryos

    DEFF Research Database (Denmark)

    Østrup, Olga; Petrovicova, Ida; Strejcek, Frantisek

    2009-01-01

    Abstract The immediate events of genomic reprogramming at somatic cell nuclear transfer (SCNT) are to high degree unknown. This study was designed to evaluate the nuclear and nucleolar changes during the first cell cycle. Bovine SCNT embryos were produced from starved bovine fibroblasts and fixed......, somatic cell nuclei introduced into enucleated oocytes displayed chromatin condensation, partial nuclear envelope breakdown, nucleolar desegregation and transcriptional quiescence already at 0.5 hpa. Somatic cell cytoplasm remained temporally attached to introduced nucleus and nucleolus was partially...... restored indicating somatic influence in the early SCNT phases. At 1-3 hpa, chromatin gradually decondensed toward the nucleus periphery and nuclear envelope reformed. From 4 hpa, the somatic cell nucleus gained a PN-like appearance and displayed NPBs suggesting ooplasmic control of development....

  7. Airway remodeling in asthma: what really matters.

    Science.gov (United States)

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  8. Herpes simplex virus glycoproteins gB and gD function in a redundant fashion to promote secondary envelopment.

    Science.gov (United States)

    Johnson, David C; Wisner, Todd W; Wright, Catherine C

    2011-05-01

    Egress of herpes simplex virus (HSV) and other herpesviruses from cells involves extensive modification of cellular membranes and sequential envelopment and deenvelopment steps. HSV glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Capsids in the nucleus undergo primary envelopment at the inner nuclear membrane (INM), and then enveloped virus particles undergo deenvelopment by fusing with the outer nuclear membrane (ONM). Capsids delivered into the cytoplasm then undergo secondary envelopment, involving trans-Golgi network (TGN) membranes. The deenvelopment step involves HSV glycoproteins gB and gH/gL acting in a redundant fashion. This fusion has features common to the fusion that occurs between the virion envelope and cellular membranes when HSV enters cells, a process requiring gB, gD, and gH/gL. Whether HSV gD also participates (in a redundant fashion with gB or gH/gL) in deenvelopment has not been characterized. Secondary envelopment in the cytoplasm is known to involve HSV gD and gE/gI, also acting in a redundant fashion. Whether gB might also contribute to secondary envelopment, collaborating with gD and gE/gI, is also not clear. To address these questions, we constructed an HSV double mutant lacking gB and gD. The HSV gB(-)/gD(-) mutant exhibited no substantial defects in nuclear egress. In contrast, secondary envelopment was markedly reduced, and there were numerous unenveloped capsids that accumulated in the cytoplasm, as well as increased numbers of partially enveloped capsids and morphologically aberrant enveloped particles with thicker, oblong tegument layers. These defects were different from those observed with HSV gD(-)/gE(-)/gI(-) mutants, which accumulated capsids in large, aggregated masses in the cytoplasm. Our results suggest that HSV gB functions in secondary envelopment, apparently acting downstream of gE/gI.

  9. Enveloped and non-enveloped viral-like particles in Trypanosoma cruzi epimastigotes

    Science.gov (United States)

    Fernández-Presas, Ana María; Padilla-Noriega, Luis; Ingeborg-Becker; Robert, Lilia; Jiménez, José Agustín; Solano, Sandra; Delgado, Jose; Tato, Patricia; Molinari, José Luis

    2017-01-01

    ABSTRACT Electron microscopy is routinely used to identify viral infections in protozoan parasites. These viruses have been described as non-enveloped and icosahedral structures with a diameter of 30-60 nm. Most of them are classified within the non-segmented dsRNA Totiviridae family. We observed virus-like particles (VLPs) through transmission electron microscopy in the cytoplasm of Trypanosoma cruzi epimastigotes grown in cultures. Clusters of electrodense enveloped VLPs having a diameter of 48 nm were also observed. These clusters appear to have been released from distended Golgi cisternae. Furthermore, a paracrystalline array of electrodense, non-enveloped VLPs (with a diameter of 32 nm) were found in distended Golgi cisternae or as smaller clusters at a distance from the RE or Golgi. We cannot rule out that the 48 nm enveloped VLPs belong to the ssRNA Flaviviridae family because they are within its size range. The localization of enveloped VLPs is consistent with the replication strategy of these viruses that transit through the Golgi to be released at the cell surface. Due to the size and shape of the 32 nm non-enveloped VLPs, we propose that they belong to the dsRNA Totiviridae family. This is the first description of cytoplasmic enveloped and non-enveloped VLPs in T. cruzi epimastigotes. PMID:28793017

  10. Morphologically complex protostellar envelopes : structure and kinematics

    Science.gov (United States)

    Tobin, John J.

    I present an in-depth study of protostars and their surrounding envelopes of dense gas and dust, using a multitude of observational methods to reveal new details of the star formation process. I use mid-infrared imaging from the Spitzer Space Telescope, combined with photometry spanning the near-infrared to millimeter wavelengths, to construct a model of the L1527 protostellar system. I modeled both the spectral energy distribution and resolved scattered light images to determine physical properties of the protostellar system. The nature of the apparent central point source in the Spitzer images was uncertain until high-resolution L-band imaging from the Gemini observatory resolved the point source into a disk in scattered light, having a radius of 200 AU. Protostellar envelopes are also often found to cast shadows against the 8 micron Galactic background in Spitzer imaging, enabling direct probes of envelope structure. The shadow images show that the dense envelopes around twenty-two Class 0 protostars are generally morphologically complex from 0.1 pc scales down to ˜1000 AU; they are often filamentary, and frequently non-axisymmetric. The observed envelope structure indicates a likely origin in turbulent cloud structure rather than a quasi-static/equilibrium formation. The complex envelope structure also may indicate an increased likelihood of fragmentation during collapse, forming close binaries. To further characterize these envelopes, I have observed them in the dense molecular gas tracers nthp and nht, both of which closely follow the 8 micron extinction morphology. The magnitude of the velocity gradients and envelope complexity on ˜10000 AU scales indicates that the velocity structure may reflect large-scale infall in addition to the often assumed rotation. Comparisons with three-dimensional filamentary and symmetric rotating collapse models reinforce the interpretation of velocities reflecting large-scale infall, showing that the structure of the envelope

  11. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  12. Advances in chromatin remodeling and human disease.

    Science.gov (United States)

    Cho, Kyoung Sang; Elizondo, Leah I; Boerkoel, Cornelius F

    2004-06-01

    Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.

  13. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  14. Inhibition of enveloped viruses infectivity by curcumin.

    Directory of Open Access Journals (Sweden)

    Tzu-Yen Chen

    Full Text Available Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter than for the pseudorabies virus (approximately 180 nm and the vaccinia virus (roughly 335 × 200 × 200 nm. These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.

  15. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    Science.gov (United States)

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  16. The linkage of chromatin remodeling to genome maintenance: contribution from a human disease gene BRIT1/MCPH1.

    Science.gov (United States)

    Peng, Guang; Lin, Shiaw-Yih

    2009-10-01

    Genomic DNA is packed into a highly condensed chromatin structure, which acts as natural barrier preventing accessibility of DNA. In various processes to maintain genomic integrity such as DNA replication, DNA repair, telomere regulation, proteins need to overcome the barrier of condensed chromatin to gain access to DNA. ATP-dependent chromatin remodeling is one of the fundamental mechanisms used by cells to relax chromatin. However, the chromatin remodeling complex does not contain intrinsic specificity for particular nuclear process, and the mechanism mediating its recruitment to DNA lesions remains to be an outstanding question. To address this question, in this review, we will discuss our current findings and future perspectives about how BRIT1/MCPH1, a human disease gene, specifies the function of chromatin remodelers and links chromatin remodeling to genome maintenance.

  17. Quasistars: Accreting black holes inside massive envelopes

    CERN Document Server

    Begelman, Mitchell C; Armitage, Philip J

    2007-01-01

    We study the structure and evolution of "quasistars," accreting black holes embedded within massive hydrostatic gaseous envelopes. These configurations may model the early growth of supermassive black hole seeds. The accretion rate onto the black hole adjusts so that the luminosity carried by the convective envelope equals the Eddington limit for the total mass. This greatly exceeds the Eddington limit for the black hole mass alone, leading to rapid growth of the black hole. We use analytic models and numerical stellar structure calculations to study the structure and evolution of quasistars. We derive analytically the scaling of the photospheric temperature with the black hole mass and envelope mass, and show that it decreases with time as the black hole mass increases. Once the photospheric temperature becomes lower than 10000 K, the photospheric opacity drops precipitously and the photospheric temperature hits a limiting value, analogous to the Hayashi track for red giants and protostars, below which no hy...

  18. Investment Costs of the Building Envelope Reconstructions

    Directory of Open Access Journals (Sweden)

    Výskala Miloslav

    2014-12-01

    Full Text Available The article is aimed at the design of the measurements improving the thermal-technical properties of the building envelope from the point of view of the economic evaluation. The starting point for the evaluation of economic aspects is the quantification of the partial and total costs according to the individual constructions of the building envelope in relation to the earlier requirements. The result is the determination of the minimal thickness of the thermal insulation i.e. the determination of the corresponding properties of the building envelope. Described procedure represents the first step for the consecutive modelling of the potential investment options while comply with the optimal level according to Directive 2010/31/ES (EPBD II.

  19. Convection in stellar envelopes a changing paradigm

    CERN Document Server

    Spruit, H C

    1996-01-01

    Progress in the theory of stellar convection over the past decade is reviewed. The similarities and differences between convection in stellar envelopes and laboratory convection at high Rayleigh numbers are discussed. Direct numerical simulation of the solar surface layers, with no other input than atomic physics, the equations of hydrodynamics and radiative transfer is now capable of reproducing the observed heat flux, convection velocities, granulation patterns and line profiles with remarkably accuracy. These results show that convection in stellar envelopes is an essentially non-local process, being driven by cooling at the surface. This differs distinctly from the traditional view of stellar convection in terms of local concepts such as cascades of eddies in a mean superadiabatic gradient. The consequences this has for our physical picture of processes in the convective envelope are illustrated with the problems of sunspot heat flux blocking, the eruption of magnetic flux from the base of the convection ...

  20. Global envelope tests for spatial processes

    DEFF Research Database (Denmark)

    Myllymäki, Mari; Mrkvička, Tomáš; Grabarnik, Pavel;

    Envelope tests are a popular tool in spatial statistics, where they are used in goodness-of-fit testing. These tests graphically compare an empirical function T(r) with its simulated counterparts from the null model. However, the type I error probability α is conventionally controlled for a fixed...... distance r only, whereas the functions are inspected on an interval of distances I. In this study, we propose two approaches related to Barnard's Monte Carlo test for building global envelope tests on I: (1) ordering the empirical and simulated functions based on their r-wise ranks among each other, and (2......) the construction of envelopes for a deviation test. These new tests allow the a priori selection of the global α and they yield p-values. We illustrate these tests using simulated and real point pattern data....

  1. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications...

  2. Raise the Floor When Remodeling Science Labs

    Science.gov (United States)

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  3. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  4. The photodissociation of CO in circumstellar envelopes

    Science.gov (United States)

    Mamon, G. A.; Glassgold, A. E.; Huggins, P. J.

    1988-01-01

    The CO photodissociation rate for the unshielded ISM is calculated using recent laboratory results which confirm that photodissociation occurs by way of line absorption. A value of 2.0 x 10 to the -10th/s, an order of magnitude higher than the rate used in the past, is obtained. The new rate and a treatment of the radiative transfer and shielding are used to develop a theory for the CO abundance in the circumstellar envelopes of cool, evolved stars, and results are presented on the spatial variation of CO, C, and C(+). It is shown that these distributions play important roles in determining the observational properties of circumstellar envelopes.

  5. The Chd Family of Chromatin Remodelers

    OpenAIRE

    Marfella, Concetta G.A.; Imbalzano, Anthony N.

    2007-01-01

    Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA-binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic,...

  6. Chromatin Modification and Remodeling in Heart Development

    Directory of Open Access Journals (Sweden)

    Paul Delgado-Olguín

    2006-01-01

    Full Text Available In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

  7. Bone remodeling as a spatial evolutionary game.

    Science.gov (United States)

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  8. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  9. Effect of Chromosome Tethering on Nuclear Organization in Yeast

    OpenAIRE

    Barış Avşaroğlu; Gabriel Bronk; Susannah Gordon-Messer; Jungoh Ham; Debra A Bressan; Haber, James E; Jane Kondev

    2014-01-01

    Interphase chromosomes in Saccharomyces cerevisiae are tethered to the nuclear envelope at their telomeres and to the spindle pole body (SPB) at their centromeres. Using a polymer model of yeast chromosomes that includes these interactions, we show theoretically that telomere attachment to the nuclear envelope is a major determinant of gene positioning within the nucleus only for genes within 10 kb of the telomeres. We test this prediction by measuring the distance between the SPB and the sil...

  10. Tegument Assembly and Secondary Envelopment of Alphaherpesviruses

    Directory of Open Access Journals (Sweden)

    Danielle J. Owen

    2015-09-01

    Full Text Available Alphaherpesviruses like herpes simplex virus are large DNA viruses characterized by their ability to establish lifelong latent infection in neurons. As for all herpesviruses, alphaherpesvirus virions contain a protein-rich layer called “tegument” that links the DNA-containing capsid to the glycoprotein-studded membrane envelope. Tegument proteins mediate a diverse range of functions during the virus lifecycle, including modulation of the host-cell environment immediately after entry, transport of virus capsids to the nucleus during infection, and wrapping of cytoplasmic capsids with membranes (secondary envelopment during virion assembly. Eleven tegument proteins that are conserved across alphaherpesviruses have been implicated in the formation of the tegument layer or in secondary envelopment. Tegument is assembled via a dense network of interactions between tegument proteins, with the redundancy of these interactions making it challenging to determine the precise function of any specific tegument protein. However, recent studies have made great headway in defining the interactions between tegument proteins, conserved across alphaherpesviruses, which facilitate tegument assembly and secondary envelopment. We summarize these recent advances and review what remains to be learned about the molecular interactions required to assemble mature alphaherpesvirus virions following the release of capsids from infected cell nuclei.

  11. Ozone Reductions Using Residential Building Envelopes

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain S.; Sherman, Max; Nazaroff, William W.

    2009-02-01

    Ozone is an air pollutant with that can have significant health effects and a significant source of ozone in some regions of California is outdoor air. Because people spend the vast majority of their time indoors, reduction in indoor levels of ozone could lead to improved health for many California residents. Ozone is removed from indoor air by surface reactions and can also be filtered by building envelopes. The magnitude of the envelope impact depends on the specific building materials that the air flows over and the geometry of the air flow paths through the envelope that can be changes by mechanical ventilation operation. The 2008 Residential Building Standards in California include minimum requirements for mechanical ventilation by referencing ASHRAE Standard 62.2. This study examines the changes in indoor ozone depending on the mechanical ventilation system selected to meet these requirements. This study used detailed simulations of ventilation in a house to examine the impacts of different ventilation systems on indoor ozone concentrations. The simulation results showed that staying indoors reduces exposure to ozone by 80percent to 90percent, that exhaust ventilation systems lead to lower indoor ozone concentrations, that opening of windows should be avoided at times of high outdoor ozone, and that changing the time at which mechanical ventilation occurs has the ability to halve exposure to ozone. Future work should focus on the products of ozone reactions in the building envelope and the fate of these products with respect to indoor exposures.

  12. The Viner-Wong Envelope Theorem.

    Science.gov (United States)

    Silberberg, Eugene

    1999-01-01

    Observes that the envelope theorem, a fundamental tool in duality analysis, is still a puzzle to many people. Argues that the essence of a solution proposed by Paul Samuelson (1947) is also unclear to many people, but can be communicated with a simple cost diagram. Presents and explains the proposed diagram. (DSK)

  13. Playing with the enveloping algebra of supersymmetry

    Science.gov (United States)

    Cattaruzza, E.; Gozzi, E.

    2016-10-01

    In this paper, we show how to obtain from a scalar superfield its first component via a similarity transformation. We prove that in D = 4 the generators of this similarity transformation live in the enveloping algebra of supersymmetry while for D = 1 they belong to the basic algebra.

  14. Core radii and common-envelope evolution

    CERN Document Server

    Hall, Philip D

    2014-01-01

    Many classes of objects and events are thought to form in binary star systems after a phase in which a core and companion spiral to smaller separation inside a common envelope (CE).Such a phase can end with the merging of the two stars or with the ejection of the envelope to leave a surviving binary system.The outcome is usually predicted by calculating the separation to which the stars must spiral to eject the envelope, assuming that the ratio of the core--envelope binding energy to the change in orbital energy is equal to a constant efficiency factor $\\alpha$. If either object would overfill its Roche lobe at this end-of-CE separation, then the stars are assumed to merge. It is unclear what critical radius should be compared to the end-of-CE Roche lobe for stars which have developed cores before the start of a CE phase. After improving the core radius formulae in the widely used BSE rapid evolution code, we compare the properties of populations in which the critical radius is chosen to be the pre-CE core ra...

  15. Multi-layered breathing architectural envelope

    DEFF Research Database (Denmark)

    Lund Larsen, Andreas; Foged, Isak Worre; Jensen, Rasmus Lund

    2014-01-01

    A multi layered breathing envelope is developed as a method of natural ventilation. The two main layers consist of mineral wool and air permeable concrete. The mineral wool works as a dynamic insulation and the permeable concrete as a heat recovery system with a high thermal mass for heat storage...

  16. Discriminating Dysarthria Type from Envelope Modulation Spectra

    Science.gov (United States)

    Liss, Julie M.; LeGendre, Sue; Lotto, Andrew J.

    2010-01-01

    Purpose: Previous research demonstrated the ability of temporally based rhythm metrics to distinguish among dysarthrias with different prosodic deficit profiles (J. M. Liss et al., 2009). The authors examined whether comparable results could be obtained by an automated analysis of speech envelope modulation spectra (EMS), which quantifies the…

  17. Shape Control of Responsive Building Envelopes

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning; Christensen, Jesper Thøger

    2010-01-01

    alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock-up concept of a secondary...

  18. Playing with the enveloping algebra of supersymmetry

    CERN Document Server

    Cattaruzza, E

    2016-01-01

    In this paper we show how to obtain from a scalar superfield its first component via a similarity transformation. We prove that in D=4 the generators of this similarity transformation live in the enveloping algebra of supersymmetry while for D=1 they belong to the basic algebra.

  19. Rsc4 Connects the Chromatin Remodeler RSC to RNA Polymerases‡

    Science.gov (United States)

    Soutourina, Julie; Bordas-Le Floch, Véronique; Gendrel, Gabrielle; Flores, Amando; Ducrot, Cécile; Dumay-Odelot, Hélène; Soularue, Pascal; Navarro, Francisco; Cairns, Bradley R.; Lefebvre, Olivier; Werner, Michel

    2006-01-01

    RSC is an essential, multisubunit chromatin remodeling complex. We show here that the Rsc4 subunit of RSC interacted via its C terminus with Rpb5, a conserved subunit shared by all three nuclear RNA polymerases (Pol). Furthermore, the RSC complex coimmunoprecipitated with all three RNA polymerases. Mutations in the C terminus of Rsc4 conferred a thermosensitive phenotype and the loss of interaction with Rpb5. Certain thermosensitive rpb5 mutations were lethal in combination with an rsc4 mutation, supporting the physiological significance of the interaction. Pol II transcription of ca. 12% of the yeast genome was increased or decreased twofold or more in a rsc4 C-terminal mutant. The transcription of the Pol III-transcribed genes SNR6 and RPR1 was also reduced, in agreement with the observed localization of RSC near many class III genes. Rsc4 C-terminal mutations did not alter the stability or assembly of the RSC complex, suggesting an impact on Rsc4 function. Strikingly, a C-terminal mutation of Rsc4 did not impair RSC recruitment to the RSC-responsive genes DUT1 and SMX3 but rather changed the chromatin accessibility of DNases to their promoter regions, suggesting that the altered transcription of DUT1 and SMX3 was the consequence of altered chromatin remodeling. PMID:16782880

  20. Validating predictions from climate envelope models

    Science.gov (United States)

    Watling, J.; Bucklin, D.; Speroterra, C.; Brandt, L.; Cabal, C.; Romañach, Stephanie S.; Mazzotti, Frank J.

