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Sample records for apobec3 restriction factors

  1. Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

    OpenAIRE

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    Summary: The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive c...

  2. HIV restriction by APOBEC3 in humanized mice.

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    John F Krisko

    2013-03-01

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

  3. HIV-1 Vif versus the APOBEC3 cytidine deaminases: an intracellular duel between pathogen and host restriction factors.

    Science.gov (United States)

    Wissing, Silke; Galloway, Nicole L K; Greene, Warner C

    2010-10-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  4. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

    Science.gov (United States)

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F. PMID:19487726

  5. Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors

    OpenAIRE

    Zhang, Zeli; Gu, Qinyong; Jaguva Vasudevan, Ananda Ayyappan; Hain, Anika; Kloke, Björn-Philipp; Hasheminasab, Sascha; Mulnaes, Daniel; Sato, Kei; Cichutek, Klaus; Häussinger, Dieter; Bravo, Ignacio G; Smits, Sander H. J.; Gohlke, Holger; Münk, Carsten

    2016-01-01

    Background Feline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion ...

  6. Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution.

    Science.gov (United States)

    McLaughlin, Richard N; Gable, Jacob T; Wittkopp, Cristina J; Emerman, Michael; Malik, Harmit S

    2016-08-01

    LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host-pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE-1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated. PMID:27189538

  7. Atomic Force Microscopy Studies Provide Direct Evidence for Dimerization of the HIV Restriction Factor APOBEC3G*

    OpenAIRE

    Shlyakhtenko, Luda S.; Lushnikov, Alexander Y.; Li, Ming; Lackey, Lela; Harris, Reuben S.; Lyubchenko, Yuri L

    2010-01-01

    APOBEC3G (A3G) is an antiviral protein that binds RNA and single-stranded DNA (ssDNA). The oligomerization state of A3G is likely to be influenced by these nucleic acid interactions. We applied the power of nanoimaging atomic force microscopy technology to characterize the role of ssDNA in A3G oligomerization. We used recombinant human A3G prepared from HEK-293 cells and specially designed DNA substrates that enable free A3G to be distinguished unambiguously from DNA-bound protein complexes. ...

  8. APOBEC1 and APOBEC3 cytidine deaminases as restriction factors for hepadnaviral genomes in non-humans in vivo.

    Science.gov (United States)

    Renard, Myrtille; Henry, Michel; Guétard, Denise; Vartanian, Jean-Pierre; Wain-Hobson, Simon

    2010-07-16

    Reverse transcription of the hepadnavirus RNA pre-genome means that nascent cDNA may be vulnerable to genetic editing by host cell APOBEC cytidine deaminases that have specificity single-stranded DNA as substrate. Hepatitis B virus (HBV) is particularly vulnerable to editing by APOBEC3G (hA3G) in late-stage disease where up to 35% of genomes can be edited. Yet, the organization of the A3 locus varies considerably among mammals with a single gene for the mouse and seven genes for Old and New World monkeys, which suggests that the outcome may be very variable for other natural hepadnavirus infections. In addition, there is the powerful mouse transgenic model of HBV replication (mHBV) that has proved to be immensely useful in understanding HBV immunopathogenesis. Here, we show that mHBV is edited in vivo by mAPOBEC1 (mA1) and not mAPOBEC3 (mA3), which follows from the fact that unlike humans, the mA1 gene is highly expressed in the liver. For woodchuck hepatitis virus, an mA3 ortholog is probably operative. For HBV-infected tree shrew primary liver cultures, the editing profile more resembles that observed in humans in keeping with fact that this species belongs to the order closest to Primates. There seems to be more genetic editing in liver or cell-associated genomes than serum or culture supernatants, suggesting that too much editing of virion cDNA might impede completion of DNA synthesis. PMID:20546753

  9. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

    OpenAIRE

    Stanley, David J.; Koen Bartholomeeusen; Crosby, David C; Dong Young Kim; Eunju Kwon; Linda Yen; Nathalie Caretta Cartozo; Ming Li; Stefanie Jäger; Jeremy Mason-Herr; Fumiaki Hayashi; Shigeyuki Yokoyama; Krogan, Nevan J; Harris, Reuben S.; Boris Matija Peterlin

    2012-01-01

    Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV). HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G). Pharmacologica...

  10. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    David J Stanley

    2012-12-01

    Full Text Available Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV. HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G. Pharmacological inhibition of the NEDD8 E1 by MLN4924 or knockdown of either UBE2F or its RING-protein binding partner RBX2 bypasses the effect of Vif, restoring the restriction of HIV by A3G. NMR mapping and mutational analyses define specificity determinants of the UBE2F NEDD8 cascade. These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.

  11. Fv1 restriction and retrovirus vaccine immunity in Apobec3-deficient 129P2 mice.

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    Kalani Halemano

    Full Text Available Understanding the host genetics of the immune response in retrovirus infection models could provide insights for basic HIV vaccine discovery. In Friend retrovirus (FV infection of mice, Fv1 differentially inhibits N-tropic versus B-tropic FV infection by mediating a capsid-dependent post-entry block, Fv2 susceptibility governs splenomegaly induction, and Rfv3 resistance primes a stronger neutralizing antibody response due to more potent Apobec3 activity. Apobec3 polymorphisms in inbred mouse strains correlate with Rfv3 resistance and susceptibility, with one unresolved exception. The 129/OlaHsd (129P2 mouse strain is Fv2 and Rfv3 susceptible based on genotyping, but infection of 129P2 mice with B-tropic FV resulted in strong neutralizing antibody responses and no splenomegaly. Here we confirm that 129P2 mice are Fv1(nr/nr, explaining its resistance to B-tropic FV. Infection of 129P2 mice with NB-tropic FV, which can efficiently infect mice independent of Fv1 genotype, resulted in severe splenomegaly, high levels of viremia and weak neutralizing antibody responses regardless of Apobec3 status. Notably, high-dose B-tropic FV infection of 129P2 Apobec3-deficient mice induced significant adaptive immune responses and conferred high levels of protection following challenge with pathogenic NB-tropic FV. This immunological protection complemented previous studies that N-tropic FV can act as a live-attenuated vaccine in Fv1 (b/b mice. Altogether, the results obtained in 129P2 mice strengthen the conclusion that Rfv3 is encoded by Apobec3, and highlight Fv1 incompatibility as a retroviral vaccine paradigm in mice. Due to its susceptibility to disease that allows for pathogenic challenge studies, B-tropic FV infection of 129P2 mice may be a useful model to study the immunological pathways induced by retroviral capsid restriction.

  12. APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells

    International Nuclear Information System (INIS)

    Cellular APOBEC3G (A3G) protein is packaged into human immunodeficiency virus type 1 (HIV-1) virions in producer cells yet restricts viral replication in target cells. To characterize this restriction in target cells, the effect of A3G on generating various HIV-1 cDNA products was measured by quantitative real-time PCR. A3G decreased cDNA products from Vif-deficient HIV-1, with minor effects on early reverse transcripts and larger declines in late reverse transcripts. However, the greatest decline was typically observed in nuclear 2-LTR circles. Moreover, the magnitude of these declines varied with A3G dose. Adding integration inhibitor did not stop the A3G-mediated loss in 2-LTR circles. Moreover, obstructing HIV-1 nuclear entry using vesicular stomatitis virus matrix protein did not stop the A3G-mediated decline in late reverse transcripts. Collectively, these data suggest that A3G has important restriction activity in the cytoplasm and progressively diminishes viral cytoplasmic and nuclear cDNA forms with increasing magnitude during restriction

  13. Vaccinia virus replication is not affected by APOBEC3 family members

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    Sutter Gerd

    2006-10-01

    Full Text Available Abstract Background The APOBEC3G protein represents a novel innate defense mechanism against retroviral infection. It facilitates the deamination of the cytosine residues in the single stranded cDNA intermediate during early steps of retroviral infection. Most poxvirus genomes are relatively A/T-rich, which may indicate APOBEC3G-induced mutational pressure. In addition, poxviruses replicate exclusively in the cytoplasm where APOBEC3G is located. It was therefore tempting to analyze whether vaccinia virus replication is affected by APOBEC3G. Results The replication of vaccinia virus, a prototype poxvirus, was not, however, inhibited in APOBEC3G-expressing cells, nor did other members of the APOBEC3 family alter vaccinia virus replication. HIV counteracts APOBEC3G by inducing its degradation. However, Western blot analysis showed that the levels of APOBEC3G protein were not affected by vaccinia virus infection. Conclusion The data indicate that APOBEC3G is not a restriction factor for vaccinia virus replication nor is vaccinia virus able to degrade APOBEC3G.

  14. APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study.

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    Iraj Hosseini

    Full Text Available The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.

  15. APOBEC3G-UBA2 fusion as a potential strategy for stable expression of APOBEC3G and inhibition of HIV-1 replication

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    Li Lin

    2008-08-01

    Full Text Available Abstract Background Although APOBEC3G protein is a potent and innate anti-HIV-1 cellular factor, HIV-1 Vif counteracts the effect of APOBEC3G by promoting its degradation through proteasome-mediated proteolysis. Thus, any means that could prevent APOBEC3G degradation could potentially enhance its anti-viral effect. The UBA2 domain has been identified as an intrinsic stabilization signal that protects protein from proteasomal degradation. In this pilot study, we tested whether APOBEC3G, when it is fused with UBA2, can resist Vif-mediated proteasomal degradation and further inhibit HIV-1 infection. Results APOBEC3G-UBA2 fusion protein is indeed more resistant to Vif-mediated degradation than APOBEC3G. The ability of UBA2 domain to stabilize APOBEC3G was diminished when polyubiquitin was over-expressed and the APOBEC3G-UBA2 fusion protein was found to bind less polyubiquitin than APOBEC3G, suggesting that UBA2 stabilizes APOBEC3G by preventing ubiquitin chain elongation and proteasome-mediated proteolysis. Consistently, treatment of cells with a proteasome inhibitor MG132 alleviated protein degradation of APOBEC3G and APOBEC3G-UBA2 fusion proteins. Analysis of the effect of APOBEC3G-UBA2 fusion protein on viral infectivity indicated that infection of virus packaged from HEK293 cells expressing APOBEC3G-UBA2 fusion protein is significantly lower than those packaged from HEK293 cells over-producing APOBEC3G or APOBEC3G-UBA2 mutant fusion proteins. Conclusion Fusion of UBA2 to APOBEC3G can make it more difficult to be degraded by proteasome. Thus, UBA2 could potentially be used to antagonize Vif-mediated APOBEC3G degradation by preventing polyubiquitination. The stabilized APOBEC3G-UBA2 fusion protein gives stronger inhibitory effect on viral infectivity than APOBEC3G without UBA2.

  16. Antiviral Warrior-APOBEC3G

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-xia; MA Yi-cai

    2005-01-01

    This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs (acquired immure deficiency syndrome).The viral infectivity factor (Vif) induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Vif protein has two domains: one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ (Y/F) LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIV.

  17. Antiretroviral Restriction Factors in Mice

    OpenAIRE

    Nair, Smita; Rein, Alan

    2014-01-01

    One of the most exciting areas in contemporary retrovirus research is the discovery of “restriction factors”. These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  18. Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes

    OpenAIRE

    Burdick, Ryan C.; Hu, Wei-Shau; Pathak, Vinay K.

    2013-01-01

    We observed that fluorescent protein-tagged host restriction factors APOBEC3F (A3F) and APOBEC3G (A3G) remain associated with HIV-1 preintegration complexes (PICs) in the nuclei of infected cells. Using A3F labeling as a tool to visualize PICs, we determined that (i) reverse transcription is not required for nuclear import of PICs, indicating that a viral core uncoating event associated with reverse transcription, and the central DNA flap that forms during reverse transcription, are not requi...

  19. APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

    Science.gov (United States)

    Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

    2012-07-12

    APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy. PMID:22645179

  20. Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response.

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    Diana S Smith

    2011-10-01

    Full Text Available Members of the APOBEC3 family of deoxycytidine deaminases counteract a broad range of retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition of reverse transcription and/or hypermutation of minus strand transcripts in the next target cell. The selective advantage to the host of this indirect restriction mechanism remains unclear, but valuable insights may be gained by studying APOBEC3 function in vivo. Apobec3 was previously shown to encode Rfv3, a classical resistance gene that controls the recovery of mice from pathogenic Friend retrovirus (FV infection by promoting a more potent neutralizing antibody (NAb response. The underlying mechanism does not involve a direct effect of Apobec3 on B cell function. Here we show that while Apobec3 decreased titers of infectious virus during acute FV infection, plasma viral RNA loads were maintained, indicating substantial release of noninfectious particles in vivo. The lack of plasma virion infectivity was associated with a significant post-entry block during early reverse transcription rather than G-to-A hypermutation. The Apobec3-dependent NAb response correlated with IgG binding titers against native, but not detergent-lysed virions. These findings indicate that innate Apobec3 restriction promotes NAb responses by maintaining high concentrations of virions with native B cell epitopes, but in the context of low virion infectivity. Finally, Apobec3 restriction was found to be saturable in vivo, since increasing FV inoculum doses resulted in decreased Apobec3 inhibition. By analogy, maximizing the release of noninfectious particles by modulating APOBEC3 expression may improve humoral immunity against pathogenic human retroviral infections.

  1. Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes.

    Science.gov (United States)

    Burdick, Ryan C; Hu, Wei-Shau; Pathak, Vinay K

    2013-12-01

    Human cytidine deaminases APOBEC3F (A3F) and APOBEC3G (A3G) are host factors that incorporate into virions and restrict virus replication. We labeled HIV-1 particles with yellow fluorescent protein (YFP)-tagged APOBEC3 proteins and examined their association with preintegration complexes (PICs) in infected cells. Labeling of PICs with A3F-YFP, and to a lesser extent A3G-YFP, could be used to visualize PICs in the nuclei, which was dependent on nuclear pore protein Nup153 but not TNPO3. We show that reverse transcription is not required for nuclear import of PICs, indicating that a viral core uncoating event associated with reverse transcription, and the central DNA flap that forms during reverse transcription, are not required for nuclear import. We also quantify association of cytoplasmic PICs with nuclear envelope (NE) and report that capsid mutations that increase or decrease core stability dramatically reduce NE association and nuclear import of PICs. In addition, we find that nuclear PICs remain close to the NE and are not distributed throughout the nuclei. These results provide tools for tracking retroviral PICs in infected cells and reveal insights into HIV-1 replication. PMID:24248339

  2. The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys

    Science.gov (United States)

    Etienne, Lucie; Bibollet-Ruche, Frederic; Sudmant, Peter H.; Wu, Lily I.; Hahn, Beatrice H.; Emerman, Michael

    2015-01-01

    Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee’s main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4+ T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses. PMID:26394054

  3. Host APOBEC3G Protein Inhibits HCV Replication through Direct Binding at NS3

    OpenAIRE

    ZHU, YAN-PING; Peng, Zong-Gen; Wu, Zhou-Yi; Jian-rui LI; Huang, Meng-Hao; Si, Shu-Yi; Jiang, Jian-Dong

    2015-01-01

    Human APOBEC3G (hA3G) is a cytidine deaminase that restricts replication of certain viruses. We have previously reported that hA3G was a host restriction factor against hepatitis C virus (HCV) replication, and hA3G stabilizers showed a significant inhibitory activity against HCV. However, the molecular mechanism of hA3G against HCV remains unknown. We show in this study that hA3G’s C-terminal directly binds HCV non-structural protein NS3 at its C-terminus, which is responsible for NS3’s helic...

  4. HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation

    OpenAIRE

    Mercenne, Gaëlle; Bernacchi, Serena; Richer, Delphine; Bec, Guillaume; Henriet, Simon; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    The HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells (including most natural HIV-1 targets) by counteracting the cellular cytosine deaminases APOBEC-3G (hA3G) and hA3F. The Vif-induced degradation of these restriction factors by the proteasome has been extensively studied, but little is known about the translational repression of hA3G and hA3F by Vif, which has also been proposed to participate in Vif function. Here, we studied Vif binding to hA3G mRNA ...

  5. Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk.

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    Mayumi Imahashi

    Full Text Available OBJECTIVE: The human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo. METHODS: Intact (I and deletion (D polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4(+ T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D. HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs. RESULTS: A total of 248 HIV-1-infected Japanese men who have sex with men (MSM patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66. In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility. CONCLUSION: Our analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo.

  6. Analysis of single-nucleotide polymorphisms in the APOBEC3H gene of domestic cats (Felis catus) and their association with the susceptibility to feline immunodeficiency virus and feline leukemia virus infections.

    Science.gov (United States)

    de Castro, Fernanda Luz; Junqueira, Dennis Maletich; de Medeiros, Rúbia Marília; da Silva, Tailene Rabello; Costenaro, Jamile Girardi; Knak, Marcus Braga; de Matos Almeida, Sabrina Esteves; Campos, Fabrício Souza; Roehe, Paulo Michel; Franco, Ana Cláudia

    2014-10-01

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are widely distributed retroviruses that infect domestic cats (Felis catus). Restriction factors are proteins that have the ability to hamper retroviruses' replication and are part of the conserved mechanisms of anti-viral immunity of mammals. The APOBEC3 protein family is the most studied class of restriction factors; they are cytidine deaminases that generate hypermutations in provirus DNA during reverse transcription, thus causing hypermutations in the viral genome, hindering virus replication. One of the feline APOBEC3 genes, named APOBEC3H, encodes two proteins (APOBEC3H and APOBEC3CH). In other mammals, APOBEC3H single-nucleotide polymorphisms (SNPs) can alter the stability and cellular localization of the encoded protein, thus influencing its subcellular localization and reducing its anti-viral effect. In cats, the association of APOBEC3H SNPs with susceptibility to retroviral infections was not yet demonstrated. Therefore, this study aimed the investigation on the variability of APOBEC3H and the possible association with FIV/FeLV infections. DNA obtained from whole blood of fifty FIV- and/or FeLV-infected cats and fifty-nine FIV- and/or FeLV-uninfected cats were used as templates to amplify two different regions of the APOBEC3H, with subsequent sequencing and analysis. The first region was highly conserved among all samples, while in the second, six single-nucleotide variation points were identified. One of the SNPs, A65S (A65I), was significantly correlated with the susceptibility to FIV and/or FeLV infections. On the other hand, the haplotype analysis showed that the combination "GGGGCC" was positively correlated with the lack of FIV and/or FeLV infections. Our results indicate that, as previously shown in other mammals, variability of restriction factors may contribute to susceptibility of domestic cats to retroviral infections; however, these results should be confirmed by more

  7. Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1.

    OpenAIRE

    Emma Chan; Towers, Greg J; Waseem Qasim

    2014-01-01

    Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy ...

  8. Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications

    Energy Technology Data Exchange (ETDEWEB)

    Holden, Lauren G.; Prochnow, Courtney; Chang, Y. Paul; Bransteitter, Ronda; Chelico, Linda; Sen, Udayaditya; Stevens, Raymond C.; Goodman, Myron F.; Chen, Xiaojiang S. (USC); (Scripps)

    2009-04-07

    The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single-stranded DNA or by RNA binding. Here we report the high-resolution crystal structure of the carboxy-terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five-stranded {beta}-sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2. A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active-site loops that are directly involved in substrate binding. In the X-ray structure, these APOBEC3G active-site loops form a continuous 'substrate groove' around the active centre. The orientation of this putative substrate groove differs markedly (by 90 degrees) from the groove predicted by the NMR structure. We have introduced mutations around the groove, and have identified residues involved in substrate specificity, single-stranded DNA binding and deaminase activity. These results provide a basis for understanding the underlying mechanisms of substrate specificity for the APOBEC family.

  9. Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

    Science.gov (United States)

    Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

    2016-05-01

    Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

  10. Inhibition of APOBEC3G activity impedes double-stranded DNA repair.

    Science.gov (United States)

    Prabhu, Ponnandy; Shandilya, Shivender M D; Britan-Rosich, Elena; Nagler, Adi; Schiffer, Celia A; Kotler, Moshe

    2016-01-01

    The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to ionizing radiation. In the current study, we show that additional peptides derived from Vif, A3G, and APOBEC3F, which contain the LYYF motif, inhibit deamination activity. Each residue in the Vif25-39 sequence moderately contributes to the inhibitory effect, whereas replacing a single residue in the LYYF motif completely abrogates inhibition of deamination. Treatment of A3G-expressing lymphoma cells exposed to ionizing radiation with the new inhibitory peptides reduces double-strand break repair after irradiation. Incubation of cultured irradiated lymphoma cells with peptides that inhibit double-strand break repair halts their propagation. These results suggest that A3G may be a potential therapeutic target that is amenable to peptide and peptidomimetic inhibition. PMID:26460502

  11. APOBEC3G inhibits elongation of HIV-1 reverse transcripts.

    Directory of Open Access Journals (Sweden)

    Kate N Bishop

    2008-12-01

    Full Text Available APOBEC3G (A3G is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.

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

    OpenAIRE

    Jeang Kuan-Teh; Luban Jeremy; Strebel Klaus

    2009-01-01

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

  13. Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1.

    Directory of Open Access Journals (Sweden)

    Luis Apolonia

    2015-01-01

    Full Text Available The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G (A3G and APOBEC3F (A3F, act as potent human immunodeficiency virus type-1 (HIV-1 restriction factors. These proteins require packaging into HIV-1 particles to exert their antiviral activities, but the molecular mechanism by which this occurs is incompletely understood. The nucleocapsid (NC region of HIV-1 Gag is required for efficient incorporation of A3G and A3F, and the interaction between A3G and NC has previously been shown to be RNA-dependent. Here, we address this issue in detail by first determining which RNAs are able to bind to A3G and A3F in HV-1 infected cells, as well as in cell-free virions, using the unbiased individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP method. We show that A3G and A3F bind many different types of RNA, including HIV-1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs. Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV-1 genomic RNA (gRNA and 7SL RNA are reduced, implying that these RNAs are not essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles formed with Gag lacking the NC domain (Gag ΔNC fail to encapsidate A3G/F. Here, we exploit this system by demonstrating that the addition of an assortment of heterologous RNA-binding proteins and domains to Gag ΔNC efficiently restored A3G/F packaging, indicating that A3G and A3F have the ability to engage multiple RNAs to ensure viral encapsidation. We propose that the rather indiscriminate RNA binding characteristics of A3G and A3F promote functionality by enabling recruitment into a wide range of retroviral particles whose packaged RNA genomes comprise divergent sequences.

  14. Human APOBEC3G incorporation into murine leukemia virus particles

    International Nuclear Information System (INIS)

    The human APOBEC3G protein exhibits broad antiretroviral activity against a variety of retroviruses. It is packaged into viral particles and executes its antiviral function in the target cell. The packaging of APOBEC3G into different viral particles requires a mechanism that confers this promiscuity. Here, APOBEC3G incorporation into murine leukemia virus (MLV) was studied using retroviral vectors. APOBEC3G uptake did not require either its cytidine deaminase activity or the presence of a retroviral vector genome. Results from immunoprecipitation and co-localization studies of APOBEC3G with a MLV Gag-CFP (cyan fluorescent protein) fusion protein imply an interaction between both proteins. RNase A treatment did not inhibit the co-precipitation of Gag-CFP and APOBEC3G, suggesting that the interaction is RNA independent. Like human immunodeficiency virus (HIV) Gag, the MLV Gag precursor protein appears to interact with APOBEC3G, indicating that Gag contains conserved structures which are used to encapsidate APOBEC3G into different retroviral particles

  15. Demonstration of a Novel HIV-1 Restriction Phenotype from a Human T Cell Line

    OpenAIRE

    Han, Yanxing; Xiaojun WANG; Dang, Ying; Zheng, Yong-Hui

    2008-01-01

    Background Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5α, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized b...

  16. A Comparison of Two Single-Stranded DNA Binding Models by Mutational Analysis of APOBEC3G

    Directory of Open Access Journals (Sweden)

    Hiroshi Matsuo

    2012-08-01

    Full Text Available APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. Several high-resolution structures of the APOBEC3G catalytic domain have been generated, but none reveal how this enzyme binds to substrate single-stranded DNA. Here, we constructed a panel of APOBEC3G amino acid substitution mutants and performed a series of biochemical, genetic, and structural assays to distinguish between “Brim” and “Kink” models for single-strand DNA binding. Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. Concordant with both models, changing the conserved arginine at position 313 to glutamate abolished both catalytic and restriction activities. In support of the Brim model, arginine to glutamate substitutions at positions 213, 215, and 320 also compromised these APOBEC3G activities. Arginine to glutamate substitutions at Kink model residues 374 and 376 had smaller effects. These observations were supported by A3G catalytic domain-ssDNA chemical shift perturbation experiments. The overall data set is most consistent with the Brim model for single-stranded DNA binding by APOBEC3G.

  17. APOBEC3 Interference during Replication of Viral Genomes

    Directory of Open Access Journals (Sweden)

    Luc Willems

    2015-06-01

    Full Text Available Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention.

  18. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein

    Science.gov (United States)

    Chaurasiya, Kathy R.; McCauley, Micah J.; Wang, Wei; Qualley, Dominic F.; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S. B.; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C.

    2014-01-01

    The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.

  19. HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation.

    Science.gov (United States)

    Mercenne, Gaëlle; Bernacchi, Serena; Richer, Delphine; Bec, Guillaume; Henriet, Simon; Paillart, Jean-Christophe; Marquet, Roland

    2010-01-01

    The HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells (including most natural HIV-1 targets) by counteracting the cellular cytosine deaminases APOBEC-3G (hA3G) and hA3F. The Vif-induced degradation of these restriction factors by the proteasome has been extensively studied, but little is known about the translational repression of hA3G and hA3F by Vif, which has also been proposed to participate in Vif function. Here, we studied Vif binding to hA3G mRNA and its role in translational repression. Filter binding assays and fluorescence titration curves revealed that Vif tightly binds to hA3G mRNA. Vif overall binding affinity was higher for the 3'UTR than for the 5'UTR, even though this region contained at least one high affinity Vif binding site (apparent K(d) = 27 +/- 6 nM). Several Vif binding sites were identified in 5' and 3'UTRs using RNase footprinting. In vitro translation evidenced that Vif inhibited hA3G translation by two mechanisms: a main time-independent process requiring the 5'UTR and an additional time-dependent, UTR-independent process. Results using a Vif protein mutated in the multimerization domain suggested that the molecular mechanism of translational control is more complicated than a simple physical blockage of scanning ribosomes. PMID:19910370

  20. NF-IL6 (C/EBPβ) induces HIV-1 replication by inhibiting cytidine deaminase APOBEC3G

    OpenAIRE

    Shigemi M Kinoshita; Taguchi, Shizuka

    2008-01-01

    T cell activation is crucial for the productive HIV-1 infection of primary T cells; however, little is known about the host molecules involved in this process. We show that the host transcription factor NF-IL6 (also called C/EBPβ) renders primary CD4+ T cells highly permissive for HIV-1 replication. NF-IL6 facilitates reverse transcription of the virus by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakened its binding to APOBEC3G and s...

  1. Human APOBEC3G drives HIV-1 evolution and the development of drug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tamoy [Los Alamos National Laboratory; Kim, Eun - Young [FEINBERG SCHOOL OF MEDS; Koning, Fransje [KING' S COLLEGE LONDON; Malim, Michael [KING' S COLLEGE LONDON; Wolinsky, Steven M [FEINBERG SCHOOL OF MEDS

    2008-01-01

    Human APOBEC3G (hA3G) is an innate virus restriction factor that induces deamination of specific cytidine residues in single-stranded human immunodeficiency virus type 1 (HIV-1) DNA. Whereas destructive hA3G editing leads to a profound loss of HIV-1 infectivity, more limited editing could be a source of adaptation and diversification. Here we show that the presence of hA3G in T-cells can drive the development of diversity in HIV-1 populations and that under selection pressure imposed by the nucleotide analog reverse transcriptase inhibitor 3TC ((-)2',3'-dideoxy-3'-thiacytidine), a single point mutation that confers 3TC resistance, methionine 184 to isoleucine (M1841), emerges rapidly and reaches fixation. These results provide strong evidence that mutation by hA3G is an important source of genetic variation on which natural selection acts to shape the structure of the viral population and drive the tempo of HIV-1 evolution.