    2013-01-01

    Climate envelope models are a potentially important conservation tool, but their ability to accurately forecast species’ distributional shifts using independent survey data has not been fully evaluated. We created climate envelope models for 12 species of North American breeding birds previously shown to have experienced poleward range shifts. For each species, we evaluated three different approaches to climate envelope modeling that differed in the way they treated climate-induced range expansion and contraction, using random forests and maximum entropy modeling algorithms. All models were calibrated using occurrence data from 1967–1971 (t1) and evaluated using occurrence data from 1998–2002 (t2). Model sensitivity (the ability to correctly classify species presences) was greater using the maximum entropy algorithm than the random forest algorithm. Although sensitivity did not differ significantly among approaches, for many species, sensitivity was maximized using a hybrid approach that assumed range expansion, but not contraction, in t2. Species for which the hybrid approach resulted in the greatest improvement in sensitivity have been reported from more land cover types than species for which there was little difference in sensitivity between hybrid and dynamic approaches, suggesting that habitat generalists may be buffered somewhat against climate-induced range contractions. Specificity (the ability to correctly classify species absences) was maximized using the random forest algorithm and was lowest using the hybrid approach. Overall, our results suggest cautious optimism for the use of climate envelope models to forecast range shifts, but also underscore the importance of considering non-climate drivers of species range limits. The use of alternative climate envelope models that make different assumptions about range expansion and contraction is a new and potentially useful way to help inform our understanding of climate change effects on species.

  1. The Psp system of Mycobacterium tuberculosis integrates envelope stress-sensing and envelope-preserving functions.

    Science.gov (United States)

    Datta, Pratik; Ravi, Janani; Guerrini, Valentina; Chauhan, Rinki; Neiditch, Matthew B; Shell, Scarlet S; Fortune, Sarah M; Hancioglu, Baris; Igoshin, Oleg A; Gennaro, Maria Laura

    2015-08-01

    The bacterial envelope integrates essential stress-sensing and adaptive functions; thus, envelope-preserving functions are important for survival. In Gram-negative bacteria, envelope integrity during stress is maintained by the multi-gene Psp response. Mycobacterium tuberculosis was thought to lack the Psp system since it encodes only pspA and no other psp ortholog. Intriguingly, pspA maps downstream from clgR, which encodes a transcription factor regulated by the MprAB-σ(E) envelope-stress-signaling system. clgR inactivation lowered ATP concentration during stress and protonophore treatment-induced clgR-pspA expression, suggesting that these genes express Psp-like functions. We identified a four-gene set - clgR, pspA (rv2744c), rv2743c, rv2742c - that is regulated by clgR and in turn regulates ClgR activity. Regulatory and protein-protein interactions within the set and a requirement of the four genes for functions associated with envelope integrity and surface-stress tolerance indicate that a Psp-like system has evolved in mycobacteria. Among Actinobacteria, the four-gene module occurred only in tuberculous mycobacteria and was required for intramacrophage growth, suggesting links between its function and mycobacterial virulence. Additionally, the four-gene module was required for MprAB-σ(E) stress-signaling activity. The positive feedback between envelope-stress-sensing and envelope-preserving functions allows sustained responses to multiple, envelope-perturbing signals during chronic infection, making the system uniquely suited to tuberculosis pathogenesis.

  2. The universal enveloping TRO of a JB*-triple system

    CERN Document Server

    Bohle, Dennis

    2010-01-01

    We associate to every JB*-triple system a so-called universal enveloping TRO and show some functorial properties of this correspondence. We compute the universal enveloping TROs of the finite dimensional Cartan factors.

  3. Novel Real-Time Flight Envelope Monitoring System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an aircraft flight envelope monitoring system that will provide real-time in-cockpit estimations of aircraft flight envelope boundaries,...

  4. Novel Real-Time Flight Envelope Monitoring System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an aircraft flight envelope monitoring system that will provide real-time in-cockpit estimations of aircraft flight envelope boundaries....

  5. The chromatin remodeller ATRX: a repeat offender in human disease.

    Science.gov (United States)

    Clynes, David; Higgs, Douglas R; Gibbons, Richard J

    2013-09-01

    The regulation of chromatin structure is of paramount importance for a variety of fundamental nuclear processes, including gene expression, DNA repair, replication, and recombination. The ATP-dependent chromatin-remodelling factor ATRX (α thalassaemia/mental retardation X-linked) has emerged as a key player in each of these processes. Exciting recent developments suggest that ATRX plays a variety of key roles at tandem repeat sequences within the genome, including the deposition of a histone variant, prevention of replication fork stalling, and the suppression of a homologous recombination-based pathway of telomere maintenance. Here, we provide a mechanistic overview of the role of ATRX in each of these processes, and propose how they may be connected to give rise to seemingly disparate human diseases.

  6. Expression of RANKL/OPG during bone remodeling in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, H., E-mail: tnk@ymghp.jp [Department of Orthopedic Surgery, Yamaguchi Grand Medical Center, 77 Ohsaki, Hofu, Yamaguchi 747-8511 (Japan); Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Mine, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Ogasa, H. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Taguchi, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Liang, C.T. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); National Health Research Institutes, Taipei 115, Taiwan (China)

    2011-08-12

    Highlights: {yields} This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. {yields} The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. {yields} Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. {yields} The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor {kappa}B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen {alpha}1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The

  7. Effects of envelope shape on interaural envelope delay sensitivity in acoustic and electric hearing.

    Science.gov (United States)

    Laback, Bernhard; Zimmermann, Inge; Majdak, Piotr; Baumgartner, Wolf-Dieter; Pok, Stefan-Marcel

    2011-09-01

    The envelope shape is important for the perception of interaural time difference (ITD) in the envelope as supported by the improved sensitivity for transposed tones compared to sinusoidally amplitude-modulated (SAM) tones. The present study investigated the effects of specific envelope parameters in nine normal-hearing (NH) and seven cochlear-implant (CI) listeners, using high-rate carriers with 27-Hz trapezoidal modulation. In NH listeners, increasing the off time (the silent interval in each modulation cycle) up to 12 ms, increasing the envelope slope from 6 to 8 dB/ms, and increasing the peak level improved ITD sensitivity. The combined effect of the off time and slope accounts for the gain in sensitivity for transposed tones relative to SAM tones. In CI listeners, increasing the off time up to 20 ms improved sensitivity, but increasing the slope showed no systematic effect. A 27-pulses/s electric pulse train, representing a special case of modulation with infinitely steep slopes and maximum possible off time, yielded considerably higher sensitivity compared to the best condition with trapezoidal modulation. Overall, the results of this study indicate that envelope-ITD sensitivity could be improved by using CI processing schemes that simultaneously increase the off time and the peak level of the signal envelope. © 2011 Acoustical Society of America

  8. Adipose tissue remodeling in pathophysiology of obesity.

    Science.gov (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K

    2010-07-01

    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  9. Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses

    Directory of Open Access Journals (Sweden)

    Wahyu eWulan

    2015-06-01

    Full Text Available Most viruses with non-segmented single stranded RNA genomes complete their life cycle in the cytoplasm of infected cells. However, despite undergoing replication in the cytoplasm, the structural proteins of some of these RNA viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. Limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. Nucleocapsid proteins of RNA viruses have a well-established, essential cytoplasmic role in virus replication and assembly. Intriguingly, nucleocapsid proteins of some RNA viruses also localize to the nucleus/nucleolus of infected cells. Their nuclear function is less well understood although significant advances have been made in recent years. This review will focus on the nucleocapsid protein of cytoplasmic enveloped RNA viruses, including their localization to the nucleus/nucleolus and function therein. A greater understanding of the nuclear localization of nucleocapsid proteins has the potential to enhance therapeutic strategies as it can be a target for the development of live-attenuated vaccines or antiviral drugs.

  10. Three-dimensional visualization of the Autographa californica multiple nucleopolyhedrovirus occlusion-derived virion envelopment process gives new clues as to its mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yang; Li, Kunpeng [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Tang, Peiping [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui (China); Li, Yinyin; Zhou, Qiang; Yang, Kai [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Zhang, Qinfen, E-mail: lsszqf@mail.sysu.edu.cn [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China)

    2015-02-15

    Baculoviruses produce two virion phenotypes, occlusion-derived virion (ODV) and budded virion (BV). ODV envelopment occurs in the nucleus. Morphogenesis of the ODV has been studied extensively; however, the mechanisms underlying microvesicle formation and ODV envelopment in nuclei remain unclear. In this study, we used electron tomography (ET) together with the conventional electron microscopy to study the envelopment of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ODV. Our results demonstrate that not only the inner but also the outer nuclear membrane can invaginate and vesiculate into microvesicles and that intranuclear microvesicles are the direct source of the ODV membrane. Five main events in the ODV envelopment process are summarized, from which we propose a model to explain this process. - Highlights: • Both the inner and outer nuclear membranes could invaginate. • Both the inner and outer nuclear membranes could vesiculate into microvesicles. • Five main events in the ODV envelopment process are summarized. • A model is proposed to explain this ODV envelopment.

  11. Solar Effective Envelope Design Advisor (SEEDA)

    Science.gov (United States)

    Mahaek, Ekkachai

    The lack of effort by mainstream architects in integrating energy-efficient strategies in architectural designing is due to the complexity in a building's energy conscious concepts and theories, the difficulties to visualize and quantify energy consumption, and the late implementing of energy consumption analysis in the conventional design process. This task would be accomplishing by a building system's engineer where results might be determined only after the basic architectural design has been completed. An effective simple tool and method should then be available to assist architects in building's energy-efficient designing at the beginning of the design. The building's energy consumption is directly and mainly influenced by the relationship of the sun, site, and its building configuration. The solar radiations will first impact on the building's envelope, which will have a direct effect on the amount of energy a building will consume. If an architect can define or map the intensity of solar energy on the site's buildable volume, and use this information to determine the levels of solar insolation, a more energy efficient building form can be proposed. This research hypothesis has shared the fundamental techniques of the Solar Envelope projection by Professor Ralph Knowles [Knowles, 1981] of the University of Southern California. However a different approach is taken by including the influence of regional restrictions and the surrounding buildings' shadows when projecting of solar volumes and solar envelope. The research methodology will discuss the development of a computer-based approach to develop a three-dimensional architectural form based on an insolation map related to the design site. The prototype computer program is referred as the Solar Effective Envelope Design Advisor (SEEDA). The solar insolation volume of the site is determined by integrating three types of computer-generated models include the Buildable Volume model based on design constraints

  12. Analysis of Building Envelope Construction in 2003 CBECS

    Energy Technology Data Exchange (ETDEWEB)

    Winiarski, David W.; Halverson, Mark A.; Jiang, Wei

    2007-06-01

    The purpose of this analysis is to determine "typical" building envelope characteristics for buildings built after 1980. We address three envelope components in this paper - roofs, walls, and window area. These typical building envelope characteristics were used in the development of DOE’s Reference Buildings .

  13. Analysis of Building Envelope Construction in 2003 CBECS

    Energy Technology Data Exchange (ETDEWEB)

    Winiarski, David W.; Halverson, Mark A.; Jiang, Wei

    2007-06-01

    The purpose of this analysis is to determine "typical" building envelope characteristics for buildings built after 1980. We address three envelope components in this paper - roofs, walls, and window area. These typical building envelope characteristics were used in the development of DOE’s Reference Buildings .

  14. Trying to resolve the two-envelope problem

    NARCIS (Netherlands)

    Albers, CJ; Kooi, BP; Schaafsma, W

    After explaining the well-known two-envelope 'paradox' by indicating the fallacy involved, we consider the two-envelope 'problem' of evaluating the 'factual' information provided to us in the form of the value contained by the envelope chosen first. We try to provide a synthesis of contributions

  15. Molecular Aspects of Exercise-induced Cardiac Remodeling.

    Science.gov (United States)

    Bernardo, Bianca C; McMullen, Julie R

    2016-11-01

    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  16. Nuclear Medicine

    Science.gov (United States)

    ... for Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive ... NIBIB-funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that ...

  17. Hydrogen sulfide in a circumstellar envelope

    Science.gov (United States)

    Ukita, N.; Morris, M.

    1983-01-01

    A search for hydrogen sulfide in the cool circumstellar envelopes of 25 stars was made using the 1(10)-1(01) rotational line at 1.8 mm. It was detected in the bipolar nebula/OH maser OH231.8+4.2, an object having a high rate of mass loss. An approximate analysis indicates that 1/60 of the sulfur in this outflowing envelope is in the form of H2S, a fraction which may be similar to that in the atmosphere of the central star. In addition, the shape of the observed line profile is discussed in terms of a possible variation of the outflow velocity with latitude above the system's equatorial plane.

  18. Nonlinear Analysis of Airship Envelop Aerolasticity

    Science.gov (United States)

    Liu, J. M.; Lu, C. J.; Xue, L. P.

    The large airship in flow field is a flexible body with low rigidity. The distribution of the peripheral flow field around the airship is closely related to its shape. It is essentially one of the Fluid-structure Interaction problems. Based on this, this paper aims at the numerical simulation of nonlinear airship envelop aeroelasticity by means of coupling aerodynamics and structure using an iteration method. The three-dimensional flow around the airship was studied numerically by means of SIMPLE method based on the Finite Volume Method. Two approaches, the linear method whose equilibrium equations are based on the membrance theory of thin shell and the nonlinear method which uses a nonlinear finite element method to account for the large deformation of the airship envelop, are introduced for geometrically deformation of the airship shape. A thin plate spline method is adopted as the interface of exchanging information between the fluid and structure models.

  19. Uses and misuses of bioclimatic envelope modeling.

    Science.gov (United States)

    Araújo, Miguel B; Peterson, A Townsend

    2012-07-01

    Bioclimatic envelope models use associations between aspects of climate and species' occurrences to estimate the conditions that are suitable to maintain viable populations. Once bioclimatic envelopes are characterized, they can be applied to a variety of questions in ecology, evolution, and conservation. However, some have questioned the usefulness of these models, because they may be based on implausible assumptions or may be contradicted by empirical evidence. We review these areas of contention, and suggest that criticism has often been misplaced, resulting from confusion between what the models actually deliver and what users wish that they would express. Although improvements in data and methods will have some effect, the usefulness of these models is contingent on their appropriate use, and they will improve mainly via better awareness of their conceptual basis, strengths, and limitations.

  20. Development of High Specific Strength Envelope Materials

    Science.gov (United States)

    Komatsu, Keiji; Sano, Masa-Aki; Kakuta, Yoshiaki

    Progress in materials technology has produced a much more durable synthetic fabric envelope for the non-rigid airship. Flexible materials are required to form airship envelopes, ballonets, load curtains, gas bags and covering rigid structures. Polybenzoxazole fiber (Zylon) and polyalirate fiber (Vectran) show high specific tensile strength, so that we developed membrane using these high specific tensile strength fibers as a load carrier. The main material developed is a Zylon or Vectran load carrier sealed internally with a polyurethane bonded inner gas retention film (EVOH). The external surface provides weather protecting with, for instance, a titanium oxide integrated polyurethane or Tedlar film. The mechanical test results show that tensile strength 1,000 N/cm is attained with weight less than 230g/m2. In addition to the mechanical properties, temperature dependence of the joint strength and solar absorptivity and emissivity of the surface are measured. 

  1. Cost Allocation and Convex Data Envelopment

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tind, Jørgen

    This paper considers allocation rules. First, we demonstrate that costs allocated by the Aumann-Shapley and the Friedman-Moulin cost allocation rules are easy to determine in practice using convex envelopment of registered cost data and parametric programming. Second, from the linear programming...... such as Data Envelopment Analysis (DEA). The convexity constraint of the BCC model introduces a non-zero slack in the objective function of the multiplier problem and we show that the cost allocation rules discussed in this paper can be used as candidates to allocate this slack value on to the input (or output...... problems involved it becomes clear that the allocation rules, technically speaking, allocate the non-zero value of the dual variable for a convexity constraint on to the output vector. Hence, the allocation rules can also be used to allocate inefficiencies in non-parametric efficiency measurement models...

  2. Constant envelope chirped OFDM power efficiency

    Science.gov (United States)

    Dida, Mussa A.; Hao, Huan; Anjum, M. R.; Ran, Tao

    2016-10-01

    Fractional Fourier OFDM or simply chirped OFDM performs better in time-frequency selective channel than its convectional OFDM. Although chirped OFDM outperforms OFDM it still inherits Peak to Average Power Ratio (PAPR) drawback as a convectional OFDM. To eliminate PAPR drawback Constant Envelope OFDM was developed and for better performance in time frequency selective channel Constant Envelope Fractional Fourier OFDM (CE-COFDM) is used. Its BER performance is analyzed and compared to chirped OFDM and OFDM in AWGN and Rayleigh channel. The simulations show the BER performance of CE-COFDM is the same as chirped OFDM and OFDM. The power efficiency of CE-COFDM is also studied and different simulations performed shows CE-COFDM is more power efficient than chirped OFDM and convectional OFDM for class A and class B Linear Power Amplifier (LPA).

  3. Envelope Soliton in Solar Radio Emission

    Institute of Scientific and Technical Information of China (English)

    WANG De-Yu; Wangde; G. P. Chernov

    2000-01-01

    Several envelope soliton fine structures have been observed in solar radio metric-wave emission. We present amodel of 1ongitudinal modulational instability to explain these fine structures. It is found that this instability canonly occur in the condition of sound velocity being larger than Alfven velocity in corona. Therefore, the envelopesoliton fine structures should display in the coronal region with high temperature and low magnetic field, whichcorresponds to the solar radio emission in the region of meter and decameter wavelength.

  4. Functional evolution of nuclear structure

    Science.gov (United States)

    Dawson, Scott C.

    2011-01-01

    The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis. PMID:22006947

  5. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  6. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  7. Genetic backgrounds determine brown remodeling of white fat in rodents

    Directory of Open Access Journals (Sweden)

    Giulia Ferrannini

    2016-10-01

    Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  8. Autophagy regulates cytoplasmic remodeling during cell reprogramming in a zebrafish model of muscle regeneration.

    Science.gov (United States)

    Saera-Vila, Alfonso; Kish, Phillip E; Louie, Ke'ale W; Grzegorski, Steven J; Klionsky, Daniel J; Kahana, Alon

    2016-10-02

    Cell identity involves both selective gene activity and specialization of cytoplasmic architecture and protein machinery. Similarly, reprogramming differentiated cells requires both genetic program alterations and remodeling of the cellular architecture. While changes in genetic and epigenetic programs have been well documented in dedifferentiating cells, the pathways responsible for remodeling the cellular architecture and eliminating specialized protein complexes are not as well understood. Here, we utilize a zebrafish model of adult muscle regeneration to study cytoplasmic remodeling during cell dedifferentiation. We describe activation of autophagy early in the regenerative response to muscle injury, while blocking autophagy using chloroquine or Atg5 and Becn1 knockdown reduced the rate of regeneration with accumulation of sarcomeric and nuclear debris. We further identify Casp3/caspase 3 as a candidate mediator of cellular reprogramming and Fgf signaling as an important activator of autophagy in dedifferentiating myocytes. We conclude that autophagy plays a critical role in cell reprogramming by regulating cytoplasmic remodeling, facilitating the transition to a less differentiated cell identity.

  9. Nuclear lamina—like filaments and nuclear matrix in allium cepa as revealed by scanning electron microscopy

    Institute of Scientific and Technical Information of China (English)

    HAOSHUI

    1992-01-01

    In this study,freeze-fractured specimens of allium cepa root tip meristems were examined under the scanning electron microscope(SEM),This technique permitted the visualization of the outer membrane of the nuclear envelope with nuclear pore complexes and polyribosomes.Some of the cell nuclei prepared with this procedure had fissures of various widths on their nuclear envelopes through which the nuclear lamina-like filaments(LLF) undernearth the nucleoplasmic side of the envelopes were clearly visible.The diameters of these filaments veried between 25 and 125nm.Many of the LLFs showed granular thickenings at places,and were attached to the inner surface of nuclear envelope in some regions .Similar LLFs were also seen at the peripheries of the freeze-fractured faces of nuclei.Meanwhile,the spatial relation between the nuclear matrix filaments(NMF) and other nuclear structures(nucleoli,chromation and peripheral lamina-like filaments) was revealed in these fractured preparations.In addition,the methods and techniques in studying the nuclear lamina morphology and the roles played by NMFs in activities of various nuclear sturctures were discessed in brief.

  10. Have NEC Coat, Will Travel: Structural Basis of Membrane Budding During Nuclear Egress in Herpesviruses.

    Science.gov (United States)

    Bigalke, J M; Heldwein, E E

    2017-01-01

    Herpesviruses are unusual among enveloped viruses because they bud twice yet acquire a single envelope. Furthermore, unlike other DNA viruses that replicate in the nucleus, herpesviruses do not exit it by passing through the nuclear pores or by rupturing the nuclear envelope. Instead, herpesviruses have a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. This makes them some of the very few known viruses that bud into the nuclear envelope. The envelope acquired during nuclear budding does not end up in the mature viral particle but instead allows the capsid to translocate from the nucleus into the cytosol. The viral nuclear egress complex (NEC) is a critical player in the nuclear egress, yet its function and mechanism have remained enigmatic. Recent studies have demonstrated that the NEC buds membranes without the help of other proteins by forming a honeycomb coat, which established the NEC as the first virally encoded budding machine that operates at the nuclear, as opposed to cytoplasmic, membrane. This review discusses our current understanding of the NEC budding mechanism, with the emphasis on studies that illuminated the structure of the NEC coat and its role in capsid budding during herpesvirus nuclear escape.