  2. APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.

    Science.gov (United States)

    Compaore, Tegwinde Rebeca; Soubeiga, Serge Theophile; Ouattara, Abdoul Karim; Obiri-Yeboah, Dorcas; Tchelougou, Damehan; Maiga, Mamoudou; Assih, Maleki; Bisseye, Cyrille; Bakouan, Didier; Compaore, Issaka Pierre; Dembele, Augustine; Martinson, Jeremy; Simpore, Jacques

    2016-01-01

    Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs) present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (pratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2) to five (5) fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso. PMID:26741797

  3. APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Tegwinde Rebeca Compaore

    Full Text Available Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05, rs8177832 (P<0.05, and rs35228531 (P<0.001 were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01. Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001. Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2 to five (5 fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso.

  4. Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Thangavelu, Pulari U.; Gupta, Vipul; Dixit, Narendra M., E-mail: narendra@chemeng.iisc.ernet.in

    2014-01-20

    The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G–Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded ∼0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R{sub 0}, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G–Vif axis. - Highlights: • We perform simulations and mathematical modeling of the role of APOBEC3G in suppressing HIV-1 infection. • In three distinct ways, we estimate that when over 80% of progeny virions carry APOBEC3G, productive HIV-1 infection would be suppressed. • Our estimate of this critical fraction presents quantitative guidelines for strategies targeting the APOBEC3G–Vif axis.

  5. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  6. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina)

    Science.gov (United States)

    ZHANG, Xiao-Liang; SONG, Jia-Hao; PANG, Wei; ZHENG, Yong-Tang

    2016-01-01

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  7. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Song, Jia-Hao; Pang, Wei; Zheng, Yong-Tang

    2016-07-18

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  8. Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Vartanian

    2010-05-01

    Full Text Available DNA viruses, retroviruses and hepadnaviruses, such as hepatitis B virus (HBV, are vulnerable to genetic editing of single stranded DNA by host cell APOBEC3 (A3 cytidine deaminases. At least three A3 genes are up regulated by interferon-alpha in human hepatocytes while ectopic expression of activation induced deaminase (AICDA, an A3 paralog, has been noted in a variety of chronic inflammatory syndromes including hepatitis C virus infection. Yet virtually all studies of HBV editing have confined themselves to analyses of virions from culture supernatants or serum where the frequency of edited genomes is generally low (HBV>alcoholic cirrhosis. A3C and A3D were up regulated for all groups while the interferon inducible A3G was over expressed in virus associated cirrhosis, as was AICDA in approximately 50% of these HBV/HCV samples. While AICDA can indeed edit HBV DNA ex vivo, A3G is the dominant deaminase in vivo with up to 35% of HBV genomes being edited. Despite these highly deleterious mutant spectra, a small fraction of genomes survive and contribute to loss of HBeAg antigenemia and possibly HBsAg immune escape. In conclusion, the cytokine storm associated with chronic inflammatory responses to HBV and HCV clearly up regulates a number of A3 genes with A3G clearly being a major restriction factor for HBV. Although the mutant spectrum resulting from A3 editing is highly deleterious, a very small part, notably the lightly edited genomes, might help the virus evolve and even escape immune responses.

  9. Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.

    Science.gov (United States)

    Vartanian, Jean-Pierre; Henry, Michel; Marchio, Agnès; Suspène, Rodolphe; Aynaud, Marie-Ming; Guétard, Denise; Cervantes-Gonzalez, Minerva; Battiston, Carlo; Mazzaferro, Vincenzo; Pineau, Pascal; Dejean, Anne; Wain-Hobson, Simon

    2010-05-01

    DNA viruses, retroviruses and hepadnaviruses, such as hepatitis B virus (HBV), are vulnerable to genetic editing of single stranded DNA by host cell APOBEC3 (A3) cytidine deaminases. At least three A3 genes are up regulated by interferon-alpha in human hepatocytes while ectopic expression of activation induced deaminase (AICDA), an A3 paralog, has been noted in a variety of chronic inflammatory syndromes including hepatitis C virus infection. Yet virtually all studies of HBV editing have confined themselves to analyses of virions from culture supernatants or serum where the frequency of edited genomes is generally low (HBV>alcoholic cirrhosis. A3C and A3D were up regulated for all groups while the interferon inducible A3G was over expressed in virus associated cirrhosis, as was AICDA in approximately 50% of these HBV/HCV samples. While AICDA can indeed edit HBV DNA ex vivo, A3G is the dominant deaminase in vivo with up to 35% of HBV genomes being edited. Despite these highly deleterious mutant spectra, a small fraction of genomes survive and contribute to loss of HBeAg antigenemia and possibly HBsAg immune escape. In conclusion, the cytokine storm associated with chronic inflammatory responses to HBV and HCV clearly up regulates a number of A3 genes with A3G clearly being a major restriction factor for HBV. Although the mutant spectrum resulting from A3 editing is highly deleterious, a very small part, notably the lightly edited genomes, might help the virus evolve and even escape immune responses. PMID:20523896

  10. APOBEC3G Impairs the Multimerization of the HIV-1 Vif Protein in Living Cells

    OpenAIRE

    Batisse, Julien; Guerrero, Santiago Xavier; Bernacchi, Serena; Richert, Ludovic; Godet, Julien; Goldschmidt, Valérie; Mély, Yves; Marquet, Roland; de Rocquigny, Hugues; Paillart, Jean-Christophe

    2013-01-01

    The HIV-1 viral infectivity factor (Vif) is a small basic protein essential for viral fitness and pathogenicity. Vif allows productive infection in nonpermissive cells, including most natural HIV-1 target cells, by counteracting the cellular cytosine deaminases APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G [A3G]) and A3F. Vif is also associated with the viral assembly complex and packaged into viral particles through interactions with the viral genomic RNA and t...

  11. A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif

    Science.gov (United States)

    Shandilya, M.D. Shivender; Bohn, Markus-Frederik; Schiffer, Celia A.

    2016-01-01

    APOBEC3s (A3) are Zn2+ dependent cytidine deaminases with diverse biological functions and implications for cancer and immunity. Four of the seven human A3s restrict HIV by 'hypermutating' the reverse-transcribed viral genomic DNA. HIV Virion Infectivity Factor (Vif) counters this restriction by targeting A3s to proteasomal degradation. However, there is no apparent correlation between catalytic activity, Vif binding, and sequence similarity between A3 domains. Our comparative structural analysis reveals features required for binding Vif and features influencing polynucleotide deaminase activity in A3 proteins. All Vif-binding A3s share a negatively charged surface region that includes residues previously implicated in binding the highly-positively charged Vif. Additionally, catalytically active A3s share a positively charged groove near the Zn2+ coordinating active site, which may accommodate the negatively charged polynucleotide substrate. Our findings suggest surface electrostatics, as well as the spatial extent of substrate accommodating region, are critical determinants of substrate and Vif binding across A3 proteins with implications for anti-retroviral and anti-cancer therapeutic design. PMID:25461536

  12. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

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    Friew Yeshitila N

    2009-06-01

    Full Text Available Abstract Background Host restriction factor APOBEC3G (A3G blocks human immunodeficiency virus type 1 (HIV-1 replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Gag interactions in living cells by reconstitution of yellow fluorescent protein (YFP from its N- or C-terminal fragments. Results The results obtained with catalytic domain 1 and 2 (CD1 and CD2 mutants indicate that A3G-A3G and A3G-Gag multimerization is dependent on an intact CD1 domain, which is required for RNA binding. A mutant HIV-1 Gag that exhibits reduced RNA binding also failed to reconstitute BiFC with wild-type A3G, indicating a requirement for both HIV-1 Gag and A3G to bind to RNA for their multimerization. Addition of a non-specific RNA binding peptide (P22 to the N-terminus of a CD1 mutant of A3G restored BiFC and virion incorporation, but failed to inhibit viral replication, indicating that the mutations in CD1 resulted in additional defects that interfere with A3G's antiviral activity. Conclusion These studies establish a robust BiFC assay for analysis of intracellular interactions of A3G with other macromolecules. The results indicate that in vivo A3G is a monomer that forms multimers upon binding to RNA. In addition, we observed weak interactions between wild-type A3G molecules and RNA binding-defective mutants of A3G, which could explain previously described protein-protein interactions between purified A3G molecules.

  13. Research progress of association between the polymorphisms of APOBEC3 G, PSIP1, SAMHD1 gene and HIV-1/AIDS%APOBEC3 G、PSIP1和AMHD1基因多态性与HIV-1/AIDS关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    李秋炎; 乔远东; 张学龙; 徐丽丹

    2015-01-01

    The host genetic background is one of the major factors causing different phenotype between individuals after HIV-1 infection.Many studies found thatAPOBEC3 G, LEDGF/p75, and SAMHD1 play an important role in HIV-1 replication cycle.APOBEC3G has a broad antiviral activity,LEDGF/p75 can tether HIV-1 to the chromosome through interacting with integrase, and SAMHD1 can inhibit HIV-1 replication by its dNTPase and RNase activities.In this review, we summarize the research progress in the polymorphisms of APOBEC3 G, PSIP1 and SAMHD1 genes that encode the aforementioned proteins, their susceptibility to HIV-1 infection and association with AIDS.%宿主遗传背景是导致人类免疫缺陷病毒(HIV)感染后不同个体间表型差异的主要因素之一.许多研究表明,APOBEC3 G、LEDGF/p75和SAMHD1在HIV-1复制周期中起到重要作用.其中,APOBEC3G具有广谱的抗逆转录病毒活性,可以有效的抑制HIV-1的复制;LEDGF/p75可以与整合酶结合,促进HIV-1整合到宿主基因组中;SAMHD1具有脱氧核苷三磷酸酶(dNTP ase)活性和核酸外切酶(RNase)活性,起到抑制病毒复制的作用.本文将对上述蛋白编码基因APOBEC3 G、PSIP1和SAMHD1基因多态性与HIV-1易感性和AIDS的相关性进展作一综述.

  14. Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients.

    Science.gov (United States)

    Zhu, Jia-Wu; Liu, Feng-Liang; Mu, Dan; Deng, De-Yao; Zheng, Yong-Tang

    2016-06-01

    Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-α, -β mRNA expression while the mRNA expression of TRIMα was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIMα and TRIM22 positively correlated with IFN-α, -β, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery. J. Med. Virol. 88:987-995, 2016. © 2015 Wiley Periodicals, Inc. PMID:26519943

  15. Multi-scale modeling of HIV infection in vitro and APOBEC3G-based anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Iraj Hosseini

    2012-02-01

    Full Text Available The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell, cellular and extracellular (multicellular events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions, whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis.

  16. APOBEC3G targets human T-cell leukemia virus type 1

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    Imada Kazunori

    2005-05-01

    Full Text Available Abstract Background Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC into deoxyuridine (dU in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1, the first identified human retrovirus. Results In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1 vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. Conclusion APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission.

  17. Requirement for Fc Effector Mechanisms in the APOBEC3/Rfv3-Dependent Neutralizing Antibody Response

    Science.gov (United States)

    Halemano, Kalani; Barrett, Bradley S.; Heilman, Karl J.; Morrison, Thomas E.

    2015-01-01

    Antiretroviral neutralizing antibody (NAb) responses are often evaluated in the absence of Fc-dependent immune effectors. In murine Friend retrovirus infection, Apobec3/Rfv3 promotes a potent polyclonal NAb response. Here, we show that the Apobec3/Rfv3-dependent NAb response correlated with virus-specific IgG2 titers and that the in vivo neutralization potency of Apobec3/Rfv3-resistant antisera was dependent on activating Fcγ receptors but not complement. The data strengthen retroviral vaccine strategies aimed at eliciting NAbs that activate specific Fcγ receptors. PMID:25589647

  18. APOBEC3G has the ability to programme T cell plasticity.

    Science.gov (United States)

    Garg, Anuradha; Kaul, Deepak

    2016-07-01

    Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-κB, CCL5, IL-6, IL-4, IFN-γ, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number. On the basis of these findings, we propose that APOBEC3G has the ability to induce T cell plasticity and modulate immune response. PMID:27282578

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

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    Bjørn A Nexø

    Full Text Available We recently described that the autoimmune, central nervous system disease, multiple sclerosis (MS, is genetically associated with the human endogenous retroviral locus, HERV-Fc1, in Scandinavians. A number of dominant human genes encoding factors that restrict retrovirus replication have been known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22 and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement.

  20. APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity

    Science.gov (United States)

    Liang, Weizi; Xu, Jiwei; Yuan, Wensu; Song, Xuan; Zhang, Jianyong; Wei, Wei; Yu, Xiao-Fang; Yang, Ying

    2016-01-01

    Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner. Moreover, A3DE binds to LINE-1 RNA and ORF1 protein in cell culture system. Fluorescence microscopy demonstrated that A3DE co-localizes with ORF1p in cytoplasm. Furthermore, A3DE inhibits LINE-1 reverse transcriptase activity in LINE-1 ribonucleoprotein particles in a cytidine deaminase-independent manner. In contrast, A3B has less inhibitory effects on LINE-1 reverse transcriptase activity despite its strong inhibition of LINE-1 retrotransposition. This study demonstrates that different A3 proteins have been evolved to inhibit LINE-1 activity through distinct mechanisms. PMID:27428332

  1. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

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    Joshua R. Kane

    2015-05-01

    Full Text Available HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac] and non-primate (FIV, BIV, and MVV viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA, for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.

  2. Inhibition of hepatitis B virus replication by APOBEC3G in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yan-Chang Lei; Dong-Liang Yang; You-Hua Hao; Zheng-Mao Zhang; Yong-Jun Tian; Bao-Ju Wang; Yan Yang; Xi-Ping Zhao; Meng-Ji Lu; Fei-Li Gong

    2006-01-01

    AIM: To investigate the effect of APOBEC3G mediated antiviral activity against hepatitis B virus (HBV) in cell cultures and replication competent HBV vector-based mouse model.METHODS: The mammalian hepatoma cells Huh7 and HepG2 were cotransfected with various amounts of CMV-driven expression vector encoding APOBEC3G and replication competent 1.3 fold over-length HBV. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA. The expression of HBcAg in transfected cells was detected by western blot. HBV DNA and RNA from intracellular core particles were examined by Northern and Southern blot analyses. To assess activity of the APOBEC3G in vivo, an HBV vector-based model was used in which APOBEC3G and the HBV vector were co-delivered via high-volume tail vein injection.Levels of HBsAg and HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by ELISA and quantitative PCR analysis respectively.RESULTS: There was a dose dependent decrease in the levels of intracellular core-associated HBV DNA and extracellular production of HBsAg and HBeAg. The levels of intracellular core-associated viral RNA also decreased,but the expression of HBcAg in transfected cells showed almost no change. Consistent with in vitro results,levels of HBsAg in the sera of mice were dramatically decreased. More than 1.5 log10 decrease in levels of serum HBV DNA and liver HBV RNA were observed in the APOBEC3G-treated groups compared with the control groups.CONCLUSION: These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection.

  3. Retroelements versus APOBEC3 family members: No great escape from the magnificent seven

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    KenzoTokunaga

    2012-08-01

    Full Text Available Retroelements comprise a large and successful family of transposable genetic elements that, through intensive infiltration, have shaped the genomes of humans and other mammals over millions of years. In fact, retrotransposons now account for approximately 45% of the human genome. Based on their genomic mobility, some retroelements are known to be the cause of genetic diseases, not only in germ and embryonic stem cells but also in somatic cells, posing a threat to genomic stability throughout all cellular populations. In response, mammals have developed intrinsic immunity mechanisms that provide resistance against the threat of the deleterious effects of retrotransposition. Among these, seven members of the APOBEC3 (A3 family of cytidine deaminases serve as highly active, intrinsic, antiretroviral host factors. Certain A3 proteins effectively counteract infections of retroviruses such as HIV-1, as well as those of other virus families, while also blocking the transposition of retroelements. Based on their preferential expression in the germ cells, in which retrotransposons may be active, it is likely that A3 proteins were acquired through mammalian evolution primarily to inhibit retrotransposition and thereby maintain genomic stability in these cells. This review summarizes the recent advances in our understanding of the interplay between the retroelements currently active in the human genome and the anti-retroelement A3 proteins.

  4. Likely role of APOBEC3G-mediated G-to-A mutations in HIV-1 evolution and drug resistance.

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    Patric Jern

    2009-04-01

    Full Text Available The role of APOBEC3 (A3 protein family members in inhibiting retrovirus infection and mobile element retrotransposition is well established. However, the evolutionary effects these restriction factors may have had on active retroviruses such as HIV-1 are less well understood. An HIV-1 variant that has been highly G-to-A mutated is unlikely to be transmitted due to accumulation of deleterious mutations. However, G-to-A mutated hA3G target sequences within which the mutations are the least deleterious are more likely to survive selection pressure. Thus, among hA3G targets in HIV-1, the ratio of nonsynonymous to synonymous changes will increase with virus generations, leaving a footprint of past activity. To study such footprints in HIV-1 evolution, we developed an in silico model based on calculated hA3G target probabilities derived from G-to-A mutation sequence contexts in the literature. We simulated G-to-A changes iteratively in independent sequential HIV-1 infections until a stop codon was introduced into any gene. In addition to our simulation results, we observed higher ratios of nonsynonymous to synonymous mutation at hA3G targets in extant HIV-1 genomes than in their putative ancestral genomes, compared to random controls, implying that moderate levels of A3G-mediated G-to-A mutation have been a factor in HIV-1 evolution. Results from in vitro passaging experiments of HIV-1 modified to be highly susceptible to hA3G mutagenesis verified our simulation accuracy. We also used our simulation to examine the possible role of A3G-induced mutations in the origin of drug resistance. We found that hA3G activity could have been responsible for only a small increase in mutations at known drug resistance sites and propose that concerns for increased resistance to other antiviral drugs should not prevent Vif from being considered a suitable target for development of new drugs.

  5. Crystal Structure of the APOBEC3G Catalytic Domain Reveals Potential Oligomerization Interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Shandilya, Shivender M.D.; Nalam, Madhavi N.L.; Nalivaika, Ellen A.; Gross, Phillip J.; Valesano, Johnathan C.; Shindo, Keisuke; Li, Ming; Munson, Mary; Royer, William E.; Harjes, Elena; Kono, Takahide; Matsuo, Hiroshi; Harris, Reuben S.; Somasundaran, Mohan; Schiffer, Celia A. (UMASS, MED); (UMM)

    2010-02-11

    APOBEC3G is a DNA cytidine deaminase that has antiviral activity against HIV-1 and other pathogenic viruses. In this study the crystal structure of the catalytically active C-terminal domain was determined to 2.25 {angstrom}. This structure corroborates features previously observed in nuclear magnetic resonance (NMR) studies, a bulge in the second {beta} strand and a lengthening of the second {alpha} helix. Oligomerization is postulated to be critical for the function of APOBEC3G. In this structure, four extensive intermolecular interfaces are observed, suggesting potential models for APOBEC3G oligomerization. The structural and functional significance of these interfaces was probed by solution NMR and disruptive variants were designed and tested for DNA deaminase and anti-HIV activities. The variant designed to disrupt the most extensive interface lost both activities. NMR solution data provides evidence that another interface, which coordinates a novel zinc site, also exists. Thus, the observed crystallographic interfaces of APOBEC3G may be important for both oligomerization and function.

  6. APOBEC3G impairs the multimerization of the HIV-1 Vif protein in living cells.

    Science.gov (United States)

    Batisse, Julien; Guerrero, Santiago Xavier; Bernacchi, Serena; Richert, Ludovic; Godet, Julien; Goldschmidt, Valérie; Mély, Yves; Marquet, Roland; de Rocquigny, Hugues; Paillart, Jean-Christophe

    2013-06-01

    The HIV-1 viral infectivity factor (Vif) is a small basic protein essential for viral fitness and pathogenicity. Vif allows productive infection in nonpermissive cells, including most natural HIV-1 target cells, by counteracting the cellular cytosine deaminases APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G [A3G]) and A3F. Vif is also associated with the viral assembly complex and packaged into viral particles through interactions with the viral genomic RNA and the nucleocapsid domain of Pr55(Gag). Recently, we showed that oligomerization of Vif into high-molecular-mass complexes induces Vif folding and influences its binding to high-affinity RNA binding sites present in the HIV genomic RNA. To get further insight into the role of Vif multimerization in viral assembly and A3G repression, we used fluorescence lifetime imaging microscopy (FLIM)- and fluorescence resonance energy transfer (FRET)-based assays to investigate Vif-Vif interactions in living cells. By using two N-terminally tagged Vif proteins, we show that Vif-Vif interactions occur in living cells. This oligomerization is strongly reduced when the putative Vif multimerization domain ((161)PPLP(164)) is mutated, indicating that this domain is crucial, but that regions outside this motif also participate in Vif oligomerization. When coexpressed together with Pr55(Gag), Vif is largely relocated to the cell membrane, where Vif oligomerization also occurs. Interestingly, wild-type A3G strongly interferes with Vif multimerization, contrary to an A3G mutant that does not bind to Vif. These findings confirm that Vif oligomerization occurs in living cells partly through its C-terminal motif and suggest that A3G may target and perturb the Vif oligomerization state to limit its functions in the cell. PMID:23576497

  7. APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.

    Science.gov (United States)

    Nowarski, Roni; Kotler, Moshe

    2013-06-15

    High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR. PMID:23598277

  8. Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer.

    Science.gov (United States)

    Harris, Reuben S

    2015-01-01

    Cancer genomic DNA sequences enable identification of all mutations and suggest targets for precision medicine. The identities and patterns of the mutations themselves also provide critical information for deducing the originating DNA damaging agents, causal molecular mechanisms, and thus additional therapeutic targets. A classic example is ultraviolet light, which crosslinks adjacent pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine deaminase APOBEC3B, which was identified recently as a source of DNA damage and mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser extents additional cancer types. This enzyme is normally an effector protein in the innate immune response to virus infection but upregulation in these cancer types causes elevated levels of genomic C-to-U deamination events, which manifest as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide contexts (preferentially 5'-TCA and 5'-TCG). Genomic C-to-U deamination events within the same trinucleotide contexts also lead to cytosine mutation clusters (kataegis), and may precipitate visible chromosomal aberrations such as translocations. Clinical studies indicate that APOBEC3B upregulation correlates with poorer outcomes for estrogen receptor-positive breast cancer patients, including shorter durations of disease-free survival and overall survival after surgery. APOBEC3B may therefore have both diagnostic and prognostic potential. APOBEC3B may also be a candidate for therapeutic targeting because inhibition of this non-essential enzyme is predicted to decrease tumor mutation rates and diminish the likelihood of undesirable mutation-dependent outcomes such as recurrence, metastasis, and the development of therapy resistant tumors. PMID:25848704

  9. APOBEC3-Mediated Hypermutation of Retroviral Vectors Produced from Some Retrovirus Packaging Cell Lines

    OpenAIRE

    Miller, A. Dusty; Metzger, Michael J.

    2011-01-01

    APOBEC3 proteins are packaged into retrovirus virions and can hypermutate retroviruses during reverse transcription. We find that HT-1080 human fibrosarcoma cells hypermutate retroviruses, and that the HT-1080 cell-derived FLYA13 retrovirus packaging cells also hypermutate a retrovirus vector produced using these cells. We found no hypermutation of the same vector produced by the mouse cell-derived packaging line PT67 or by human 293 cells transfected with the vector and retrovirus packaging ...

  10. Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells

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    Goila-Gaur Ritu

    2004-09-01

    Full Text Available Abstract Background The human immunodeficiency virus Vif protein overcomes the inhibitory activity of the APOBEC3G cytidine deaminase by prohibiting its packaging into virions. Inhibition of APOBEC3G encapsidation is paralleled by a reduction of its intracellular level presumably caused by the Vif-induced proteasome-dependent degradation of APOBEC3G. Results In this report we employed confocal microscopy to study the effects of Vif on the expression of APOBEC3G on a single cell level. HeLa cells dually transfected with Vif and APOBEC3G expression vectors revealed efficient co-expression of the two proteins. Under optimal staining conditions approximately 80% of the transfected cells scored double-positive for Vif and APOBEC3G. However, the proportion of double-positive cells observed in identical cultures varied dependent on the fixation protocol and on the choice of antibodies used ranging from as low as 40% to as high as 80% of transfected cells. Importantly, single-positive cells expressing either Vif or APOBEC3G were observed both with wild type Vif and a biologically inactive Vif variant. Thus, the lack of APOBEC3G in some Vif-expressing cells cannot be attributed to Vif-induced degradation of APOBEC3G. These findings are consistent with our results from immunoblot analyses that revealed only moderate effects of Vif on the APOBEC3G steady state levels. Of note, viruses produced under such conditions were fully infectious demonstrating that the Vif protein used in our analyses was both functional and expressed at saturating levels. Conclusions Our results suggest that Vif and APOBEC3G can be efficiently co-expressed. Thus, depletion of APOBEC3G from Vif expressing cells as suggested previously is not a universal property of Vif and thus is not imperative for the production of infectious virions.

  11. The Binding Interface between Human APOBEC3F and HIV-1 Vif Elucidated by Genetic and Computational Approaches

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    Christopher Richards

    2015-12-01

    Full Text Available APOBEC3 family DNA cytosine deaminases provide overlapping defenses against pathogen infections. However, most viruses have elaborate evasion mechanisms such as the HIV-1 Vif protein, which subverts cellular CBF-β and a polyubiquitin ligase complex to neutralize these enzymes. Despite advances in APOBEC3 and Vif biology, a full understanding of this direct host-pathogen conflict has been elusive. We combine virus adaptation and computational studies to interrogate the APOBEC3F-Vif interface and build a robust structural model. A recurring compensatory amino acid substitution from adaptation experiments provided an initial docking constraint, and microsecond molecular dynamic simulations optimized interface contacts. Virus infectivity experiments validated a long-lasting electrostatic interaction between APOBEC3F E289 and HIV-1 Vif R15. Taken together with mutagenesis results, we propose a wobble model to explain how HIV-1 Vif has evolved to bind different APOBEC3 enzymes and, more generally, how pathogens may evolve to escape innate host defenses.

  12. Direct Evidence that RNA Inhibits APOBEC3G ssDNA Cytidine Deaminase Activity

    OpenAIRE

    McDougall, William M.; Smith, Harold C.

    2011-01-01

    APOBEC3G (A3G) is a deoxycytidine deaminase active on ssDNA substrates. In HIV infected cells A3G interacted with reverse transcription complexes where its activity as a deoxycytidine deaminase led to mutation of the viral genome. A3G not only bound ssDNA, but it also had an intrinsic ability to bind RNA. In many cell types that can support HIV replication, A3G ssDNA deaminase activity was suppressed and the enzyme resided in high molecular mass, ribonucleoprotein complexes associated with cy...

  13. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. PMID:24859335

  14. APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete "all or nothing" phenomenon

    DEFF Research Database (Denmark)

    Armitage, Andrew E; Deforche, Koen; Chang, Chih-Hao;

    2012-01-01

    The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of ongoing host-pathogen interactions. One key selective host factor is APOBEC3G (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A) mutation on HIV plus-strand DNA (termed hypermutation). HIV......-lethal frequencies that could increase viral diversification. We show in vitro that limiting-levels of hA3G-activity (i.e. when only a single hA3G-unit is likely to act on HIV) produce hypermutation frequencies similar to those in patients and demonstrate in silico that potentially non-lethal G-to-A mutation rates...... are ∼10-fold lower than the lowest observed hypermutation levels in vitro and in vivo. Our results suggest that even a single incorporated hA3G-unit is likely to cause extensive and inactivating levels of HIV hypermutation and that hypermutation therefore is typically a discrete "all or nothing...

  15. SAMHD1——A HIV-1 restriction factor derived from myeloid lineage monocytes%髓系单核细胞来源的HIV-1限制性因子——SAMHD1

    Institute of Scientific and Technical Information of China (English)

    李佩璐; 陈倩倩; 张驰宇

    2012-01-01

    天然抗病毒限制因子是HIV-1研究最热点的领域.继APOBEC3G、Trim5α、Tetherin被发现之后,SAMHD1于2011年被发现为新的抗HIV-1限制因子.它主要在髓系来源的单核细胞中表达,如巨噬细胞和树突状细胞.该文对SAMHD1的结构、抗病毒机制、与Vpx的相互作用以及进化等方面的研究进行了综述.SAMHD1的发现为深入研究SAMHD1在慢病毒致病机理中作用打开了一扇门.%HIV-1 restriction factors have became one of the hottest fields of AIDS researches. In 2011, SAMHD1 was demonstrated to be a novel HIV-1 restriction factor, adding to a list of HIV-1 restriction factors that include APOBEC3G, TRIM5a and Tetherin. SAMHD1 is highly expressed in myeloid-lineage monocytes, such as macrophages and dendritic cells. In this paper, we review the current research progress on the structure of SAMHD1, its antiviral mechanism, interaction with the lentivirus Vpx, and evolution. The identification of SAMHD1 opens the door towards understanding the role of SAMHD1 in lentiviral pathogenesis.

  16. Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals

    Directory of Open Access Journals (Sweden)

    Anita Shet

    2013-02-01

    Full Text Available Introduction: Human APOBEC3G/F (hA3G/F restricts retroviral replication through G-to-A hypermutations, which can generate drug-resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F-mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART. Methods: In 88 HIV-1-positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G-mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations. Results: hA3G/F-mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88 subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART-naïve individuals (p=0.03. In therapy failure patients, proviral hypermutation were associated with greater intra-compartmental genetic diversity (p<0.001. In therapy-naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA. Conclusions: hA3G lethal hypermutation was significantly associated with ART failure in Indian HIV-1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo.

  17. APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Manikandan Periyasamy

    2015-10-01

    Full Text Available Estrogen receptor α (ERα is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER and to repair by non-homologous end-joining (NHEJ pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action.

  18. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  19. 宿主细胞对HIV-1复制的限制性%The host restriction factors targeted HIV-1 replication

    Institute of Scientific and Technical Information of China (English)

    贾彦辉; 徐庆刚

    2013-01-01

    HIV-1感染的主要靶细胞是宿主的CD4+T淋巴细胞,使宿主的免疫机能下降.在HIV-1与宿主的长期进化中,它们之间逐渐形成了复杂的入侵与反入侵关系.人类已经进化出多种机制来抵制HIV-1的感染和复制.宿主细胞内的限制性因子是抑制HIV-1复制的主要机制之一,也是研究人员比较关注的一类机制.SAMHD1作为最新发现的一个限制性因子,成为一个研究热点.通过阐述SAMHD1,APOBEC3G/F,TRIM5α及Tetherin在HIV-1复制中的关键作用,了解宿主细胞对病毒感染的限制性,有助于理解宿主与病毒之间的抗衡关系,宿主抗病毒机制,为治疗HIV-1寻找新的靶点.%The CD4 + T cells are the most important targeted cells of HIV-1 infection leading to immunity dysfunction.A long history of human infection by HIV-1 has resulted in complicated relationship between human and HIV-1.Among the many mechanisms to inhibit HIV-1 infection and replication in human,the host restriction factors are an attentive mechanism.Recently,researchers pay much attention to SAMHD1 which is a new discovered restriction factor.This review mainly discussed the effect of SAMHD1,APOBEC3G/ F,TRIM5α and Tetherin on HIV-1 life cycle.Description of HIV-1 restriction in host cells helps us to understand viral pathogenesis and searching for a new antiviral strategy.

  20. Real Moments of the Restrictive Factor

    Indian Academy of Sciences (India)

    Andrew Ledoan; Alexandru Zaharescu

    2009-09-01

    Let be a real number such that 0 < < 1. We establish asymptotic formulas for the weighted real moments $\\sum_{n≤ x}R^(n)(1-n/x)$, where $R(n)=\\prod^k_{v=1}p^{ v-1}_v$ is the Atanassov strong restrictive factor function and $n=\\prod^k_{v=1}p^{ v}_v$ is the prime factorization of .

  1. APOBEC3H polymorphisms and susceptibility to HIV-1 infection in an Indian population.

    Science.gov (United States)

    Naruse, Taeko K; Sakurai, Daisuke; Ohtani, Hitoshi; Sharma, Gaurav; Sharma, Surendra K; Vajpayee, Madhu; Mehra, Narinder K; Kaur, Gurvinder; Kimura, Akinori

    2016-03-01

    Human APOBEC3H (A3H) is a member of APOBEC cytidine deaminase family intensively constraining the HIV-1 replication. A3H is known to be polymorphic with different protein stability and anti-HIV-1 activity in vitro. We recently reported that A3H haplotypes composed of two functional polymorphisms, rs139292 (N15del) and rs139297 (G105R), were associated with the susceptibility to HIV-1 infection in Japanese. To confirm the association of A3H and HIV-1 infection in another ethnic group, a total of 241 HIV-1-infected Indian individuals and ethnic-matched 286 healthy controls were analyzed for the A3H polymorphisms. The frequency of 15del allele was high in the HIV-1-infected subjects as compared with the controls (0.477 vs 0.402, odds ratio (OR)=1.36, P=0.014). Haplotype analysis showed that the frequencies of 15del-105R was high (0.475 vs 0.400, OR=1.36, permutation P=0.037) in the HIV-1-infected subjects, confirming the association of A3H polymorphisms with the susceptibility to HIV-1 infection. PMID:26559750

  2. Direct Evidence that RNA Inhibits APOBEC3G ssDNA Cytidine Deaminase Activity

    Science.gov (United States)

    McDougall, William M.; Smith, Harold C.

    2011-01-01

    APOBEC3G (A3G) is a deoxycytidine deaminase active on ssDNA substrates. In HIV infected cells A3G interacted with reverse transcription complexes where its activity as a deoxycytidine deaminase led to mutation of the viral genome. A3G not only bound ssDNA, but it also had an intrinsic ability to bind RNA. In many cell types that can support HIV replication, A3G ssDNA deaminase activity was suppressed and the enzyme resided in high molecular mass, ribonucleoprotein complexes associated with cytoplasmic P-bodies and stress granules. Using a defined in vitro system, we show that RNA alone was sufficient to suppress A3G deaminase activity and did so in an RNA concentration-dependent manner. RNAs of diverse sequences and as short as 25 nucleotides were effective inhibitors. Native PAGE analyses showed that RNA formed ribonucleoprotein complexes with A3G and in so doing prevented ssDNA substrates from binding to A3G. The data provided direct evidence that A3G binding to cellular RNAs constituted a substantial impediment to the enzyme’s ability to interact with ssDNA. PMID:21856286

  3. The design of artificial retroviral restriction factors

    International Nuclear Information System (INIS)

    In addition to the ability to bind the retroviral capsid protein, the retroviral restriction factors Fv1, Trim5α and Trim5-CypA share the common property of containing sequences that promote self-association. Otherwise Fv1 and Trim5α appear unrelated. Mutational analyses showed that restriction was invariably lost when changes designed to disrupt the sequences responsible for multimerization were introduced. A novel restriction protein could be obtained by substituting sequences from the self-associating domain of Fv1 for the Trim5 sequences in Trim5-CypA. Similarly, a fusion protein containing cyclophilin A joined to arfaptin2, a protein known to form extended dimers, was also shown to restrict HIV-1. Hence, multimerization of a capsid-binding domain could be the common minimum design feature for capsid-dependent retroviral restriction factors. However, not all domains that promote multimerization can substitute for the N-terminal domains of Fv1 and Trim5α. Moreover, only CypA can provide a capsid-binding site with different N-terminal domains. It is suggested that the spatial relationship between the multiple target binding sites may be important for restriction

  4. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B.

    Directory of Open Access Journals (Sweden)

    Monica K Akre

    Full Text Available Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs. Cells were subjected to 10 rounds of A3B-eGFP exposure that each caused 80-90% cell death. Control pools were subjected to parallel rounds of non-toxic eGFP exposure, and dilutions were done each round to mimic A3B-eGFP induced population fluctuations. Targeted sequencing of portions of TP53 and MYC demonstrated greater mutation accumulation in the A3B-eGFP exposed pools. Clones were generated and microarray analyses were used to identify those with the greatest number of SNP alterations for whole genome sequencing. A3B-eGFP exposed clones showed global increases in C-to-T transition mutations, enrichments for cytosine mutations within A3B-preferred trinucleotide motifs, and more copy number aberrations. Surprisingly, both control and A3B-eGFP clones also elicited strong mutator phenotypes characteristic of defective mismatch repair. Despite this additional mutational process, the 293-based system characterized here still yielded a genome-wide view of A3B-catalyzed mutagenesis in human cells and a system for additional studies on the compounded effects of simultaneous mutation mechanisms in cancer cells.

  5. Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity

    Directory of Open Access Journals (Sweden)

    Strebel Klaus

    2007-08-01

    Full Text Available Abstract Background APOBEC3 (A3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA, unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. Results Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC, virus-associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N-terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. Conclusion Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity.

  6. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates

    OpenAIRE

    Polevoda, Bogdan; McDougall, William M.; Tun, Bradley N.; Cheung, Michael; Salter, Jason D.; Friedman, Alan E.; Smith, Harold C.

    2015-01-01

    APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose assembly on nascent viral reverse transcripts initiates with A3G dimers binding to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered process involving A3G d...

  7. Lower HIV provirus levels are associated with more APOBEC3G protein in blood resting memory CD4+ T lymphocytes of controllers in vivo.

    Directory of Open Access Journals (Sweden)

    Mariapia De Pasquale

    Full Text Available Immunodeficiency does not progress for prolonged periods in some HLA B57- and/or B27-positive subjects with human immunodeficiency virus type 1 (HIV infection, even in the absence of antiretroviral therapy (ART. These "controllers" have fewer HIV provirus-containing peripheral blood mononuclear cells than "non-controller" subjects, but lymphocytes that harbor latent proviruses were not specifically examined in studies to date. Provirus levels in resting memory cells that can serve as latent reservoirs of HIV in blood were compared here between controllers and ART-suppressed non-controllers. APOBEC3G (A3G, a cellular factor that blocks provirus formation at multiple steps if not antagonized by HIV virion infectivity factor (Vif, was also studied. HLA-linked HIV control was associated with less provirus and more A3G protein in resting CD4+ T central memory (Tcm and effector memory (Tem lymphocytes (provirus: p = 0.01 for Tcm and p = 0.02 for Tem; A3G: p = 0.02 for Tcm and p = 0.02 for Tem. Resting memory T cells with the highest A3G protein levels (>0.5 RLU per unit of actin had the lowest levels of provirus (<1,000 copies of DNA per million cells in vivo (p = 0.03, Fisher's exact test. Using two different experimental approaches, Vif-positive viruses with more A3G were found to have decreased virion infectivity ex vivo. These results raise the hypothesis that HIV control is associated with increased cellular A3G that may be packaged into Vif-positive virions to add that mode of inhibition of provirus formation to previously described adaptive immune mechanisms for HIV control.

  8. Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins.

    Directory of Open Access Journals (Sweden)

    Wenyan Zhang

    Full Text Available BACKGROUND: APOBEC3G (A3G and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized. METHODS AND FINDINGS: In the present study, we have demonstrated that the regions of APOBEC3F (A3F that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE. CONCLUSIONS: Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors.

  9. The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

    Science.gov (United States)

    Background: APOBEC3 (A3) proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinc-coordinating motifs (Z1, Z2 or Z3). The presence of one A3 gene in mice (Z2-Z3) and seven in humans, A3A-H (Z1a, Z2a...

  10. Insights into the dual activity of SIVmac239 Vif against human and African green monkey APOBEC3G.

    Directory of Open Access Journals (Sweden)

    Ritu Gaur

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 Vif is essential for viral evasion of the host antiviral protein APOBEC3G (APO3G. The Vif protein from a distantly related African green monkey (Agm simian immunodeficiency virus (SIVagm is unable to suppress the antiviral activity of human APO3G but is active against Agm APO3G. SIVmac Vif on the other hand, possesses antiviral activity against both human and Agm APO3G. In this study, we were interested in mapping domains in SIVmac Vif that are responsible for its dual activity against human and Agm APO3G. We constructed a series of Vif chimeras by swapping domains in SIVmac Vif with equivalent regions from SIVagm Vif and determined their activity against human and Agm APO3G. We found that replacing any region in SIVmac Vif by corresponding fragments from SIVagm Vif only moderately reduced the activity of the chimeras against Agm APO3G but in all cases resulted in a severe loss of activity against human APO3G. These results suggest that the domains in SIVmac Vif required for targeting human and Agm APO3G are distinct and cannot be defined as linear amino acid motifs but rather appear to depend on the overall structure of full-length SIVmac Vif.

  11. Incomplete APOBEC3G/F Neutralization by HIV-1 Vif Mutants Facilitates the Genetic Evolution from CCR5 to CXCR4 Usage

    Science.gov (United States)

    Alteri, Claudia; Surdo, Matteo; Bellocchi, Maria Concetta; Saccomandi, Patrizia; Continenza, Fabio; Armenia, Daniele; Parrotta, Lucia; Carioti, Luca; Costa, Giosuè; Fourati, Slim; Di Santo, Fabiola; Scutari, Rossana; Barbaliscia, Silvia; Fedele, Valentina; Carta, Stefania; Balestra, Emanuela; Alcaro, Stefano; Marcelin, Anne Genevieve; Calvez, Vincent; Ceccherini-Silberstein, Francesca; Artese, Anna

    2015-01-01

    Incomplete APOBEC3G/F neutralization by a defective HIV-1Vif protein can promote genetic diversification by inducing G-to-A mutations in the HIV-1 genome. The HIV-1 Env V3 loop, critical for coreceptor usage, contains several putative APOBEC3G/F target sites. Here, we determined if APOBEC3G/F, in the presence of Vif-defective HIV-1 virus, can induce G-to-A mutations at V3 positions critical to modulation of CXCR4 usage. Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) from 2 HIV-1-negative donors were infected with CCR5-using 81.A-VifWT virus (i.e., with wild-type [WT] Vif protein), 81.A-VifE45G, or 81.A-VifK22E (known to incompletely/partially neutralize APOBEC3G/F). The rate of G-toA mutations was zero or extremely low in 81.A-VifWT- and 81.A-VifE45G-infected PBMC from both donors. Conversely, G-to-A enrichment was detected in 81.A-VifK22E-infected PBMC (prevalence ranging from 2.18% at 7 days postinfection [dpi] to 3.07% at 21 dpi in donor 1 and from 10.49% at 7 dpi to 8.69% at 21 dpi in donor 2). A similar scenario was found in MDM. G-to-A mutations occurred at 8 V3 positions, resulting in nonsynonymous amino acid substitutions. Of them, G24E and E25K strongly correlated with phenotypically/genotypically defined CXCR4-using viruses (P = 0.04 and 5.5e−7, respectively) and increased the CXCR4 N-terminal binding affinity for V3 (WT, −40.1 kcal/mol; G24E, −510 kcal/mol; E25K, −522 kcal/mol). The analysis of paired V3 and Vif DNA sequences from 84 HIV-1-infected patients showed that the presence of a Vif-defective virus correlated with CXCR4 usage in proviral DNA (P = 0.04). In conclusion, incomplete APOBEC3G/F neutralization by a single Vif amino acid substitution seeds a CXCR4-using proviral reservoir. This can have implications for the success of CCR5 antagonist-based therapy, as well as for the risk of disease progression. PMID:26055363

  12. Incomplete APOBEC3G/F Neutralization by HIV-1 Vif Mutants Facilitates the Genetic Evolution from CCR5 to CXCR4 Usage.

    Science.gov (United States)

    Alteri, Claudia; Surdo, Matteo; Bellocchi, Maria Concetta; Saccomandi, Patrizia; Continenza, Fabio; Armenia, Daniele; Parrotta, Lucia; Carioti, Luca; Costa, Giosuè; Fourati, Slim; Di Santo, Fabiola; Scutari, Rossana; Barbaliscia, Silvia; Fedele, Valentina; Carta, Stefania; Balestra, Emanuela; Alcaro, Stefano; Marcelin, Anne Genevieve; Calvez, Vincent; Ceccherini-Silberstein, Francesca; Artese, Anna; Perno, Carlo Federico; Svicher, Valentina

    2015-08-01

    Incomplete APOBEC3G/F neutralization by a defective HIV-1Vif protein can promote genetic diversification by inducing G-to-A mutations in the HIV-1 genome. The HIV-1 Env V3 loop, critical for coreceptor usage, contains several putative APOBEC3G/F target sites. Here, we determined if APOBEC3G/F, in the presence of Vif-defective HIV-1 virus, can induce G-to-A mutations at V3 positions critical to modulation of CXCR4 usage. Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) from 2 HIV-1-negative donors were infected with CCR5-using 81.A-VifWT virus (i.e., with wild-type [WT] Vif protein), 81.A-VifE45G, or 81.A-VifK22E (known to incompletely/partially neutralize APOBEC3G/F). The rate of G-toA mutations was zero or extremely low in 81.A-VifWT- and 81.A-VifE45G-infected PBMC from both donors. Conversely, G-to-A enrichment was detected in 81.A-VifK22E-infected PBMC (prevalence ranging from 2.18% at 7 days postinfection [dpi] to 3.07% at 21 dpi in donor 1 and from 10.49% at 7 dpi to 8.69% at 21 dpi in donor 2). A similar scenario was found in MDM. G-to-A mutations occurred at 8 V3 positions, resulting in nonsynonymous amino acid substitutions. Of them, G24E and E25K strongly correlated with phenotypically/genotypically defined CXCR4-using viruses (P = 0.04 and 5.5e-7, respectively) and increased the CXCR4 N-terminal binding affinity for V3 (WT, -40.1 kcal/mol; G24E, -510 kcal/mol; E25K, -522 kcal/mol). The analysis of paired V3 and Vif DNA sequences from 84 HIV-1-infected patients showed that the presence of a Vif-defective virus correlated with CXCR4 usage in proviral DNA (P = 0.04). In conclusion, incomplete APOBEC3G/F neutralization by a single Vif amino acid substitution seeds a CXCR4-using proviral reservoir. This can have implications for the success of CCR5 antagonist-based therapy, as well as for the risk of disease progression. PMID:26055363

  13. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates.

    Science.gov (United States)

    Polevoda, Bogdan; McDougall, William M; Tun, Bradley N; Cheung, Michael; Salter, Jason D; Friedman, Alan E; Smith, Harold C

    2015-10-30

    APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose assembly on nascent viral reverse transcripts initiates with A3G dimers binding to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered process involving A3G dimers and multimers thereof. Although, fluorescence anisotropy showed that A3G had similar nanomolar affinity for RNA and ssDNA, RNA stochastically dissociated A3G dimers and higher-order oligomers from ssDNA, suggesting a different modality for RNA binding. Mass spectrometry mapping of A3G peptides cross-linked to nucleic acid suggested ssDNA only bound to three peptides, amino acids (aa) 181-194 in the N-terminus and aa 314-320 and 345-374 in the C-terminus that were part of a continuous exposed surface. RNA bound to these peptides and uniquely associated with three additional peptides in the N- terminus, aa 15-29, 41-52 and 83-99, that formed a continuous surface area adjacent to the ssDNA binding surface. The data predict a mechanistic model of RNA inhibition of ssDNA binding to A3G in which competitive and allosteric interactions determine RNA-bound versus ssDNA-bound conformational states. PMID:26424853

  14. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates

    Science.gov (United States)

    Polevoda, Bogdan; McDougall, William M.; Tun, Bradley N.; Cheung, Michael; Salter, Jason D.; Friedman, Alan E.; Smith, Harold C.

    2015-01-01

    APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose assembly on nascent viral reverse transcripts initiates with A3G dimers binding to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered process involving A3G dimers and multimers thereof. Although, fluorescence anisotropy showed that A3G had similar nanomolar affinity for RNA and ssDNA, RNA stochastically dissociated A3G dimers and higher-order oligomers from ssDNA, suggesting a different modality for RNA binding. Mass spectrometry mapping of A3G peptides cross-linked to nucleic acid suggested ssDNA only bound to three peptides, amino acids (aa) 181–194 in the N-terminus and aa 314–320 and 345–374 in the C-terminus that were part of a continuous exposed surface. RNA bound to these peptides and uniquely associated with three additional peptides in the N- terminus, aa 15–29, 41–52 and 83–99, that formed a continuous surface area adjacent to the ssDNA binding surface. The data predict a mechanistic model of RNA inhibition of ssDNA binding to A3G in which competitive and allosteric interactions determine RNA-bound versus ssDNA-bound conformational states. PMID:26424853

  15. An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals

    Directory of Open Access Journals (Sweden)

    Münk Carsten

    2012-05-01

    Full Text Available Abstract Background The APOBEC3 (A3 genes play a key role in innate antiviral defense in mammals by introducing directed mutations in the DNA. The human genome encodes for seven A3 genes, with multiple splice alternatives. Different A3 proteins display different substrate specificity, but the very basic question on how discerning self from non-self still remains unresolved. Further, the expression of A3 activity/ies shapes the way both viral and host genomes evolve. Results We present here a detailed temporal analysis of the origin and expansion of the A3 repertoire in mammals. Our data support an evolutionary scenario where the genome of the mammalian ancestor encoded for at least one ancestral A3 gene, and where the genome of the ancestor of placental mammals (and possibly of the ancestor of all mammals already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication events of the A3 genes have occurred independently in different lineages: humans, cats and horses. In all of them, gene duplication has resulted in changes in enzyme activity and/or substrate specificity, in a paradigmatic example of convergent adaptive evolution at the genomic level. Finally, our results show that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have significantly decreased in the last 100 Mya. The analysis constitutes a textbook example of the evolution of a gene locus by duplication and sub/neofunctionalization in the context of virus-host arms race. Conclusions Our results provide a time framework for identifying ancestral and derived genomic arrangements in the APOBEC loci, and to date the expansion of this gene family for different lineages through time, as a response to changes in viral/retroviral/retrotransposon pressure.

  16. TRIM5 Acts as More Than a Retroviral Restriction Factor

    OpenAIRE

    Li Wu; Suresh De Silva

    2011-01-01

    The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiq...

  17. Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

    OpenAIRE

    Hillman, Sara; Peebles, Donald M.; Williams, David J.

    2013-01-01

    OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who...

  18. Identification of a Cullin5-ElonginB-ElonginC E3 Complex in Degradation of Feline Immunodeficiency Virus Vif-Mediated Feline APOBEC3 Proteins▿

    OpenAIRE

    Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

    2011-01-01

    Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interact...

  19. Deaminase Activity on Single-stranded DNA (ssDNA) Occurs in Vitro when APOBEC3G Cytidine Deaminase Forms Homotetramers and Higher-order Complexes*

    OpenAIRE

    McDougall, William M.; Okany, Chinelo; Smith, Harold C.

    2011-01-01

    APOBEC3G (A3G) is a cytidine deaminase that catalyzes deamination of deoxycytidine (dC) on single-stranded DNA (ssDNA). The oligomeric state of A3G required to support deaminase activity remains unknown. We show under defined in vitro conditions that full-length and native A3G formed complexes with ssDNA in an A3G concentration-dependent but temperature-independent manner. Complexes assembled and maintained at 4 °C did not have significant deaminase activity, but their enzymatic function coul...

  20. TRIM5 Acts as More Than a Retroviral Restriction Factor

    Directory of Open Access Journals (Sweden)

    Li Wu

    2011-07-01

    Full Text Available The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5α to its ability to restrict retrovirus infection. In a recent study, Pertel and colleagues have uncovered the link between the two, providing compelling evidence to suggest that following the interaction with the retroviral capsid, TRIM5 triggers an antiviral innate immune response by functioning as a pattern recognition receptor [1]. This unique function of TRIM5 is dependent on its association with the E2 ubiquitin-conjugating enzyme complex UBC13-UEV1A and subsequent activation of the TAK1 kinase complex and downstream genes involved in innate immune responses. These findings have defined a novel function for TRIM5 as a pattern recognition receptor in innate immune recognition and provided valuable mechanistic insight into its role as a retroviral restriction factor. Here we discuss the significance of these new findings in understanding TRIM5-mediated HIV restriction.

  1. TRIM5 acts as more than a retroviral restriction factor.

    Science.gov (United States)

    de Silva, Suresh; Wu, Li

    2011-07-01

    The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5α to its ability to restrict retrovirus infection. In a recent study, Pertel and colleagues have uncovered the link between the two, providing compelling evidence to suggest that following the interaction with the retroviral capsid, TRIM5 triggers an antiviral innate immune response by functioning as a pattern recognition receptor. This unique function of TRIM5 is dependent on its association with the E2 ubiquitin-conjugating enzyme complex UBC13-UEV1A and subsequent activation of the TAK1 kinase complex and downstream genes involved in innate immune responses. These findings have defined a novel function for TRIM5 as a pattern recognition receptor in innate immune recognition and provided valuable mechanistic insight into its role as a retroviral restriction factor. Here we discuss the significance of these new findings in understanding TRIM5-mediated HIV restriction. PMID:21866272

  2. APOBEC3A is implicated in a novel class of G-to-A mRNA editing in WT1 transcripts.

    Science.gov (United States)

    Niavarani, Ahmadreza; Currie, Erin; Reyal, Yasmin; Anjos-Afonso, Fernando; Horswell, Stuart; Griessinger, Emmanuel; Luis Sardina, Jose; Bonnet, Dominique

    2015-01-01

    Classic deamination mRNA changes, including cytidine to uridine (C-to-U) and adenosine to inosine (A-to-I), are important exceptions to the central dogma and lead to significant alterations in gene transcripts and products. Although there are a few reports of non-classic mRNA alterations, as yet there is no molecular explanation for these alternative changes. Wilms Tumor 1 (WT1) mutations and variants are implicated in several diseases, including Wilms tumor and acute myeloid leukemia (AML). We observed two alternative G-to-A changes, namely c.1303G>A and c.1586G>A in cDNA clones and found them to be recurrent in a series of 21 umbilical cord blood mononuclear cell (CBMC) samples studied. Two less conserved U-to-C changes were also observed. These alternative changes were found to be significantly higher in non-progenitor as compared to progenitor CBMCs, while they were found to be absent in a series of AML samples studied, indicating they are targeted, cell type-specific mRNA editing modifications. Since APOBEC/ADAR family members are implicated in RNA/DNA editing, we screened them by RNA-interference (RNAi) for WT1-mRNA changes and observed near complete reversal of WT1 c.1303G>A alteration upon APOBEC3A (A3A) knockdown. The role of A3A in mediating this change was confirmed by A3A overexpression in Fujioka cells, which led to a significant increase in WT1 c.1303G>A mRNA editing. Non-progenitor CBMCs showed correspondingly higher levels of A3A-mRNA and protein as compared to the progenitor ones. To our knowledge, this is the first report of mRNA modifying activity for an APOBEC3 protein and implicates A3A in a novel G-to-A form of editing. These findings open the way to further investigations into the mechanisms of other potential mRNA changes, which will help to redefine the RNA editing paradigm in both health and disease. PMID:25807502

  3. Growth restriction factor in Al-Si-Mg-Cu alloys

    International Nuclear Information System (INIS)

    The Growth Restriction Factor, Q, proved to be useful to analyse and control grain refinement during solidification of alloys. It is known that in multicomponent alloys a simple summation of the Qi values of the individual constituents taken from the binary phase diagrams can lead to grossly wrong results and that the ternary or higher-level phase diagram needs to be evaluated. This work demonstrates that the actual evaluation of Q using the liquidus gradient and partition coefficients of the multicomponent phase diagram requires some precautions and may be cumbersome. More importantly, this approach entirely fails if an intermetallic phase turns out to be the primary solidifying phase even in tiny amount. A very simple and general solution of this problem is illustrated for Al-Si-Mg-Cu alloys.