  11. Retinal remodeling in human retinitis pigmentosa.

    Science.gov (United States)

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  12. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  13. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  14. Mechanisms of Airway Remodeling in Asthma

    Directory of Open Access Journals (Sweden)

    Etsuko Tagaya

    2007-01-01

    To date, many studies have identified candidate mechanisms and mediators for these observed structural changes, which are thus potential targets in the treatment of asthma. In this review, we describe the recent knowledge of the mechanisms and clinical implications of airway remodeling in asthma.

  15. Immune modulation of resistance artery remodelling.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2012-01-01

    Low-grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (that produce interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone-salt and aldosterone-salt, as well as in models of hypertension such as the Dahl-salt-sensitive rat. The mechanism whereby the immune system is activated is unclear, but it has been suggested that neo-antigens may be generated by the elevation of blood pressure or other stimuli, leading to the activation of the immune response. Activated Th1 may contribute to vascular remodelling directly on blood vessels via effects of the cytokines produced or indirectly by actions on the kidney. The protective effect of Treg may be mediated similarly directly or via renal effects. These data offer promise for the discovery of new therapeutic targets to ameliorate vascular remodelling, which could lead to improved outcome in cardiovascular disease in humans.

  16. Targeting and biogenesis of transporters and channels in chloroplast envelope membranes: Unsolved questions.

    Science.gov (United States)

    Oh, Young Jun; Hwang, Inhwan

    2015-07-01

    Chloroplasts produce carbohydrates, hormones, vitamins, amino acids, pigments, nucleotides, ATP, and secondary metabolites. Channels and transporters are required for the movement of molecules across the two chloroplast envelope membranes. These transporters and channel proteins are grouped into two different types, including β-barrel proteins and transmembrane-domain (TMD) containing proteins. Most β-barrel proteins are localized at the outer chloroplast membrane, and TMD-containing proteins are localized at the inner chloroplast membrane. Many of these transporters and channels are encoded by nuclear genes; therefore, they have to be imported into chloroplasts after translation on cytosolic ribosomes. These proteins should have specific targeting signals for their final destination in the chloroplast membrane and for assembly into specific complexes. In this review, we summarize recent progress in the identification, functional characterization, and biogenesis of transporters and channels at the chloroplast envelope membranes, and discuss outstanding questions regarding transporter and channel protein biogenesis.

  17. [Remodeling of cardiac gap junctions and arrhythmias].

    Science.gov (United States)

    Yu, Zhi-Bin; Sheng, Juan-Juan

    2011-12-25

    In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.

  18. ELECTRICALLY CONDUCTIVE OF NANOCOMPOSITES FOR SYSTEMS DIAGNOSTICS OF THE ENVELOPE WALLS TECHNICAL CONDITION OF NPP

    Directory of Open Access Journals (Sweden)

    BOLSHAKOV V. I.

    2016-05-01

    Full Text Available Raising of the problem. Enveloped concrete wall type structures of localizing safety systems for restaint and localization of radioactive decay products or in the case of special natural or man-made impacts on the power unit is one of the most important components to ensure the safety of nuclear power. The promising direction for the development of the NPP technical system monitoring is to use conductive nanocomposites as primary elements of information. The purpose of the article is to review the theoretical background and experience in the conductive nanocomposites creating for diagnostics of localizing nuclear safety systems. Conclusions. A promising area for the development of diagnostic systems of localizing nuclear safety systems is the use of electrically conductive nanocomposites (conductive concrete - bethels, plasters, paint coatings. A mechanism for conductive nanocomposites creating is the use of the filler metal and carbon nanoparticles. As binders is promising to use nanocomposites of the mineral binders (cement and water glass.

  19. The RSC chromatin remodeling complex has a crucial role in the complete remodeler set for yeast PHO5 promoter opening.

    Science.gov (United States)

    Musladin, Sanja; Krietenstein, Nils; Korber, Philipp; Barbaric, Slobodan

    2014-04-01

    Although yeast PHO5 promoter chromatin opening is a founding model for chromatin remodeling, the complete set of involved remodelers remained unknown for a long time. The SWI/SNF and INO80 remodelers cooperate here, but nonessentially, and none of the many tested single or combined remodeler gene mutations could prevent PHO5 promoter opening. RSC, the most abundant and only remodeler essential for viability, was a controversial candidate for the unrecognized remodeling activity but unassessed in vivo. Now we show that remodels the structure of chromatin (RSC) is crucially involved in PHO5 promoter opening. Further, the isw1 chd1 double deletion also delayed chromatin remodeling. Strikingly, combined absence of RSC and Isw1/Chd1 or Snf2 abolished for the first time promoter opening on otherwise sufficient induction in vivo. Together with previous findings, we recognize now a surprisingly complex network of five remodelers (RSC, SWI/SNF, INO80, Isw1 and Chd1) from four subfamilies (SWI/SNF, INO80, ISWI and CHD) as involved in PHO5 promoter chromatin remodeling. This is likely the first described complete remodeler set for a physiological chromatin transition. RSC was hardly involved at the coregulated PHO8 or PHO84 promoters despite cofactor recruitment by the same transactivator and RSC's presence at all three promoters. Therefore, promoter-specific chromatin rather than transactivators determine remodeler requirements.

  20. Modeling pollutant penetration across building envelopes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, De-Ling; Nazaroff, William W.

    2001-04-01

    As air infiltrates through unintentional openings in building envelopes, pollutants may interact with adjacent surfaces. Such interactions can alter human exposure to air pollutants of outdoor origin. We present modeling explorations of the proportion of particles and reactive gases (e.g., ozone) that penetrate building envelopes as air enters through cracks and wall cavities. Calculations were performed for idealized rectangular cracks, assuming regular geometry, smooth inner crack surface and steady airflow. Particles of 0.1-1.0 {micro}m diameter are predicted to have the highest penetration efficiency, nearly unity for crack heights of 0.25 mm or larger, assuming a pressure difference of 4 Pa or greater and a flow path length of 3 cm or less. Supermicron and ultrafine particles are significantly removed by means of gravitational settling and Brownian diffusion, respectively. In addition to crack geometry, ozone penetration depends on its reactivity with crack surfaces, as parameterized by the reaction probability. For reaction probabilities less than {approx}10{sup -5}, penetration is complete for cracks heights greater than 1 mm. However, penetration through mm scale cracks is small if the reaction probability is {approx}10{sup -4} or greater. For wall cavities, fiberglass insulation is an efficient particle filter, but particles would penetrate efficiently through uninsulated wall cavities or through insulated cavities with significant airflow bypass. The ozone reaction probability on fiberglass fibers was measured to be 10{sup -7} for fibers previously exposed to high ozone levels and 6 x 10{sup -6} for unexposed fibers. Over this range, ozone penetration through fiberglass insulation would vary from >90% to {approx}10-40%. Thus, under many conditions penetration is high; however, there are realistic circumstances in which building envelopes can provide substantial pollutant removal. Not enough is yet known about the detailed nature of pollutant penetration

  1. Computer Language Effciency via Data Envelopment Analysis

    Directory of Open Access Journals (Sweden)

    Andrea Ellero

    2011-01-01

    Full Text Available The selection of the computer language to adopt is usually driven by intuition and expertise, since it is very diffcult to compare languages taking into account all their characteristics. In this paper, we analyze the effciency of programming languages through Data Envelopment Analysis. We collected the input data from The Computer Language Benchmarks Game: we consider a large set of languages in terms of computational time, memory usage, and source code size. Various benchmark problems are tackled. We analyze the results first of all considering programming languages individually. Then, we evaluate families of them sharing some characteristics, for example, being compiled or interpreted.

  2. Cost Allocation and Convex Data Envelopment

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tind, Jørgen

    problems involved it becomes clear that the allocation rules, technically speaking, allocate the non-zero value of the dual variable for a convexity constraint on to the output vector. Hence, the allocation rules can also be used to allocate inefficiencies in non-parametric efficiency measurement models...... such as Data Envelopment Analysis (DEA). The convexity constraint of the BCC model introduces a non-zero slack in the objective function of the multiplier problem and we show that the cost allocation rules discussed in this paper can be used as candidates to allocate this slack value on to the input (or output...

  3. An Envelope Hammerstein Model for Power Amplifiers

    Institute of Scientific and Technical Information of China (English)

    Hua-Dong Wang; Song-Bai He; Jing-Fu Bao; Zheng-De Wu

    2007-01-01

    In this paper, an envelope Hammerstein(EH) model is introduced to describe dynamic inputoutput characteristics of RF power amplifiers. In the modeling approach, we use a new truncation method and an established nonlinear time series method to determine model structure. Then, we discuss the process of model parameter extraction in detailed. Finally, a 2 W WCDMA power amplifier is measured to verify the performance of EH model, and good agreement between model output and measurement result shows our model can accurately predict output characteristic of the power amplifier.

  4. Nuclear Actin in Development and Transcriptional Reprogramming.

    Science.gov (United States)

    Misu, Shinji; Takebayashi, Marina; Miyamoto, Kei

    2017-01-01

    Actin is a highly abundant protein in eukaryotic cells and dynamically changes its polymerized states with the help of actin-binding proteins. Its critical function as a constituent of cytoskeleton has been well-documented. Growing evidence demonstrates that actin is also present in nuclei, referred to as nuclear actin, and is involved in a number of nuclear processes, including transcriptional regulation and chromatin remodeling. The contribution of nuclear actin to transcriptional regulation can be explained by its direct interaction with transcription machineries and chromatin remodeling factors and by controlling the activities of transcription factors. In both cases, polymerized states of nuclear actin affect the transcriptional outcome. Nuclear actin also plays an important role in activating strongly silenced genes in somatic cells for transcriptional reprogramming. When these nuclear functions of actin are considered, it is plausible to speculate that nuclear actin is also implicated in embryonic development, in which numerous genes need to be activated in a well-coordinated manner. In this review, we especially focus on nuclear actin's roles in transcriptional activation, reprogramming and development, including stem cell differentiation and we discuss how nuclear actin can be an important player in development and cell differentiation.

  5. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1

    DEFF Research Database (Denmark)

    Bai, Bo; Man, Andy W C; Yang, Kangmin;

    2016-01-01

    for the prevention of vascular ageing. Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site...... association of LKB1 with the positive regulatory elements of TGFβ1 promoter. In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling. Lentiviral-mediated knockdown of HERC2 abolishes...... the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control. Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain...

  6. The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation

    Institute of Scientific and Technical Information of China (English)

    Danila Coradini; Saro Oriana

    2014-01-01

    During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cellidentity. This identity is maintained during cellreplication in a heritable but DNA-independent manner. The preservation of cellidentity is fundamental, especialy when cels must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cellidentity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cellidentity, mammary gland remodeling, and breast cancer initiation.

  7. Association Between Myocardial Mechanics and Ischemic LV Remodeling.

    Science.gov (United States)

    D'Elia, Nicholas; D'hooge, Jan; Marwick, Thomas H

    2015-12-01

    The outcomes associated with heart failure after myocardial infarction are still poor. Both global and regional left ventricular (LV) remodeling are associated with the progression of the post-infarct patient to heart failure, but although global remodeling can be accurately measured, regional LV remodeling has been more difficult to investigate. Preliminary evidence suggests that post-MI assessment of LV mechanics using stress and strain may predict global (and possibly regional) LV remodeling. A method of predicting both global and regional LV remodeling might facilitate earlier, targeted, and more extensive clinical intervention in those most likely to benefit from novel interventions such as cell therapy.

  8. Histone-poly(A) hybrid molecules as tools to block nuclear pores.

    Science.gov (United States)

    Cremer, G; Wojtech, E; Kalbas, M; Agutter, P S; Prochnow, D

    1995-04-01

    Histone-poly(A) hybrid molecules were used for transport experiments with resealed nuclear envelopes and after attachment of a cleavable cross-linker (SASD) to identify nuclear proteins. In contrast to histones, the hybrid molecules cannot be accumulated in resealed nuclear envelopes, and in contrast to poly(A), the export of hybrids from preloaded nuclear envelopes is completely impaired. The experiments strongly confirm the existence of poly(A) as an export signal in mRNA which counteracts the nuclear location signals (NLS) in histones. The contradicting transport signals in the hybrid molecules impair translocation through the nuclear pore complex. The failure to accumulate hybrid molecules into resealed nuclear envelopes results from the covalent attachment of polyadenylic acid to histones in a strict 1:1 molar ratio. This was demonstrated in control transport experiments where radiolabeled histones were simply mixed with nonlabeled poly(A) or radiolabeled poly(A) mixed with nonlabeled histones. In comparison, control uptake experiments with histones covalently linked to a single UMP-mononucleotide are strongly enhanced. Such controls exclude the conceivable possibility of a simple masking of the nuclear location signal in the histones by the covalent attached poly(A) moiety. Photoreactive histone-poly(A) hybrid analogs serve to identify nuclear envelope proteins--presumably in the nuclear pore--with molecular weights of 110, 80, and 71.4 kDa.

  9. Envelope as Climate Negotiator: Evaluating adaptive building envelope's capacity to moderate indoor climate and energy

    Science.gov (United States)

    Erickson, James

    Through manipulation of adaptable opportunities available within a given environment, individuals become active participants in managing personal comfort requirements, by exercising control over their comfort without the assistance of mechanical heating and cooling systems. Similarly, continuous manipulation of a building skin's form, insulation, porosity, and transmissivity qualities exerts control over the energy exchanged between indoor and outdoor environments. This research uses four adaptive response variables in a modified software algorithm to explore an adaptive building skin's potential in reacting to environmental stimuli with the purpose of minimizing energy use without sacrificing occupant comfort. Results illustrate that significant energy savings can be realized with adaptive envelopes over static building envelopes even under extreme summer and winter climate conditions; that the magnitude of these savings are dependent on climate and orientation; and that occupant thermal comfort can be improved consistently over comfort levels achieved by optimized static building envelopes. The resulting adaptive envelope's unique climate-specific behavior could inform designers in creating an intelligent kinetic aesthetic that helps facilitate adaptability and resiliency in architecture.

  10. Effects of lyophilization on the infectivity of enveloped and non-enveloped viruses in bone tissue.

    Science.gov (United States)

    Uhlenhaut, Christine; Dörner, Thomas; Pauli, Georg; Pruss, Axel

    2005-11-01

    Recently reported qualitative experiments proved that retroviral infectivity is not destroyed by lyophilization performed on systemically infected bone and tendon. The now accomplished quantitative determination of residual infectivity for enveloped and non-enveloped viruses allows a validation of the production process regarding viral safety in freeze-dried bone transplants. The lyophilization effect on the infectivity of two non-enveloped viruses (Maus Elberfeld virus, MEV; Porcine parvovirus, PPV) and one enveloped virus (Vesicular Stomatitis virus, VSV) was examined for virus-spiked bone material in comparison to lyophilized viruses, original virus stock, and air-dried viruses. All experiments were carried out with both cell-free and cell-associated virus. Significant differences were observed regarding the reduction of virus titers (TCID50). Infectivity of VSV was reduced by about 3-4 log10 using lyophilization in presence of bone matrix and of MEV by 6-7 log10, while no substantial reduction in virus titers was observed for PPV. Lyophilization of cell-free or cell-associated virus is not sufficient to inactivate viruses completely. However, lyophilization could have an additive effect in line with other production steps used in the manufacturing process.

  11. Functional organization of the HIV lipid envelope

    Science.gov (United States)

    Huarte, Nerea; Carravilla, Pablo; Cruz, Antonio; Lorizate, Maier; Nieto-Garai, Jon A.; Kräusslich, Hans-Georg; Pérez-Gil, Jesús; Requejo-Isidro, Jose; Nieva, José L.

    2016-01-01

    The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope. PMID:27678107

  12. Nuclear Confidence

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Fukushima nuclear accident provides valuable lessons for China national nuclear Corp.as it continues to expand its operations AS Japan’s Fukushima nuclear crisis sparks a global debate over nuclear safety,China National Nuclear Corp. (CNNC),the country’s largest nuclear plant operator, comes under the spotlight.

  13. Envelope Thermal Design Optimization for Urban Residential Buildings in Malawi

    OpenAIRE

    2016-01-01

    This study sought to optimize the envelope thermal design of free-running urban residential buildings in Malawi. It specifically set out to improve the urban residential buildings’ thermal comfort and suggest optimal envelope thermal design features for these buildings. The research study was primarily dependent on computer simulations in EnergyPlus to replicate the typical Malawian urban residential building’s thermal behaviour and then study the impacts of various envelope configurations on...

  14. Metabolic remodeling in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Tao GUO

    2013-01-01

    Although the management of chronic heart failure (CHF) has made enormous progress over the past decades,CHF is still a tremendous medical and societal burden.Metabolic remodeling might play a crucial role in the pathophysiology of CHF.The characteristics and mechanisms of metabolic remodeling remained unclear,and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability.In the early phases of the disease,metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation.Along with the progress of the disease,the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation.In addition,a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.

  15. Chromatin remodeling in cardiovascular development and physiology.

    Science.gov (United States)

    Han, Pei; Hang, Calvin T; Yang, Jin; Chang, Ching-Pin

    2011-02-04

    Chromatin regulation provides an important means for controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various transcription factors in the fine regulation of gene expression, essential for all aspects of cardiovascular biology. Aberrant cardiac gene expression, triggered by a variety of pathological insults, can cause heart diseases in both animals and humans. The severity of cardiomyopathy and heart failure correlates strongly with abnormal cardiac gene expression. Therefore, controlling cardiac gene expression presents a promising approach to the treatment of human cardiomyopathy. This review focuses on the roles of ATP-dependent chromatin-remodeling factors and chromatin-modifying enzymes in the control of gene expression during cardiovascular development and disease.

  16. DipM, a new factor required for peptidoglycan remodelling during cell division in Caulobacter crescentus.

    Science.gov (United States)

    Möll, Andrea; Schlimpert, Susan; Briegel, Ariane; Jensen, Grant J; Thanbichler, Martin

    2010-07-01

    In bacteria, cytokinesis is dependent on lytic enzymes that facilitate remodelling of the cell wall during constriction. In this work, we identify a thus far uncharacterized periplasmic protein, DipM, that is required for cell division and polarity in Caulobacter crescentus. DipM is composed of four peptidoglycan binding (LysM) domains and a C-terminal lysostaphin-like (LytM) peptidase domain. It binds to isolated murein sacculi in vitro, and is recruited to the site of constriction through interaction with the cell division protein FtsN. Mutational analyses showed that the LysM domains are necessary and sufficient for localization of DipM, while its peptidase domain is essential for function. Consistent with a role in cell wall hydrolysis, DipM was found to interact with purified murein sacculi in vitro and to induce cell lysis upon overproduction. Its inactivation causes severe defects in outer membrane invagination, resulting in a significant delay between cytoplasmic compartmentalization and final separation of the daughter cells. Overall, these findings indicate that DipM is a periplasmic component of the C. crescentus divisome that facilitates remodelling of the peptidoglycan layer and, thus, coordinated constriction of the cell envelope during the division process.

  17. Membrane remodeling by the double-barrel scaffolding protein of poxvirus.

    Directory of Open Access Journals (Sweden)

    Jae-Kyung Hyun

    2011-09-01

    Full Text Available In contrast to most enveloped viruses, poxviruses produce infectious particles that do not acquire their internal lipid membrane by budding through cellular compartments. Instead, poxvirus immature particles are generated from atypical crescent-shaped precursors whose architecture and composition remain contentious. Here we describe the 2.6 Å crystal structure of vaccinia virus D13, a key structural component of the outer scaffold of viral crescents. D13 folds into two jellyrolls decorated by a head domain of novel fold. It assembles into trimers that are homologous to the double-barrel capsid proteins of adenovirus and lipid-containing icosahedral viruses. We show that, when tethered onto artificial membranes, D13 forms a honeycomb lattice and assembly products structurally similar to the viral crescents and immature particles. The architecture of the D13 honeycomb lattice and the lipid-remodeling abilities of D13 support a model of assembly that exhibits similarities with the giant mimivirus. Overall, these findings establish that the first committed step of poxvirus morphogenesis utilizes an ancestral lipid-remodeling strategy common to icosahedral DNA viruses infecting all kingdoms of life. Furthermore, D13 is the target of rifampicin and its structure will aid the development of poxvirus assembly inhibitors.

  18. Nuclear Exodus: Herpesviruses Lead the Way.

    Science.gov (United States)

    Bigalke, Janna M; Heldwein, Ekaterina E

    2016-09-29

    Most DNA viruses replicate in the nucleus and exit it either by passing through the nuclear pores or by rupturing the nuclear envelope. Unusually, herpesviruses have evolved a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. Although this general scheme is accepted in the field, the players and their roles are still debated. Recent studies illuminated critical mechanistic features of this enigmatic process and uncovered surprising parallels with a novel cellular nuclear export process. This review summarizes our current understanding of nuclear egress in herpesviruses, examines the experimental evidence and models, and outlines outstanding questions with the goal of stimulating new research in this area.