  4. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    Zalman, L S; Wood, L M; Frank, M M; Müller-Eberhard, H J

    1987-02-01

    The affected E of two patients with paroxysmal nocturnal hemoglobinuria (PNH) were enriched by lysing the unaffected, normal E with anti-human decay-accelerating factor (DAF) and guinea pig serum. The membranes of the unlysed, DAF-deficient cells (PNH-E) were dissolved and examined by SDS-PAGE and immunoblotting using an antiserum to homologous restriction factor (HRF). Whereas the 65 kD complement regulatory protein was readily detectable in the normal controls, it was completely lacking in both samples of PNH-E membranes. Functional studies likewise indicated the absence of HRF activity from PNH-E. When radiolabeled, isolated HRF protein was offered to PNH-E, it became firmly attached to the cell. Approximately 1,000 molecules of HRF per cell reduced the characteristic susceptibility of these cells to reactive lysis by C5b-9 to nearly normal levels. The results suggest that HRF, which is known to control the action of C8 and C9 on normal human E membranes, is deficient in PNH, as well as acetylcholinesterase and DAF. PMID:2434597

  5. Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35

    Directory of Open Access Journals (Sweden)

    Zhixin Zhang

    2013-07-01

    Full Text Available APOBEC3G(A3G is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication. The virally encoded protein Vif binds to A3G and induces its degradation, thereby counteracting the antiviral activity of A3G. Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development. Currently, there is an urgent need for understanding the three dimensional structure of full-length A3G. In this work, we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2 (APO2 and the catalytic domain structure of A3G. Two compounds, IMB26 and IMB35, which have been shown to bind to A3G and block degradation by Vif, were docked into the A3G model and the binding modes were generated for further analysis. The results may be used to design or optimize molecules targeting Vif–A3G interaction, and lead to the development of novel anti-HIV drugs.

  6. Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins.

    Science.gov (United States)

    Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

    2011-12-01

    Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex. PMID:21957297

  7. Deaminase Activity on Single-stranded DNA (ssDNA) Occurs in Vitro when APOBEC3G Cytidine Deaminase Forms Homotetramers and Higher-order Complexes*

    Science.gov (United States)

    McDougall, William M.; Okany, Chinelo; Smith, Harold C.

    2011-01-01

    APOBEC3G (A3G) is a cytidine deaminase that catalyzes deamination of deoxycytidine (dC) on single-stranded DNA (ssDNA). The oligomeric state of A3G required to support deaminase activity remains unknown. We show under defined in vitro conditions that full-length and native A3G formed complexes with ssDNA in an A3G concentration-dependent but temperature-independent manner. Complexes assembled and maintained at 4 °C did not have significant deaminase activity, but their enzymatic function could be restored by subsequent incubation at 37 °C. This approach enabled complexes of a defined size range to be isolated and subsequently evaluated for their contribution to enzymatic activity. The composition of A3G bound to ssDNA was determined by protein-protein chemical cross-linking. A3G-ssDNA complexes of 16 S were necessary for deaminase activity and consisted of cross-linked A3G homotetramers and homodimers. At lower concentrations, A3G only formed 5.8 S homodimers on ssDNA with low deaminase activity. Monomeric A3G was not identified in 5.8 S or 16 S complexes. We propose that deaminase-dependent antiviral activity of A3G in vivo may require a critical concentration of A3G in viral particles that will promote oligomerization on ssDNA during reverse transcription. PMID:21737457

  8. Restricting Factors at Modification of Parameters of Associative Engineering Objects

    Science.gov (United States)

    Horváth, László

    Advancements in product development have reached full integration of engineering activities and processes in product lifecycle management (PLM) systems. PLM systems are based on high-level modeling, simulation and data management. Despite significant development of modeling in PLM systems, a strong demand was recognized for improved decision assistance in product development. Decision assistance can be improved by application of methods from the area of computer intelligence. In order for a product development company to stay competitive, it is important for its modeling system to be relied on local even personal knowledge. The authors analyzed current PLM systems for shortcomings and possibilities for extended intelligence at decision-making during product development. They propose methods in order to increase suitability of current modeling systems to accommodate knowledge based IT at definition of sets of parameters of modeled objects and in the management of frequent changes of modeled objects. In the center of the proposed methodology, constrained parameters act as restricting factors at definition and modification of parameters of associative engineering objects. Paper starts with an outlook to modeling in current engineering systems and preliminary results by the authors. Following this, groups of essential information as handled by he proposed modeling are summarized and procedures for processing of that groups of information are detailed. Next, management of chains of changes along chains of associa-tive product objects and a new style of decision assistance in modeling systems are explained. Changes are created or verified by behavior analysis. Finally, behavior analysis, human intent combination, product data view creation, and change management are discussed as the proposed integrated and coordinated methodology for enhanced support of decision-making in product development.

  9. A Study of Evaluation System of Restricting Factors in Training Students' Qualities

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-yan

    2002-01-01

    This paper studies evaluation system of restricting factors in training students' qualities by modern mathematical method of analysis hierarchy process and principal factor analysis, and to build up a mathematical model of evaluation system.

  10. Instability restricts signaling of multiple fibroblast growth factors

    Czech Academy of Sciences Publication Activity Database

    Buchtová, Marcela; Chaloupková, R.; Zakrzewska, M.; Veselá, I.; Celá, Petra; Barathová, J.; Gudernová, I.; Zajíčková, R.; Trantírek, L.; Martin, J.; Kostas, M.; Otlewski, J.; Damborský, J.; Kozubík, Alois; Wiedlocha, A.; Krejčí, P.

    2015-01-01

    Roč. 72, č. 12 (2015), s. 2445-2459. ISSN 1420-682X R&D Projects: GA ČR(CZ) GA14-31540S; GA ČR GBP302/12/G157 Institutional support: RVO:67985904 ; RVO:68081707 Keywords : fibroblast growth factor * FGF * unstable Subject RIV: EA - Cell Biology Impact factor: 5.808, year: 2014

  11. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    OpenAIRE

    Wang, Ning; Liu, Fang

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization, industrialization, informationization and ecological development. In this process, it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method, this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then, it came up with countermeasures in cultivation objective ...

  12. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

    OpenAIRE

    Stremlau, Matthew; Perron, Michel; Lee, Mark; Li, Yuan; Song, Byeongwoon; Javanbakht, Hassan; Diaz-Griffero, Felipe; Anderson, Donovan J.; Sundquist, Wesley I.; Sodroski, Joseph

    2006-01-01

    The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30.2 domain. Human and New World monkey TRIM5α proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells...

  13. Automobile Driving in Older Adults: Factors Affecting Driving Restriction in Men and Women

    OpenAIRE

    MARIE-DIT-ASSE, Laetitia; Fabrigoule, Colette; Helmer, Catherine; Laumon, Bernard; Lafont, Sylviane

    2014-01-01

    OBJECTIVES: To identify factors associated with driving restriction in elderly men and women. DESIGN: Prospective cohort study of French drivers from 2003 to 2009. SETTING: The Three-City Cohort of Bordeaux, a prospective study of 2,104 people aged 65 and older. PARTICIPANTS: Five hundred twenty-three drivers with a mean age of 76 (273 male, 250 female). MEASUREMENTS: Sociodemographic characteristics, driving habits, health variables, cognitive evaluation and dementia diagnosis. Predementia w...

  14. Macrophage Migration Inhibitory Factor in Fetoplacental Tissues from Preeclamptic Pregnancies with or without Fetal Growth Restriction

    OpenAIRE

    Roberta Romagnoli; Tullia Todros; Ettore Piccoli; Alessandro Rolfo; Elena Vasario; Mario Castellucci; Francesca Ietta; Daniela Marzioni; Simona Cardaropoli; Luana Paulesu

    2012-01-01

    The proinflammatory cytokine MIF (macrophage migration inhibitory factor) is involved in physiological and pathological processes in pregnancy. MIF maternal serum levels are increased in preeclampsia (PE). We hypothesize that pregnancy tissues are the source of MIF overexpression in PE. MIF protein was studied in maternal sera, placental tissues, fetal membranes, and umbilical cord of 8 control and 20 PE pregnancies: 10 with normal fetal growth (PE-AGA) and 10 with fetal growth restriction (P...

  15. Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease

    Science.gov (United States)

    Wieck, Minna M.; Spurrier, Ryan G.; Levin, Daniel E.; Mojica, Salvador Garcia; Hiatt, Michael J.; Reddy, Raghava; Hou, Xiaogang; Navarro, Sonia; Lee, Jooeun; Lundin, Amber; Driscoll, Barbara; Grikscheit, Tracy C.

    2016-01-01

    Rationale Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function. Objectives To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function. Methods Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model. Measurements and Main Results Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes. Conclusions These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions. PMID:26863115

  16. Sequestration of Vascular Endothelial Growth Factor (VEGF Induces Late Restrictive Lung Disease.

    Directory of Open Access Journals (Sweden)

    Minna M Wieck

    Full Text Available Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF, which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1 were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.

  17. Quantification and control of restrictive ecological factors in acidogenic de-sulfate bioreactor

    Institute of Scientific and Technical Information of China (English)

    王爱杰; 任南琪

    2002-01-01

    As an artificial microbial ecosystem, acidogenic de-sulfate bioreactor has high efficiency of sulfate removal. The restrictive ecological factors, including causing ecological factors, such as COD/SO42- ratio and sulfate loading rate (Ns), and following ecological factors, such as pH value, oxidation reduction potential (ORP) and alkalinity (ALK) have significant effect on the ability and stability of acidogenic de-sulfate bio-reactor. Continuous flow and batch test were carried out to investigate the quantification and control of COD/SO42- ratio, Ns, pH value, ORP and ALK in acidogenic de-sulfate bioreactor supplied with molasses wastewater as sole organic carbon source and sodium sulfate as electron donor. It was demonstrated that In order to maintain high sulfate removal rate (SRR) of 80% to 90%, the restrictive factors should meet all the requirement as follows: kCOD/ SO42- ratio≥2.0, Ns≤7.5 kg (m3·d)-1,pH=5.7~6.2,ORP=-320~-420 mV and ALK=1 500~2 000 mg/L.

  18. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Directory of Open Access Journals (Sweden)

    Debrah A Fine

    Full Text Available The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

  19. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    Science.gov (United States)

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  20. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Science.gov (United States)

    Fine, Debrah A; Rozenblatt-Rosen, Orit; Padi, Megha; Korkhin, Anna; James, Robert L; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A; Hill, David E; Cusick, Michael E; Vidal, Marc; Florens, Laurence; Washburn, Michael P; Litovchick, Larisa; DeCaprio, James A

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  1. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    Institute of Scientific and Technical Information of China (English)

    Ning; WANG; Fang; LIU

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization,industrialization,informationization and ecological development. In this process,it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method,this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then,it came up with countermeasures in cultivation objective of rural vocational education,arrangement of specialized disciplines,key development tasks,and establishment of diversified investment system.

  2. Model identification with BPNN on restrictive ecological factors of SRB for sulfate-reduction

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The model of back-propagation neural network(BPNN)was presented to demonstrate the effect of restrictive ecological factors,COD/SO42-ratio,pH value,alkalinity(ALK)and SO42-loading rate(Ns),on sulfate-reduction of Sulfate Reducing Bacteria(SRB)in an acidogenic sulfate-reducing reactor supplied with molasses as sole organic carbon source and sodium sulfate as electron acceptor.The compare of experimental results and computer simulation was also discussed.It was shown that the method of BPNN had a powerful ability to analyze the ecological characteristic of acidogenic sulfate-reducing ecosystem quantitatively.

  3. Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats.

    Science.gov (United States)

    Crespo, Helena; Bertolotti, Luigi; Proffiti, Margherita; Cascio, Paolo; Cerruti, Fulvia; Acutis, Pier Luigi; de Andrés, Damián; Reina, Ramsés; Rosati, Sergio

    2016-08-30

    Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection. In this study, we analyse two goat populations within the same herd, harbouring low or high proviral SRLV loads respectively, both showing a robust antibody response. In vivo findings were confirmed in vitro since fibroblastic cell lines obtained from one high and one low proviral load representative goats, showed respectively a high and a faint production of virus upon infection with reference and field circulating SRLV strains. Differences in virus production were relieved when strain CAEV-Co was used for experimental infection. We analysed LTR promoter activity, proviral load, entry step and production of virus and viral proteins. Intriguingly, proteasomal activity was higher in fibroblasts from low proviral load animals and proteasome inhibition increased viral production in both cell lines, suggesting the implication of active proteasome-dependent restriction factors. Among them, we analysed relative expression and sequences of TRIM5α, APOBEC3 (Z1, Z2, Z3 and Z2-Z3) and BST-2 (Tetherin) and found a global antiviral status in low proviral carriers that may confer protection against viral shedding and disease onset. PMID:27527777

  4. Demand Forecasting at Low Aggregation Levels using Factored Conditional Restricted Boltzmann Machine

    DEFF Research Database (Denmark)

    Mocanu, Elena; Nguyen, Phuong H.; Gibescu, Madeleine;

    2016-01-01

    approaches have been proposed in the literature. As an evolution of neural network-based prediction methods, deep learning techniques are expected to increase the prediction accuracy by allowing stochastic formulations and bi-directional connections between neurons. In this paper, we investigate a newly...... developed deep learning model for time series prediction, namely Factored Conditional Restricted Boltzmann Machine (FCRBM), and extend it for electrical demand forecasting. The assessment is made on the EcoGrid dataset, originating from the Bornholm island experiment in Denmark, consisting of aggregated......The electrical demand forecasting problem can be regarded as a nonlinear time series prediction problem depending on many complex factors since it is required at various aggregation levels and at high temporal resolution. To solve this challenging problem, various time series and machine learning...

  5. Evolution of the antiretroviral restriction factor TRIMCyp in Old World primates.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Dietrich

    Full Text Available The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5-6 million years before present (ybp, likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species.

  6. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  7. Feed-borne Outbreak of Salmonella Cubana in Swedish Pig Farms: Risk Factors and Factors Affecting the Restriction Period in Infected Farms

    OpenAIRE

    Österberg J; Vågsholm I; Boqvist S; Lewerin S Sternberg

    2006-01-01

    In 2003, a feed-borne outbreak of Salmonella Cubana occurred in Sweden as a result of contamination in a feed plant. Salmonella Cubana was detected in 49 out of 77 pig farms having received possibly contaminated feed. In this study, potential risk factors for farms being salmonella positive were examined, and a survival analysis was performed to investigate risk factors affecting the restriction period for salmonella positive farms. The median restriction time for all 49 farms was 17 weeks. ...

  8. Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

    Institute of Scientific and Technical Information of China (English)

    Julie L Frey; David P Stonko; Marie-Claude Faugere; Ryan C Riddle

    2014-01-01

    The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of b-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

  9. Evaluation of Arable Land Reserve Resources and Analysis of Restrictive Factors: A Case Study of Hangjin Banner in Inner Mongolia

    Institute of Scientific and Technical Information of China (English)

    Xia; YANG; Xiangjun; YUN

    2015-01-01

    Taking land available for cultivation and mining land available for reclamation in Hangjin Banner of Inner Mongolia Autonomous Region,using land use database of 2012 as evaluation base,it made evaluation of arability of 677 021. 40 hm2 reserve land resources by the restrictive factor evaluation method. Besides,it analyzed main restrictive factors of arable land reserve resources in Hangjin Banner. Results indicate that the total area arable land reserve resources is 52 200. 02 hm2,accounting for 7. 71% of total area evaluated. Irrigation condition and soil thickness are major factors restricting development of arable land reserve resources in the study area. It is expected to provide reference for development of arable land reserve resources and land consolidation project in Hangjin Banner.

  10. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    Science.gov (United States)

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  11. Using restricted factor analysis with latent moderated structures to detect uniform and nonuniform measurement bias; a simulation study

    OpenAIRE

    Barendse, M. T.; Oort, F. J.; Garst, G.J.A.

    2010-01-01

    Factor analysis is an established technique for the detection of measurement bias. Multigroup factor analysis (MGFA) can detect both uniform and nonuniform bias. Restricted factor analysis (RFA) can also be used to detect measurement bias, albeit only uniform measurement bias. Latent moderated structural equations (LMS) enable the estimation of nonlinear interaction effects in structural equation modelling. By extending the RFA method with LMS, the RFA method should be suited to detect nonuni...

  12. Is abnormal vaginal microflora a risk factor for intrauterine fetal growth restriction?

    Institute of Scientific and Technical Information of China (English)

    NatalijaVedmedovska; Dace Rezeberga; GilbertG G Donders

    2015-01-01

    Objective:To conduct a literature review in search of possible preventable causes for fetal growth restriction.Methods:We performed a systematic literature search regarding abnormal vaginal microflora and fetal growth encompassing the last 27-year (starting from 1986) in PubMed, Embase, and Cochrane Central to study the evidence that abnormal vaginal microflora is may be related to diminished fetal growth or small for date birth.Results:Most of the 14 studies suggested a significant role of vaginal organisms in impaired fetal growth, unrelated to preterm birth. The neonatal outcome has shown to be largely linked to the preventable or foreseeable fetal factors, such as genetic abnormalities, but also ascending intrauterine infections. Our previous work suggested a role of vaginal organisms in adverse pregnancy outcome, not only preterm birth, but also impaired fetal growth.Conclusions:There is a need for cohort studies designed to unravel this link between abnormal microflora and FGR, in order to enable preventive actions to protect these small babies from severe damage and death by early screening and treatment.

  13. Intrauterine growth restriction: distribution, risk factors, management of labour and outcome

    Directory of Open Access Journals (Sweden)

    Diana Andzane

    2015-08-01

    Full Text Available Background: The development of Intrauterine growth restriction (IUGR determines maternal, fetal and placental factors. Many of these factors are preventable. There is still no enough developed effective pregnancy and labour management tactics that could protect both mother and child from the unintended consequences. Methods: The research was made in Riga Maternity Hospital. In the research there were included pregnant women who gave birth neonates with weight under 10th percentile (IUGR group as well there was compiled the control group. The weight of neonates was evaluated using the percentile scales - Intrauterine Growth Curves based on US data. Results: According to the criteria, in the IUGR group were included 209 pregnant women and in the control group was the same number of patients. In the IUGR group mothers discharged from the hospital one day later than it was in the control group both after vaginal delivery (4.0 +/- 1.5 vs. 3.3 +/- 1.0, p and #706;0.0001 and after caesarean (5.6 +/- 1.5 vs. 4.5 +/- 1.0, p=0.0001. Comparing the evaluations after Apgar scale after spontaneous birth, induced labour and caesarean it was discovered that there is no statistically significant difference. Conclusions: IUGR negatively affect not just the fetus but also the mother and this is the reason why she should stay in the hospital for a longer period due to the child or experience the caesarean. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1117-1121

  14. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

    Science.gov (United States)

    Bristol, Sarah K; Woodruff, Teresa K

    2004-03-01

    Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2

  15. KAP1 is a host restriction factor that promotes HAdV E1B-55K SUMO modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia; Kieweg, Lisa; Müncheberg, Sarah; Dobner, Thomas; Schreiner, Sabrina

    2016-01-01

    minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. IMPORTANCE: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin...

  16. BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection

    OpenAIRE

    Lee, Song Hee; Kalejta, Robert F; Kerry, Julie; Semmes, Oliver John; O’Connor, Christine M.; Khan, Zia; Garcia, Benjamin A.; Shenk, Thomas; Murphy, Eain

    2012-01-01

    Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regula...

  17. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signalling in the mouse hypothalamus

    OpenAIRE

    AntonioGiordano; SaverioCinti

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  18. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus

    OpenAIRE

    Severi, Ilenia; Perugini, Jessica; Mondini, Eleonora; Smorlesi, Arianna; Frontini, Andrea; Cinti, Saverio; Giordano, Antonio

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  19. Retroviral restriction factors TRIM5α: therapeutic strategy to inhibit HIV-1 replication.

    Science.gov (United States)

    Zhang, Jing; Ge, Weiying; Zhan, Peng; De Clercq, Erik; Liu, Xinyong

    2011-01-01

    Tripartite motif protein 5-alpha (TRIM5α) is a cytoplasmic protein that efficiently recognizes the incoming capsid (CA) protein of retroviruses and potently inhibits virus infection in a species-specific manner. Through directly recognizing and interacting with HIV CA, TRIM5α is capable of disrupting the ordered process of viral uncoating, eventually interfering with HIV-1 reverse transcription and virus replication. TRIM5α protein contains four domains: RING domain, B-box 2 domain, coiled-coil domain, and B30.2 domain (SPRY) domain. All of the domains are necessary for efficient retrovirus restriction and the B30.2 domain has been shown to be the determinant of the specificity of restriction. Species-specific innate resistance against viral infections offers novel avenues for antiviral therapeutics. Various mutants of TRIM5α have been described which differently affect the HIV-1 reverse transcription process. This makes the establishment of new and improved models for HIV replication and AIDS pathogenesis by monitoring endogenous TRIM5α an attractive approach. TRIM5α-mediated restriction is modulated by the host protein Cyclophilin A (Cyp A) which could effectively interact with the CA of HIV-1. Here we will review the structure and roles of TRIM5α protein, the interaction between Cyp A and TRIM5α, as well as gene therapy strategies associated with TRIM5α to inhibit HIV-1 infection. PMID:21568899

  20. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

    Science.gov (United States)

    Landolfo, Santo; De Andrea, Marco; Dell’Oste, Valentina; Gugliesi, Francesca

    2016-01-01

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed “restriction factors” (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell’s intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  1. Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Sarah L Londrigan

    Full Text Available BST-2 (tetherin, CD317, HM1.24 restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV is controversial. Here, we assessed the capacity of endogenous BST-2 to restrict IAV in primary murine cells. IAV infection increased BST-2 surface expression by primary macrophages, but not alveolar epithelial cells (AEC. BST-2-deficient AEC and macrophages displayed no difference in susceptibility to IAV infection relative to wild type cells. Furthermore, BST-2 played little role in infectious IAV release from either AEC or macrophages. To examine BST-2 during IAV infection in vivo, we infected BST-2-deficient mice. No difference in weight loss or in viral loads in the lungs and/or nasal tissues were detected between BST-2-deficient and wild type animals. This study rules out a major role for endogenous BST-2 in modulating IAV in the mouse model of infection.

  2. Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression

    International Nuclear Information System (INIS)

    Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity

  3. Feed-borne Outbreak of Salmonella Cubana in Swedish Pig Farms: Risk Factors and Factors Affecting the Restriction Period in Infected Farms

    Directory of Open Access Journals (Sweden)

    Österberg J

    2006-03-01

    Full Text Available In 2003, a feed-borne outbreak of Salmonella Cubana occurred in Sweden as a result of contamination in a feed plant. Salmonella Cubana was detected in 49 out of 77 pig farms having received possibly contaminated feed. In this study, potential risk factors for farms being salmonella positive were examined, and a survival analysis was performed to investigate risk factors affecting the restriction period for salmonella positive farms. The median restriction time for all 49 farms was 17 weeks. An increased risk for farms being salmonella infected (positive in feed and/or faeces was seen for fattening farms and farms feeding soy. The survival analysis showed that herds with a low level of infection and farms with a high hygiene level had shorter restriction times. This study is unique as it investigates a real outbreak of feed-borne salmonella, where the source of infection was reliably identified, the period of exposure could be defined and data were collected from all exposed farms.

  4. On the Restricting Factors & System Arrangements of Chinese Land Tenure Marketization

    Institute of Scientific and Technical Information of China (English)

    YU Peng-yi; ZHANG Wei-dong

    2003-01-01

    As a general rule of Economics of Development,economic growth and development require rational institution guarantee.Land Tenure.As a main institution factor in agricultural development,closely relates to the reform of Chinese agriculture.Based on the relevant theories of Economics of Institution and Economics of Development,and combined with the marketization process of Chinese Land Tenure of Property Rights,the article studied the effects of institutional factors and put forward some choices in the development of agriculture,which is of both significant and practical importance.

  5. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  6. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  7. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus.

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  8. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  9. Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF can regulate HSV-1 immediate-early transcription via histone modification

    Directory of Open Access Journals (Sweden)

    Hill James M

    2007-06-01

    Full Text Available Abstract Background During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1 establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (REST/NRSF regulates expression of ICP22 and ICP4. Results Transient cotransfection indicated that REST/NRSF inhibited the activity of both promoters. In contrast, cotransfection of a mutant form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in less inhibition. Stably transformed cell lines containing episomal reporter plasmids with a chromatin structure showed that REST/NRSF specifically inhibited the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4 promoter was reversed by histone deacetylase (HDAC inhibitor Trichostatin A (TSA. Additionally, chromatin immuno-precipitation (ChIP assays indicated that the corepressor CoREST was recruited to the proximity of ICP4 promoter and that acetylation of histone H4 was reduced in the presence of REST/NRSF. Conclusion Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression.

  10. CryoEM analysis of capsid assembly and structural changes upon interactions with a host restriction factor, TRIM5α.

    Science.gov (United States)

    Zhao, Gongpu; Zhang, Peijun

    2014-01-01

    After virus fusion with a target cell, the viral core is released into the host cell cytoplasm and undergoes a controlled disassembly process, termed uncoating, before or as reverse transcription takes place. The cellular protein TRIM5α is a host cell restriction factor that blocks HIV-1 infection in rhesus macaque cells by targeting the viral capsid and inducing premature uncoating. The molecular mechanism of the interaction between capsid and TRIM5α remains unclear. Here, we describe an approach that utilizes cryo-electron microscopy (cryoEM) to examine the structural changes exerted on HIV-1 capsid (CA) assembly by TRIM5α binding. The TRIM5α interaction sites on CA assembly were further dissected by combining cryoEM with pair-wise cysteine mutations that crosslink CA either within a CA hexamer or between CA hexamers. Based on the structural information from cryoEM and crosslinking results from in vitro CA assemblies and purified intact HIV-1 cores, we demonstrate that direct binding of TRIM5α CC-SPRY domains to the viral capsid results in disruption and fragmentation of the surface lattice of HIV-1 capsid, specifically at inter-hexamer interfaces. The method described here can be easily adopted to study other important interactions in multi-protein complexes. PMID:24158810

  11. Dopaminergic and brain-derived neurotrophic factor signalling in inbred mice exposed to a restricted feeding schedule.