  19. On the role of recombination in common-envelope ejections

    CERN Document Server

    Ivanova, N; Podsiadlowski, Ph

    2014-01-01

    The energy budget in common-envelope events (CEEs) is not well understood, with substantial uncertainty even over to what extent the recombination energy stored in ionised hydrogen and helium might be used to help envelope ejection. We investigate the reaction of a red-giant envelope to heating which mimics limiting cases of energy input provided by the orbital decay of a binary during a CEE, specifically during the post-plunge-in phase during which the spiral-in has been argued to occur on a time-scale longer than dynamical. We show that the outcome of such a CEE depends less on the total amount of energy by which the envelope is heated than on how rapidly the energy was transferred to the envelope and on where the envelope was heated. The envelope always becomes dynamically unstable before receiving net heat energy equal to the envelope's initial binding energy. We find two types of outcome, both of which likely lead to at least partial envelope ejection: "runaway" solutions in which the expansion of the ra...

  20. Multislice behavioral modeling based on envelope domain for power amplifiers

    Institute of Scientific and Technical Information of China (English)

    Wang Huadong; Bao Jingfu; Wu Zhengde

    2009-01-01

    An envelope domain multislice behavioral modeling is introduced. The tradition AM-AM and AM-PM characteristics of power amplifiers are extended to envelope domain and base-band filter is applied to distortion complex envelope signal for description of the envelope memory effect. Using traditional one and two-tone tests, the coefficients of nonlinear model and the FIR filter can be extracted. At last the model has been applied to a 10 W WCDMA power amplifier to predict its output signal. And simulation results show that the model output conforms very well to the traditional transistor level simulation results.

  1. INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair.

    Science.gov (United States)

    Morrison, Ashby J; Highland, Jessica; Krogan, Nevan J; Arbel-Eden, Ayelet; Greenblatt, Jack F; Haber, James E; Shen, Xuetong

    2004-12-17

    While the role of ATP-dependent chromatin remodeling in transcription is well established, a link between chromatin remodeling and DNA repair has remained elusive. We have found that the evolutionarily conserved INO80 chromatin remodeling complex directly participates in the repair of a double-strand break (DSB) in yeast. The INO80 complex is recruited to a HO endonuclease-induced DSB through a specific interaction with the DNA damage-induced phosphorylated histone H2A (gamma-H2AX). This interaction requires Nhp10, an HMG-like subunit of the INO80 complex. The loss of Nhp10 or gamma-H2AX results in reduced INO80 recruitment to the DSB. Finally, components of the INO80 complex show synthetic genetic interactions with the RAD52 DNA repair pathway, the main pathway for DSB repair in yeast. Our findings reveal a new role of ATP-dependent chromatin remodeling in nuclear processes and suggest that an ATP-dependent chromatin remodeling complex can read a DNA repair histone code.

  2. Chromatin remodeling in cardiovascular development and physiology

    OpenAIRE

    Han, Pei; Hang, Calvin T.; Yang, Jin; Chang, Ching-Pin

    2011-01-01

    Chromatin regulation provides an important means of controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various tran...

  3. Psoriatic architecture constructed by epidermal remodeling.

    Science.gov (United States)

    Iizuka, Hajime; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2004-08-01

    Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.

  4. Stepwise nucleosome translocation by RSC remodeling complexes.

    Science.gov (United States)

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-02-19

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome.

  5. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  6. Nuclear safeguards; Salvaguardias nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Zurron, O.

    2015-07-01

    Safeguards control at the Juzbado Plant is implemented through the joint IAEA/EURATOM partnership approach in force within the European Union for all nuclear facilities. this verification agreement is designed to minimize burden on the operators whilst ensuring that both inspectorate achieve the objectives related to their respective safeguards regimes. This paper outlines the safeguards approaches followed by the inspectorate and the particularities of the Juzbado Plants nuclear material accountancy and control system. (Authors)

  7. Pushing the Envelope of Extreme Space Weather

    Science.gov (United States)

    Pesnell, W. D.

    2014-12-01

    Extreme Space Weather events are large solar flares or geomagnetic storms, which can cost billions of dollars to recover from. We have few examples of such events; the Carrington Event (the solar superstorm) is one of the few that had superlatives in three categories: size of solar flare, drop in Dst, and amplitude of aa. Kepler observations show that stars similar to the Sun can have flares releasing millions of times more energy than an X-class flare. These flares and the accompanying coronal mass ejections could strongly affect the atmosphere surrounding a planet. What level of solar activity would be necessary to strongly affect the atmosphere of the Earth? Can we map out the envelope of space weather along the evolution of the Sun? What would space weather look like if the Sun stopped producing a magnetic field? To what extreme should Space Weather go? These are the extremes of Space Weather explored in this talk.

  8. Integrated Energy Design of the Building Envelope

    DEFF Research Database (Denmark)

    Nielsen, Martin Vraa

    project analysed how the implementation of technical knowledge early in the building design process can quantify the effect of a building’s façades on its energy efficiency and indoor climate and thereby facilitate a more qualified design development. The project was structured in the following way: 1......This thesis describes the outcome of the PhD project Integrated energy design of the building envelope carried out through a combination of scientific dissemination reported through peer-reviewed journals and a wide range of affiliated projects involved in at an architectural firm. The research...... layout, window geometry and transparency, design of the window aperture, etc. Through the wide range of affiliated project involved in at the architectural firm over the course of this project, this approach resulted in building designs with an energy demand at least 25% below the minimum requirements...

  9. Antireflection Pyrex envelopes for parabolic solar collectors

    Science.gov (United States)

    McCollister, H. L.; Pettit, R. B.

    1983-11-01

    Antireflective (AR) coatings, applied to the glass envelopes used in parabolic trough solar collectors around the receiver tube in order to reduce thermal losses, can increase solar transmittance by 7 percent. An AR surface has been formed on Pyrex by first heat treating the glass to cause a compositional phase separation, removing a surface layer after heat treatment through the use of a preetching solution, and finally etching in a solution that contains hydrofluorosilic and ammonium bifluoride acids. AR-coated samples with solar transmittance values of more than 0.97, by comparison to an untreated sample value of 0.91, have been obtained for the 560-630 C range of heat treatment temperatures. Optimum values have also been determined for the other processing parameters.

  10. Data envelopment analysis of randomized ranks

    Directory of Open Access Journals (Sweden)

    Sant'Anna Annibal P.

    2002-01-01

    Full Text Available Probabilities and odds, derived from vectors of ranks, are here compared as measures of efficiency of decision-making units (DMUs. These measures are computed with the goal of providing preliminary information before starting a Data Envelopment Analysis (DEA or the application of any other evaluation or composition of preferences methodology. Preferences, quality and productivity evaluations are usually measured with errors or subject to influence of other random disturbances. Reducing evaluations to ranks and treating the ranks as estimates of location parameters of random variables, we are able to compute the probability of each DMU being classified as the best according to the consumption of each input and the production of each output. Employing the probabilities of being the best as efficiency measures, we stretch distances between the most efficient units. We combine these partial probabilities in a global efficiency score determined in terms of proximity to the efficiency frontier.

  11. Enveloping branes and brane-world singularities

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, Ignatios; Cotsakis, Spiros [CERN-Theory Division, Department of Physics, Geneva 23 (Switzerland); Klaoudatou, Ifigeneia [University of the Aegean, Research Group of Geometry, Dynamical Systems and Cosmology, Department of Information and Communication Systems Engineering, Samos (Greece)

    2014-12-01

    The existence of envelopes is studied for systems of differential equations in connection with the method of asymptotic splittings which allows one to determine the singularity structure of the solutions. The result is applied to brane-worlds consisting of a 3-brane in a five-dimensional bulk, in the presence of an analog of a bulk perfect fluid parameterizing a generic class of bulk matter. We find that all flat brane solutions suffer from a finite-distance singularity contrary to previous claims. We then study the possibility of avoiding finite-distance singularities by cutting the bulk and gluing regular solutions at the position of the brane. Further imposing physical conditions such as finite Planck mass on the brane and positive energy conditions on the bulk fluid, excludes, however, this possibility as well. (orig.)

  12. Performance measurement with fuzzy data envelopment analysis

    CERN Document Server

    Tavana, Madjid

    2014-01-01

    The intensity of global competition and ever-increasing economic uncertainties has led organizations to search for more efficient and effective ways to manage their business operations.  Data envelopment analysis (DEA) has been widely used as a conceptually simple yet powerful tool for evaluating organizational productivity and performance. Fuzzy DEA (FDEA) is a promising extension of the conventional DEA proposed for dealing with imprecise and ambiguous data in performance measurement problems. This book is the first volume in the literature to present the state-of-the-art developments and applications of FDEA. It is designed for students, educators, researchers, consultants and practicing managers in business, industry, and government with a basic understanding of the DEA and fuzzy logic concepts.

  13. Diversity in the fertilization envelopes of echinoderms.

    Science.gov (United States)

    Oulhen, Nathalie; Reich, Adrian; Wong, Julian L; Ramos, Isabela; Wessel, Gary M

    2013-01-01

    Cell surface changes in an egg at fertilization are essential to begin development and for protecting the zygote. Most fertilized eggs construct a barrier around themselves by modifying their original extracellular matrix. This construction usually results from calcium-induced exocytosis of cortical granules, the contents of which in sea urchins function to form the fertilization envelope (FE), an extracellular matrix of cortical granule contents built upon a vitelline layer scaffold. Here, we examined the molecular mechanism of this process in sea stars, a close relative of the sea urchins, and analyze the evolutionary changes that likely occurred in the functionality of this structure between these two organisms. We find that the FE of sea stars is more permeable than in sea urchins, allowing diffusion of molecules in excess of 2 megadaltons. Through a proteomic and transcriptomic approach, we find that most, but not all, of the proteins present in the sea urchin envelope are present in sea stars, including SFE9, proteoliaisin, and rendezvin. The mRNAs encoding these FE proteins accumulated most densely in early oocytes, and then beginning with vitellogenesis, these mRNAs decreased in abundance to levels nearly undetectable in eggs. Antibodies to the SFE9 protein of sea stars showed that the cortical granules in sea star also accumulated most significantly in early oocytes, but different from sea urchins, they translocated to the cortex of the oocytes well before meiotic initiation. These results suggest that the preparation for cell surface changes in sea urchins has been shifted to later in oogenesis, and perhaps reflects the meiotic differences among the species-sea star oocytes are stored in prophase of meiosis and fertilized during the meiotic divisions, as in most animals, whereas sea urchins are one of the few taxons in which eggs have completed meiosis prior to fertilization.

  14. ASYMMETRIC ACCRETION FLOWS WITHIN A COMMON ENVELOPE

    Energy Technology Data Exchange (ETDEWEB)

    MacLeod, Morgan; Ramirez-Ruiz, Enrico [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)

    2015-04-10

    This paper examines flows in the immediate vicinity of stars and compact objects dynamically inspiralling within a common envelope (CE). Flow in the vicinity of the embedded object is gravitationally focused, leading to drag and potentially to gas accretion. This process has been studied numerically and analytically in the context of Hoyle–Lyttleton accretion (HLA). Yet, within a CE, accretion structures may span a large fraction of the envelope radius, and in so doing sweep across a substantial radial gradient of density. We quantify these gradients using detailed stellar evolution models for a range of CE encounters. We provide estimates of typical scales in CE encounters that involve main sequence stars, white dwarfs, neutron stars, and black holes with giant-branch companions of a wide range of masses. We apply these typical scales to hydrodynamic simulations of three-dimensional HLA with an upstream density gradient. This density gradient breaks the symmetry that defines HLA flow, and imposes an angular momentum barrier to accretion. Material that is focused into the vicinity of the embedded object thus may not be able to accrete. As a result, accretion rates drop dramatically, by one to two orders of magnitude, while drag rates are only mildly affected. We provide fitting formulae to the numerically derived rates of drag and accretion as a function of the density gradient. The reduced ratio of accretion to drag suggests that objects that can efficiently gain mass during CE evolution, such as black holes and neutron stars, may grow less than implied by the HLA formalism.

  15. Diversity in the fertilization envelopes of echinoderms

    Science.gov (United States)

    Oulhen, Nathalie; Reich, Adrian; Wong, Julian L.; Wessel, Gary M.

    2013-01-01

    Cell surface changes in an egg at fertilization are essential to begin development and for protecting the zygote. Most fertilized eggs construct a barrier around themselves by modifying their original extracellular matrix. This construction usually results from calcium induced exocytosis of cortical granules, the contents of which in sea urchins function to form the fertilization envelope (FE), an extracellular matrix of cortical granule contents built upon a vitelline layer scaffold. Here we examined the molecular mechanism of this process in sea stars, a close relative of the sea urchins, and analyze the evolutionary changes that likely occurred in the functionality of this structure between these two organisms. We find that the FE of sea stars is more permeable than in sea urchins, allowing diffusion of molecules in excess of 2 megadaltons. Through a proteomic and transcriptomic approach, we find that most, but not all of the proteins present in the sea urchin envelope are present in sea stars, including SFE9, proteoliaisin, rendezvin, and ovoperoxidase. The mRNAs encoding these FE proteins accumulated most densely in early oocytes, and then beginning with vitellogenesis, these mRNAs deceased in abundance to levels nearly undetectable in eggs. Antibodies to the SFE9 protein of sea stars showed that the cortical granules in sea star also accumulated most significantly in early oocytes, and different from sea urchins, they translocated to the cortex of the oocytes well before meiotic initiation. These results suggest that the preparation of the cell surface changes in sea urchins has been shifted to later in oogenesis and perhaps reflects the meiotic differences among the species–sea star oocytes are stored in prophase of meiosis and fertilized during the meiotic divisions, as in most animals, whereas sea urchins are one of the few taxa in which eggs have completed meiosis prior to fertilization. PMID:23331915

  16. Extreme Value Estimates for Arbitrary Bandwidth Gaussian Processes Using the Analytic Envelope.

    Science.gov (United States)

    1984-03-01

    Dugundji 1.) This envelope is defined by using the Hilbert transform. In a recent paper by Rice15 this envelope is called the analytic envelope. 5 tI...Processes for Envelopes of Normal Noise," IRE Transactions on Information Theory, Vol. IT-3, p. 204 (Sept 1957). 14. Dugundji , J., "Envelopes and Pre

  17. Rolling bearing feature frequency extraction using extreme average envelope decomposition

    Science.gov (United States)

    Shi, Kunju; Liu, Shulin; Jiang, Chao; Zhang, Hongli

    2016-09-01

    The vibration signal contains a wealth of sensitive information which reflects the running status of the equipment. It is one of the most important steps for precise diagnosis to decompose the signal and extracts the effective information properly. The traditional classical adaptive signal decomposition method, such as EMD, exists the problems of mode mixing, low decomposition accuracy etc. Aiming at those problems, EAED(extreme average envelope decomposition) method is presented based on EMD. EAED method has three advantages. Firstly, it is completed through midpoint envelopment method rather than using maximum and minimum envelopment respectively as used in EMD. Therefore, the average variability of the signal can be described accurately. Secondly, in order to reduce the envelope errors during the signal decomposition, replacing two envelopes with one envelope strategy is presented. Thirdly, the similar triangle principle is utilized to calculate the time of extreme average points accurately. Thus, the influence of sampling frequency on the calculation results can be significantly reduced. Experimental results show that EAED could separate out single frequency components from a complex signal gradually. EAED could not only isolate three kinds of typical bearing fault characteristic of vibration frequency components but also has fewer decomposition layers. EAED replaces quadratic enveloping to an envelope which ensuring to isolate the fault characteristic frequency under the condition of less decomposition layers. Therefore, the precision of signal decomposition is improved.

  18. Inversion of Auditory Spectrograms, Traditional Spectrograms, and Other Envelope Representations

    DEFF Research Database (Denmark)

    Decorsière, Remi Julien Blaise; Søndergaard, Peter Lempel; MacDonald, Ewen

    2015-01-01

    , or reconstruct a time-domain signal from, an arbitrary envelope representation. To address this problem, a general optimization approach in the time domain is proposed here, which iteratively minimizes the distance between a target envelope representation and that of a reconstructed time-domain signal. Two...

  19. 10 CFR 434.516 - Building exterior envelope.

    Science.gov (United States)

    2010-01-01

    ... Buildings for calculating the Energy Cost Budget. In calculating the Design Energy Consumption of the... 10 Energy 3 2010-01-01 2010-01-01 false Building exterior envelope. 434.516 Section 434.516 Energy... RESIDENTIAL BUILDINGS Building Energy Cost Compliance Alternative § 434.516 Building exterior envelope....

  20. Modeling Protostar Envelopes and Disks Seen With ALMA

    Science.gov (United States)

    Terebey, Susan; Flores-Rivera, Lizxandra; Willacy, Karen

    2017-01-01

    Thermal continuum emission from protostars comes from both the envelope and circumstellar disk. The dust emits on a variety of spatial scales, ranging from sub-arcseconds for disks to roughly 10 arcseconds for envelopes for nearby protostars. We present models of what ALMA should detect that incorporate a self-consistent collapse solution, radiative transfer, and realistic dust properties.

  1. RELAXATION OF FUNCTIONALS INVOLVING HOMOGENEOUS FUNCTIONS AND INVARIANCE OF ENVELOPES

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The authors compute the quasiconvex envelope of certain functions defined on the space Mmn of real m× n matrices via a homogeneous function on Mmn. They also deduce invariance properties for various convex envelopes from corresponding invariance properties satisfied by a function. Some applications related in particular to nonlinear elasticity are given.

  2. 10 CFR 434.402 - Building envelope assemblies and materials.

    Science.gov (United States)

    2010-01-01

    ... Spaces. The area weighted average thermal transmittance of roofs and also of floors and walls adjacent to... Information. 402.1.1Material Properties. Information on thermal properties, building envelope system.... The overall thermal transmittance of the building envelope shall be calculated in accordance...

  3. Nuclear physics

    Energy Technology Data Exchange (ETDEWEB)

    Sang, David (Bishop Luffa Comprehensive School, Chichester (UK))

    1990-01-01

    Nuclear Physics covers the aspects of radioactivity and nuclear physics dealt with in the syllabuses of all the A-level examination boards; in particular, it provides detailed coverage of the Joint Matriculation Board option in nuclear physics. It deals with the discovery of the atomic nucleus, the physics of nuclear processes, and nuclear technology. (author).

  4. Use of response envelopes for seismic margin assessment of reinforced concrete walls and slabs

    Energy Technology Data Exchange (ETDEWEB)

    Ile, Nicolas; Frau, Alberto, E-mail: alberto.frau@cea.fr

    2017-04-01

    Highlights: • Proposal of a method for application of the elliptical envelope to RC shell elements. • Proposal of new algorithms for the seismic margin evaluation for RC shell elements. • Verification of a RC wall 3D structure, using the proposed assessment approach. - Abstract: Seismic safety evaluations of existing nuclear facilities are usually based on the assumption of structural linearity. For the design basis earthquake (DBE), it is reasonable to apply a conventional evaluation of the seismic safety of building structures and carry out a linear elastic analysis to assess the load effects on structural elements. Estimating the seismic capacity of a structural element requires an estimation of the critical combination of responses acting in this structural element and compare this combination with the capacity of the element. By exploiting the response-spectrum-based procedure for predicting the response envelopes in linear structures formulated by Menun and Der Kiureghian (2000a), algorithms are developed for the seismic margin assessment of reinforced concrete shell finite elements. These algorithms facilitate the comparison of the response-spectrum-based envelopes to prescribed capacity surfaces for the purpose of assessing the safety margin of this kind of structures. The practical application of elliptical response envelopes in case of shell finite elements is based on the use of layer models such as those developed by Marti (1990), which transfer the generalized stress field to three layers under the assumption that the two outer layers carry membrane forces and the internal layer carries only the out-of-plane shears. The utility of the assessment approach is discussed with reference to a case study of a 3D structure made of reinforced concrete walls.

  5. Interactions between remodelling, architecture and tissue properties in cancellous bone

    OpenAIRE

    Linden, Jacqueline

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancellous bone. For this reason, the research presented in this thesis focussed on bone remodeling in cancellous bone. We used computer modeling, finite element calculations and in vivo labeled bone speci...

  6. Diverse functions of ATP-dependent chromatin remodeling complexes in development and cancer

    Institute of Scientific and Technical Information of China (English)

    Jiang I. Wu

    2012-01-01

    Mammalian SWI/SNF like Brg1/Brm associated factors (BAF) chromatin-remodeling complexes are able to use energy derived from adenosine triphosphate (ATP) hydrolysis to change chromatin structures and regulate nuclear processes such as transcription.BAF complexes contain multiple subunits and the diverse subunit compositions provide functional specificities to BAF complexes.In this review,we summarize the functions of BAF subunits during mammalian development and in progression of various cancers.The mechanisms underlying the functional diversity and specificities of BAF complexes will be discussed.

  7. Remodeling of the metabolome during early frog development.

    Directory of Open Access Journals (Sweden)

    Livia Vastag

    Full Text Available A rapid series of synchronous cell divisions initiates embryogenesis in many animal species, including the frog Xenopus laevis. After many of these cleavage cycles, the nuclear to cytoplasmic ratio increases sufficiently to somehow cause cell cycles to elongate and become asynchronous at the mid-blastula transition (MBT. We have discovered that an unanticipated remodeling of core metabolic pathways occurs during the cleavage cycles and the MBT in X. laevis, as evidenced by widespread changes in metabolite abundance. While many of the changes in metabolite abundance were consistently observed, it was also evident that different female frogs laid eggs with different levels of at least some metabolites. Metabolite tracing with heavy isotopes demonstrated that alanine is consumed to generate energy for the early embryo. dATP pools were found to decline during the MBT and we have confirmed that maternal pools of dNTPs are functionally exhausted at the onset of the MBT. Our results support an alternative hypothesis that the cell cycle lengthening at the MBT is triggered not by a limiting maternal protein, as is usually proposed, but by a decline in dNTP pools brought about by the exponentially increasing demands of DNA synthesis.

  8. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  9. Pregnancy-induced remodeling of heart valves.

    Science.gov (United States)

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-11-01

    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.

  10. Electrical and myocardial remodeling in primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Mario eCurione

    2014-11-01

    Full Text Available Objective and design: primary aldosteronism (PA represents the most common cause of secondary hypertension. An higher risk of cardiovascular events has been reported in patients with PA than otherwise similar patients with essential hypertension (EH. At today few studies has been investigated the electrocardiographic changes in PA patients compared to EH patients.Methods: to investigate the electrocardiographic changes and heart remodeling in PA we enrolled 61 consecutive patients, 30 with PA (12 with aldosterone producing adenoma-APA and 18 with bilateral adrenal hyperplasia-IHA and 30 with EH. In all subjects electrelectrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram.Results: no significant differences in age, sex , body mass index (BMI and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patientswith PA respect to EH (p< 0.003 and p< 0.002, respectively. First degree atrioventricular block was present in 16% patient with PA and only in 3.2% patients with EH. In PA patients the interventricular septum thickness (IVST correlated with left ventricular mass indecized (LVMi (r= 0.54; p< 0.04, and with PR duration (r= 0.51; p< 0.03. Left ventricular hypertrophy (LVH was present in 53% patients with PA and in 26% patients with EH (χ2 p<0.03.Conclusions: in this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.

  11. Envelope enhancement increases cortical sensitivity to interaural envelope delays with acoustic and electric hearing.

    Directory of Open Access Journals (Sweden)

    Douglas E H Hartley

    Full Text Available Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs. In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps was assessed in response to dichotically-presented i sinusoidal amplitude-modulated (SAM and ii half-wave rectified (HWR tones (100-ms duration; 70 dB SPL presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli

  12. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  13. Phospholipid remodeling and eicosanoid signaling in colon cancer cells.

    Science.gov (United States)

    Das, Siddhartha; Martinez, Leobarda Robles; Ray, Suparna

    2014-12-01

    Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

  14. Nuclear ventriculography

    Science.gov (United States)

    ... ventriculography (RNV); Multiple gate acquisition scan (MUGA); Nuclear cardiology; Cardiomyopathy - nuclear ventriculography ... 56. Udelson JE, Dilsizian V, Bonow RO. Nuclear cardiology. In: Bonow RO, Mann DL, Zipes DP, Libby ...

  15. Nuclear Medicine.

    Science.gov (United States)

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  16. Anchoring a Leviathan: How the Nuclear Membrane Tethers the Genome.

    Science.gov (United States)

    Czapiewski, Rafal; Robson, Michael I; Schirmer, Eric C

    2016-01-01

    It is well established that the nuclear envelope has many distinct direct connections to chromatin that contribute to genome organization. The functional consequences of genome organization on gene regulation are less clear. Even less understood is how interactions of lamins and nuclear envelope transmembrane proteins (NETs) with chromatin can produce anchoring tethers that can withstand the physical forces of and on the genome. Chromosomes are the largest molecules in the cell, making megadalton protein structures like the nuclear pore complexes and ribosomes seem small by comparison. Thus to withstand strong forces from chromosome dynamics an anchoring tether is likely to be much more complex than a single protein-protein or protein-DNA interaction. Here we will briefly review known NE-genome interactions that likely contribute to spatial genome organization, postulate in the context of experimental data how these anchoring tethers contribute to gene regulation, and posit several hypotheses for the physical nature of these tethers that need to be investigated experimentally. Significantly, disruption of these anchoring tethers and the subsequent consequences for gene regulation could explain how mutations in nuclear envelope proteins cause diseases ranging from muscular dystrophy to lipodystrophy to premature aging progeroid syndromes. The two favored hypotheses for nuclear envelope protein involvement in disease are (1) weakening nuclear and cellular mechanical stability, and (2) disrupting genome organization and gene regulation. Considerable experimental support has been obtained for both. The integration of both mechanical and gene expression defects in the disruption of anchoring tethers could provide a unifying hypothesis consistent with both.

  17. Myocardial Tissue Remodeling in Adolescent Obesity

    OpenAIRE

    Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G; Hulten, Edward; Coelho‐Filho, Otavio; Hoppin, Alison; Levitsky, Lynne; de Ferranti, Sarah; Rhodes, Erinn T.; Traum, Avram; Goodman, Elizabeth; Feng, Henry; Heydari, Bobak; Harris, William S.; Hoefner, Daniel M.

    2013-01-01

    Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described. Methods and Results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years...

  18. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  19. Transient Receptor Potential Channels Contribute to Pathological Structural and Functional Remodeling After Myocardial Infarction

    Science.gov (United States)

    Davis, Jennifer; Correll, Robert N.; Trappanese, Danielle M.; Hoffman, Nicholas E.; Troupes, Constantine D.; Berretta, Remus M.; Kubo, Hajime; Madesh, Muniswamy; Chen, Xiongwen; Gao, Erhe; Molkentin, Jeffery D.; Houser, Steven R.

    2014-01-01

    Rationale The cellular and molecular basis for post myocardial infarction (MI) structural and functional remodeling is not well understood. Objective To determine if Ca2+ influx through transient receptor potential (canonical) (TRPC) channels contributes to post-MI structural and functional remodeling. Methods and Results TRPC1/3/4/6 channel mRNA increased after MI in mice and was associated with TRPC-mediated Ca2+ entry. Cardiac myocyte specific expression of a dominant negative (dn: loss of function) TRPC4 channel increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling after MI while increasing survival. We used adenovirus-mediated expression of TRPC3/4/6 channels in cultured adult feline myocytes (AFMs) to define mechanistic aspects of these TRPC-related effects. TRPC3/4/6 over expression in AFMs induced calcineurin (Cn)-Nuclear Factor of Activated T cells (NFAT) mediated hypertrophic signaling, which was reliant on caveolae targeting of TRPCs. TRPC3/4/6 expression in AFMs increased rested state contractions and increased spontaneous sarcoplasmic reticulum (SR) Ca2+ sparks mediated by enhanced phosphorylation of the ryanodine receptor. TRPC3/4/6 expression was associated with reduced contractility and response to catecholamines during steady state pacing, likely due to enhanced SR Ca2+ leak. Conclusions Ca2+ influx through TRPC channels expressed after MI activates pathological cardiac hypertrophy and reduces contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac structure and function. PMID:25047165

  20. Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation.

    Science.gov (United States)

    Kim, Min Hwan; Kim, Jongshin; Hong, Hyowon; Lee, Si-Hyung; Lee, June-Koo; Jung, Eunji; Kim, Joon

    2016-03-01

    The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. Melanoma cells resistant to the BRAF inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ reduces the viability of resistant melanoma cells, whereas overexpression of constitutively active YAP induces resistance. Moreover, inhibition of actin polymerization and actomyosin tension in melanoma cells suppresses both YAP/TAZ activation and PLX4032 resistance. Our siRNA library screening identifies actin dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent resistance pathway. These results suggest that inhibition of actin remodeling is a potential strategy to suppress resistance in BRAF inhibitor therapies.

  1. The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

    Directory of Open Access Journals (Sweden)

    Shanshan Zhou

    2014-01-01

    Full Text Available Heart failure (HF is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2- related factor 2 (Nrf2 is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

  2. Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches.

    Directory of Open Access Journals (Sweden)

    Ghia M Euskirchen

    2011-03-01

    Full Text Available A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate, and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function, and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate, we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5' ends, RNA Polymerases II and III, and enhancers as well as regions critical for chromosome organization (e.g. CTCF, lamins, and DNA replication origins. Interestingly we also find that certain configurations of SWI/SNF subunits are associated with transcripts that have higher levels of expression, whereas other configurations of SWI/SNF factors are associated with transcripts that have lower levels of expression. To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins, we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members, as well as with cellular constituents such as nuclear matrix proteins, key transcription factors, and centromere components, implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of

  3. Understanding three-dimensional damage envelopes

    Science.gov (United States)

    Browning, John; Harland, Sophie; Meredith, Philip; Healy, David; Mitchell, Tom

    2017-04-01

    Microcrack damage leading to failure in rocks evolves in response to differential loading. This loading is often visualized in a two-dimensional stress space through the use of Mohr-Coulomb diagrams. The vast majority of experimental studies investigate damage evolution and rock failure using conventional triaxial stress states (σ1 > σ2 = σ3) in which the results can be easily represented in a Mohr-Coulomb plot. However, in nature the stress state is in general truly triaxial (σ1 > σ2 > σ3) and as such comprises a 3D stress state potentially leading to more complexity. By monitoring acoustic wave velocities and acoustic emissions we have shown that damage is generated in multiple orientations depending on the loading directions and hence principal stress directions. Furthermore, crack growth is shown to be a function of differential stress regardless of the mean stress. As such, new cracks can form due to a decrease in the minimum principal stress, which reduces mean stress but increases the differential stress. Although the size of individual cracks is not affected by the intermediate principal stress it has been shown that the σ2 plays a key role in suppressing the total amount of crack growth and concentrates this damage in a single plane. Hence, the differential stress at which rocks fail (i.e. the rock strength) will be significantly increased under true triaxial stress conditions than under the much more commonly applied condition of conventional triaxial stress. Through a series of cyclic loading tests we investigated the Kaiser effect, we show that while individual stress states are important, the stress path by which this stress state is reached is equally important. Whether or not a stress state has been 'visited' before is also vitally important in determining and understanding damage envelopes. Finally, we show that damage evolution can be anisotropic and must be considered as a three-dimensional problem. It is unclear how damage envelopes

  4. Mushroom body neuronal remodelling is necessary for short-term but not for long-term courtship memory in Drosophila.

    Science.gov (United States)

    Redt-Clouet, Christelle; Trannoy, Séverine; Boulanger, Ana; Tokmatcheva, Elena; Savvateeva-Popova, Elena; Parmentier, Marie-Laure; Preat, Thomas; Dura, Jean-Maurice

    2012-06-01

    The remodelling of neurons during their development is considered necessary for their normal function. One fundamental mechanism involved in this remodelling process in both vertebrates and invertebrates is axon pruning. A well-documented case of such neuronal remodelling is the developmental axon pruning of mushroom body γ neurons that occurs during metamorphosis in Drosophila. The γ neurons undergo pruning of larval-specific dendrites and axons at metamorphosis, followed by their regrowth as adult-specific dendrites and axons. We recently revealed a molecular cascade required for this pruning. The nuclear receptor ftz-f1 activates the expression of the steroid hormone receptor EcR-B1, a key component for γ remodelling, and represses expression of Hr39, an ftz-f1 homologous gene. If ectopically expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. The mushroom bodies are a bilaterally symmetric structure in the larval and adult brain and are involved in the processing of different types of olfactory memory. How memory is affected in pruning-deficient adult flies that possess larval-stage neuronal circuitry will help to explain the functional role of neuron remodelling. Flies overexpressing Hr39 are viable as adults and make it possible to assess the requirement for wild-type mushroom body pruning in memory. While blocking mushroom body neuron remodelling impaired memory after short-term courtship conditioning, long-term memory was normal. These results show that larval pruning is necessary for adult memory and that expression of courtship short-term memory and long-term memory may be parallel and independent. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Hymenolepis nana: the fine structure of the embryonic envelopes.

    Science.gov (United States)

    Fairweather, I; Threadgold, L T

    1981-06-01

    The fine structure of the envelopes surrounding hatched and unhatched oncospheres of Hymenolepis nana has been investigated by transmission and scanning electron microscopy (SEM), together with light microscope histochemical observations of JB-4 embedded material. The oncosphere is surrounded by 3 layers--the capsule, the outer envelope and the inner envelope, the latter giving rise to the embryophore and the 'oncospheral membrane'. An additional layer--the polar filament layer--lies between the 'oncospheral membrane' and the oncosphere. Shell material is deposited on the capsule as a thin layer. It is secreted by the outer envelope, which degenerates once shell formation is complete. The uterus may also contribute to shell formation. The embryophore forms a thin incomplete and peripheral layer within the inner envelope. In the basal region of this envelope, partial development of an 'oncospheral membrane' takes place, but it does not become detached as a separate layer. The polar filaments, which are characteristic of the oncosphere of H. nana, are derived from the epithelial covering of the oncosphere itself, which delaminates to form a separate polar filament layer. The filaments arise from knob-like projections at opposite poles of this layer. The design of the embryonic envelopes in H. nana show a number of modifications from the basic cyclophyllidean pattern, and these can be related to the demands of its 'direct' life-cycle.

  6. Nuclear Theory - Nuclear Power

    Science.gov (United States)

    Svenne, J. P.; Canton, L.; Kozier, K. S.

    2008-01-01

    The results from modern nuclear theory are accurate and reliable enough to be used for practical applications, in particular for scattering that involves few-nucleon systems of importance to nuclear power. Using well-established nucleon-nucleon (NN) interactions that fit well the NN scattering data, and the AGS form of the three-body theory, we have performed precise calculations of low-energy neutron-deuteron (n+d) scattering. We show that three-nucleon force effects that have impact on the low-energy vector analyzing powers have no practical effects on the angular distribution of the n+d cross-section. There appear to be problems for this scattering in the evaluated nuclear data file (ENDF) libraries, at the incident neutron energies less than 3.2 MeV. Supporting experimental data in this energy region are rather old (>25 years), sparse and often inconsistent. Our three-body results at low energies, 50 keV to 10.0 MeV, are compared to the ENDF/B-VII.0 and JENDL (Japanese Evaluated Nuclear Data Library) -3.3 evaluated angular distributions. The impact of these results on the calculated reactivity for various critical systems involving heavy water is shown.

  7. Specific remodeling of splenic architecture by cytomegalovirus.

    Science.gov (United States)

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F

    2006-03-01

    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  8. Vascular remodeling underlies rebleeding in hemophilic arthropathy.

    Science.gov (United States)

    Bhat, Vikas; Olmer, Merissa; Joshi, Shweta; Durden, Donald L; Cramer, Thomas J; Barnes, Richard Fw; Ball, Scott T; Hughes, Tudor H; Silva, Mauricio; Luck, James V; Moore, Randy E; Mosnier, Laurent O; von Drygalski, Annette

    2015-11-01

    Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

  9. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  10. Specific remodeling of splenic architecture by cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Chris A Benedict

    2006-03-01

    Full Text Available Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21. The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  11. ECG manifestations of left ventricular electrical remodeling.

    Science.gov (United States)

    Estes, E Harvey

    2012-01-01

    Research and thinking about the electrocardiographic manifestations of left ventricular hypertrophy has been constrained by a limited conceptual model of the process: heart disease produces chamber enlargement (increased mass), which in turn produces an altered electrocardiogram. The process is much more complex than can be represented in this simple model. A more robust and intricate model is proposed, in which heart (and vascular) disease causes structural changes, electrical changes, biochemical changes, and others, all of which interact to produce electrical remodeling of ventricular myocardium. This electrical remodeling results in a variety of ECG changes. All of these changes interact, leading to an altered clinical course, and to premature death. It is suggested that research, based on this model, can provide new clues to the processes involved, and improve the prediction of clinical outcomes. New directions in research, in recording equipment, and in organizational activities are suggested to test this new model, and to improve the usefulness of the electrocardiogram as a research and diagnostic tool.

  12. Airway remodelling in the transplanted lung.

    Science.gov (United States)

    Kuehnel, Mark; Maegel, Lavinia; Vogel-Claussen, Jens; Robertus, Jan Lukas; Jonigk, Danny

    2017-03-01

    Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.

  13. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  14. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  15. System and method for investigating arterial remodeling.

    Science.gov (United States)

    Rachev, Alexander; Dominguez, Zachary; Vito, Raymond

    2009-10-01

    Organ culture systems are used to study remodeling of arteries and to fabricate tissue engineered vascular grafts. Investigations to date focused on changes in geometry and mechanical response of arteries or constructs associated with controlled sustained alterations in the global load parameters such as the arterial pressure, flow, or axial stretch. A new experimental paradigm is proposed, which is based on the simultaneous independent control of local mechanical parameters such as mean strain or stress in the arterial wall and flow-induced shear at the intima. An organ culture system and methodology were developed, which controls pressure, flow, and axial length of a specimen in order to maintain the local mechanical parameters at prescribed values. The operation of the system is illustrated by maintenance of elevated axial medial stress in porcine carotid artery, while keeping the mean circumferential stress and flow-induced shear stress at baseline values. Previously unknown aspects of remodeling that might be revealed by the novel approach are discussed.

  16. [Semiology for gluteal remodeling by lipofilling].

    Science.gov (United States)

    Ho Quoc, C; Mojallal, A

    2012-12-01

    Gluteal augmentation is a consultation request for many patients. The most common surgical techniques performed for gluteal augmentation employ gluteal implants. However, the results can be frustrating. Liposuction is one of the most common surgical procedures in aesthetic surgery. This surgical procedure can provide some complications. Fat grafting is an effective and predictable way to remodel the buttocks. To get better results, it's important to understand gluteal compartments with a descriptive study. The aim of this study is to describe gluteal semiology for buttocks remodeling with fat grafting. We have described gluteal semiology with our review of literature. We have analyzed fat compartments of gluteal region: volume, links between every compartments, connections with major gluteal muscle and with the skin. We have also analyzed shape and volume of the buttocks. We have described 11 aesthetic subunits, the volume and the shape of the buttocks, and the skin laxity. We did an important literature review to understand the most important gluteal zones to improve for patients' satisfaction. Our gluteal semiology description is very useful to understand liposuction/lipoinjection of gluteal areas. Fat grafting may be a reliable technique, simple and safe procedure. Surgery for correction of the buttocks may involve more than projection and volume. However, these must be in a balanced proportion with the rest of the body. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, Tomohiro [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Sugiura, Hisatoshi, E-mail: sugiura@rm.med.tohoku.ac.jp [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Ichinose, Masakazu [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

    2013-05-01

    Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-β{sub 1} production (P<0.01) and a neutralizing anti-TGF-β antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-β{sub 1} release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway.

  18. ANALYSES AND INFLUENCES OF GLAZED BUILDING ENVELOPES

    Directory of Open Access Journals (Sweden)

    Sabina Jordan

    2011-01-01

    Full Text Available The article presents the results of an analytical study of the functioning of glazing at two different yet interacting levels: at the level of the building as a whole, and at that of glazing as a building element. At the building level, analyses were performed on a sample of high-rise business buildings in Slovenia, where the glazing"s share of the building envelope was calculated, and estimates of the proportion of shade provided by external blinds were made. It is shown that, especially in the case of modern buildings with large proportions of glazing and buildings with no shading devices, careful glazing design is needed, together with a sound knowledge of energy performance. In the second part of the article, the energy balance values relating to selected types of glazing are presented, including solar control glazing. The paper demonstrates the need for a holistic energy approach to glazing problems, as well as how different types of glazing can be methodically compared, thus improving the design of sustainability-orientated buildings.