    Science.gov (United States)

    Gelegen, C; van den Heuvel, J; Collier, D A; Campbell, I C; Oppelaar, H; Hessel, E; Kas, M J H

    2008-07-01

    Increased physical activity and decreased motivation to eat are common features in anorexia nervosa. We investigated the development of these features and the potential implication of brain-derived neurotrophic factor (BDNF) and dopaminergic signalling in their development in C57BL/6J and A/J inbred mice, using the 'activity-based anorexia' model. In this model, mice on a restricted-feeding schedule are given unlimited access to running wheels. We measured dopamine receptor D2 and BDNF expression levels in the caudate putamen and the hippocampus, respectively, using in situ hybridization. We found that in response to scheduled feeding, C57BL/6J mice reduced their running wheel activity and displayed food anticipatory activity prior to food intake from day 2 of scheduled feeding as an indication of motivation to eat. In contrast, A/J mice increased running wheel activity during scheduled feeding and lacked food anticipatory activity. These were accompanied by increased dopamine receptor D2 expression in the caudate putamen and reduced BDNF expression in the hippocampus. Consistent with human linkage and association studies on BDNF and dopamine receptor D2 in anorexia nervosa, our study shows that dopaminergic and BDNF signalling are altered as a function of susceptibility to activity-based anorexia. Differences in gene expression and behaviour between A/J and C57BL/6J mice indicate that mouse genetic mapping populations based on these progenitor lines are valuable for identifying molecular determinants of anorexia-related traits. PMID:18363853

  12. Caloric restriction.

    Science.gov (United States)

    Speakman, John R; Mitchell, Sharon E

    2011-06-01

    generalized shift from carbohydrate to fat metabolism. Four pathways have been implicated in mediating the CR effect. These are the insulin like growth factor (IGF-1)/insulin signaling pathway, the sirtuin pathway, the adenosine monophosphate (AMP) activated protein kinase (AMPK) pathway and the target of rapamycin (TOR) pathway. These different pathways may interact and may all play important roles mediating different aspects of the response. Exactly how they generate the health benefits remains open for debate, however CR results in reduced oxidative stress and enhanced autophagy, both of which could be essential components of the beneficial effects. Most data about the effects of CR in mammals comes from work on rodents. There is limited work on non-human primates that shows promising effects and one randomized controlled trial in humans where physiological markers of the CR response are consistent with the responses in mice and rats. There are also populations of humans voluntarily restricting themselves. Humans on long term restriction report similar negative side effects to those observed in animals - perpetual hunger, reduced body temperature leading to a feeling of being cold, and diminished libido. Considerable effort has been directed in recent years to find drugs that mimic the CR response. Promising candidates are those that intersect with the critical signaling pathways identified above and include biguanides such as metformin that target the insulin signaling pathway, stilbenes (e.g. resveratrol) that affect sirtuin activity and drugs such as rapamycin that interact with mTOR signaling. Whether it will ever be possible to find drugs that capture the health benefits of CR without the negative side-effects remains unclear. Moreover, even if such drugs are developed how the current licensing system for drug use in western societies would cope with them may be a further obstacle to their use. PMID:21840335

  13. Restrictive cardiomyopathy

    Science.gov (United States)

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy ... In a case of restrictive cardiomyopathy, the heart muscle is normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does not ...

  14. Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo

    OpenAIRE

    Paquette, Alice J.; Perez, Sharon E.; Anderson, David J.

    2000-01-01

    The neuron-restrictive silencer factor (NRSF; also known as REST for repressor element-1 silencing transcription factor) is a transcriptional repressor of multiple neuronal genes, but little is known about its function in vivo. NRSF is normally down-regulated upon neuronal differentiation. Constitutive expression of NRSF in the developing spinal cord of chicken embryos caused repression of two endogenous target genes, N-tubulin and Ng-CAM, but did not prevent overt...

  15. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signalling in the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    AntonioGiordano

    2013-12-01

    Full Text Available In the mouse hypothalamus, ciliary neurotrophic factor (CNTF is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD, of ob/ob obese mice, and of mice fed a calorie restriction (CR regimen. RT-PCR showed that CNTF mRNA increased significantly in HFD mice and decreased significantly in CR animals. Western blotting confirmed that CNTF expression was higher in HFD mice and reduced in CR mice, but high interindividual variability blunted the significance of these differences. By immunohistochemistry, hypothalamic tuberal and mammillary region tanycytes stained strongly for CNTF in HFD mice, whereas CR mice exhibited markedly reduced staining. RT-PCR and Western blotting disclosed that changes in CNTF expression were paralleled by changes in the expression of its specific receptor, CNTF receptor α (CNTFRα. Injection of recombinant CNTF and detection of phospho-signal transducer and activator of transcription 3 (P-STAT3 showed that CNTF responsiveness by the ependymal layer, mainly by tanycytes, was higher in HFD than CR mice. In addition, in HFD mice CNTF administration induced distinctive STAT3 signalling in a large neuron population located in the dorsomedial and ventromedial nuclei, perifornical area and mammillary body. The hypothalamic expression of CNTF and CNTFRα did not change in the hyperphagic, leptin-deficient ob/ob obese mice; accordingly, P-STAT3 immunoreactivity in CNTF-treated ob/ob mice was confined to ependymal layer and arcuate neurons. Collectively, these data suggest that hypothalamic CNTF is involved in controlling the energy balance and that CNTF signalling plays a role in HFD obese mice at specific sites.

  16. In vitro and in vivo analyses of a genetically—restricted antigen specific factor from mixed cell cultures of macrophage,T and B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    CHAURMW; LAUASK

    1990-01-01

    An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

  17. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

    OpenAIRE

    Lees, Emma K.; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W.; Delibegovic, Mirela

    2014-01-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) o...

  18. Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice

    NARCIS (Netherlands)

    Norren, van K.; Rusli, F.; Dijk, van M.; Lute, C.; Nagel, J.C.; Dijk, F.J.; Dwarkasing, J.T.; Boekschoten, M.V.; Luiking, Y.; Witkamp, R.F.; Müller, M.R.; Steegenga, W.T.

    2015-01-01

    Background - In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of

  19. 农村群众体育活动的制约因素发展对策%Study on Restricting Factors of Rural Mass Sports

    Institute of Scientific and Technical Information of China (English)

    高小爱; 陈巧弟

    2011-01-01

    采用问卷调查法,数理统计法等分析研究,认为制约农村群众体育活动的因素主要有:经济因素、社会因素、农民自身因素及自然环境因素。针对这些因素,提出相应的发展对策与建议。%Through using the method of literature review and mathematical statistics,this paper finds out the factors restricting the rural mass sports development including economic factors,social factors,natural factors and farmer factors.Based on existing factors

  20. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

    Science.gov (United States)

    Lees, Emma K; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W; Delibegovic, Mirela

    2014-10-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. PMID:24935677

  1. 甘孜州畜牧业发展的制约因素及对策%Restrictive Factors and Countermeasures of Animal Husbandry Development in Ganzi Prefecture

    Institute of Scientific and Technical Information of China (English)

    邓竹佳

    2012-01-01

    介绍了甘孜州畜牧业发展的优势,分析了其发展畜牧业的制约因素,并提出了相应的对策,以供参考。%The advantages of animal husbandry development were introduced,the restrictive factors of animal husbandry development were analyzed.Countermeasures were proposed for reference.

  2. Restricted Airspace

    Data.gov (United States)

    Federal Laboratory Consortium — Redstone Technical Test Center has restricted airspace up to 30,000 feet ASL. Airspace encompasses R-2104 (Redstone). Airspace is used extensively for airborne/UAV...

  3. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene.

    OpenAIRE

    Ho, I C; Vorhees, P; Marin, N; Oakley, B K; Tsai, S F; Orkin, S H; Leiden, J. M.

    1991-01-01

    In addition to its role in the recognition of foreign antigens, the T cell receptor (TCR) alpha gene serves as a model system for studies of developmentally-regulated, lineage-specific gene expression in T cells. TCR alpha gene expression is restricted to cells of the TCR alpha/beta+ lineage, and is controlled by a T cell-specific transcriptional enhancer located 4.5 kb 3' to the C alpha gene segment. The TCR alpha enhancer contains four nuclear protein binding sites called T alpha 1-T alpha ...

  4. The surprising activities of APOBEC3B and 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Emma L Walton

    2015-04-01

    Full Text Available In this mini-special issue on cancer, we learn how DNA editing enzymes can accelerate the development of cancer and we discover some remarkable effects of the chemotherapeutic agent, 5-fluorouracil, on the immune system. We also discuss a study revealing the continuing problem of vitamin B deficiencies in children in developing countries, and we determine how to distinguish two near-identical forms of necrotizing fasciitis.

  5. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

    Directory of Open Access Journals (Sweden)

    Kroeger Cynthia M

    2012-10-01

    Full Text Available Abstract Background The ability of an intermittent fasting (IF-calorie restriction (CR regimen (with or without liquid meals to modulate adipokines in a way that is protective against coronary heart disease (CHD has yet to be tested. Objective Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women. Methods Subjects (n = 54 were randomized to either the IFCR-liquid (IFCR-L or IFCR-food based (IFCR-F diet for 10 weeks. Results Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm. Similar reductions (P Conclusion These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

  6. Differential binding of the Bombyx silk gland-specific factor SGFB to its target DNA sequence drives posterior-cell-restricted expression.

    OpenAIRE

    Horard, B; Julien, E; Nony, P; Garel, A; Couble, P

    1997-01-01

    The gene encoding the silk protein P25 in Bombyx mori is expressed in the posterior silk gland (PSG) cells and repressed in the middle silk gland (MSG) cells. To identify the factors involved in this transcription-dependent spatial restriction, we examined the P25 chromatin in PSG and MSG nuclei by DNase I-aided ligation-mediated PCR and analyzed the expression of various P25-lacZ constructs in biolistically treated silk glands. P25 promoter activation depends on two cis-acting elements. One ...

  7. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction.

    Science.gov (United States)

    Watson, Carole S; Bialek, Peter; Anzo, Makoto; Khosravi, Javad; Yee, Siu-Pok; Han, Victor K M

    2006-03-01

    IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs. Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal growth restriction (FGR). To establish a causal relationship between high circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP-1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474 +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g compared with 1.62 +/- 0.04 g for wild type (WT); P catch-up growth. The placentas of the AFP-BP1 mice were larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT at E16.5; P catch-up growth. Overall, these data clearly demonstrate that high concentrations of circulating IGFBP-1 are sufficient to cause FGR. PMID:16293667

  8. Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

    Institute of Scientific and Technical Information of China (English)

    In(ě)s Tomada; Nuno Tomada; Henrique Almeida; Delminda Neves

    2012-01-01

    The purpose of the current study was to evaluate the effect of a high-fat (HF) diet,energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF),angiopoietin (Ang) 1 and 2,and their receptors in rat corpus cavernosum (CC).Male Wistar rats were fed adlibitum with an HF diet for 8 or 16 weeks.After 8 weeks of the HF diet,a group of rats was subjected to energy restriction with or without exercise for 8 weeks.Control animals had free access to standard diet for the same period.After euthanasia,blood was collected and the penises removed for immunofluorescence assays (VEGF,VEGF receptor (VEGFR) 1 and 2,Ang1,Ang2 and Tie2) and semiquantification of VEGF,VEGFR1,VEGFR2,Ang1,Ang2,Tie2,endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting.HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels,higher systolic blood pressure and an increased atherogenic index.A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs.The Akt pathway was activated by the HF diet.Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression.These results emphasize the role of diet on vascular function regulation,demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/rie2 systems occurs before serum lipid changes and obesity onset,antedating structural atherosclerotic features.

  9. The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

    Directory of Open Access Journals (Sweden)

    Jyh-Ming Liou

    Full Text Available The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.The defined daily dose (DDD of antibiotics was analyzed using the Taiwan National Health Insurance (NHI research database. H. pylori strains isolated from treatment naïve (N=1395 and failure from prior eradication therapies (N=360 from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001. The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001, which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

  10. Hepatic insulin-like growth-factor binding protein (igfbp) responses to food restriction in Atlantic salmon smolts.

    Science.gov (United States)

    Breves, Jason P; Phipps-Costin, Silas K; Fujimoto, Chelsea K; Einarsdottir, Ingibjörg E; Regish, Amy M; Björnsson, Björn Thrandur; McCormick, Stephen D

    2016-07-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon (Salmo salar). Fish were fasted for 3 or 10days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3days and condition factor by 10days. Plasma Gh, cortisol, and thyroxine (T4) were not altered in response to fasting, whereas Igf1 and 3,5,3'-triiodo-l-thyronine (T3) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1, -1b2, -2a, -2b1 and -2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10days of fasting. Fasting did not alter hepatic igf1 or igf2; however, muscle igf1 was diminished by 10days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na(+)/K(+)-ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism. PMID:27210270

  11. Hepatic insulin-like growth-factor binding protein (igfbp) responses tofood restriction in Atlantic salmon smolts

    Science.gov (United States)

    Breves, Jason P.; Phipps-Costin, Silas K.; Fujimoto, Chelsea K.; Einarsdottir, Ingibjörg E.; Regish, Amy M.; Björnsson, Björn Thrandur; McCormick, Stephen

    2016-01-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon ( Salmo salar ). Fish were fasted for 3 or 10 days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3 days and condition factor by 10 days. Plasma Gh, cortisol, and thyroxine (T 4 ) were not altered in response to fasting, whereas Igf1 and 3,5,3′-triiodo- l -thyronine (T 3 ) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1 , - 1b2 , - 2a , - 2b1 and - 2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10 days of fasting. Fasting did not alter hepatic igf1or igf2 ; however, muscle igf1 was diminished by 10 days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na + /K + -ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism.

  12. Study on the Factors Restricting the Development of Rural Specialized Cooperatives%农村专业合作社发展制约因素研究

    Institute of Scientific and Technical Information of China (English)

    张建宁

    2012-01-01

    As an organization carrier of new rural economic order, the rural specialized cooperatives could not only promote the development of rural economic, but could also play a positive role in standardization of rural social management. Factors restricting the development of rural specialized cooperatives were analyzed; and suggestions were proposed accordingly, which could help improving and solving problems of agriculture, rural areas and farmers.%农村专业合作社作为农村经济新秩序中的一个组织载体,不仅能推动农村经济的繁荣发展,而且对农村的社会管理也有规范作用.分析制约农村专业合作社发展的因素,提出建议,对改进并解决“三农”问题具有现实意义.

  13. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T; Breum, Leif; Christiansen, J S; Hilsted, J

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated by...... anthropometric computed tomography (CT)-calibrated equations. In females, IGF-1 was inversely associated with the abdominal sagittal diameter (SagD) and with the visceral AT (r = -.41, P = .006). No significant correlations were found between IGF-1 and BMI or other indices of adiposity. Weight loss caused a...

  14. Phloem restriction of viroids in three citrus hosts is overcome by grafting with Etrog citron: potential involvement of a translocatable factor.

    Science.gov (United States)

    Bani-Hashemian, Seyed Mehdi; Pensabene-Bellavia, Giovanni; Duran-Vila, Nuria; Serra, Pedro

    2015-08-01

    Viroid systemic spread involves cell-to-cell movement from initially infected cells via plasmodesmata, long-distance movement within the phloem and again cell-to-cell movement to invade distal tissues including the mesophyll. Citrus exocortis viroid (CEVd), hop stunt viroid, citrus bent leaf viroid, citrus dwarfing viroid, citrus bark cracking viroid and citrus viroid V remained phloem restricted when singly infecting Citrus karna, Citrus aurantium and Poncirus trifoliata, but not Etrog citron, where they were additionally detected in mesophyll protoplasts. However, when CEVd-infected C. karna was side-grafted with Etrog citron--with the resulting plants being composed of a C. karna stock and an Etrog citron branch--the viroid was detected in mesophyll protoplasts of the former, thus indicating that the ability of Etrog citron to support viroid invasion of non-vascular tissues was transferred to the stock. Further results suggest that a translocatable factor from Etrog citron mediates this viroid trafficking. PMID:25888624

  15. Calorie restriction and stroke

    Directory of Open Access Journals (Sweden)

    Manzanero Silvia

    2011-09-01

    Full Text Available Abstract Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR or intermittent fasting (IF, extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF and basic fibroblast growth factor (bFGF; protein chaperones, including heat shock protein 70 (Hsp70 and glucose regulated protein 78 (GRP78; antioxidant enzymes, such as superoxide dismutases (SOD and heme oxygenase-1 (HO-1, silent information regulator T1 (SIRT1, uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.

  16. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

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

  17. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  18. Detection of Polymorphism at the Insulin Like Growth Factor-I Gene in Mazandaran Native Chicken using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Method

    Directory of Open Access Journals (Sweden)

    Hossein A. Abbasi

    2011-01-01

    Full Text Available Problem statement: Molecular genetics selection on individual genes is a promising method to genetically improve economically important traits in chickens. The Insulin like Growth Factor-I (IGF1 gene may play important roles in growth of multiple tissues, including muscle cells, cartilage and bone. Approach: In the present study polymorphism of the promoter and 5' untranslated region of IGF-1 gene of Mazandaran native fowls was investigated. In order to evaluate the IGF-1 gene polymorphism we have used a Restriction Fragment Length Polymorphism (RFLP method. Blood samples were collected from randomly chosen 100 Mazandaran native fowls. Genomic DNA was extracted using modified salting-out method and used amplified polymerase chain reaction technique. The promoter and 5' untranslated region of the fowl IGF-1 gene was amplified to produce a 621 bp fragment. The PCR products were electrophoresed on 2.5% agarose gel and stained by etidium bromide. Results: Then, they were digested of amplicon with PstI and revealed two alleles A and B. Data were analyzed using Pop Gene 32 package. In this population, AA, AB, BB genotype have been identified with the 25.88, 50.23, 23.89% frequencies. A and B alleles frequencies were 0.51, 0.49, respectively. The Chi-square (÷2 test was significant and the population was in Hardy-Weinberg equilibrium (pConclusion: The PCR technique amplified a DNA fragment of IGF-1 with 621 bp. The results of the RFLP analysis showed two fragment 257 and 354bp after restriction with enzyme with PstI that identify changes in 5' untranslated region. In according to action modes and importance of IGF-1, its polymorphisms can be related to economical traits such as body weight, muscle cells and bone.

  19. Evaluation of udder health parameters and risk factors for clinical mastitis in Dutch dairy herds in the context of a restricted antimicrobial usage policy.

    Science.gov (United States)

    Santman-Berends, I M G A; Swinkels, J M; Lam, T J G M; Keurentjes, J; van Schaik, G

    2016-04-01

    study indicated that udder health had not deteriorated compared with udder health in previous Dutch studies where herd sizes were somewhat smaller and before the restrictions in antimicrobial use. Several of the risk factors that were found can be influenced by the farmer and can prevent the occurrence of CMI. Still, when cases of CM occur, treatment with antimicrobials might be necessary to cure the CM case and is beneficial for the overall udder health in the herd. PMID:26874413

  20. A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication.

    Science.gov (United States)

    McKinney, Caleb; Yu, Dong; Mohr, Ian

    2013-08-15

    The capacity of polyadenylate-binding protein PABPC1 (PABP1) to stimulate translation is regulated by its repressor, Paip2. Paradoxically, while PABP accumulation promotes human cytomegalovirus (HCMV) protein synthesis, we show that this is accompanied by an analogous increase in the abundance of Paip2 and EDD1, an E3 ubiquitin ligase that destabilizes Paip2. Coordinate control of PABP1, Paip2, and EDD1 required the virus-encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1. Paip2 synthesis also increased following serum stimulation of uninfected normal fibroblasts, suggesting that this coregulation may play a role in how uninfected cells respond to stress. Significantly, Paip2 accumulation was dependent on PABP accrual, as preventing PABP1 accumulation suppressed viral replication and inhibited the corresponding Paip2 increase. Furthermore, depleting Paip2 restored the ability of infected cells to assemble the translation initiation factor eIF4F, promoting viral protein synthesis and replication without increasing PABP1. This establishes a new role for the cellular PABP1 inhibitor Paip2 as an innate defense that restricts viral protein synthesis and replication. Moreover, it illustrates how a stress-induced rise in PABP1 triggered by virus infection can counter and surpass a corresponding increase in Paip2 abundance and stability. PMID:23964095

  1. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  2. The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia

    NARCIS (Netherlands)

    Faassen, A. van; Ploeg, E.M.C. van der; Habets, H.M.L.; Meer, R. van der; Hermus, R.J.J.; Janknegt, R.A.

    1998-01-01

    The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-r

  3. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

    Directory of Open Access Journals (Sweden)

    Susan E Olivo-Marston

    Full Text Available Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO would increase (and CR would decrease colon tumorigenesis in the mouse azoxymethane (AOM model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1 control diet; 2 30% CR diet; or 3 DIO diet. Mice were euthanized at week 5 (n = 12/group, 10 (n = 12/group, and 20 (n = 20/group after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1, IGF binding protein 3 (IGFBP-3, adipokines, proliferation, apoptosis, and expression of microRNAs (miRs were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat, while CR induced a lean phenotype (∼14% body fat; controls were intermediate (∼26% body fat. Relative to controls, DIO increased (and CR decreased the number of colon tumors (p = 0.01, cytokines (p<0.001, IGF-1 (p = 0.01, and proliferation (p<0.001. DIO decreased (and CR increased IGFBP-3 and apoptosis (p<0.001. miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs.

  4. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney

    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  5. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    Science.gov (United States)

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  6. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  7. Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

    OpenAIRE

    Dapp, Michael J.; Bonnac, Laurent; Patterson, Steven E.; Louis M Mansky

    2014-01-01

    Reverse transcription is an important early step in retrovirus replication and is a key point targeted by evolutionarily conserved host restriction factors (e.g., APOBEC3G, SamHD1). Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target of antiretroviral drugs, and concerns regarding drug resistance and off-target effects have led to continued efforts for identifying novel approaches to targeting HIV-1 RT. Several observations, including those obtained from m...

  8. Achieving Salt Restriction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Emma J. McMahon

    2012-01-01

    Full Text Available There is consistent evidence linking excessive dietary sodium intake to risk factors for cardiovascular disease and chronic kidney disease (CKD progression in CKD patients; however, additional research is needed. In research trials and clinical practice, implementing and monitoring sodium intake present significant challenges. Epidemiological studies have shown that sodium intake remains high, and intervention studies have reported varied success with participant adherence to a sodium-restricted diet. Examining barriers to sodium restriction, as well as factors that predict adherence to a low sodium diet, can aid researchers and clinicians in implementing a sodium-restricted diet. In this paper, we critically review methods for measuring sodium intake with a specific focus on CKD patients, appraise dietary adherence, and factors that have optimized sodium restriction in key research trials and discuss barriers to sodium restriction and factors that must be considered when recommending a sodium-restricted diet.

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

    Science.gov (United States)

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

    2009-01-01

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

  10. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

    OpenAIRE

    Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

    2009-01-01

    Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholi...

  11. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  12. Selectional Restrictions in HPSG

    OpenAIRE

    Androutsopoulos, Ion; Dale, Robert

    2000-01-01

    Selectional restrictions are semantic sortal constraints imposed on the participants of linguistic constructions to capture contextually-dependent constraints on interpretation. Despite their limitations, selectional restrictions have proven very useful in natural language applications, where they have been used frequently in word sense disambiguation, syntactic disambiguation, and anaphora resolution. Given their practical value, we explore two methods to incorporate selectional restrictions...

  13. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  14. Massively parallel characterization of restriction endonucleases

    OpenAIRE

    Kamps-Hughes, Nick; Quimby, Aine; Zhu, Zhenyu; Johnson, Eric A.

    2013-01-01

    Restriction endonucleases are highly specific in recognizing the particular DNA sequence they act on. However, their activity is affected by sequence context, enzyme concentration and buffer composition. Changes in these factors may lead to either ineffective cleavage at the cognate restriction site or relaxed specificity allowing cleavage of degenerate ‘star’ sites. Additionally, uncharacterized restriction endonucleases and engineered variants present novel activities. Traditionally, restri...

  15. SAMHD1, the Aicardi-Goutières syndrome gene and retroviral restriction factor, is a phosphorolytic ribonuclease rather than a hydrolytic ribonuclease.

    Science.gov (United States)

    Ryoo, Jeongmin; Hwang, Sung-Yeon; Choi, Jongsu; Oh, Changhoon; Ahn, Kwangseog

    2016-09-01

    SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1. PMID:27387229

  16. Investigation Analysis of the City Inhabitants Participate Community Sports Motivation and Its Restrictive Factors%城市居民参加社区体育动机及其制约因素的调查分析

    Institute of Scientific and Technical Information of China (English)

    葛冰

    2012-01-01

    Take the Jilin Province partial city community inhabitants as the sample,investigate the motivation and the restrictive factors from the questionnaire that city inhabitants participates in the community sports,using the mathematical statistic method,discussion the difference of the motivation and the restrictive factors that community inhabitants participates in community sports.Result show:24.1% city inhabitants participate in community sports above 3 time/week;The first three motivation that inhabitants participates in the community sports is the enhance physical,the leisure and entertainment,the fitness and loses weight;The restriction factors existence significant differences that the city inhabitants participate in community sports in physiology,psychology,facilities,society and so on.%以吉林省部分城市社区居民为样本,对城市居民参加社区体育动机及其制约因素进行问卷调查,运用数理统计方法探讨城市居民参加社区体育动机和制约因素的差异。结果显示:有24.1%的城市居民参加3次/周以上的社区体育活动;参加社区体育动机前三位的是增强体质、休闲娱乐、健美减肥;城市居民参加社区体育的制约因素在生理、心理、设施和社会等层面存在显著差异。

  17. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration

    OpenAIRE

    Chujo, Yoshikazu; Fujii, Namiki; Okita, Naoyuki; Konishi, Tomokazu; Narita, Takumi; Yamada, Atsushi; Haruyama, Yushi; Tashiro, Kosuke; Chiba, Takuya; Shimokawa, Isao; Higami, Yoshikazu

    2012-01-01

    The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although ...

  18. Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 2007–2010

    OpenAIRE

    Kurth, Laura; Hnizdo, Eva

    2015-01-01

    Background Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restr...

  19. Restricting retrotransposons: a review.

    Science.gov (United States)

    Goodier, John L

    2016-01-01

    Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research. PMID:27525044

  20. Effect of Vitamin D Receptor Gene Foki Restriction Sites and Gastric Factors%维生素D受体基因FokI酶切位点与胃癌的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    方法; 高洁; 王海江

    2016-01-01

    目的:探讨维生素D受体基因 Fok I酶切位点多态性与胃癌的影响因素。方法随机选取2013年5月—2015年5月该院就诊的维吾尔族胃癌患者143例(A组)及维吾尔族健康对照者147例(B组),采用多聚酶链反应-限制性酶切片段长度多态性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)方法测定维生素D受体基因Fok I酶切位点多态性,进行两组间比较。结果单因素Logistic回归分析显示:胃癌患者的f等位基因频率高于对照组(58.0%vs 47.3%,P<0.05)。多因素Logistic回归分析显示:带有f等位基因(Ff+ ff)的受试者表现出较高的患胃癌的风险(OR值2.87)。结论 VDR的FokI酶切位点多态性是胃癌易感性影响因素。 f等位基因可能是胃癌发生的危险因素之一,而F等位基因可能是胃癌的保护因素。%Objective Discussion of vitamin D receptor gene Fok I restriction site polymorphism influencing factors and gastric cancer. Methods 143 cases of Uygur patients with gastric cancer treated in our hospital from May 2013 to May 2015 were randomly selected as the group A, 147 cases of Uygur healthy people treated in our hospital at the same period were selected as the group B (control group ), the polymorphism of vitamin D acceptor gene FokI restriction enzyme cutting site was measured by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method,PCR-RFLP and com-pared between the two groups. Results The single factor Logistic regression analysis showed that F allele frequency in the gastric cancer group was higher than that in the control group (58.0% vs 47.3%,P<0.05), multi-factor Logistic regression analysis showed that the subjects with F allele(Ff + ff)had a higher risk of gastric cancer(OR value was 2.87). Conclusion VDR FokI restriction site polymorphisms are susceptibility factors in gastric cancer. F allele may be one of the risk factors of occurrence of gastric cancer, however, F allele

  1. CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

    OpenAIRE

    Le Borgne, Sylvie; Février, Michèle; Callebaut, Christian; Lee, Steven P.; Rivière, Yves

    2000-01-01

    CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector pha...