  19. Localization of phosphatidylcholine in outer envelope membrane of spinach chloroplasts

    Science.gov (United States)

    1985-01-01

    We have examined the effects of phospholipase C from Bacillus cereus on the extent of phospholipid hydrolysis in envelope membrane vesicles and in intact chloroplasts. When isolated envelope vesicles were incubated in presence of phospholipase C, phosphatidylcholine and phosphatidylglycerol, but not phosphatidylinositol, were totally converted into diacylglycerol if they were available to the enzyme (i.e., when the vesicles were sonicated in presence of phospholipase C). These experiments demonstrate that phospholipase C can be used to probe the availability of phosphatidylcholine and phosphatidylglycerol in the cytosolic leaflet of the outer envelope membrane from spinach chloroplasts. When isolated, purified, intact chloroplasts were incubated with low amounts of phospholipase C (0.3 U/mg chlorophyll) under very mild conditions (12 degrees C for 1 min), greater than 80% of phosphatidylcholine molecules and almost none of phosphatidylglycerol molecules were hydrolyzed. Since we have also demonstrated, by using several different methods (phase-contrast and electron microscopy, immunochemical and electrophoretic analyses) that isolated spinach chloroplasts, and especially their outer envelope membrane, remained intact after mild treatment with phospholipase C, we can conclude that there is a marked asymmetric distribution of phospholipids across the outer envelope membrane of spinach chloroplasts. Phosphatidylcholine, the major polar lipid of the outer envelope membrane, is almost entirely accessible from the cytosolic side of the membrane and therefore is probably localized in the outer leaflet of the outer envelope bilayer. On the contrary, phosphatidylglycerol, the major polar lipid in the inner envelope membrane and the thylakoids, is probably not accessible to phospholipase C from the cytosol and therefore is probably localized mostly in the inner leaflet of the outer envelope membrane and in the other chloroplast membranes. PMID:3988805

  20. DATA ENVELOPMENT ANALYSIS OF BANKING SECTOR IN BANGLADESH

    Directory of Open Access Journals (Sweden)

    Md. Rashedul Hoque

    2012-05-01

    Full Text Available Banking sector of Bangladesh is flourishing and contributing to its economy. In this aspect measuring efficiency is important. Data Envelopment Analysis technique is used for this purpose. The data are collected from the annual reports of twenty four different banks in Bangladesh. Data Envelopment Analysis is mainly of two types - constant returns to scale and variable returns to scale. Since this study attempts to maximize output, so the output oriented Data Envelopment Analysis is used. The most efficient bank is one that obtains the highest efficiency score.

  1. Revisiting the envelope approximation: gravitational waves from bubble collisions

    CERN Document Server

    Weir, David J

    2016-01-01

    We study the envelope approximation and its applicability to first-order phase transitions in the early universe. We demonstrate that the power laws seen in previous studies exist independent of the nucleation rate. We also compare the envelope approximation prediction to results from large-scale phase transition simulations. For phase transitions where the contribution to gravitational waves from scalar fields dominates over that from the coupled plasma of light particles, the envelope approximation is in agreement, giving a power spectrum of the same form and order of magnitude. In all other cases the form and amplitude of the gravitational wave power spectrum is markedly different and new techniques are required.

  2. Revisiting the envelope approximation: Gravitational waves from bubble collisions

    Science.gov (United States)

    Weir, David J.

    2016-06-01

    We study the envelope approximation and its applicability to first-order phase transitions in the early Universe. We demonstrate that the power laws seen in previous studies exist independently of the nucleation rate. We also compare the envelope approximation prediction to results from large-scale phase transition simulations. For phase transitions where the contribution to gravitational waves from scalar fields dominates over that from the coupled plasma of light particles, the envelope approximation is in agreement, giving a power spectrum of the same form and order of magnitude. In all other cases the form and amplitude of the gravitational wave power spectrum is markedly different and new techniques are required.

  3. On various definitions of the envelope of a random process

    Science.gov (United States)

    Langley, R. S.

    1986-03-01

    Statistical properties of the envelope deefinitions of Rice [1], Crandall and Mark [2] and Dugundji [3] are derived and compared. It is shown that the definitions of Rice [1] and Dugudji [3] are equivalent, which implies that the envelope of Rice [1] is independent of the choice of a central frequency. This contradicts results which have appeared in the literature [4, 5] and the reason for this contradiction is explained. The envelopes of Crandall and Mark [2] and Dugundji [3] are found to have the same first order probability density function but different crossing rates and mean frequencies.

  4. Pre-paid envelopes commemorating the 2013 Open Days

    CERN Multimedia

    2013-01-01

    The post office on CERN's Prévessin site is still selling pre-paid envelopes commemorating the 2013 Open Days. Hurry while stocks last!   The special envelopes, which are valid in France for non-priority letters weighing up to 20 grams, are ideal for your Christmas and New Year correspondence. A set of ten envelopes, each featuring a different image, costs € 8.70 or 10 CHF. The post office is located in Building 866 on the Prévessin site and is open Mondays to Thursdays from 9.30 a.m. to 12.30 p.m.

  5. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  6. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  7. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  8. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  9. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  10. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  11. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    Science.gov (United States)

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  12. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon

    2011-01-01

    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates......, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG......2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited...

  13. Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

    Science.gov (United States)

    Chen, Jessie Z-J; Sheehan, Penelope M; Brennecke, Shaun P; Keogh, Rosemary J

    2012-02-26

    During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

  14. Loss of progesterone receptor-mediated actions induce preterm cellular and structural remodeling of the cervix and premature birth.

    Science.gov (United States)

    Yellon, Steven M; Dobyns, Abigail E; Beck, Hailey L; Kurtzman, James T; Garfield, Robert E; Kirby, Michael A

    2013-01-01

    A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.

  15. Differentiating founder and chronic HIV envelope sequences

    Science.gov (United States)

    Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D.

    2017-01-01

    Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178–346 Asn-Val, 232–236 Thr-Ser, 240–340 Lys-Lys, 279–315 Asp-Lys, 291–792 Ala-Ile, 322–347 Asp-Thr, 535–620 Leu-Asp, 742–837 Arg-Phe, and 750–836 Asp-Ile; the most common optimal pairs for subtype C were 644–781 Lys-Ala (74 of 75 networks), 133–287 Ala-Gln (73/75) and 307–337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553–624 (Ser-Asn), 724–747 (Arg-Arg), or 46–293 (Arg-Glu). PMID:28187204

  16. Envelope Determinants of Equine Lentiviral Vaccine Protection

    Science.gov (United States)

    Craigo, Jodi K.; Ezzelarab, Corin; Cook, Sheila J.; Chong, Liu; Horohov, David; Issel, Charles J.; Montelaro, Ronald C.

    2013-01-01

    Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for

  17. Envelope determinants of equine lentiviral vaccine protection.

    Directory of Open Access Journals (Sweden)

    Jodi K Craigo

    Full Text Available Lentiviral envelope (Env antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0, and roughly 40% protection against challenge by virus (EV13 with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes

  18. Algebra Automorphisms of Quantized Enveloping Algebras Uq(■)

    Institute of Scientific and Technical Information of China (English)

    查建国

    1994-01-01

    The algebra automorphisms of the quantized enveloping algebra Uq(g) are discussed, where q is generic. To some extent, all quantum deformations of automorphisms of the simple Lie algebra g have been determined.

  19. Periodic envelopes of waves over non-uniform depth

    Science.gov (United States)

    Rajan, Girish K.; Bayram, Saziye; Henderson, Diane M.

    2016-04-01

    The envelope of narrow-banded, periodic, surface-gravity waves propagating in one dimension over water of finite, non-uniform depth may be modeled by the Djordjević and Redekopp ["On the development of packets of surface gravity waves moving over an uneven bottom," Z. Angew. Math. Phys. 29, 950-962 (1978)] equation (DRE). Here we find five approximate solutions of the DRE that are in the form of Jacobi-elliptic functions and discuss them within the framework of ocean swell. We find that in all cases, the maximum envelope-amplitude decreases/increases when the wave group propagates on water of decreasing/increasing depth. In the limit of the elliptic modulus approaching one, three of the solutions reduce to the envelope soliton solution. In the limit of the elliptic modulus approaching zero, two of the solutions reduce to an envelope-amplitude that is uniform in an appropriate reference frame.

  20. Photon Bubbles in the Circumstellar Envelopes of Young Massive Stars

    CERN Document Server

    Turner, N J; Yorke, H W

    2007-01-01

    We show that the optically-thick dusty envelopes surrounding young high-mass stars are subject to the photon bubble instability. The infrared radiation passing through the envelope amplifies magnetosonic disturbances, with growth rates in our local numerical radiation MHD calculations that are consistent with a linear analysis. Modes with wavelengths comparable to the gas pressure scale height grow by more than two orders of magnitude in a thousand years, reaching non-linear amplitudes within the envelope lifetime. If the magnetic pressure in the envelope exceeds the gas pressure, the instability develops into trains of propagating shocks. Radiation escapes readily through the low-density material between the shocks, enabling accretion to continue despite the Eddington limit imposed by the dust opacity. The supersonic motions arising from the photon bubble instability can help explain the large velocity dispersions of hot molecular cores, while conditions in the shocked gas are suitable for maser emission. We...

  1. Low Permeation Envelope Material Development for Titan Aerobot Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Aerobot vehicles for missions on Titan require envelope materials that are strong, light and durable. Unlike terrestrial balloon materials, these must be able to...

  2. Intelligent building envelopes. Architectural concept and applications for daylighting quality

    Energy Technology Data Exchange (ETDEWEB)

    Wyckmans, Annemie

    2005-11-15

    How does an intelligent building envelope manage the variable and sometimes conflictive occupant requirements that arise in a day lit indoor environment. This is the research question that provides the basis for this Ph.D. work. As it touches upon several fields of application, the research question is untangled into four steps, each of which corresponds to a chapter of the thesis. 1) What characterises intelligent behaviour for a building envelope. 2) What characterises indoor day lighting quality. 3) Which functions can an intelligent building envelope be expected to perform in the context of day lighting quality. 4) How are the materials, components and composition of an intelligent building envelope designed to influence this performance. The emphasis is on design, environmental aspects, energy conservation, functional analysis and physical applications.

  3. Filamentary Star Formation: Observing the Evolution toward Flattened Envelopes

    CERN Document Server

    Lee, Katherine; Johnstone, Doug; Tobin, John

    2012-01-01

    Filamentary structures are ubiquitous from large-scale molecular clouds (few parsecs) to small-scale circumstellar envelopes around Class 0 sources (~1000 AU to ~0.1 pc). In particular, recent observations with the Herschel Space Observatory emphasize the importance of large-scale filaments (few parsecs) and star formation. The small-scale flattened envelopes around Class 0 sources are reminiscent of the large-scale filaments. We propose an observationally derived scenario for filamentary star formation that describes the evolution of filaments as part of the process for formation of cores and circumstellar envelopes. If such a scenario is correct, small-scale filamentary structures (0.1 pc in length) with higher densities embedded in starless cores should exist, although to date almost all the interferometers have failed to observe such structures. We perform synthetic observations of filaments at the prestellar stage by modeling the known Class 0 flattened envelope in L1157 using both the Combined Array for...

  4. Envelope Protection for In-Flight Ice Contamination

    Science.gov (United States)

    Gingras, David R.; Barnhart, Billy P.; Ranaudo, Richard J.; Ratvasky, Thomas P.; Morelli, Eugene A.

    2010-01-01

    Fatal loss-of-control (LOC) accidents have been directly related to in-flight airframe icing. The prototype system presented in this paper directly addresses the need for real-time onboard envelope protection in icing conditions. The combinations of a-priori information and realtime aerodynamic estimations are shown to provide sufficient input for determining safe limits of the flight envelope during in-flight icing encounters. The Icing Contamination Envelope Protection (ICEPro) system has been designed and implemented to identify degradations in airplane performance and flying qualities resulting from ice contamination and provide safe flight-envelope cues to the pilot. Components of ICEPro are described and results from preliminary tests are presented.

  5. Transport of Ions Across the Inner Envelope Membrane of Chloroplasts

    Energy Technology Data Exchange (ETDEWEB)

    McCarty, R. E.

    2004-06-02

    The technical report outlines the results of nine years of research on how ions cross the inner envelope membrane of chloroplasts. The ions include protons, nitrite, calcium and ferrous iron. Bicarbonate transport was also studied.

  6. Polarimetry and the Envelopes of Magellanic B[e] Supergiants

    CERN Document Server

    Magalhães, A M; Melgarejo, R; Pereyra, A

    2006-01-01

    We discuss the nature of the circumstellar envelopes around the B[e] supergiants (B[e]SG) in the Magellanic Clouds (MC). Contrary to those in the Galaxy, the MC B[e]SG have a well defined luminosity and can be considered members of a well defined class. We discuss spectroscopy and optical broadband polarimetry and spectropolarimetry data. These data show for the first time detailed changes in the polarization across several spectral features. We show that the envelopes of the B[e]SG are generally variable. Broadband polarimetry data show that the envelopes are definitely non-spherically symmetric and large non-axisymmetric ejections may occur. In addition to that, spectropolarimetry is coming of age as a tool to study the B[e]SG envelope structure.

  7. Low Permeation Envelope Material Development for Titan Aerobot Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Aerobot vehicles for missions on Titan require envelope materials that are strong, light and durable. In particular they must be able to withstand flexing at liquid...

  8. Nuclear control

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Wan Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    International cooperation in nuclear industries requires nuclear control as prerequisites. The concept of nuclear control is based on the Treaty on the Non-proliferation of Nuclear Weapon (NPT). The International Atomic Energy Agency (IAEA) plays central role in implementing nuclear control. Nuclear control consists of nuclear safeguards, physical protection, and export/import control. Each member state of NPT is subject to the IAEA`s safeguards by concluding safeguards agreements with the IAEA. IAEA recommends member states to implement physical protection on nuclear materials by `The Physical Protection of Nuclear Material` and `The Convention on the Physical Protection of Nuclear Material` of IAEA. Export/Import Control is to deter development of nuclear weapons by controlling international trade on nuclear materials, nuclear equipments and technology. Current status of domestic and foreign nuclear control implementation including recent induction of national inspection system in Korea is described and functions of recently set-up Technology Center for Nuclear Control (TCNC) under the Korea Atomic Energy Research Institute (KAERI) are also explained. 6 tabs., 11 refs. (Author).

  9. The CKH2/PKL chromatin remodeling factor negatively regulates cytokinin responses in Arabidopsis calli.

    Science.gov (United States)

    Furuta, Kaori; Kubo, Minoru; Sano, Kiyomi; Demura, Taku; Fukuda, Hiroo; Liu, Yao-Guang; Shibata, Daisuke; Kakimoto, Tatsuo

    2011-04-01

    Cytokinins promote cell division and chloroplast development in tissue culture. We previously isolated two mutants of Arabidopsis thaliana, ckh1 (cytokinin-hypersensitive 1) and ckh2, which produce rapidly growing green calli in response to lower levels of cytokinins than those found in the wild type. Here we report that the product of the CKH2 gene is PICKLE, a protein resembling the CHD3 class of SWI/SNF chromatin remodeling factors. We also show that inhibition of histone deacetylase by trichostatin A (TSA) partially substituted for cytokinins, but not for auxin, in the promotion of callus growth, indicating that chromatin remodeling and histone deacetylation are intimately related to cytokinin-induced callus growth. A microarray experiment revealed that either the ckh1 mutation or the ckh2 mutation caused hypersensitivity to cytokinins in terms of gene expression, especially of photosynthesis-related genes. The ckh1 and ckh2 mutations up-regulated nuclear-encoded genes, but not plastid-encoded genes, whereas TSA deregulated both nuclear- and plastid-encoded genes. The ckh1 ckh2 double mutant showed synergistic phenotypes: the callus grew with a green color independently of exogenous cytokinins. A yeast two-hybrid experiment showed protein interaction between CKH1/EER4/AtTAF12b and CKH2/PKL. These results suggest that CKH1/EER4/AtTAF12b and CKH2/PKL may act together on cytokinin-regulated genes.

  10. CISBAT 2003 proceedings. BuildingEnvelopes.org. Innovation in building envelopes and environmental systems

    Energy Technology Data Exchange (ETDEWEB)

    Scartezzini, J.-L.

    2003-07-01

    Hosted by the Swiss Federal Institute of Technology (EPFL) in Lausanne and jointly organised by EPFL and the Harvard University, Cambridge, MA, USA, the international conference 'Innovation in building envelopes and environmental systems' enjoyed the attendance of 140 participants from 14 countries all around the world. The conference proceedings include the 63 presentations grouped in 9 sections. The 3 keynote speakers addressed the following topics: Sustainable buildings, USA research; Nanostructured materials for solar energy conversion; From smart buildings to ambient intelligence. The 9 groups of topics were: Building envelopes design and renovation; Solar collectors and systems; Indoor environment quality and health; Daylighting and visual ergonomy; Advanced building control systems; New construction materials; Environmental impacts of construction; Cities, infrastructures and sustainable development; Software. Organised each second year for now 20 years, the international conference CISBAT is amongst the leading ones in its field. The 2003 edition closed with a video conference from the USA, entitled 'Cradle to cradle - A design revolution', presented by the architect W. Mc Donough, Winner of 1996 Presidential Prize for Sustainable Development.

  11. Evolutionary genomic remodelling of the human 4q subtelomere (4q35.2

    Directory of Open Access Journals (Sweden)

    Riva Paola

    2007-03-01

    Full Text Available Abstract Background In order to obtain insights into the functionality of the human 4q35.2 domain harbouring the facioscapulohumeral muscular dystrophy (FSHD locus, we investigated in African apes genomic and chromatin organisations, and the nuclear topology of orthologous regions. Results A basic block consisting of short D4Z4 arrays (10–15 repeats, 4q35.2 specific sequences, and approximately 35 kb of interspersed repeats from different LINE subfamilies was repeated at least twice in the gorilla 4qter. This genomic organisation has undergone evolutionary remodelling, leading to the single representation of both the D4Z4 array and LINE block in chimpanzee, and the loss of the LINE block in humans. The genomic remodelling has had an impact on 4qter chromatin organisation, but not its interphase nuclear topology. In comparison with humans, African apes show very low or undetectable levels of FRG1 and FRG2 histone 4 acetylation and gene transcription, although histone deacetylase inhibition restores gene transcription to levels comparable with those of human cells, thus indicating that the 4qter region is capable of acquiring a more open chromatin structure. Conversely, as in humans, the 4qter region in African apes has a very peripheral nuclear localisation. Conclusion The 4q subtelomere has undergone substantial genomic changes during evolution that have had an impact on chromatin condensation and the region's transcriptional regulation. Consequently, the 4qter genes in African apes and humans seem to be subjected to a different strategy of regulation in which LINE and D4Z4 sequences may play a pivotal role. However, the effect of peripheral nuclear anchoring of 4qter on these regulation mechanisms is still unclear. The observed differences in the regulation of 4qter gene expression between African apes and humans suggest that the human 4q35.2 locus has acquired a novel functional relevance.

  12. A Partial Differential Equation for the Rank One Convex Envelope

    Science.gov (United States)

    Oberman, Adam M.; Ruan, Yuanlong

    2017-02-01

    A partial differential equation (PDE) for the rank one convex envelope is introduced. The existence and uniqueness of viscosity solutions to the PDE is established. Elliptic finite difference schemes are constructed and convergence of finite difference solutions to the viscosity solution of the PDE is proven. Computational results are presented and laminates are computed from the envelopes. Results include the Kohn-Strang example, the classical four gradient example, and an example with eight gradients which produces nontrivial laminates.

  13. Responsive envelope tessellation and stochastic rotation of 4-fold penttiles

    OpenAIRE

    2014-01-01

    This paper reports on the design and control of a responsive envelope based on the rotation of tessellated components. The study investigates responsive and dynamic approaches for building facades and envelopes to regulate solar shading, light control, views and thermal gain within the building. It is well known that near real-time visual output from computational simulation can significantly impact the prediction of dynamic building-environment interactions and lead to the development of sma...

  14. Representation Theory of Quantized Enveloping Algebras with Interpolating Real Structure

    Directory of Open Access Journals (Sweden)

    Kenny De Commer

    2013-12-01

    Full Text Available Let g be a compact simple Lie algebra. We modify the quantized enveloping ∗-algebra associated to g by a real-valued character on the positive part of the root lattice. We study the ensuing Verma module theory, and the associated quotients of these modified quantized enveloping ∗-algebras. Restricting to the locally finite part by means of a natural adjoint action, we obtain in particular examples of quantum homogeneous spaces in the operator algebraic setting.

  15. Episodic mass ejections from common-envelope objects

    Science.gov (United States)

    Clayton, Matthew; Podsiadlowski, Philipp; Ivanova, Natasha; Justham, Stephen

    2017-09-01

    After the initial fast spiral-in phase experienced by a common-envelope binary, the system may enter a slow, self-regulated phase, possibly lasting hundreds of years, in which all the energy released by orbital decay can be efficiently transported to the surface, where it is radiated away. If the remaining envelope is to be removed during this phase, this removal must occur through some as-yet-undetermined mechanism. We carried out 1D hydrodynamic simulations of a low-mass red giant undergoing a synthetic common-envelope event in such a slow spiral-in phase, using the stellar evolutionary code mesa. We simulated the heating of the envelope due to frictional dissipation from a binary companion's orbit in multiple configurations and investigated the response of the giant's envelope. We find that our model envelopes become dynamically unstable and develop large-amplitude pulsations, with periods in the range 3-20 yr and very short growth time-scales of similar order. The shocks and associated rebounds that emerge as these pulsations grow are in some cases strong enough to dynamically eject shells of matter of up to 0.1 M⊙, ∼10 per cent of the mass of the envelope, from the stellar surface at above escape velocity. These ejections are seen to repeat within a few decades, leading to a time-averaged mass-loss rate of the order of 10-3 M⊙ yr-1, which is sufficiently high to represent a candidate mechanism for removing the entire envelope over the duration of the slow spiral-in phase.

  16. Universal enveloping crossed module of Leibniz crossed modules and representations

    Science.gov (United States)

    Casado, Rafael F.; García-Martínez, Xabier; Ladra, Manuel

    2016-03-01

    The universal enveloping algebra functor UL: Lb → Alg, defined by Loday and Pirashvili [1], is extended to crossed modules. Then we construct an isomorphism between the category of representations of a Leibniz crossed module and the category of left modules over its universal enveloping crossed module of algebras. Note that the procedure followed in the proof for the Lie case cannot be adapted, since the actor in the category of Leibniz crossed modules does not always exist.

  17. A Constant Envelope OFDM Implementation on GNU Radio

    Science.gov (United States)

    2015-02-02

    Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/5524--15-9575 A Constant Envelope OFDM Implementation on GNU Radio February 2, 2015...NUMBER OF PAGES 17. LIMITATION OF ABSTRACT A Constant Envelope OFDM Implementation on GNU Radio Andrew Robertson, Amos Ajo, Sastry Kompella, Joe...successful implementation of such a waveform via the GNU radio framework on Ettus software-defined radios . We measure the bit error performance of the link

  18. Investigating the periodicity of transient-evoked otoacoustic emission envelopes

    DEFF Research Database (Denmark)

    Verhulst, Sarah

    2011-01-01

    This study investigates the cochlear origin of the multiple temporal lobes that are often observed in the transient-evoked otoacoustic emission (TEOAE) envelope. This "waxing and waning" of the OAE amplitude can be observed in tone-burst (TB) OAEs and sometimes also in click-evoked (CE) OAEs. TBOAE...... and the middle-ear boundary may contribute to the TBOAE envelope periodicity, but were not the main modulation component in waxing and waning of the investigated TBOAEs....

  19. Chondromodulin I Is a Bone Remodeling Factor

    Science.gov (United States)

    Nakamichi, Yuko; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor. PMID:12509461

  20. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  1. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  2. Small artery remodeling in hypertension and diabetes.

    Science.gov (United States)

    Rizzoni, Damiano; Agabiti Rosei, Enrico

    2006-04-01

    The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small artery smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, whereas in some secondary forms of hypertension and in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling may be detected. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients. Various antihypertensive drugs seem to have different effects on vascular structure. A complete normalization of small resistance artery structure was demonstrated in hypertensive patients, after prolonged and effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard.

  3. Nuclear trafficking in health and disease.

    Science.gov (United States)

    Mor, Amir; White, Michael A; Fontoura, Beatriz M A

    2014-06-01

    In eukaryotic cells, the cytoplasm and the nucleus are separated by a double-membraned nuclear envelope (NE). Thus, transport of molecules between the nucleus and the cytoplasm occurs via gateways termed the nuclear pore complexes (NPCs), which are the largest intracellular channels in nature. While small molecules can passively translocate through the NPC, large molecules are actively imported into the nucleus by interacting with receptors that bind nuclear pore complex proteins (Nups). Regulatory factors then function in assembly and disassembly of transport complexes. Signaling pathways, cell cycle, pathogens, and other physiopathological conditions regulate various constituents of the nuclear transport machinery. Here, we will discuss several findings related to modulation of nuclear transport during physiological and pathological conditions, including tumorigenesis, viral infection, and congenital syndrome. We will also explore chemical biological approaches that are being used as probes to reveal new mechanisms that regulate nucleocytoplasmic trafficking and that are serving as starting points for drug development.

  4. Evolution: functional evolution of nuclear structure.

    Science.gov (United States)

    Wilson, Katherine L; Dawson, Scott C

    2011-10-17

    The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis.

  5. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts

    OpenAIRE

    Kemi, Ole J.; Hoydal, Morten A; MacQuaide, Niall; Haram, Per M; Koch, Lauren G.; Steven L Britton; Ellingsen, Oyvind; Smith, Godfrey L.; Wisloff, Ulrik

    2011-01-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologi...

  6. Close stellar binary systems by grazing envelope evolution

    CERN Document Server

    Soker, Noam

    2014-01-01

    I suggest a spiral-in process by which a stellar companion graze the envelope of a giant star while both the orbital separation and the giant radius shrink simultaneously, and a close binary system is formed. The binary system might be viewed as evolving in a constant state of `just entering a common envelope (CE) phase'. In cases where this process takes place it can be an alternative to the CE evolution where the secondary star is immerses in the giant's envelope. The grazing envelope evolution (GEE) is made possible only if the companion manages to accreted mass at a high rate and launch jets that remove the outskirts of the giant envelope, hence preventing the formation of a CE . The high accretion rate is made possible by the accretion disk that launches jets that efficiently carry the excess angular momentum and energy from the accreted mass. Mass loss through the second Lagrangian point can carry additional angular momentum and envelope mass. The GEE lasts for tens to hundreds of years. The high accret...

  7. Thermal performance of integration of solar collectors and building envelopes

    Institute of Scientific and Technical Information of China (English)

    于国清; 龚小辉; 曹双华

    2009-01-01

    The integration of building with solar collector was studied. The theoretical model of integration of building envelopes and flat plate solar collectors was set up and the thermal performance of integration was studied in winter and summer,and compared to envelopes without solar collectors. The results show that the solar collection efficiency is raised in the integration of building envelopes and solar collectors with the air layer doors closed. This is true whether in winter or summer. The increment is higher as the inlet water temperature increases or the ambient temperature is low. In winter,the heat loss is significantly reduced through integration of the building envelopes and solar collectors with the closed air layer doors. The integration with the open air layer door is worse than that without collectors. In summer,the heat gains of the integration of envelopes and solar collectors are more obviously reduced than envelopes without collectors,the integration with the open air layer door is a little better than the closed one,but the difference is very small.

  8. Planet formation with envelope enrichment: new insights on planetary diversity

    CERN Document Server

    Venturini, Julia; Benz, Willy

    2016-01-01

    We compute, for the first time, self-consistent models of planet growth including the effect of envelope enrichment. The change of envelope metallicity is assumed to be the result of planetesimal disruption or icy pebble sublimation. We solve internal structure equations taking into account global energy conservation for the envelope to compute in-situ planetary growth. We consider different opacities and equations of state suited for a wide range of metallicities. We find that envelope enrichment speeds up the formation of gas giants. It also explains naturally the formation of low and intermediate mass objects with large fractions of H-He (~ 20 - 30 % in mass). High opacity models explain well the metallicity of the giant planets of the solar system, whereas low opacity models are suited for forming small mass objects with thick H-He envelopes and gas giants with sub-solar envelope metallicities. We find good agreement between our models and the estimated water abundance for WASP-43b. For HD 189733b, HD 209...

  9. Preserving Envelope Efficiency in Performance Based Code Compliance

    Energy Technology Data Exchange (ETDEWEB)

    Thornton, Brian A. [Thornton Energy Consulting (United States); Sullivan, Greg P. [Efficiency Solutions (United States); Rosenberg, Michael I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baechler, Michael C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-06-20

    The City of Seattle 2012 Energy Code (Seattle 2014), one of the most progressive in the country, is under revision for its 2015 edition. Additionally, city personnel participate in the development of the next generation of the Washington State Energy Code and the International Energy Code. Seattle has pledged carbon neutrality by 2050 including buildings, transportation and other sectors. The United States Department of Energy (DOE), through Pacific Northwest National Laboratory (PNNL) provided technical assistance to Seattle in order to understand the implications of one potential direction for its code development, limiting trade-offs of long-lived building envelope components less stringent than the prescriptive code envelope requirements by using better-than-code but shorter-lived lighting and heating, ventilation, and air-conditioning (HVAC) components through the total building performance modeled energy compliance path. Weaker building envelopes can permanently limit building energy performance even as lighting and HVAC components are upgraded over time, because retrofitting the envelope is less likely and more expensive. Weaker building envelopes may also increase the required size, cost and complexity of HVAC systems and may adversely affect occupant comfort. This report presents the results of this technical assistance. The use of modeled energy code compliance to trade-off envelope components with shorter-lived building components is not unique to Seattle and the lessons and possible solutions described in this report have implications for other jurisdictions and energy codes.

  10. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts.

    Science.gov (United States)

    Kemi, Ole J; Hoydal, Morten A; Macquaide, Niall; Haram, Per M; Koch, Lauren G; Britton, Steven L; Ellingsen, Oyvind; Smith, Godfrey L; Wisloff, Ulrik

    2011-09-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P Exercise training further increased cardiomyocyte volume by 8% (P eccentric and concentric hypertrophy and 55% (P Exercise training reversed 50% (P hypertrophy, whereas the T-tubule density increased by 40% (P hypertrophy associated with conserved T-tubule spacing (~1.8-1.9 µm), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density.

  11. Light signaling controls nuclear architecture reorganization during seedling establishment

    NARCIS (Netherlands)

    Bourbousse, C.; Mestiri, I.; Zabulon, G.; Bourge, M.; Formiggini, F.; Koini, M.A.; Brown, S.C.; Fransz, P.; Bowler, C.; Barneche, F.

    2015-01-01

    The spatial organization of chromatin can be subject to extensive remodeling in plant somatic cells in response to developmental and environmental signals. However, the mechanisms controlling these dynamic changes and their functional impact on nuclear activity are poorly understood. Here, we determ

  12. The effect of common-envelope evolution on the visible population of post-common-envelope binaries

    OpenAIRE

    Toonen, S.; Nelemans, G.

    2013-01-01

    Context. An important ingredient in binary evolution is the common-envelope (CE) phase. Although this phase is believed to be responsible for the formation of many close binaries, the process is not well understood. Aims. We investigate the characteristics of the population of post-common-envelope binaries (PCEB). As the evolution of these binaries and their stellar components are relatively simple, this population can be directly used to constraint CE evolution. Methods. We use the binary po...

  13. Multicriteria approach to data envelopment analysis

    Directory of Open Access Journals (Sweden)

    Hélcio Vieira Junior

    2008-08-01

    Full Text Available With the aim of making Data Envelopment Analysis (DEA more acceptable to the managers' community, the Weights Restrictions approaches were born. They allow DEA to not dispose of any data and permit the Decision Maker (DM to have some management over the method. The purpose of this paper is to suggest a Weights Restrictions DEA model that incorporates the DM preference. In order to perform that, we employed the MACBETH methodology as a tool to find out the bounds of the weights to be used in a Weights Restrictions approach named Virtual Weights Restrictions. Our proposal achieved an outcome that has an expressive correlation with three widely used decision-aids methodologies: the ELECTRE III, the SMART and the PROMETHEE I and II. In addition, our approach was able to join the most significant outcomes of all the above three Multicriteria decision-aids methodologies in one unique outcome.Com o objetivo de fazer a Análise Envoltória de Dados (DEA mais aceitável pela comunidade gerencial, as abordagens de Restrição aos Pesos foram criadas. Estas abordagens fazem com que a DEA não descarte nenhum dado e permitem que o Decisor (DM tenha alguma gerência sobre o método. O objetivo deste artigo é sugerir um modelo de restrição aos pesos que incorpore as preferências do DM. Para realizar isto, nós empregamos a metodologia MACBETH como ferramenta para descobrir os limites dos pesos a serem utilizados na abordagem de restrição aos pesos chamada "Restrição aos Pesos Virtuais". Nossa proposta alcançou um resultado que apresenta uma correlação expressiva com três metodologias de apoio à decisão amplamente utilizadas: o ELECTRE III, o SMART e o PROMETHEE I e II. Adicionalmente, nossa abordagem foi capaz de reunir os resultados mais significativos de todas estas três metodologias de apoio à decisão em um único resultado.

  14. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.

    Science.gov (United States)

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K

    2016-08-02

    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  15. The redox state of transglutaminase 2 controls arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Jeroen van den Akker

    Full Text Available While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2, the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall.

  16. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  17. Envelope: interactive software for modeling and fitting complex isotope distributions

    Directory of Open Access Journals (Sweden)

    Sykes Michael T

    2008-10-01

    Full Text Available Abstract Background An important aspect of proteomic mass spectrometry involves quantifying and interpreting the isotope distributions arising from mixtures of macromolecules with different isotope labeling patterns. These patterns can be quite complex, in particular with in vivo metabolic labeling experiments producing fractional atomic labeling or fractional residue labeling of peptides or other macromolecules. In general, it can be difficult to distinguish the contributions of species with different labeling patterns to an experimental spectrum and difficult to calculate a theoretical isotope distribution to fit such data. There is a need for interactive and user-friendly software that can calculate and fit the entire isotope distribution of a complex mixture while comparing these calculations with experimental data and extracting the contributions from the differently labeled species. Results Envelope has been developed to be user-friendly while still being as flexible and powerful as possible. Envelope can simultaneously calculate the isotope distributions for any number of different labeling patterns for a given peptide or oligonucleotide, while automatically summing these into a single overall isotope distribution. Envelope can handle fractional or complete atom or residue-based labeling, and the contribution from each different user-defined labeling pattern is clearly illustrated in the interactive display and is individually adjustable. At present, Envelope supports labeling with 2H, 13C, and 15N, and supports adjustments for baseline correction, an instrument accuracy offset in the m/z domain, and peak width. Furthermore, Envelope can display experimental data superimposed on calculated isotope distributions, and calculate a least-squares goodness of fit between the two. All of this information is displayed on the screen in a single graphical user interface. Envelope supports high-quality output of experimental and calculated

  18. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC.

  19. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  20. Nuclear Chemistry.

    Science.gov (United States)

    Chemical and Engineering News, 1979

    1979-01-01

    Provides a brief review of the latest developments in nuclear chemistry. Nuclear research today is directed toward increased activity in radiopharmaceuticals and formation of new isotopes by high-energy, heavy-ion collisions. (Author/BB)

  1. Patch-clamp detection of macromolecular translocation along nuclear pores

    Directory of Open Access Journals (Sweden)

    Bustamante J.O.

    1998-01-01

    Full Text Available The present paper reviews the application of patch-clamp principles to the detection and measurement of macromolecular translocation along the nuclear pores. We demonstrate that the tight-seal 'gigaseal' between the pipette tip and the nuclear membrane is possible in the presence of fully operational nuclear pores. We show that the ability to form a gigaseal in nucleus-attached configurations does not mean that only the activity of channels from the outer membrane of the nuclear envelope can be detected. Instead, we show that, in the presence of fully operational nuclear pores, it is likely that the large-conductance ion channel activity recorded derives from the nuclear pores. We conclude the technical section with the suggestion that the best way to demonstrate that the nuclear pores are responsible for ion channel activity is by showing with fluorescence microscopy the nuclear translocation of ions and small molecules and the exclusion of the same from the cisterna enclosed by the two membranes of the envelope. Since transcription factors and mRNAs, two major groups of nuclear macromolecules, use nuclear pores to enter and exit the nucleus and play essential roles in the control of gene activity and expression, this review should be useful to cell and molecular biologists interested in understanding how patch-clamp can be used to quantitate the translocation of such macromolecules into and out of the nucleus

  2. Nuclear weapons, nuclear effects, nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  3. Exogenous Expression of Human Protamine 1 (hPrm1 Remodels Fibroblast Nuclei into Spermatid-like Structures

    Directory of Open Access Journals (Sweden)

    Domenico Iuso

    2015-12-01

    Full Text Available Protamines confer a compact structure to the genome of male gametes. Here, we find that somatic cells can be remodeled by transient expression of protamine 1 (Prm1. Ectopically expressed Prm1 forms scattered foci in the nuclei of fibroblasts, which coalescence into spermatid-like structures, concomitant with a loss of histones and a reprogramming barrier, H3 lysine 9 methylation. Protaminized nuclei injected into enucleated oocytes efficiently underwent protamine to maternal histone TH2B exchange and developed into normal blastocyst stage embryos in vitro. Altogether, our findings present a model to study male-specific chromatin remodeling, which can be exploited for the improvement of somatic cell nuclear transfer.

  4. Nuclear Ambitions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    China will begin to build the world’s first third-generation nuclear power plant at the Sanmen Nuclear Power Project in Sanmen City, coastal Zhejiang Province, in March 2009, accord-ing to the State Nuclear Power Technology Corp.

  5. Nuclear structure

    CERN Document Server

    Nazarewicz, W

    1999-01-01

    Current developments in nuclear structure are discussed from a theoretical perspective. The studies of the nuclear many-body system provide us with invaluable information about the nature of the nuclear interaction, nucleonic correlations at various energy-distance scales, and the modes of the nucleonic matter.

  6. Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

    DEFF Research Database (Denmark)

    Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

    2006-01-01

    So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...

  7. Integrated energy design of the building envelope

    Energy Technology Data Exchange (ETDEWEB)

    Vraa Nielsen, M.

    2012-07-01

    This thesis describes the outcome of the PhD project Integrated energy design of the building envelope carried out through a combination of scientific dissemination reported through peer-reviewed journals and a wide range of affiliated projects involved in at an architectural firm. The research project analysed how the implementation of technical knowledge early in the building design process can quantify the effect of a building's facades on its energy efficiency and indoor climate and thereby facilitate a more qualified design development. The project was structured in the following way: 1) the importance of integrating knowledge in the early stages of design, and how it can be done; 2) understanding the facade's typology; and 3) the complex notion of comfort. The project touched not only on the technical capabilities and requirements governing facade design, but also the process by which it takes place. This was done by applying the methodology of Integrated Energy Design (IED) and analysing its applicability in the design of facades. A major part of the project was an actual engagement in the architectural process to test out incorporating a consciousness about energy and comfort as part of a more holistic performance evaluation. The research project illustrates the great potential in taking passive properties into account through a geometrical optimisation inherent in the development of the architectural concept. It demonstrates that integration of technical knowledge at the early stages of design not only can qualify the geometrical processing, but also facilitate the design development of the facade. Thereby a more holistic performance optimisation can be obtained through parameters such as overall facade geometry and orientation, functional organisation, room height and depth, facade layout, window geometry and transparency, design of the window aperture, etc. Through the wide range of affiliated project involved in at the architectural firm over

  8. On mixing at the core-envelope interface during classical nova outbursts

    CERN Document Server

    Casanova, Jordi; Garcia-Berro, Enrique; Calder, Alan; Shore, Steven N; 10.1051/0004-6361/201014178

    2010-01-01

    Classical novae are powered by thermonuclear runaways that occur on the white dwarf component of close binary systems. During these violent stellar events, whose energy release is only exceeded by gamma-ray bursts and supernova explosions, about 10-4 10-5 Msun of material is ejected into the interstellar medium. Because of the high peak temperatures attained during the explosion, Tpeak ~ (1-4)x10+8 K, the ejecta are enriched in nuclear-processed material relative to solar abundances, containing significant amounts of 13C, 15N, and 17O and traces of other isotopes. The origin of these metal enhancements observed in the ejecta is not wellknown and has puzzled theoreticians for about 40 years. In this paper, we present new 2-D simulations of mixing at the core-envelope interface. We show that Kelvin-Helmholtz instabilities can naturally lead to self-enrichment of the solar-like accreted envelopes with material from the outermost layers of the underlying white dwarf core, at levels that agree with observations.

  9. Nuclear lamina in plant cells

    Institute of Scientific and Technical Information of China (English)

    汪健; 杨澄; 翟中和

    1996-01-01

    By using selective extraction and diethylene glycol distearate (DGD) embedment and embedment-free electron microscopy, the nuclear lamina was demonstrated in carrot and Ginkgo male generative cells. Western blotting revealed that the nuclear lamina was composed of A-type and B-type lamins which contained at least 66-ku and 84-ku or 66-ku and 86-ku polypeptides, respectively. These lamin proteins were localized at the nudear periphery as shown by immunogold-labelling. In situ hybridization for light microscope and electron microscope showed that plant cells have the homologous sequences of animal lamin cDNA. The sorting site of lamin mRNA is mainly distributed in the cytoplasm near the nudear envelope. The data have verified that there indeed exists nudear lamina in plant cells.

  10. The metallicity dependence of envelope inflation in massive stars

    CERN Document Server

    Sanyal, D; Szécsi, D; Yoon, S -C; Grassitelli, L

    2016-01-01

    Recently it has been found that models of massive stars reach the Eddington limit in their interior, which leads to dilute extended envelopes. We perform a comparative study of the envelope properties of massive stars at different metallicities, with the aim to establish the impact of the stellar metallicity on the effect of envelope inflation. We analyse published grids of core-hydrogen burning massive star models computed with metallicities appropriate for massive stars in the Milky Way, the LMC and the SMC, the very metal poor dwarf galaxy I Zwicky 18, and for metal-free chemical composition. Stellar models of all the investigated metallicities reach and exceed the Eddington limit in their interior, aided by the opacity peaks of iron, helium and hydrogen, and consequently develop inflated envelopes. Envelope inflation leads to a redward bending of the zero-age main sequence and a broadening of the main sequence band in the upper part of the Hertzsprung-Russell diagram. We derive the limiting L/M-values as ...

  11. Solar envelope concepts: moderate density building applications. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, R.L.; Berry, R.D.