  2. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

    NARCIS (Netherlands)

    Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

    2011-01-01

    ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely inter

  3. Alphavirus Restriction by IFITM Proteins.

    Science.gov (United States)

    Weston, Stuart; Czieso, Stephanie; White, Ian J; Smith, Sarah E; Wash, Rachael S; Diaz-Soria, Carmen; Kellam, Paul; Marsh, Mark

    2016-09-01

    Interferon inducible transmembrane proteins (IFITMs) are broad-spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus. IFITM3 inhibits release of the SFV capsid into the cytosol, without inhibiting binding, internalization, trafficking to endosomes or low pH-induced conformational changes in the envelope glycoprotein. Infection by SFV fusion at the cell surface was inhibited by IFITM1, but was equally inhibited by IFITM3. Furthermore, an IFITM3 mutant (Y20A) that is localized to the plasma membrane inhibited infection by cell surface fusion more potently than IFITM1. Together, these results indicate that IFITMs, in particular IFITM3, can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. That IFITM3 can restrict SFV infection by fusion at the cell surface equivalently to IFITM1 suggests that IFITM3 has greater antiviral potency against SFV. PMID:27219333

  4. Psychological factors in analogous thinking and their restriction%类比思维的心理因素及其制约

    Institute of Scientific and Technical Information of China (English)

    张晓芒

    2006-01-01

    AIM: To investigate the role of certain psychological factors in the process of new analogous combination on the basis of complete perceptual materials.METHODS: By means of evaluation of critical thinking, the psychological factors in the process of analogous thinking were investigated.RESULTS: In the process of analogous thinking, how to choose and reflect the analogous objects has its proper use of analogous mode of thinking. At the same time, it is also influenced by certain psychological factors.CONCLUSION: Analogous thinking plays an important role as thinking tool in the process of recognizing new things and solving new problems, or explaining abstract affair with simple reasons.%目的:探讨一定的心理因素在完整的知觉材料基础上进行新的类比组合过程中的作用.方法:以批判性思维的评价方法,对类比思维过程中心理因素进行研究.结果:在类比思维的过程中,如何选择、映射类比事物,不但有着正确的类比思维方法的运用,同时它也受到一定的心理因素的影响.结论:类比思维在认识新事物、解决新问题的过程中,或者以简单的道理说明抽象事理的过程中,都发挥着重要的思维工具作用.

  5. Temperature based Restricted Boltzmann Machines

    Science.gov (United States)

    Li, Guoqi; Deng, Lei; Xu, Yi; Wen, Changyun; Wang, Wei; Pei, Jing; Shi, Luping

    2016-01-01

    Restricted Boltzmann machines (RBMs), which apply graphical models to learning probability distribution over a set of inputs, have attracted much attention recently since being proposed as building blocks of multi-layer learning systems called deep belief networks (DBNs). Note that temperature is a key factor of the Boltzmann distribution that RBMs originate from. However, none of existing schemes have considered the impact of temperature in the graphical model of DBNs. In this work, we propose temperature based restricted Boltzmann machines (TRBMs) which reveals that temperature is an essential parameter controlling the selectivity of the firing neurons in the hidden layers. We theoretically prove that the effect of temperature can be adjusted by setting the parameter of the sharpness of the logistic function in the proposed TRBMs. The performance of RBMs can be improved by adjusting the temperature parameter of TRBMs. This work provides a comprehensive insights into the deep belief networks and deep learning architectures from a physical point of view.

  6. Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors

    DEFF Research Database (Denmark)

    Stocks, Tanja; Taylor, Moira A; Ängquist, Lars;

    2013-01-01

    Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal...... increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet. Copyright © 2013 S. Karger GmbH, Freiburg....... energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2) on outcomes...

  7. Restrictions of stable bundles

    CERN Document Server

    Balaji, V

    2011-01-01

    The Mehta-Ramanathan theorem ensures that the restriction of a stable vector bundle to a sufficiently high degree complete intersection curve is again stable. We improve the bounds for the "sufficiently high degree" and propose a possibly optimal conjecture.

  8. The Affecting Factors to Restrict Increasing Convert Ratio of Fluid Catalytic Cracking Unit%制约提高催化裂化转化率的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    曹小伟

    2012-01-01

    通过运用催化裂化相关理论并结合惠州炼油分公司催化裂化装置的实际生产情况,对影响催化裂化转化率的因素进行了分析,通过分析各操作参数间的相互关系,确定在装置掺炼加氢尾油后,油浆系统是制约提高转化率的关键因素。%On the basis of the fluid catalytic cracking theory,the main process parameters of FCC unit in Huizhou Oil Refining Company were analyzed,that the slurry oil system was the important restrict factor to increase the convert ratio when FCC unit process the feed mixed with hydro-cracking unconverted oil.

  9. Intermediation under Trade Restrictions.

    OpenAIRE

    Winkler, G Michael

    1989-01-01

    Intermediation is the activity of buying and selling simultaneously in one market. In this paper, intermediation in the market for an arbitrary good is derived from trade restrictions in a general equilibrium exchange model. The trade restrictions are given by a trade feasibility relation defined on the set of households, and they necessitate dropping the one price assumption of standard general equilibrium theory. It is shown that, in this setting, equilibria need not exist in spite of well-...

  10. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-01-01

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated. PMID:26986509

  11. Bilinear Fourier restriction theorems

    CERN Document Server

    Demeter, Ciprian

    2012-01-01

    We provide a general scheme for proving $L^p$ estimates for certain bilinear Fourier restrictions outside the locally $L^2$ setting. As an application, we show how such estimates follow for the lacunary polygon. In contrast with prior approaches, our argument avoids any use of the Rubio de Francia Littlewood--Paley inequality.

  12. Neuroaesthetics: range and restrictions.

    Science.gov (United States)

    Chatterjee, Anjan

    2013-04-01

    Bullot & Reber (B&R) should be commended for highlighting tensions between scientific aesthetics and art history. The question of how each tradition can learn from the other is timely. While I am sympathetic to their views, their diagnosis of the problem appears exaggerated and their solution partial. They underestimate the reach of scientific aesthetics while failing to identify its inherent restrictions. PMID:23507092

  13. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  14. MULTIPLE WAYS OF TARGETING APOBEC3/VIF INTERACTIONS FOR ANTI-HIV-1 DRUG DEVELOPMENT

    OpenAIRE

    Smith, Jessica L.; Bu, Wei; Burdick, Ryan C.; Pathak, Vinay K.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) infections and the resulting acquired immunodeficiency syndrome (AIDS) pandemic remain a global challenge in the absence of a protective vaccine and because of rapid selection of drug-resistant viral variants in response to all currently available antiviral therapies. Development of new and highly active antiviral agents would greatly facilitate effective clinical management of HIV-1 infections and delay the onset of AIDS. Recent advances in our und...

  15. Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity

    OpenAIRE

    Pinto, Yishay; Gabay, Orshay; Arbiza, Leonardo; Sams, Aaron J.; Keinan, Alon; Levanon, Erez Y.

    2016-01-01

    The gradual accumulation of mutations by any of a number of mutational processes is a major driving force of divergence and evolution. Here, we investigate a potentially novel mutational process that is based on the activity of members of the AID/APOBEC family of deaminases. This gene family has been recently shown to introduce—in multiple types of cancer—enzyme-induced clusters of co-occurring somatic mutations caused by cytosine deamination. Going beyond somatic mutations, we hypothesized t...

  16. 海洋无脊椎动物细胞培养的制约因素及改进方法%Restrictive Factor and Improved Strategy of Cell Culture from Marine Invertebrates

    Institute of Scientific and Technical Information of China (English)

    张晓燕; 王昌留; 李琳

    2015-01-01

    Attempts to development cell culture from marine invertebrates dated back to 1970s. The cell culture from marine invertebrates lags far behind that from vertebrates,there is no single immortal cell line available from marine invertebrates yet. This review outlines the progress of marine invertebrates’ cell culture,points out restrictive factor,and proposes improved strategy. This article provides the reference on the establishment of im-mortal cell lines from marine invertebrates.%海洋无脊椎动物细胞培养的研究始于20世纪70年代,至今未得到永生化细胞系,远远落后于脊椎动物细胞培养的研究。本文概述了海洋无脊椎动物细胞培养的进展,指出了制约因素,参考脊椎动物的研究成果进而提出了海洋无脊椎动物细胞培养的改进方法,为进一步建立起海洋无脊椎动物的永生化细胞系提供参考。

  17. 高校网络法制教育效果的制约因素研究%On the Restrictive Factors of Internet Legal Education in Colleges and Universities

    Institute of Scientific and Technical Information of China (English)

    何庆江; 石浩旭

    2015-01-01

    目前很多高校陆续对大学生开展了网络法制教育,但教育效果不佳。制约高校网络法制教育效果的因素主要包括教育者的观念、受教育者的心理、教育的内容与方法、教育环境等。只有针对这些因素提出相应的改进措施,才能提高高校网络法制教育的效果。%Now many colleges and universities have carried out internet legal education for their students in suc-cession, but the effectiveness is poor. There are many factors restricting internet legal education, which mainly in-clude idea of educators, psychology of educatee, content and methods of education, educational environment, etc. In order to improve the effectiveness of internet legal education in colleges and universities, corresponding measures must be put forward.

  18. The Examination of China’s New Medical Reform Based on Restrictive Factors in British Medical Reform%基于英国医改制约性因素审视我国新医改

    Institute of Scientific and Technical Information of China (English)

    王演艺

    2014-01-01

    As the first country established universal health insurance in the world, UK has been devoted to construct the fairness and welfare of National Health Service(NHS) with constant development and improvement. It focuses on the reform process of NHS since the beginning of this century and studies the deep factors restricted the reform, compared with the current situation of health care system under China’s new medical reform since 2006, putting forward enlightenment to China’s reform.%作为世界上最早建立全民医疗保障的国家,英国一直致力于其医疗服务系统(NHS)公平性与福利性的构建,不断进行发展与完善。文章重点关注本世纪以来NHS 的改革历程,研究影响其改革成效的深层次制约性因素,同时对照我国2006年启动新医疗改革后国内卫生医疗服务体系的现状,提出其对我国新医改的启示。

  19. Restriction of Helmholtz Model

    Directory of Open Access Journals (Sweden)

    V.M. Polunin

    2014-07-01

    Full Text Available The results of the experimental studies of physical mechanisms of energy dissipation in the oscillating system in which air cavity held by the forces of magnetic levitation is used as the elastic element, and magnetic fluid prepared on the basis of dispersing media with different viscosity level is used as the inertial element are considered in the article. Based on the obtained results the conclusion on the restriction of the applicability of Helmholtz equation, caused by boundary effects is made.

  20. License restrictions at Barnwell

    Energy Technology Data Exchange (ETDEWEB)

    Autry, V.R. [S.C. Dept. of Health and Environmental Control, Columbia, SC (United States). Bureau of Radiological Health

    1991-12-31

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low-level waste contains numerous restrictions to ensure environmental protection and compliance with shallow land disposal performance criteria. Low-level waste has evolved from minimally contaminated items to complex waste streams containing high concentrations of radionuclides and processing chemicals which necessitated these restrictions. Additionally, some waste with their specific radionuclides and concentration levels, many classified as low-level radioactive waste, are not appropriate for shallow land disposal unless additional precautions are taken. This paper will represent a number of these restrictions, the rationale for them, and how they are being dealt with at the Barnwell disposal facility.

  1. 中国职业经理人市场发展的制约因素分析%On the Restricting Factors in the Development of Professional Manager Market in China

    Institute of Scientific and Technical Information of China (English)

    张金艳; 张帆

    2013-01-01

    职业经理人市场是为适应市场经济发展的内在需求而产生的一种新的人力资源配置方式。职业经理人市场的建立和完善涉及到一系列有关因素。相对而言,中国市场经济的建设时期较短,并且具有特殊国情。这决定了不完善的职业经理人价值评价体系、企业主和职业经理人之间的信息不对称、企业主和职业经理人相互信任的缺失、公司治理结构的缺陷和职业经理人市场法律制度的不健全等成为中国职业经理人市场发展的制约因素。%As a new way of human resource allocation, the professional manager market is created to meet the internal demand of the development of market economy. The creation and improvement of professional manager market involves a se-ries of relevant factors. Relatively, China, with special national condition, has established the market economy for a short time period. This determines that the restricting factors for the development of professional manager market in China include the non-perfect value evaluation system for professional managers, asymmetry of information, mutual trust deficiencies between enterprise owners and professional managers, drawback in corporate governance structure and imperfection of relevant legal system and so on.

  2. Problems and Restricting Factor Analysis of Leisure Sports Industry in Shaanxi Province%陕西省休闲体育产业面临的问题及制约因素分析

    Institute of Scientific and Technical Information of China (English)

    姜健

    2012-01-01

    通过对陕西省休闲体育产业面临的问题及制约因素进行深入细致的分析,认为目前面临的主要问题有休闲体育消费市场城乡差别较明显;现有体育场馆设施面向休闲体育市场的开放不够;经营性休闲健身场所与竞赛表演产业发展较成熟,休闲体育培训服务产业较滞后;休闲体育文化产业市场尚待开发。制约陕西省休闲体育产业发展的主要因素包括经济、体制、政策、场地设施、人才等方面。%Through the analysis of problems and factors of Shaanxi leisure sports industry, the paper concludes that the main prob- lem facing leisure sports consumer market gap between urban and rural areas is obvious; Existing sports facilities for leisure sports market opening up enough; Business leisure fitness place and competition demonstration industry development are more mature, leisure sports training service industry is lag; Leisure sports culture industry market is yet to be developed. Restriction of the de- velopment of leisure sports industry of shaanxi province, the main factors including economy, system, policy, the ground equip- ment, personnel, etc.

  3. Do Economic Restrictions Improve Forecasts?

    OpenAIRE

    Murphy, Elizabeth A.; Norwood, F. Bailey; Wohlgenant, Michael K.

    2003-01-01

    A previous study showed that imposing economic restrictions improves the forecasting ability of food demand systems, thus warranting their use even when they are rejected in-sample. This article evaluates whether this result is due to economic restrictions enhancing degrees of freedom or containing nonsample information. Results indicate that restrictions improve forecasting ability even when they are not derived from economic theory, but theoretical restrictions forecast best.

  4. 制约大学生体育能力发展的因素分析与对策研究%The Factor Analysis and Countermeasure Research of Restricting the University Students Sports Ability

    Institute of Scientific and Technical Information of China (English)

    余丁友

    2011-01-01

    运用问卷和建模等方法,对制约大学生体育能力发展的因素进行了分析讨论。结果表明:在高中阶段,切勿随意调停体育课,学校和家长要积极鼓动他们体育锻炼,努力营造良好的体育氛围;大学阶段,优化教师队伍,大力发展体育社团,加强身体健康的重要性教育;临近毕业阶段,通过各种途径积极提高大学生自我认知能力。同时也提出了针对性的发展对策。%This paper analyzes and disscusses the factors of the restrict on the university sports ability development by the the methods of questionnaire and modeling.The results show that:In the high school stage,PE class can not be stop.Teachers and students parents should actively encouraged student to exercise body and tried to create a fine sports atmosphere.At University phase,optimizing the teachers team,devotes to developing sports organization and strengthen health education of exercising.During the graduation stages,improves the university students' selfcognitive ability by some actively means.Finally,the paper also puts forward corresponding develope countermeasures of how to improve the university students ablity of sports.

  5. 我国公共政策参与中公民层面的制约因素分析%AN ANALYSIS OF FACTORS RESTRICTING CITIZENS FROM PARTICIPATING IN PUBLIC POLICIES

    Institute of Scientific and Technical Information of China (English)

    李占乐

    2011-01-01

    在现代社会,公民积极主动地参与政府的公共政策,除了基于自身利益追求的参与动机外,实现和促进与全体社会成员相联系的公共利益也是一个重要动机。改革开放以后,在公民个体的政策参与逐渐增多的同时,我国以民间组织为主体的各种利益团体参与政府公共政策的活动也逐渐增多。同时在我国公民的公共政策参与过程中存在的问题也十分突出。公共政策参与中公民层面的制约因素主要包括参与意识不强、参与能力不足和参与的组织化程度不高3个方面。%In modern society, citizens actively participate in the government' s public policies. In addition to participation based on the pursuit of self-interests, the achieving and promoting of the public interest involving all members of society can be another important motivation. After the reform and opening up, an increasing number of individual citizens participate in policies and meanwhile more various interest groups in China take part in more policy-related activities with civil organizations as the main body. There exist some prominent problems in the participating process. The factors restricting citizens from participating in public policy include weak sense of participation, lack of capacity for involvement and participation and low degree of organization.

  6. 贫困地区民营经济发展的制约因素及对策分析%Restricting Factors for the Growth of Private Economy in Poverty-Stricken Areas and the Strategy

    Institute of Scientific and Technical Information of China (English)

    彭贞贞; 马骥

    2014-01-01

    民营经济发展水平低是贫困地区经济发展不发达的重要原因。制约贫困地区民营经济发展的因素有脱贫致富的思想、人力资源状况、金融生态环境和技术创新水平等。促进贫困地区民营经济发展与脱贫致富必须根据民营经济产业发展需求,大力发展职业教育;优化环境,承接产业转移;创新贫困地区新型城镇化发展机制,推动地区民营经济发展;大力发展交通基础设施,破解民营经济发展瓶颈;创新民营企业管理,做大做强民营经济。%Inadequate development of the private economy is a major reason of economic underdevelopment in poverty-driven areas. Fac-tors restricting the growth of the private economy in these areas include people's lack of eagerness for creating a fortune, human resource shortage, and the poor financial environment and technological innovation ability. To shake off poverty, the areas must develop the private economy by proactively develop vocational education, improve environment for carrying on industry transfer, innovate new-type urbaniza-tion mechanism, enhance the transportation infrastructure construction, and innovate the management of private enterprises.

  7. Deconfinement from action restriction

    International Nuclear Information System (INIS)

    The effect of restricting the plaquette to be greater than a certain cutoff value is studied. The action considered is the standard Wilson action with the addition of a plaquette restriction, which should not affect the continuum limit of the theory. In this investigation, the strong coupling limit is also taken. It is found that a deconfining phase transition occurs as the cutoff is increased, on all lattices studied (up to 204). The critical cutoff on the infinite lattice appears to be around 0.55. For cutoffs above this, a fixed point behavior is observed in the normalized fourth cumulant of the Polyakov loop, suggesting the existence of a line of critical points corresponding to a massless gluon phase, not unlike the situation in compact U(1). The Polyakov loop susceptibility also appears to be diverging with lattice size at these cutoffs. A strong finite volume behavior is observed in the pseudo-specific heat. It is discussed whether these results could still be consistent with the standard crossover picture which precludes the existence of a deconfining phase transition on an infinite symmetric lattice. (orig.)

  8. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

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

  9. Factoring

    OpenAIRE

    Lenstra, Arjen K.

    1994-01-01

    Factoring, finding a non-trivial factorization of a composite positive integer, is believed to be a hard problem. How hard we think it is, however, changes almost on a daily basis. Predicting how hard factoring will be in the future, an important issue for cryptographic applications of composite numbers, is therefore a challenging task. The author presents a brief survey of general purpose integer factoring algorithms and their implementations

  10. MRI of restrictive cardiomyopathy

    International Nuclear Information System (INIS)

    Objective: To evaluate the diagnostic value of MRI in combination of delayed gadolinium-enhanced MR imaging for the identification of restrictive cardiomyopathy (RCM). Methods: One hundred sixteen patients with RCM underwent ECG, thoracic radiography, echocardiography and MRI. The final diagnosis was made on comprehensive evaluation in consideration of patient history, clinical symptoms and imaging appearances. Fifty-five normal subjects were used as the controls. All patients were divided into two groups according to contrast-enhanced MRI patterns: RCM with delayed enhancement (RCM with DE, n=35) and RCM without delayed enhancement (RCM without DE, n=81). Bi-atrial and bi-ventricular size, ventricular septal and left free wall thickness were measured. A paired t-test was used for statistic analysis. Results: Bi-atrial size, right ventricular diastolic diameter (RVDD), ventricular septal and left free wall thickness were significantly larger in RCM patients than in normal subjects (P0.05). Visual observation showed mild mitral regurgitation (50 cases), moderate mitral regurgitation (24 cases ), mild tricuspid regurgitation (32 cases) and severe tricuspid regurgitation (46 cases). Thirty-five RCMs with DE presented diffuse (15 cases) or segmental (20 cases) enhancement. Twelve RCMs with diffuse delayed enhancement showed powdery, enhancement, and 3 showed petaline enhancement. Three cases with powdery enhancement were histologically proven as myocardial amyloidosis. Ventricular septum was the most vulnerable segment in patients with segmental enhancement. Six cases presented subendocardial enhancement that corresponded to apical obliteration, of which one case was confirmed as hypereosinophilia by bone marrow biopsy and the other 14 cases didn't present any regular enhancement. In 81 RCMs without DE, marked bi-atrial dilation, near-normal ventricular chambers and near-normal ventricular thickness were presented. Conclusion: MRI is an excellent imaging modality for

  11. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

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

  12. Geometry of the restricted Boltzmann machine

    OpenAIRE

    Cueto, Maria Angelica; Morton, Jason; Sturmfels, Bernd

    2009-01-01

    The restricted Boltzmann machine is a graphical model for binary random variables. Based on a complete bipartite graph separating hidden and observed variables, it is the binary analog to the factor analysis model. We study this graphical model from the perspectives of algebraic statistics and tropical geometry, starting with the observation that its Zariski closure is a Hadamard power of the first secant variety of the Segre variety of projective lines. We derive a dimension formula for the ...

  13. Stroke and restricted sensory syndromes

    International Nuclear Information System (INIS)

    There have been sporadic case reports of a restricted sensory syndrome caused by stroke, most often as a cheiro-oral syndrome. We describe 14 patients with stroke who showed various restricted sensory syndromes and correlated their symptoms with the radiological findings. (orig./MG)

  14. Epigenetic regulation of caloric restriction in aging

    Directory of Open Access Journals (Sweden)

    Daniel Michael

    2011-08-01

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

  15. How harmful are adaptation restrictions

    OpenAIRE

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

    2009-01-01

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

  16. Photoperiod interacts with food restriction on performance in the Barnes maze in female California mice

    OpenAIRE

    Steinman, Michael Q.; Crean, Katie K.; Trainor, Brian C.

    2010-01-01

    Food restriction has been reported to have positive effects on cognition. This study examines how another environmental factor, daylength, can alter the impact of food restriction on the brain and behavior. Female California mice (Peromyscus californicus), housed on either long days (16L:8D) or short days (8L:16D) were restricted to 80% of their normal baseline food intake or provided food ad libitum. Testing in a Barnes maze revealed that the effects of food restriction depend on photoperiod...

  17. The Ability of Multimerized Cyclophilin A to Restrict Retrovirus Infection

    OpenAIRE

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

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cycl...

  18. Neutron inelastic scattering from {sup 4}He in restricted geometries

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, M.R. [Keele Univ. (United Kingdom). Dept. of Physics; Sokol, P.E. [Dept. of Physics, Pennsylvania State Univ., University Park, PA (United States); Azuah, R.T. [Keele Univ. (United Kingdom). Dept. of Physics]|[Rutherford Appleton Lab., Chilton, Didcot (United Kingdom); Stirling, W.G. [Keele Univ. (United Kingdom). Dept. of Physics; Adams, M.A. [Rutherford Appleton Lab., Chilton, Didcot (United Kingdom)

    1995-08-01

    When liquid {sup 4}He is condensed in porous aerogel glass (typical pore size {approx}5000 A), many of the superfluid properties are significantly altered. Measurements have been made of the dynamic structure factor S(Q,{omega}) of liquid {sup 4}He in restricted geometries. The collective phonon-roton excitations are shown to have an intrinsic broadening associated with the restricted geometry. The temperature dependence of the excitation spectrum is discussed. (orig.).

  19. Genetics Home Reference: familial restrictive cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions familial restrictive cardiomyopathy familial restrictive cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Familial restrictive cardiomyopathy is a genetic form of heart disease. For ...

  20. Entanglement with restricted measurement setups

    CERN Document Server

    Meznaric, Sebastian

    2010-01-01

    We consider what is the effective amount of entanglement when the measurement operators one has at their disposal are restricted. Such a scenario occurs when superselection rules are in effect or when there are imperfections in our measurement setup. Given a quantum state and the restrictions on measurements, we consider the following scenario. Imagine we have an ideal, or non-restricted, measurement setup and a state $\\rho_1$ and a non-ideal, or restricted, measurement setup and a state $\\rho_2$. Then the minimum amount of entanglement in $\\rho_1$ so that all quantum communication protocols still perform with the same fidelity as with $\\rho_2$ is effectively the entanglement with restricted measurement setup. For indistinguishable particles, we find that any quantum communication protocol that can be performed with indistinguishable particles, can thus be performed with a ``normal'' state of no more than $E_P$ of entanglement. For the imperfect measurement apparatus we find an upper bound for the effective e...

  1. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Siddharth Gautam; S Mitra; R Mukhopadhyay

    2008-10-01

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time scales involved in the motion and the geometry of motion can be studied using QENS. Molecular dynamics (MD) simulation not only provides insight into the details of the different types of motion possible but also does not suffer limitations of the experimental set-up. Here we report the effect of confinement on molecular dynamics in various restricted geometries as studied by QENS and MD simulations: An example where the QENS technique provided direct evidence of phase transition associated with change in the dynamical behaviour of the molecules is also discussed.

  2. Bridge Decomposition of Restriction Measures

    CERN Document Server

    Alberts, Tom

    2009-01-01

    Motivated by Kesten's bridge decomposition for two-dimensional self-avoiding walks in the upper half plane, we show that the conjectured scaling limit of the half-plane SAW, the SLE(8/3) process, also has an appropriately defined bridge decomposition. This continuum decomposition turns out to entirely be a consequence of the restriction property of SLE(8/3), and as a result can be generalized to the wider class of restriction measures. Specifically we show that the restriction hulls with index less than one can be decomposed into a Poisson Point Process of irreducible bridges in a way that is similar to Ito's excursion decomposition of a Brownian motion according to its zeros.

  3. Telomere Restriction Fragment (TRF) Analysis

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

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

  4. CDRL - company dose restriction level

    International Nuclear Information System (INIS)

    For a number of year's close constraints and controls have been used as effective measures in aiding restricting exposure to ionising radiation. Predecessor companies to British Energy Generation (BEG) originally established the Company Dose Restriction Level (CDRL) as a consequence of the revision of risk estimates, then with the revised Ionising Radiations Regulations 1999 (IRR99) the CDRL for BEG was also revised. The background, influences and consequences of CDRL appliance in a commercial organisation in calendar year 2000/1 are presented below. (author)

  5. HFB in a restricted space

    International Nuclear Information System (INIS)

    A restricted Hartree-Fock-Bogoliubov method is developed with a restriction on the angular momenta of the Cooper pairs that conform the vacuum (SD or SDG). The method is applied to 176Yb. The quadrupole moment in the SD subspace is found to be 80% for neutrons and 91% for protons of its value in the full space. The inclusion of the G part of the Cooper pairs improves that agreement. The descriptions in terms of boson condensate and coherent states are discussed. (author)

  6. Space-restricted attribute grammars

    DEFF Research Database (Denmark)

    Schmidt, Erik Meineche

    1980-01-01

    Restricting the size of attribute values, relative to the length of the string under consideration, leads to a model of attribute grammars in which grammars with both inherited and synthesized attributes can be significantly more economical than grammars with synthesized attributes only....