    1980-04-01

    Solar energy utilization in urban areas requires public guarantees that all property owners have direct access to the sun. The study examines the implications of this premise in relation to the need for cities to also encourage or accommodate rebuilding and future development. The public policy mechanism for guaranteeing solar access is conceptualized as a solar zoning envelope that allows the largest possible building bulk on a land parcel without shadowing neighboring properties during specified times. Step-by-step methods for generating solar envelopes are described with extensive drawings, showing a variety of urban platting and lot configurations. Development and design possibilities are examined on a selected set of Los Angeles sites with typically diverse urban characteristics. Envelope attributes suitable for encouraging moderate-density commercial and residential building are examined in the context of two hypothetical but realistic development programs: one for speculative office buildings and one for condominium housing. Numerous illustrations of envelope forms and prototypical building designs are provided. The results of development simulation studies on all test sites are tabulated to show building bulk, density, land-coverage and open space characteristics obtainable under the hypothesized envelopes.

  12. Optically thick envelopes around ULXs powered by accreating neutron stars

    Science.gov (United States)

    Mushtukov, Alexander A.; Suleimanov, Valery F.; Tsygankov, Sergey S.; Ingram, Adam

    2017-01-01

    Magnetized neutron stars power at least some ultra-luminous X-ray sources. The accretion flow in these cases is interrupted at the magnetospheric radius and then reaches the surface of a neutron star following magnetic field lines. Accreting matter moving along magnetic field lines forms the accretion envelope around the central object. We show that, in case of high mass accretion rates ≳ 1019 g s-1 the envelope becomes closed and optically thick, which influences the dynamics of the accretion flow and the observational manifestation of the neutron star hidden behind the envelope. Particularly, the optically thick accretion envelope results in a multi-color black-body spectrum originating from the magnetospheric surface. The spectrum and photon energy flux vary with the viewing angle, which gives rise to pulsations characterized by high pulsed fraction and typically smooth pulse profiles. The reprocessing of radiation due to interaction with the envelope leads to the disappearance of cyclotron scattering features from the spectrum. We speculate that the super-orbital variability of ultra-luminous X-ray sources powered by accreting neutron stars can be attributed to precession of the neutron star due to interaction of magnetic dipole with the accretion disc.

  13. The ionization structure of the circumstellar envelope of Alpha Orionis

    Science.gov (United States)

    Glassgold, A. E.; Huggins, P. J.

    1986-01-01

    The physical processes which affect the ionization of the outer circumstellar envelope of Alpha Ori are analyzed and evaluated. The ultraviolet radiation fields of the chromosphere and the interstellar medium dominate the envelope, and the most common forms of all species are neutral atoms and first ions. Hydrogen recombines just outside the chromosphere, where atoms with smaller ionization potential are essentially fully ionized. The heavier ions gradually recombine with increasing distance from the star, until the interstellar radiation field reverses this trend. The electron fraction in the outer envelope is approximately equal to the abundance of all such heavy atoms, i.e., of the order of 0.0001. The analysis is applied to the case of neutral K, whose density in the envelope has been determined by scattering experiments. The theory predicts that the slope of the K I density distribution should decrease from -1.5 to -3.5 in the outer envelope. The mass loss rate of Alpha Ori implied by the K I scattering experiments is 4 x 10 to the -6th solar mass/yr.

  14. Responsive envelope tessellation and stochastic rotation of 4-fold penttiles

    Directory of Open Access Journals (Sweden)

    Sambit Datta

    2014-06-01

    Full Text Available This paper reports on the design and control of a responsive envelope based on the rotation of tessellated components. The study investigates responsive and dynamic approaches for building facades and envelopes to regulate solar shading, light control, views and thermal gain within the building. It is well known that near real-time visual output from computational simulation can significantly impact the prediction of dynamic building-environment interactions and lead to the development of smart, adaptable, net zero energy buildings. To address these motivations, this paper reports the development of an experimental simulation of a responsive envelope based on using a 4-fold penttile scheme. The simulation is developed using a novel pentagonal approach involving component (tile design, tessellation and control methods. The paper further elaborates on the geometry and control aspects of the facade subdivision and presents the results of applying this tessellation geometry to a building envelope shading study based on facade components with rotation. Finally, it tests the “responsiveness” to multiple performance metrics by applying a non-deterministic exploration method for the stochastic rotation of individual panels. The sophisticated evaluation of alternative envelope configurations for a set of performance criteria require a tighter computational coupling between modelling and control of dynamic geometry.

  15. On the {\\alpha} formalism for the common envelope interaction

    CERN Document Server

    De Marco, Orsola; Moe, Maxwell; Herwig, Falk; Mac Low, Mordecai-Mark; Paxton, Bill

    2010-01-01

    The {\\alpha}-formalism is a common way to parametrize the common envelope interaction between a giant star and a more compact companion. The {\\alpha} parameter describes the fraction of orbital energy released by the companion that is available to eject the giant star's envelope. By using new, detailed stellar evolutionary calculations we derive a user-friendly prescription for the {\\lambda} parameter and an improved approximation for the envelope binding energy, thus revising the {\\alpha} equation. We then determine {\\alpha} both from simulations and observations in a self consistent manner. By using our own stellar structure models as well as population considerations to reconstruct the primary's parameters at the time of the common envelope interaction, we gain a deeper understanding of the uncertainties. We find that systems with very low values of q (the ratio of the companion's mass to the mass of the primary at the time of the common envelope interaction) have higher values of {\\alpha}. A fit to the da...

  16. Solar envelope concepts: moderate density building applications. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, R.L.; Berry, R.D.

    1980-04-01

    Solar energy utilization in urban areas requires public guarantees that all property owners have direct access to the sun. The study examines the implications of this premise in relation to the need for cities to also encourage or accommodate rebuilding and future development. The public policy mechanism for guaranteeing solar access is conceptualized as a solar zoning envelope that allows the largest possible building bulk on a land parcel without shadowing neighboring properties during specified times. Step-by-step methods for generating solar envelopes are described with extensive drawings, showing a variety of urban platting and lot configurations. Development and design possibilities are examined on a selected set of Los Angeles sites with typically diverse urban characteristics. Envelope attributes suitable for encouraging moderate-density commercial and residential building are examined in the context of two hypothetical but realistic development programs: one for speculative office buildings and one for condominium housing. Numerous illustrations of envelope forms and prototypical building designs are provided. The results of development simulation studies on all test sites are tabulated to show building bulk, density, land-coverage and open space characteristics obtainable under the hypothesized envelopes.

  17. The South Carolina bridge-scour envelope curves

    Science.gov (United States)

    Benedict, Stephen T.; Feaster, Toby D.; Caldwell, Andral

    2016-09-30

    The U.S. Geological Survey, in cooperation with the South Carolina Department of Transportation, conducted a series of three field investigations to evaluate historical, riverine bridge scour in the Piedmont and Coastal Plain regions of South Carolina. These investigations included data collected at 231 riverine bridges, which lead to the development of bridge-scour envelope curves for clear-water and live-bed components of scour. The application and limitations of the South Carolina bridge-scour envelope curves were documented in four reports, each report addressing selected components of bridge scour. The current investigation (2016) synthesizes the findings of these previous reports into a guidance manual providing an integrated procedure for applying the envelope curves. Additionally, the investigation provides limited verification for selected bridge-scour envelope curves by comparing them to field data collected outside of South Carolina from previously published sources. Although the bridge-scour envelope curves have limitations, they are useful supplementary tools for assessing the potential for scour at riverine bridges in South Carolina.

  18. Building envelope innovation: smart facades for non residential buildings

    Directory of Open Access Journals (Sweden)

    Marco Sala

    2011-11-01

    Full Text Available The research analyzes the evolution of smart façade systems in the area of design and industrial production, in order to investigate the technological, functional and qualitative standards of dynamic façade and evaluate the energy performance of the building envelope as a dynamic system that interacts between indoor and outdoor environment. The study focused on dynamic envelopes for office building analyzing the evolution of façade systems in terms of: building construction, innovative systems, smart materials, dynamic system. Aiming to improve building energy performances. The research, developed during the PhD thesis “Smart Envelope - dynamic and innovative technologies for energy saving” and the research “Abitare Mediterraneo”, aims to identify and define the energy performances of smart envelopes trough the analysis of the state of art, related to dynamic building envelope of double skin façade, and the development of a new dynamic façade system.

  19. Nuclear spectroscopy

    CERN Document Server

    Ajzenberg-Selove, Fay

    1960-01-01

    Nuclear Spectroscopy, Part B focuses on the ways in which experimental data may be analyzed to furnish information about nuclear parameters and nuclear models in terms of which the data are interpreted.This book discusses the elastic and inelastic potential scattering amplitudes, role of beta decay in nuclear physics, and general selection rules for electromagnetic transitions. The nuclear shell model, fundamental coupling procedure, vibrational spectra, and empirical determination of the complex potential are also covered. This publication is suitable for graduate students preparing for exper

  20. Gap Junction Remodeling in Skin Repair Following Wounding and Disease

    National Research Council Canada - National Science Library

    Jared M. Churko; Dale W. Laird

    2013-01-01

    In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change...

  1. p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

    Science.gov (United States)

    Mardaryev, Andrei N.; Gdula, Michal R.; Yarker, Joanne L.; Emelianov, Vladimir N.; Poterlowicz, Krzysztof; Sharov, Andrey A.; Sharova, Tatyana Y.; Scarpa, Julie A.; Chambon, Pierre; Botchkarev, Vladimir A.; Fessing, Michael Y.

    2014-01-01

    Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development. PMID:24346698

  2. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  3. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  4. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    OpenAIRE

    Cowling, Belinda S; Anne Toussaint; Jean Muller; Jocelyn Laporte

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Too...

  5. The Initiation and Propagation of Helium Detonations in White Dwarf Envelopes

    CERN Document Server

    Shen, Ken J

    2014-01-01

    Detonations in helium-rich envelopes surrounding white dwarfs have garnered attention as triggers of faint thermonuclear ".Ia" supernovae and double detonation Type Ia supernovae. However, recent studies have found that the minimum size of a hotspot that can lead to a helium detonation is comparable to, or even larger than, the white dwarf's pressure scale height, casting doubt on the successful ignition of helium detonations in these systems. In this paper, we examine the previously neglected effects of C/O pollution and a full nuclear reaction network, and we consider hotspots with spatially constant pressure in addition to constant density hotspots. We find that the inclusion of these effects significantly decreases the minimum hotspot size for helium-rich detonation ignition, making detonations far more plausible during turbulent shell convection or during double white dwarf mergers. The increase in burning rate also decreases the minimum shell mass in which a helium detonation can successfully propagate ...

  6. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Directory of Open Access Journals (Sweden)

    Chi-Li Chiu

    2013-01-01

    Full Text Available Extracellular matrix (ECM remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7, which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3. We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

  7. KyoT2 downregulates airway remodeling in asthma.

    Science.gov (United States)

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  8. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats

    Directory of Open Access Journals (Sweden)

    Chun Lei Li

    2014-01-01

    Full Text Available Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, P<0.001 and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P<0.001 in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.

  9. Second-order envelope equation of graphene electrons

    Science.gov (United States)

    Luo, Ji

    2014-10-01

    A treatment of graphene's electronic states based on the tight-binding method is presented. Like Dirac equation, this treatment uses envelope functions to eliminate crystal potential. Besides, a density-functional-theory Kohn-Sham (KS) orbital of an isolated carbon atom is employed. By locally expanding envelope functions into second-order polynomials and by involving up to third-nearest atoms in calculating orbital integrals, the second-order envelope equation is obtained. This equation does not contain any experimental data except graphene's crystal structure, and its coefficients are determined through several kinds of integrals of the carbon KS orbital. As an improvement, it leads to more accurate energy dispersion than Dirac equation including the triangular warping effect and asymmetry for electrons and holes, and gives the Fermi velocity which is in good agreement with the experimental value.

  10. Structure of Phage P22 Cell Envelope-Penetrating Needle

    Energy Technology Data Exchange (ETDEWEB)

    Olia, A.S.; Casjens, S.; Cingolani, G.

    2009-06-02

    Bacteriophage P22 infects Salmonella enterica by injecting its genetic material through the cell envelope. During infection, a specialized tail needle, gp26, is injected into the host, likely piercing a hole in the host cell envelope. The 2.1-{angstrom} crystal structure of gp26 reveals a 240-{angstrom} elongated protein fiber formed by two trimeric coiled-coil domains interrupted by a triple {beta}-helix. The N terminus of gp26 plugs the portal protein channel, retaining the genetic material inside the virion. The C-terminal tip of the fiber exposes {beta}-hairpins with hydrophobic tips similar to those seen in class II fusion peptides. The {alpha}-helical core connecting these two functionally polarized tips presents four trimerization octads with consensus sequence IXXLXXXV. The slender conformation of the gp26 fiber minimizes the surface exposed to solvent, which is consistent with the idea that gp26 traverses the cell envelope lipid bilayers.

  11. Planetary Gearbox Fault Diagnosis Using Envelope Manifold Demodulation

    Directory of Open Access Journals (Sweden)

    Weigang Wen

    2016-01-01

    Full Text Available The important issue in planetary gear fault diagnosis is to extract the dependable fault characteristics from the noisy vibration signal of planetary gearbox. To address this critical problem, an envelope manifold demodulation method is proposed for planetary gear fault detection in the paper. This method combines complex wavelet, manifold learning, and frequency spectrogram to implement planetary gear fault characteristic extraction. The vibration signal of planetary gear is demodulated by wavelet enveloping. The envelope energy is adopted as an indicator to select meshing frequency band. Manifold learning is utilized to reduce the effect of noise within meshing frequency band. The fault characteristic frequency of the planetary gear is shown by spectrogram. The planetary gearbox model and test rig are established and experiments with planet gear faults are conducted for verification. All results of experiment analysis demonstrate its effectiveness and reliability.

  12. AN EFFICIENT SIMULATION OF MULTIPLE CORRELATED RAYLEIGH FADING ENVELOPES

    Institute of Scientific and Technical Information of China (English)

    Zhou Ke; Cao Shike; Song Rongfang

    2008-01-01

    In order to better assess the performance of wireless communication systems,it is desirable to produce multiple Rayleigh fading envelopes with specified correlations. In this paper,we analyze theoretically a procedure which generates correlated Gaussian random variables from independent Gaussian random variables and give a physical explanation for the limitation of this procedure. Then,based on some uncorrelated Rayleigh fading envelopes,a simple but efficient procedure for generating an arbitrary number of cross-correlated Rayleigh fading envelopes is proposed. Simulation results and computational complexity analysis are presented,which show that the proposed method has some advantages,such as high accuracy,low computational complexity and easy implementation,over the conventional simulation method.

  13. The envelope Hamiltonian for electron interaction with ultrashort pulses

    CERN Document Server

    Toyota, Koudai; Rost, Jan M

    2014-01-01

    For ultrashort VUV pulses with a pulse length comparable to the orbital time of the bound electrons they couple to we propose a simplified envelope Hamiltonian. It is based on the Kramers-Henneberger representation in connection with a Floquet expansion of the strong-field dynamics but keeps the time dependence of the pulse envelope explicit. Thereby, the envelope Hamiltonian captures the essence of the physics, -- light-induced shifts of bound states, single-photon absorption, and non-adiabatic electronic transitions. It delivers quantitatively accurate ionization dynamics and allows for physical insight into the processes occurring. Its minimal requirements for construction in terms of laser parameters make it ideally suited for a large class of atomic and molecular problems.

  14. Final common envelope ejection by migration and jets

    CERN Document Server

    Soker, Noam

    2014-01-01

    I summarize recent analytical and numerical studies of the common envelope (CE) process and suggest to replace the commonly used alpha-prescription for the CE ejection by a prescription based on final migration and jets launched by the companion or the core of the giant stellar primary. In the migration process the core-companion binary systems is surrounded by a highly oblate (flatten) envelope, a thick circumbinary disk, formed by the large angular momentum transferred from the core-companion system to the envelope. I then show that the energy that can be released by an accreting main sequence companion can surpass the mutual gravitational energy of the core and the companion. An efficient channel to leash the accretion energy to expel the CE is through jets operating via a feedback mechanism (JFM).

  15. Experimental evaluation of envelope tracking techniques for voltage disturbances

    Energy Technology Data Exchange (ETDEWEB)

    Marei, Mostafa I. [Electrical Power and Machines Dept., Faculty of Engineering, Ain Shams University, 1 El-Sarayat St., Abbasia, 11517 Cairo (Egypt); El-Saadany, Ehab F.; Salama, Magdy M.A. [Electrical and Computer Engineering Dept., University of Waterloo, 200 University Avenue West, Waterloo, ON (Canada)

    2010-03-15

    In this paper a digital signal processor (DSP) based real time voltage envelope tracking system is developed and examined. The ADAptive LINEar neuron (ADALINE) and the Recursive Least Square (RLS) algorithms are adopted for envelope tracking. The proposed ADALINE and RLS algorithms give accurate results even under rapid dynamic changes. The paper investigates the effects of different parameters on the performance of the ADALINE algorithm and that of the RLS algorithm. The experimental system is cantered around a Texas Instrument 16 bit fixed-point arithmetic (TMS320LF2407A) evaluation board. Both the ADALINE and the RLS tracking algorithms are developed using the DSP-assembly language. A simple voltage flicker generator is implemented to produce various voltage disturbances. Extensive tests of the proposed envelope tracking algorithms are conducted to evaluate their dynamic performance. (author)

  16. Simulating the onset of grazing envelope evolution of binary stars

    Science.gov (United States)

    Shiber, Sagiv; Kashi, Amit; Soker, Noam

    2017-02-01

    We present the first three-dimensional gas-dynamical simulations of the grazing envelope evolution (GEE) of stars, with the goal of exploring the basic flow properties and the role of jets at the onset of the GEE. In the simulated runs, a secondary main-sequence star grazes the envelope of the primary asymptotic giant branch (AGB) star. The orbit is circular at the radius of the AGB primary star on its equator. We inject two opposite jets perpendicular to the equatorial plane from the location of the secondary star, and follow the evolution for several orbital periods. We explore the flow pattern by which the jets eject the outskirts of the AGB envelope. After one orbit, the jets start to interact with gas ejected in previous orbits and inflate hot low-density bubbles.

  17. Efficiency of Planetesimal Ablation in Giant Planetary Envelopes

    CERN Document Server

    Pinhas, Arazi; Clarke, Cathie

    2016-01-01

    Observations of exoplanetary spectra are leading to unprecedented constraints on their atmospheric elemental abundances, particularly O/H, C/H, and C/O ratios. Recent studies suggest that elemental ratios could provide important constraints on formation and migration mechanisms of giant exoplanets. A fundamental assumption in such studies is that the chemical composition of the planetary envelope represents the sum-total of compositions of the accreted gas and solids during the formation history of the planet. We investigate the efficiency with which accreted planetesimals ablate in a giant planetary envelope thereby contributing to its composition rather than sinking to the core. From considerations of aerodynamic drag causing `frictional ablation' and the envelope temperature structure causing `thermal ablation', we compute mass ablations for impacting planetesimals of radii 30 m to 1 km for different compositions (ice to iron) and a wide range of velocities and impact angles, assuming spherical symmetry. I...

  18. New Approach of Envelope Dynamic Analysis for Milling Process

    CERN Document Server

    Bisu, Claudiu-Florinel; Gérard, Alain; Vijelea, V; Anica, Marin

    2012-01-01

    This paper proposes a method to vibration analysis in order to on-line monitoring of milling process quality. Adapting envelope analysis to characterize the milling tool materials is an important contribution to the qualitative and quantitative characterization of milling capacity and a step by modeling the three-dimensional cutting process. An experimental protocol was designed and developed for the acquisition, processing and analyzing three-dimensional signal. The vibration envelope analysis is proposed to detect the cutting capacity of the tool with the optimization application of cutting parameters. The research is focused on FFT Fourier transform optimization of vibration analysis and vibration envelope to evaluate the dynamic behavior of the machine/ tool/workpiece

  19. Photochemistry and molecular ions in carbon-rich circumstellar envelopes

    Science.gov (United States)

    Glassgold, A. E.; Mamon, G. A.; Omont, A.; Lucas, R.

    1987-01-01

    An earlier theory of ionization of C-rich circumstellar envelopes based on the photochemical model is extended to include the temperature dependence of ion-molecule reactions with polar molecules, particularly HCN, and line self-shielding of CO dissociating radiation. The results are applied to the abundances of HCO(+) and HNC in C-rich circumstellar envelopes. With standard parameters for IRC + 10216, the model is found to be consistent with the new upper limit to the antenna temperature of the J = 1-0 line of HCO(+) obtained with the IRAM 30-m telescope. The photochemical model provides a natural explanation of the relatively large ratio of HCN to HNC observed for C-rich circumstellar envelopes, and good agreement is obtained for the H(C-13)N/HNC antenna temperature ratio measured for IRC + 10216.

  20. Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2.

    Science.gov (United States)

    Zhou, Xiang; Zhao, Liangping; Mao, Jinning; Huang, Jian; Chen, Jianchang

    2015-03-01

    There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.