  7. Restrictive dermopathy and fetal behaviour

    NARCIS (Netherlands)

    Mulder, EJH; Beemer, FA; Stoutenbeek, P

    2001-01-01

    We report three siblings from consecutive pregnancies affected with restrictive dermopathy (RD). During the second pregnancy, fetal behavioural development and growth were studied extensively using ultrasound at 1-4 week intervals. Dramatic and sudden changes occurred in fetal body movements and gro

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

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

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

  9. The "occlusis" model of cell fate restriction.

    Science.gov (United States)

    Lahn, Bruce T

    2011-01-01

    A simple model, termed "occlusis", is presented here to account for both cell fate restriction during somatic development and reestablishment of pluripotency during reproduction. The model makes three assertions: (1) A gene's transcriptional potential can assume one of two states: the "competent" state, wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, and the "occluded" state, wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans-acting factors such that it remains silent irrespective of whether transcriptional activators are present in the milieu. (2) As differentiation proceeds in somatic lineages, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thereby leading to the restriction of cell fate. (3) During reproduction, global deocclusion takes place in the germline and/or early zygotic cells to reset the genome to the competent state in order to facilitate a new round of organismal development. PMID:20954221

  10. 制约少数民族生态移民可持续发展的因素探究%Probing into the Factors Restricting the Sustainable Development of the Minority Ecological Migration

    Institute of Scientific and Technical Information of China (English)

    金莲; 王永平; 周丕东; 黄海燕

    2012-01-01

    To realize the sustainable development of the minority ecological migration, we must consider four constraints that are social factors, economical factors, ecological factors and own factors. Social factors involve the constraints of government, community, enterprise and NGO. Economic factors mainly include three aspects that are economic development foundation, the development level of the industry and the urbanization level. Ecological factors are considered from the angle of natural conditions, such as land and water. Economic conditions, cultural quality, ideology and family structure of eco-migrants themselves also affect the sustainable development of the minority ecological migration.%实现可持续发展受到社会、经济、生态及移民自身方面因素的制约,其中社会因素,涉及政府、社区、企业及民间组织四个方面;经济因素主要包括经济发展基础、产业发展水平和城镇化水平三个方面;生态因素主要是从自然条件(如土地、水等资源)的角度去考虑其制约因素;移民自身的经济条件、文化素质、思想观念和家庭结构也是影响少数民族生态移民可持续发展的因素.

  11. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

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

  12. Study on the Restricting Factors and Countermeasures in Resource - based Industries Green Development of Poyang Lake Ecological Economic Zone%鄱阳湖生态经济区资源型产业绿色发展制约因素及对策研究

    Institute of Scientific and Technical Information of China (English)

    李胜连

    2014-01-01

    鄱阳湖生态经济区作为国家的战略发展区域,应该具有超前思维,大力发展绿色产业,而资源型产业容易造成外部不经济,因此更需要健康、绿色发展。本文利用 AHP 方法对环鄱区资源型产业绿色发展的制约因素进行分层排序,得到如下结论:技术因素和生态因素是主要制约因素;制约因素排名前5位的分别是:空气质量、政府及社会第三方的技术监督、水资源质量、外部不经济补救成本、绿色检测技术的推广与应用。%As a strategic development areas of the country ,Poyang Lake Ecological Economic Zone should have advanced thinking ,to vigorously develop the green industry .But the resources industry is easy to cause the external diseconomy , therefore it need more healthy and green development .In this paper ,by using the AHP method ,hierarchical ranking con-straints of Poyang Lake Ecological Economic Zone is conducted and conclusion is as follows :technical factors and ecological factors are the main restricting factors and the top five restricting factors should be air quality ,the technological supervision of the third party government and society ,the quality of water resources ,external non economic recovery cost ,promotion and application of green detection technology .

  13. Nullity Restrictions and Comparative Static Analysis.

    OpenAIRE

    Chavas, Jean-Paul; Pope, Rulon

    1992-01-01

    While homogeneity restrictions of optimal choice functions are well known in the context of neoclassical economic theory, the existence and implications of "homogeneity-like" restrictions in more general optimization models have not received much attention in the literature. The authors call such restrictions "nullity" restrictions since they involve the null space of the matrix of slopes of choice functions. The existence, nature, and implications of nullity restrictions are investigated in ...

  14. Decision Making and Cooperation Restrictions.

    OpenAIRE

    2000-01-01

    Decision making by various individuals can result in conflicts or cooperation between these individuals. Game theory deals with both the mathematical modeling of these situations of conflict and cooperation and with the analysis of these models using math atical techniques. This thesis focuses on decision making and cooperation restrictions and can roughly be divided into two parts. The first part provides an analysis of cooperative games with exogenously given cooperation structures. Three t...

  15. Decision making and cooperation restrictions

    OpenAIRE

    Slikker, M.

    2000-01-01

    Decision making by various individuals can result in conflicts or cooperation between these individuals. Game theory deals with both the mathematical modeling of these situations of conflict and cooperation and with the analysis of these models using math atical techniques. This thesis focuses on decision making and cooperation restrictions and can roughly be divided into two parts. The first part provides an analysis of cooperative games with exogenously given cooperation structures. Three t...

  16. Management of fetal growth restriction

    OpenAIRE

    Alberry, M; Soothill, P

    2007-01-01

    Fetal growth restriction (FGR) is challenging because of the difficulties in reaching a definitive diagnosis of the cause and planning management. FGR is associated not only with a marked increased risk in perinatal mortality and morbidity but also with long‐term outcome risks. Combinations of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables allow a comprehensive fetal evaluation of FGR. However, no evidence supports that the u...

  17. Judgment aggregation on restricted domains

    OpenAIRE

    Dietrich Franz; List Christian

    2006-01-01

    We show that, when a group takes independent majority votes on interconnected propositions, the outcome is consistent once the profile of individual judgment sets respects appropriate structural conditions. We introduce several such conditions on profiles, based on ordering the propositions or ordering the individuals, and we clarify the relations between these conditions. By restricting the conditions to appropriate subagendas, we obtain local conditions that are less demanding but still gua...

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

    Directory of Open Access Journals (Sweden)

    Felicia Chang

    2013-06-01

    a finding that is relevant to migrant populations and travel medicine providers alike. Despite international pressure to remove travel restrictions, many countries continue to implement these restrictions for HIV-positive individuals on entry and stay. Since 2010, the United States and China have engaged in high profile removals. This may be indicative of an increasing trend, facilitated by various factors, including international advocacy and the setting of a UNAIDS goal to halve the number of countries with restrictions by 2015.

  19. 制约我国地方性国有资产证券化的因素与对策研究%The Research on the Restrict Factors to Local State- owned Assets Securitization and Countermeasure

    Institute of Scientific and Technical Information of China (English)

    李国义; 杨果

    2012-01-01

    Securitization is the local state - owned assets important means for increment. But some factors exist in the local state - owned asset securitization process, including the subjective and objective factors, the subjective factors are enor of understanding in state - owned asset function, efficiency of public ownership theory. In order to promote the local state- owned asset securitizafion, it is necessary to undertake an analysis to these elements, put forward according to these factors the countermeasures to solve the problems, to further promote the local state - owned assets securitization. We can take the induction, inference analysis method to study. Securitization of state - owned assets, should from the dynamic asset expanded to static asset, from artificial assets expanded to natural assets.%证券化是地方性国有资产保值增值的重要手段。但是在地方性国有资产证券化过程中存在一些制约因素,包括主观因素和客观因素,其中主观因素主要是在国有资产功能、公有制效率等理论方面存在认识偏差。为了顺利推进地方性国有资产证券化工作,有必要对这些因素进行分析,针对这些因素提出解决问题的对策,进一步推进地方性国有资产证券化。可以采取归纳、推理分析方法进行研究。可证券化的国有资产范围,应该从动态资产扩大到静态资产,从人工资产扩大到自然资产。

  20. Requirements for nucleocapsid-mediated regulation of reverse transcription during the late steps of HIV-1 assembly.

    Science.gov (United States)

    Racine, Pierre-Jean; Chamontin, Célia; de Rocquigny, Hugues; Bernacchi, Serena; Paillart, Jean-Christophe; Mougel, Marylène

    2016-01-01

    HIV-1 is a retrovirus replicating within cells by reverse transcribing its genomic RNA (gRNA) into DNA. Within cells, virus assembly requires the structural Gag proteins with few accessory proteins, notably the viral infectivity factor (Vif) and two copies of gRNA as well as cellular factors to converge to the plasma membrane. In this process, the nucleocapsid (NC) domain of Gag binds to the packaging signal of gRNA which consists of a series of stem-loops (SL1-SL3) ensuring gRNA selection and packaging into virions. Interestingly, mutating NC activates a late-occurring reverse transcription (RT) step in producer cells, leading to the release of DNA-containing HIV-1 particles. In order to decipher the molecular mechanism regulating this late RT, we explored the role of several key partners of NC, such as Vif, gRNA and the cellular cytidine deaminase APOBEC3G that restricts HIV-1 infection by targeting the RT. By studying combinations of deletions of these putative players, we revealed that NC, SL1-SL3 and in lesser extent Vif, but not APOBEC3G, interplay regulates the late RT. PMID:27273064

  1. Conformal restriction: the chordal case

    OpenAIRE

    Lawler, Gregory; Schramm, Oded; Werner, Wendelin

    2002-01-01

    We characterize and describe all random subsets $K$ of a given simply connected planar domain (the upper half-plane $\\H$, say) which satisfy the ``conformal restriction'' property, i.e., $K$ connects two fixed boundary points (0 and $\\infty$, say) and the law of $K$ conditioned to remain in a simply connected open subset $D$ of $\\H$ is identical to that of $\\Phi(K)$, where $\\Phi$ is a conformal map from $\\H$ onto $D$ with $\\Phi(0)=0$ and $\\Phi(\\infty)=\\infty$. The construction of this family ...

  2. Electromagnetic Fields Restrictions and Approximation

    CERN Document Server

    Katsenelenbaum, Boris Z

    2003-01-01

    The fields scattered by metallic bodies or radiated by some types of antennas are created by the surfaces currents and therefore they are subject to some restrictions. The book is the first one where the properties of these fields are investigated in details. The properties have the important significance for the antenna synthesis, body shape reconstruction and other diffraction problems. The material of the book lies in the meetingpoint of the antenna theory, highfrequency electrodynamics and inverse scattering problems. The author is an internationally renowned investigator in the field of e

  3. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli

    2011-02-01

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

  4. Restrictions on trade in distribution services

    OpenAIRE

    Kaleeswaran Kalirajan

    2001-01-01

    Identifies and quantifies restrictions affecting domestic and international trade in distribution services - mainly wholesaling and retailing - in 38 economies, including Australia. The paper also explores the price and cost implications of restrictions in food distribution services.

  5. Bronchial Responsiveness in Patients with Restrictive Spirometry

    OpenAIRE

    Keddissi, Jean I.; Elya, Marwan K.; Farooq, Saif U.; Youness, Houssein A.; Kellie R. Jones; Ahmed Awab; Kinasewitz, Gary T.

    2013-01-01

    Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defi...

  6. Restrictive Cardiomyopathy: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Bilal Bin Abdullah*, Mehboob.M.Kalburgi, Sahana Shetty and Satyasrinivas

    2011-04-01

    Full Text Available We report a 28 years old male presenting with heart failure. A thorough clinical evaluation directed us towards restrictive heart disease. Doppler echocardiographic study was used as a main modality of diagnosis and cardiac catheterization confirmed the diagnosis of idiopathic restrictive cardiomyopathy. We express the contribution of clinical findings and appropriate diagnostic measures in approaching a case of Restrictive cardiomyopathy (RCM.

  7. 试析贫困大学生就业难的深层社会因素%A Deep Social Factor Analysis on the Restriction of Poor College Students Employment Difficulty

    Institute of Scientific and Technical Information of China (English)

    彭仲生; 罗筑华

    2012-01-01

    当前大学生就业难已经成了大学生、学生家长、高等学校及社会共同的感受和普遍关注的问题,而作为大学生中的弱势群体——贫困大学生的就业则更是得到了有关各方的高度重视.为进一步探明当前贫困大学生就业难的潜因,为今后解决贫困大学生就业问题打好前期基础,文章对贫困大学生就业困难的深层社会因素进行了初步分析,并提出了一些可操作性的对策和措施.%Employment difficulty of college students has become consensus and concern of college students, parents, colleges and society in recent years, and for poor college students, the vulnerable group of the university, their employment problem has attracted more intensive attention from the society. In order to explore the potent factors of employment difficulty of poor college students and to make a good preparation for the solution to this problem, this article attempts to make an analysis of the reasons and countermeasure of poor college students' employment difficulty from the perspective of society.

  8. Observability in electric power networks: a method of ways of factorization in state estimation with equality restrictions; Observabilidade em redes de energia: um metodo de caminhos de fatoracao em estimacao de estado com restricoes de igualdade

    Energy Technology Data Exchange (ETDEWEB)

    Vicentino, Flavio Antonio

    1997-07-01

    A theory of network observability that mixes graph concepts and factorization of the gain matrix G has been recently developed. It uses data already available in Power System Operating Centers. That theory is easy to understand and implement and does not require subroutines other than the ones used in static state estimation. However, this new theory has been implemented only for the case of state estimation in Normal Equation Formulation (N E). However, the N E Method presents some inherent numerical difficulties. Such numerical difficulties are usually related to the disparity in the measurements weights (high values for zero-injections measurements and low values for pseudo-measurements) and the presence of short lines in the network, as well. In order to solve such numerical difficulties, new methods have come up, such as: Normal Equation Method with Equality Constraints (N E/C), where Lagrange's Multiplier Method can be applied to minimize a function while satisfying a set of constraints; Hachtel's Method, which is formulated the same way as N E/C Method, although an equation of residual vector is introduced in solution process; Hybrid Method, which is a general formulation behaving as the N E/C Method at one extreme, and as Hachtel's Method at the other. Thus, the aim of this work is to treat the adaptation of the network observability Method by using path graphs, with the state estimation in the form of a minimization problem with equality constraints. As the Hybrid Method is a generalization form of the state estimator with constraints, this formulation is used to develop the proposed theory. Extreme case (as the pure Hachtel's Method) are also considered. (author)

  9. 21世纪初波兰的东方政策及其制约因素%Poland’s Eastern Policy and Its Restricting Factors in the Early 21st Century

    Institute of Scientific and Technical Information of China (English)

    赵艳霞; 唐更田

    2013-01-01

      21世纪初,随着波兰“入约加盟”,东方问题开始凸显,积极活跃的东方政策遂成为波兰的优先外交政策。地缘政治与现实利益、历史积淀与文化传统以及精英集团的政策理念与公众情绪等各种复杂的国内外因素,决定21世纪波兰的东方政策仍以对俄政策为核心,防范俄罗斯对波兰的威胁是其主要战略意图,并以此为基础在一定程度上决定着波兰对乌克兰、白俄罗斯和南高加索等东欧中亚国家的政策。而欧盟、美国则成为波兰推行东方政策的主要借助力量,实现欧盟东方政策的“波兰化”是波兰实现东方政策的最理想方式。%In the early 21st century, with Poland’s accession to NATO, Eastern problem became prominent. An active eastern policy became a prior foreign policy. In the 21st century, Poland’s eastern policy still kept Russia as the center, which was decided by complex factors at home and abroad like geopolitics, practical interests, historical accumulation, cultural tradition, elite crew’s policy principle and public mood. Preventing Russian threaten was the main strategic idea, which also decided Poland’s policies toward Ukraine, Belarus and the Southern Caucasus, and other Central Asian Eastern Europe countries. EU and U.S.A. became Poland’s main relay powers to push“eastern policy”. Therefore, the“Polonization”of EU’s“eastern policy”was the best way to realize its own“eastern policy”.

  10. Factors Restricting the Healthy Development of Non-governmental Institutions of Higher Learning from the Perspective of Public Spirit%从公共精神看民办高校健康发展的制约因素

    Institute of Scientific and Technical Information of China (English)

    薛金玲; 宋秋蓉

    2012-01-01

      公共精神是西方现代公民文化的核心观念,指在承认个人独立自主性的前提下,公民所拥有的着眼于社会整体的公共精神。目前我国部分民办高校办学者缺乏诚信自律意识、法制规则意识、公共责任意识等公共精神,并在一定程度上存在着背离公共精神的家族化意识。办学者缺乏相关的公共精神,是制约民办高校健康发展的重要因素。我国君主专制制度和儒家文化的负面效应是办学者缺乏公共精神的主要原因。昔日私立南开大学校长张伯苓所拥有的公共精神,值得当今民办高校的办学者学习。%  Public spirit, as the core concept of modern citizen culture in western world , refers to the consciousness of society as a whole held by citizens with the acknowledgement of full personal independence and autonomy .Some of the current administrators in non-governmental institutions of higher learning in China lack the public spirit of the awareness of integrity and self -discipline, regulation and legislation, as well as the sense of public responsibility .To some extends, they depart from public spirit and be-lieve in family consciousness.This is one of the main factors that prevent non-governmental institutions of higher learning from their healthy developments .The negative effect from China's autocratic monarchy and Confucian culture is one of the main reasons for administrators'lack of public spirit.The lifelong affection of public spirit of Zhang Boling , a former president of Nankai Uni-versity, is well worth learning by his peers today .

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

    Science.gov (United States)

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

    2007-10-10

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5alpha, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection. PMID:17574642

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

    International Nuclear Information System (INIS)

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

  13. Restriction of Retroviral Replication by Tetherin/BST-2

    Directory of Open Access Journals (Sweden)

    Jason Hammonds

    2012-01-01

    Full Text Available Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens.

  14. Asymptotics for restricted integer compositions

    CERN Document Server

    Malandro, Martin E

    2011-01-01

    We study the compositions of an integer n where the part sizes of the compositions are restricted to lie in a finite set. We obtain asymptotic formulas for the number of such compositions, the total and average number of parts among all such compositions, and the total and average number of times a particular part size appears among all such compositions. Several of our asymptotics have the additional property that their absolute errors---not just their percentage errors---go to 0 as n goes to infinity. Along the way we also obtain recurrences and generating functions for calculating several of these quantities. Our asymptotic formulas come from the meromorphic analysis of our generating functions. Our results also apply to questions about certain kinds of tilings and rhythm patterns.

  15. INTERPOLATION WITH RESTRICTED ARC LENGTH

    Institute of Scientific and Technical Information of China (English)

    Petar Petrov

    2003-01-01

    For given data (ti,yi), I= 0,1,…,n,0 = t0 <t1 <…<tn = 1we study constrained interpolation problem of Favard type inf{‖f"‖∞|f∈W2∞[0,1],f(ti)=yi,i=0,…,n,l(f;[0,1])≤l0}, wherel(f";[0,1])=∫1 0 / 1+f'2(x)dx is the arc length off in [0,1]. We prove the existence of a solution f* of the above problem, that is a quadratic spline with a second derivative f"* , which coincides with one of the constants - ‖f"*‖∞,0,‖f"*‖∞ between every two consecutive knots. Thus, we extend a result ofKarlin concerning Favard problem, to the case of restricted length interpolation.

  16. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    C S Srivatsan; M V N Murthy; R K Bhaduri

    2006-03-01

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured partitions $p_{k}^{s} (n)$, which is the number of partitions of an integer into the summand of th powers of integers such that each power of a given integer may occur utmost times. While the method is not rigorous, it reproduces the well-known asymptotic results for = 1 apart from yielding more general results for arbitrary values of .

  17. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  18. Analyzing the Restrictive Factors of Student Practice Intention Cultivation and Countermeasure in the University History Teaching%大学历史教学中学生实践动机培养的制约因素及对策分析

    Institute of Scientific and Technical Information of China (English)

    王小丽; 肖守库; 勾正刚; 许广灵

    2012-01-01

    实践动机是实践能力的构成要素之一。大学历史教学中存在着诸多制约学生实践动机培养的因素,历史教学应从培养实践兴趣,形成实践内驱力;构建研究性课堂,激发实践成就动机;加强实践教学环节,创设实践压力场景;营造实践氛国,优化实践动机培养外部环境来构建学生实践动机培养的对策,为学生实践能力发展创造条件。%Practice intention is one of component factors of practice ability. There are many factors to restrict cultivation of practice intention in the course of history teaching. Therefore, history teaching cultivates practice intention of student from cultivating practice interest and coming into practice interior power;building up study class and arousing practice achievement intention;beefing up practice teaching segment and setting up practice pressure scene;making practice atmosphere and perfecting external environment of practice intention cultivation. These countermeasures will create advantageous conditions for student cultivating practice intention cultivation and developing practice ability.

  19. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS

    2016-02-01

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

  20. Tumor Restrictions to Oncolytic Virus

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-04-01

    Full Text Available Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models. One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents. However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response. Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection. Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants. In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them.

  1. Cardiac MRI in restrictive cardiomyopathy

    International Nuclear Information System (INIS)

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

  2. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-15

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

  3. Nonparametric estimation and inference under shape restrictions

    OpenAIRE

    Horowitz, Joel; LEE, Sokbae

    2015-01-01

    Economic theory often provides shape restrictions on functions of interest in applications, such as monotonicity, convexity, non-increasing (non-decreasing) returns to scale, or the Slutsky inequality of consumer theory; but economic theory does not provide finite-dimensional parametric models. This motivates nonparametric estimation under shape restrictions. Nonparametric estimates are often very noisy. Shape restrictions stabilize nonparametric estimates without imposing arbitrary restricti...

  4. Measuring Regulatory Restrictions in Logistics Services

    OpenAIRE

    Hollweg, Claire; Marn-Heong WONG

    2009-01-01

    This study measures the extent of restrictions on trade in logistics services in the ASEAN+6 economies by constructing a logistics regulatory restrictiveness index for each economy that quantifies the extent of government regulations faced by logistics service providers. This is the first study of its kind to construct a regulatory index of the entire logistics sector, which includes the main modes of international transport and customs restrictions. The indices show that large differences ex...

  5. Measuring the Restrictiveness of International Trade Policy.

    OpenAIRE

    Anderson, James E.; Neary, J. Peter

    1994-01-01

    This article provides an introduction to the trade restrictiveness index (TRI), which equals the uniform tariff that is welfare equivalent to a given pattern of trade protection. Unlike standard measures of trade restrictiveness, the TRI has a solid theoretical basis, can incorporate both tariffs and quantitative restrictions, and can be adapted to construct the trade policy equivalent of domestic distortions, the article compares a number of applications and describes procedures for operatio...

  6. SAMHD1: a new insight into HIV-1 restriction in myeloid cells

    OpenAIRE

    Wu Li; St Gelais Corine

    2011-01-01

    Abstract Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 ...

  7. Incorporating theoretical restrictions into forecasting by projection methods

    OpenAIRE

    Raffaella Giacomini

    2012-01-01

    We propose a method for modifying a given density forecast in a way that incorporates the information contained in theory-based moment conditions. An example is "improving" the forecasts from atheoretical econometric models, such as factor models or Bayesian VARs, by ensuring that they satisfy theoretical restrictions given for example by Euler equations or Taylor rules. The method yields a new density (and thus point-) forecast which has a simple and convenient analytical expression and whic...

  8. Incorporating theoretical restrictions into forecasting by projection methods

    OpenAIRE

    Giacomini, Raffaella; Ragusa, Giuseppe

    2011-01-01

    We propose a method for modifying a given density forecast in a way that incorporates the information contained in theory-based moment conditions. An example is "improving" the forecasts from atheoretical econometric models, such as factor models or Bayesian VARs, by ensuring that they satisfy theoretical restrictions given for example by Euler equations or Taylor rules. The method yields a new density (and thus point-) forecast which has a simple and convenient analytical expression and whic...

  9. The Restriction .on Educational Quality in Rural Schools

    Institute of Scientific and Technical Information of China (English)

    艾丽娜

    2012-01-01

    In order to understand the educational quality in rural schools, I went deep into Huangjia Middle School( situated in Northern China) to make the research. In this article, I focus on the restrictions on educational qualitys, which is one of the main themes about rural education. The factors influencing quality in rural schools are analyzed in this article .It is concluded that educational quality depends on the relationship of teaching and learning and its supporting context.

  10. Does Intellectual Property Restrict Output? An Analysis of Pharmaceutical Markets*

    OpenAIRE

    Darius Lakdawalla; Tomas Philipson

    2012-01-01

    Standard analysis of intellectual property focuses on the balance between incentives for research and the welfare costs of restraining output through monopoly pricing. We present evidence from the pharmaceutical industry that output often fails to rise after patent expirations. Patents restrict output by allowing monopoly pricing but may also boost output and welfare by improving incentives for marketing, a form of nonprice competition. We analyze how nonprice factors such as marketing mitiga...

  11. Estimation of average causal effect using the restricted mean residual lifetime as effect measure

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben

    2016-01-01

    Although mean residual lifetime is often of interest in biomedical studies, restricted mean residual lifetime must be considered in order to accommodate censoring. Differences in the restricted mean residual lifetime can be used as an appropriate quantity for comparing different treatment groups ...... is also applied to an observational data set of patients after an acute myocardial infarction event....... with respect to their survival times. In observational studies where the factor of interest is not randomized, covariate adjustment is needed to take into account imbalances in confounding factors. In this article, we develop an estimator for the average causal treatment difference using the restricted...

  12. An Event Restriction Interval Theory of Tense

    Science.gov (United States)

    Beamer, Brandon Robert

    2012-01-01

    This dissertation presents a novel theory of tense and tense-like constructions. It is named after a key theoretical component of the theory, the event restriction interval. In Event Restriction Interval (ERI) Theory, sentences are semantically evaluated relative to an index which contains two key intervals, the evaluation interval and the event…

  13. 44 CFR 402.2 - Restricted commodities.

    Science.gov (United States)

    2010-10-01

    ... Positive List (15 CFR part 399) (as amended from time to time) of the Comprehensive Export Schedule of the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Restricted commodities. 402.2... SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.2 Restricted commodities. The...

  14. Restricting mutualistic partners to enforce trade reliance

    Science.gov (United States)

    Wyatt, Gregory A. K.; Kiers, E. Toby; Gardner, Andy; West, Stuart A.

    2016-01-01

    Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise-cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID:26813888

  15. 42 CFR 73.13 - Restricted experiments.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Restricted experiments. 73.13 Section 73.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING... restricted experiment with a HHS select agent or toxin unless approved by and conducted in accordance...

  16. 30 CFR 56.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11008 Restricted clearance. Where...

  17. 50 CFR 648.203 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Herring Fishery § 648.203 Gear restrictions. (a) Midwater trawl gear may only be used by a vessel issued a... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.203 Section 648.203 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  18. 50 CFR 648.144 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Fishery § 648.144 Gear restrictions. (a) Trawl gear restrictions—(1) General. (i) Otter trawlers whose... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.144 Section 648.144 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  19. 50 CFR 660.506 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... restrictions. The only fishing gear authorized for use in the reduction fishery for northern anchovy off... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 660.506 Section 660.506 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  20. 50 CFR 648.163 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Bluefish Fishery § 648.163 Gear restrictions. If the Council determines through its annual review or... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.163 Section 648.163 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  1. 50 CFR 665.664 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 665.664 Section 665.664 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... § 665.664 Gear restrictions. Only selective gear may be used to harvest coral from any precious...

  2. 50 CFR 665.464 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 665.464 Section 665.464 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Gear restrictions. Only selective gear may be used to harvest coral from any precious coral permit area....

  3. 40 CFR 1033.740 - Credit restrictions.

    Science.gov (United States)

    2010-07-01

    ... restrictions. Use of emission credits generated under this part 1033 or 40 CFR part 92 is restricted depending on the standards against which they were generated. (a) Credits from 40 CFR part 92. NOX and PM credits generated under 40 CFR part 92 may be used under this part in the same manner as NOX and...

  4. Near BPS skyrmions and restricted harmonic maps

    Science.gov (United States)

    Speight, J. M.

    2015-06-01

    Motivated by a class of near BPS Skyrme models introduced by Adam, Sánchez-Guillén and Wereszczyński, the following variant of the harmonic map problem is introduced: a map φ :(M, g) →(N, h) between Riemannian manifolds is restricted harmonic if it locally extremizes E2 on its SDiff(M) orbit, where SDiff(M) denotes the group of volume preserving diffeomorphisms of (M, g), and E2 denotes the Dirichlet energy. It is conjectured that near BPS skyrmions tend to restricted harmonic maps in the BPS limit. It is shown that φ is restricted harmonic if and only if φ∗ h has exact divergence, and a linear stability theory of restricted harmonic maps is developed, from which it follows that all weakly conformal maps are stable restricted harmonic. Examples of restricted harmonic maps in every degree class R3 → SU(2) and R2 →S2 are constructed. It is shown that the axially symmetric BPS skyrmions on which all previous analytic studies of near BPS Skyrme models have been based, are not restricted harmonic, casting doubt on the phenomenological predictions of such studies. The problem of minimizing E2 for φ :Rk → N over all linear volume preserving diffeomorphisms is solved explicitly, and a deformed axially symmetric family of Skyrme fields constructed which are candidates for approximate near BPS skyrmions at low baryon number. The notion of restricted harmonicity is generalized to restricted F-criticality where F is any functional on maps (M, g) →(N, h) which is, in a precise sense, geometrically natural. The case where F is a linear combination of E2 and E4, the usual Skyrme term, is studied in detail, and it is shown that inverse stereographic projection R3 →S3 ≡ SU(2) is stable restricted F-critical for every such F.

  5. 胰岛素样生长因子Ⅰ受体基因突变与宫内生长受限的研究进展%Development of mutation of insulin-like growth factor Ⅰreceptor and intrauterine growth restriction

    Institute of Scientific and Technical Information of China (English)

    唐梅; 杨凡

    2016-01-01

    目前有关胰岛素生长因子(IGF)家族与胎儿宫内生长受限(IUGR)的研究逐渐增多。在胰岛素样生长因子Ⅰ受体(IGF-ⅠR)基因突变所致 IUGR 患儿中,除了常见的体格生长发育落后,还常合并头小畸形,以及运动、语言发育落后等不同程度的精神发育迟滞。关于 IUGR 发生机制有较多研究,但其确切机制目前尚未明确。目前有关IGF-ⅠR 不同位点的杂合突变导致 IUGR 的研究较多,本文就IGF-ⅠR 不同位点基因突变导致的 IUGR 临床表现及其可能机制进行综述。%In recently years,the amount of researches about relationship between insulin-like growth factor(IGF)family and intrauterine growth restriction(IUGR)was increasing.IUGR which caused by insulin-like growth factor-Ⅰ receptor (IGF-Ⅰ R )mutation usually can lead to mental retardation,such as microcephaly abnormal development in motor and language besides physical growth backwardness.The mechanism of IUGR is still not clear.Now many researches focus on different point heterozygous mutation of IGF-ⅠR which leads to IUGR,and this review will make a summary of the different point mutations.

  6. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

    Directory of Open Access Journals (Sweden)

    I-Chueh Huang

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  7. Restriction beyond the restriction point: mitogen requirement for G2 passage

    Directory of Open Access Journals (Sweden)

    te Riele Hein

    2006-05-01

    Full Text Available Abstract Cell proliferation is dependent on mitogenic signalling. When absent, normal cells cannot pass the G1 restriction point, resulting in cell cycle arrest. Passage through the G1 restriction point involves inactivation of the retinoblastoma protein family. Consequently, loss of the retinoblastoma protein family leads to loss of the G1 restriction point. Recent work in our lab has revealed that cells possess yet another mechanism that restricts proliferation in the absence of mitogens: arrest in the G2 phase of the cell cycle. Here, we discuss the similarities and differences between these restriction points and the roles of cyclin-dependent kinase inhibitors (CKIs herein.

  8. Urban water restrictions: Attitudes and avoidance

    Science.gov (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin

    2011-12-01

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

  9. Restrictive extraocular myopathy: A presenting feature of acromegaly

    Directory of Open Access Journals (Sweden)

    Steven Heireman

    2011-01-01

    Full Text Available A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

  10. Some restrictions on the existence of second order limit language

    Science.gov (United States)

    Ahmad, Muhammad Azrin; Sarmin, Nor Haniza; Yusof, Yuhani; Fong, Wan Heng

    2015-10-01

    The cut and paste phenomenon on DNA molecules with the presence of restriction enzyme and appropriate ligase has led to the formalism of mathematical modelling of splicing system. A type of splicing system named Yusof-Goode splicing system is used to present the transparent behaviour of the DNA splicing process. The limit language that is defined as the leftover molecules after the system reaches its equilibrium point has been extended to a second order limit language. The non-existence of the second order limit language biologically has lead to this study by using mathematical approach. In this paper, the factors that restrict the formation of the second order limit language are discussed and are presented as lemmas and theorem using Y-G approach. In addition, the discussion focuses on Yusof- Goode splicing system with at most two initial strings and two rules with one cutting site and palindromic crossing site and recognition sites.

  11. Age-restricted housing in New England

    OpenAIRE

    Peter Francese

    2008-01-01

    Fair Housing Act amendments exempt housing restricted to “older persons” from provisions protecting families with children from discrimination. But municipal leaders who believe that promoting over-55 housing will reduce education costs are in for a rude awakening.

  12. Restrictions and extensions of semibounded operators

    CERN Document Server

    Jorgensen, Palle; Tian, Feng

    2012-01-01

    We study restriction and extension theory for semibounded Hermitian operators in the Hardy space of analytic functions on the disk D. Starting with the operator zd/dz, we show that, for every choice of a closed subset F in T=bd(D) of measure zero, there is a densely defined Hermitian restriction of zd/dz corresponding to boundary functions vanishing on F. For every such restriction operator, we classify all its selfadjoint extension, and for each we present a complete spectral picture. We prove that different sets F with the same cardinality can lead to quite different boundary-value problems, inequivalent selfadjoint extension operators, and quite different spectral configurations. As a tool in our analysis, we prove that the von Neumann deficiency spaces, for a fixed set F, have a natural presentation as reproducing kernel Hilbert spaces, with a Hurwitz zeta-function, restricted to FxF, as reproducing kernel.

  13. Avoidant/Restrictive Food Intake Disorder

    Science.gov (United States)

    ... Intake Disorder Binge Eating Disorder Bulimia Nervosa Pica Rumination Disorder Avoidant/restrictive food intake disorder is characterized ... Intake Disorder Binge Eating Disorder Bulimia Nervosa Pica Rumination Disorder NOTE: This is the Consumer Version. CONSUMERS: ...

  14. Bound on m-restricted Edge Connectivity

    Institute of Scientific and Technical Information of China (English)

    Jian-ping Ou; Fu-ji Zhang

    2003-01-01

    An m-restricted edge cut is an edge cut that separates a connected graph into a disconnected one with no components having order less than m. m-restricted edge connectivity λm is the cardinality of a minimum m-restricted edge cut. Let G be a connected k-regular graph of order at least 2m that contains m-restricted edge cuts and X be a subgraph of G. Let( )(X) denote the number of edges with one end in X and the other not in X and ξm = min{( )(X): X is a connected vertex-induced subgraph of order m}. It is proved in this paper that if G has girth at least m/2 + 2, then λm ≤ξm. The upper bound of λm is sharp.

  15. The Frattini Subalgebra of Restricted Lie Superalgebras

    Institute of Scientific and Technical Information of China (English)

    Liang Yun CHEN; Dao Ji MENG; Yong Zheng ZHANG

    2006-01-01

    In the present paper, we study the Frattini subalgebra of a restricted Lie superalgebra (L, [p]). We show first that if L = A1 (⊙) A2 (⊙) … (⊙) An, then φp (L) = φp (A1) + φp (A2) +… +φp (An),where each Ai is a p-ideal of L. We then obtain two results: F(L) = φ(L) = J(L) = L(1) if and only if L is nilpotent; Fp(L) and F(L) are nilpotent ideals of L if L is solvable. In addition, necessary and sufficient conditions are found for φp-free restricted Lie superalgebras. Finally, we discuss the relationships of E-p-restricted Lie superalgebras and E-restricted Lie superalgebras.

  16. Restrictions on Database Use: Are They Necessary?

    Science.gov (United States)

    Molster, H. C.

    1979-01-01

    Discusses restrictions regarding use of bibliographic data bases, cites their rationale in terms of cooperation in input creation, economics and administrative control, and notes their effect on use. (Author/CWM)

  17. The Family Context of Low-Income Parents Who Restrict Child Screen Time

    Science.gov (United States)

    Jurkowski, Janine M.; Davison, Kirsten K.

    2013-01-01

    Abstract Background The American Academy of Pediatrics recommends that parents restrict child screen time to two hours per day, but many preschool-aged children exceed this viewing recommendation. Modifying children's viewing habits will require collaborating with parents, but little is known about the factors that influence parents' capacity for effective screen-related parenting. This study aimed to identify the demographic, family and community contextual factors associated with low-income parents' restriction of child screen time. Methods Parents (N=146) of children (age 2–5 years) attending Head Start centers in the United States completed a self-report survey in 2010 assessing parent and child screen use (television, DVD, video, video games, and leisure-time computer use), parent restriction of child screen time, and family (parent stress, social support, and life pressures) and community (neighborhood safety and social capital) factors. Results Children were more likely to meet the American Academy of Pediatrics screen time recommendation if their parent reported high restriction of child screen time. Parent and child demographic characteristics were not associated with parents' restriction of child screen time. In multivariate analysis, less parent screen time, fewer parent life pressures, and greater social support were associated with parents' high restriction of screen time. Conclusion Family contextual factors may play an important role in enabling low-income parents to restrict their children's screen time. When counseling low-income parents about the importance of restricting child screen time, practitioners should be sensitive to family contextual factors that may influence parents' capacity to implement this behavior change. PMID:24004326

  18. Behavioral and Physiological Consequences of Sleep Restriction

    OpenAIRE

    Banks, Siobhan; Dinges, David F.

    2007-01-01

    Adequate sleep is essential for general healthy functioning. This paper reviews recent research on the effects of chronic sleep restriction on neurobehavioral and physiological functioning and discusses implications for health and lifestyle. Restricting sleep below an individual's optimal time in bed (TIB) can cause a range of neurobehavioral deficits, including lapses of attention, slowed working memory, reduced cognitive throughput, depressed mood, and perseveration of thought. Neurobehavio...

  19. Public Investment, Revenue Shocks, and Borrowing Restrictions

    OpenAIRE

    Büttner, Thiess; David E. Wildasin

    2010-01-01

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

  20. Counting planar diagrams with various restrictions

    OpenAIRE

    1998-01-01

    Explicit expressions are considered for the generating functions concerning the number of planar diagrams with given numbers of 3- and 4-point vertices. It is observed that planar renormalization theory requires diagrams with restrictions, in the sense that one wishes to omit `tadpole' inserions and `seagull' insertions; at a later stage also self-energy insertions are to be removed, and finally also the dressed 3-point inserions and the dressed 4-point insertions. Diagrams with such restrict...

  1. Counting Planar Diagrams with Various Restrictions

    OpenAIRE

    Hooft, G. 't

    1999-01-01

    Explicit expressions are considered for the generating functions concerning the number of planar diagrams with given numbers of 3- and 4-point vertices. It is observed that planar renormalization theory requires diagrams with restrictions, in the sense that one wishes to omit `tadpole' inserions and `seagull' insertions; at a later stage also self-energy insertions are to be removed, and finally also the dressed 3-point inserions and the dressed 4-point insertions. Diagrams with such restrict...

  2. Feed restriction in broiler chickens production

    OpenAIRE

    Sahraei M.

    2012-01-01

    The feed restriction program is on of the main techniques in growth curve manipulation for increasing production efficiency in broiler chicken. Quantities and qualitative feed restriction are procedures that can be used to manipulate the feeding strategies of poultry in order to decrease growth and metabolic rate to some extent and so alleviate the incidence of some metabolic diseases such as ascites, lameness, mortality, and sudden death syndrome and so im...

  3. Restricted three body problems at the nanoscale

    OpenAIRE

    Chan, Yue; Thamwattana, Ngamta; Hill, James M.

    2009-01-01

    In this paper, we investigate some of the classical restricted three body problems at the nanoscale, such as the circular planar restricted problem for three C60 fullerenes, and a carbon atom and two C60 fullerenes. We model the van der Waals forces between the fullerenes by the Lennard-Jones potential. In particular, the pairwise potential energies between the carbon atoms on the fullerenes are approximated by the continuous approach, so that the total molecular energy between two fullerenes...

  4. Date restricted queries in web search engines

    OpenAIRE

    Lewandowski, Dirk

    2004-01-01

    Search engines usually offer a date restricted search on their advanced search pages. But determining the actual update of a web page is not without problems. We conduct a study testing date restricted queries on the search engines Google, Teoma and Yahoo!. We find that these searches fail to work properly in the examined engines. We discuss implications of this for further research and search engine development.

  5. Temporary Tariffs and Capital Market Restrictions

    OpenAIRE

    Saqib Jafarey; Sajal Lahiri

    2004-01-01

    We develop a two-period model with endogenous investment and credit flows. Credit is subject to quantitative restrictions. With an exogenous restriction, we analyze the welfare effects of temporary tariffs. We then consider three scenarios under which a monopoly lender optimally decides the level of credit and a borrower country chooses an import tariff: one in which the two parties act simultaneously and two scenarios where one of them has a first-mover advantage. The equilibrium under the l...

  6. Regional restriction, strategic delegation, and welfare

    OpenAIRE

    Matsumura, Toshihiro; Matsushima, Noriaki

    2009-01-01

    We investigate the effects of restricting locations of firms into Hotelling duopoly models. In the standard location-price models, the equilibrium distance between firms is too large from the viewpoint of consumer welfare. Thus, restricting locations of firms and reducing the distance between firms improve consumer welfare, through lower prices and smaller transportation costs for consumers. We introduce strategic reward contracts into the location-price models. We find that in contrast to th...

  7. Placental Nutrient Transport and Intrauterine Growth Restriction

    OpenAIRE

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and...

  8. An Adjustment Restriction on Fish Quota

    OpenAIRE

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

    2016-01-01

    Management objectives of the European Union for North Sea fish stocks are shifting towards considering both biological sustainability and economic benefits. As part of multiannual management plans, an adjustment restriction on fish quota has been introduced. Its objective is to obtain an efficient fish stock and to reduce overcapacity for the fishing industry. We develop and apply a bi-level stochastic dynamic programming model to study the effect of a quota adjustment restriction on the net ...

  9. The pathophysiology of restricted repetitive behavior

    OpenAIRE

    Lewis, Mark; Kim, Soo-Jeong

    2009-01-01

    Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, l...

  10. Emotion regulation training to reduce problematic dietary restriction: An experimental analysis.

    Science.gov (United States)

    Haynos, Ann F; Hill, Bailey; Fruzzetti, Alan E

    2016-08-01

    Evidence suggests that emotion regulation may be a process relevant to problematic dietary restriction. However, emotion regulation has not been evaluated as an intervention target across a range of restriction severity. This study utilized an experimental design to examine whether targeting emotion regulation reduced problematic dietary restriction. Within a self-identified restrictive sample (n = 72), the effects of an emotion regulation condition (i.e., emotion regulation training) were compared to those of a control condition (i.e., nutrition information training) on dietary restriction indices (i.e., effort to reduce intake on a progressive ratio task, work towards an alternate reinforcer on a progressive ratio task, intake by dietary recall) following a stressor. Exploratory analyses of potential moderators (i.e., restraint, BMI, binge eating and purging status, emotion regulation difficulties) were conducted to examine whether these factors affected the impact of training on dietary restriction. No significant main effects of condition were detected on any outcome measure. However, results were moderated by BMI status. Participants with lower BMIs exerted less effort towards dietary restriction following the emotion regulation condition versus the control condition (p = 0.02). Results suggest that targeting emotion regulation may help to reduce problematic dietary restriction among lower weight individuals. PMID:27105583

  11. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction*

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Xiaofeng Wang; Ying Liu; Na Yang; Jing Xu; Xiaotun Ren

    2013-01-01

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neo-natal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cel s in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cel apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cel line-derived neuro-trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cel apoptosis through the glial cel line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  12. The impacts of time access restrictions and vehicle weight restrictions on food retailers and the environment

    OpenAIRE

    Quak, Hans; Koster, René

    2006-01-01

    textabstractUrban freight transport has many sustainable aspects. It contributes to economic vitality and the competitiveness of a region. However, the less socially and environmentally friendly effects such as noise, pollutant emissions, and nuisance, are usually the central theme in designing urban freight transport policies. Restricting policies as time access restrictions and vehicle restrictions gain popularity among Dutch local authorities. More than half of the municipalities uses time...

  13. [Is restriction of physical activity indicated in the prevention of retinal detachment?].

    Science.gov (United States)

    Karel, I

    1993-06-01

    The author evaluates the importance of different vitreoretinal factors and the role of indirect injury in the pathogenesis of detachment of the retina/DR/and holds the following view as regards subjects inclined to pursue physical activity. Numerous and frequent vitreoretinal risk factors are a forecast of DR only in a small fraction of patients. Indirect injury is not recognized as a cause of DR. Risk factors incl. medium-grade and high-grade myopia are not an indication for restriction of physical activity nor for Caesarean section in pregnant women. Restriction of physical activity acts as a psychic trauma and does not prevent the development of DR. PMID:8348645

  14. Protein Expressions and Their Immunogenicity from Riemerella anatipestifer Cultured in Iron Restriction Medium

    OpenAIRE

    Yifei Yang; Changqin Gu; Yonghong Liao; Qingping Luo; Xueying Hu; Wanpo Zhang; Huabin Shao; Guofu Cheng

    2013-01-01

    Riemerella anatipestifer was cultured in both iron restriction media and normal media. Two-dimensional gel electrophoresis identified 23 proteins that significantly increased in the iron restriction media. Of them 12 proteins were analyzed with mass spectrography. Nine of 12 proteins belong to 6 different protein families: fibronectin type iii domain protein, secreted subtilase family protein, phosphoglycerate kinase, translation elongation factor, leucine-rich repeat-containing protein, and ...

  15. Fasting and Caloric Restriction in Cancer Prevention and Treatment.

    Science.gov (United States)

    Brandhorst, Sebastian; Longo, Valter D

    2016-01-01

    Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapy is to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance. PMID:27557543

  16. Newer antidiabetic drugs and calorie restriction mimicry

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

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

  17. Potentializing and restrictive factors in the implementation of the balanced scorecard: a study in a contruction firm in the state of Ceará Fatores potencializadores e restritivos à implantação do Balanced Scorecard:um estudo em uma empresa de construção civil do Ceará

    Directory of Open Access Journals (Sweden)

    Roberta Catrib de Azevedo Lemos

    2011-12-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The Balanced Scorecard (BSC, better known as a method to translate a firm’s mission and strategy into a broad set of performance measurements, has been used for the strategic management of organizations, serving as a measurement system  that, besides the financial goals, includes performance characteristics. This research, which was carried out through a case study, aims at identifying the main potentializing and restrictive factors in the implementation of the BSC in a civil construction firm in the state of Ceará, the Porto Freire Engineering. The bibliographical research, which was based on the managerial reports of the 2003 to 2009 period, showed that the firm conducted the process necessary to the implementation of the BSC for the management of its strategy. The field data were collected through questionnaires and interviews applied, respectively, to the employees and managers who already were in the firm when the BSC was implemented. The questionnaire data show that, among the set of twenty factors considered in the research, only three were deemed potentializing in the implementation of the BSC: technical support, balancing of the four perspectives and preservation of

  18. Risk Factors for Eating Disorders

    Science.gov (United States)

    Striegel-Moore, Ruth H.; Bulik, Cynthia M.

    2007-01-01

    The authors review research on risk factors for eating disorders, restricting their focus to studies in which clear precedence of the hypothesized risk factor over onset of the disorder is established. They illustrate how studies of sociocultural risk factors and biological factors have progressed on parallel tracks and propose that major advances…

  19. Optimal control of entanglement under restrictions

    International Nuclear Information System (INIS)

    We present a novel iterative algorithm with a special presearching step that can optimize the entanglement of a coupled quantum system while fulfilling restrictions of the control function. As an example we regard two atoms in a harmonic trap which interact via point-like collisions. Our aim is to improve the entanglement at a fixed time by dynamically varying the trap frequency within a fixed interval. In order to get rid of the restrictions for the trap frequency, we use a suitable parameterization that transforms the optimization problem from a restricted to an unrestricted one. By applying the pre-searching step we get a reasonable initial guess for the optimal trap frequency. Finally, we use a standard method based on optimal control theory to further increase the entanglement.

  20. Quantum Game with Restricted Matrix Strategies

    Institute of Scientific and Technical Information of China (English)

    CHENBo; MAYing-Jun; LONGGui-Lu

    2003-01-01

    We study a quantum game played by two players with restricted multiple strategies. It is found that in this restricted quantum game Nash equilibrium does not always exist when the initial state is entangled. At the same time,we find that when Nasli equilibrium exists the payoff function is usually different from that in the classical counterpart except in some special cases. This presents an explicit example showing quantum game and classical game may differ.When designing a quantum game with limited strategies, the allowed strategy should be carefully chosen according to the type of initial state.

  1. Quantum Game with Restricted Matrix Strategies

    Institute of Scientific and Technical Information of China (English)

    CHEN Bo; MA Ying-Jun; LONG Gui-Lu

    2003-01-01

    We study a quantum game played by two players with restricted multiple strategies. It is found that in this restricted quantum game Nash equilibrium does not always exist when the initial state is entangled. At the same time,we find that when Nash equilibrium exists the payoff function is usually different from that in the classical counterpart except in some special cases. This presents an explicit example showing quantum game and classical game may differ.When designing a quantum game with limited strategies, the allowed strategy should be carefully chosen according to the type of initial state.

  2. Social–Cognitive Predictors of Low-Income Parents’ Restriction of Screen Time Among Preschool-Aged Children

    Science.gov (United States)

    Lampard, Amy M.; Jurkowski, Janine M.; Davison, Kirsten K.

    2015-01-01

    Parents’ rules regarding child television, DVD, video game, and computer use (screen time) have been associated with lower screen use in children. This study aimed to identify modifiable correlates of this behavior by examining social–cognitive predictors of parents’ restriction of child screen time. Low-income parents (N = 147) of preschool-aged children (2–6 years) completed self-administered questionnaires examining parent and child screen time, parent restriction of screen time, self-efficacy to restrict screen time, and beliefs about screen time. Structural equation modeling results indicated that greater self-efficacy to restrict screen time (β = .29, p = .016) and greater perceived importance of restricting child screen use (β = .55, p child screen use, after controlling for parent screen time. Family-based interventions that consider broader attitudinal factors around child screen time may be necessary to engage parents in restricting screen use. PMID:23239766

  3. Restricted Liberty, Parental Choice and Homeschooling

    Science.gov (United States)

    Merry, Michael S.; Karsten, Sjoerd

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequality, worsens societal conflict and works against…

  4. Restricted liberty, parental choice and homeschooling

    NARCIS (Netherlands)

    M.S. Merry; S. Karsten

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequalit

  5. 21 CFR 203.20 - Sales restrictions.

    Science.gov (United States)

    2010-04-01

    ... drug that was: (a) Purchased by a public or private hospital or other health care entity; or (b... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sales restrictions. 203.20 Section 203.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS:...

  6. Fusion Frames and the Restricted Isometry Property

    OpenAIRE

    Bodmann, Bernhard,; Cahill, Jameson; Casazza, Peter G.

    2011-01-01

    We will show that tight frames satisfying the restricted isometry property give rise to nearly tight fusion frames which are nearly orthogonal and hence are nearly equi-isoclinic. We will also show how to replace parts of the RIP frame with orthonormal sets while maintaining the RIP property.

  7. 12 CFR 1805.808 - Lobbying restrictions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Lobbying restrictions. 1805.808 Section 1805.808 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Terms and Conditions of Assistance § 1805.808...

  8. 9 CFR 77.32 - General restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false General restrictions. 77.32 Section 77.32 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive...

  9. 7 CFR 3430.905 - Funding restrictions.

    Science.gov (United States)

    2010-01-01

    ... Program § 3430.905 Funding restrictions. (a) Prohibition against construction. Grant funds awarded under... space; the purchase or installation of fixed equipment in such space; or the planning, repair, rehabilitation, acquisition, or construction of buildings or facilities. (b) Prohibition on tuition...

  10. 50 CFR 648.105 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.105 Section 648.105 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... November 1 through April 30, unless the vessel possesses a valid summer flounder small-mesh exemption...

  11. 9 CFR 166.2 - General restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false General restrictions. 166.2 Section 166.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.2 General...

  12. Observing Behavior and Atypically Restricted Stimulus Control

    Science.gov (United States)

    Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

  13. 30 CFR 57.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground §...

  14. 50 CFR 648.123 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.123 Section 648.123 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Management Measures for the Scup...

  15. 50 CFR 654.22 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 654.22 Section 654.22 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE STONE CRAB FISHERY OF THE GULF OF MEXICO Management Measures § 654.22...

  16. 46 CFR 119.405 - Fuel restrictions.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Fuel restrictions. 119.405 Section 119.405 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150 PASSENGERS OR WITH OVERNIGHT ACCOMMODATIONS FOR MORE THAN 49 PASSENGERS MACHINERY INSTALLATION...

  17. Design implications of extremely restricted patterning

    Science.gov (United States)

    Vaidyanathan, Kaushik; Liu, Renzhi; Liebmann, Lars; Lai, Kafai; Strojwas, Andzrej J.; Pileggi, Larry

    2014-07-01

    Escalating manufacturing cost and complexity is challenging the premise of affordable scaling. With lithography accounting for a large fraction of wafer costs, researchers are actively exploring several cost-effective alternative lithographic techniques, such as directed self-assembly, self-aligned multiple patterning, etc. However, most of the alternative lithographic techniques are restrictive, and it is important to understand the impact of such pattering restrictions on system-on-chip (SoC) design. To this end, we artificially restricted all layers in a 14 nm process to be pure gratings and observed that the pure gratings approach results in an inefficient SoC design with several process integration concerns. To come up with a technology definition that is mindful of designer requirements, it is essential to undertake a holistic design technology co-optimization (DTCO) considering several SoC design elements, such as standard cell logic, static random access memory bitcells, analog blocks, and physical synthesis. Our DTCO on the IBM 14 nm process with additional 10- and 7-nm node-like pattern restrictions leads us to converge on a set of critical pattern constructs that are required for an efficient and affordable SoC design.

  18. 40 CFR 170.112 - Entry restrictions.

    Science.gov (United States)

    2010-07-01

    .... (2) Entry-restricted areas in greenhouses are specified in column D in table 2 under § 170.110(c)(4... at the appropriate address as set forth in 40 CFR 150.17(a) or (b) and must be accompanied by two...; using an alternative to the hand labor tasks, such as machine cultivation; or substituting a...

  19. Material and Cultural Restriction of Political Life

    Institute of Scientific and Technical Information of China (English)

    马国祥

    2015-01-01

    Material and culture have a certain influence on the political life. In general, the higher level of economic development of the country, people's political life is more democratic. Culture has some negative effect on the political life. China's traditional cul-ture has restricted the people's political life in some ways.

  20. Maternal determinants of intrauterine growth restriction in Goa, India: a case-control study

    Directory of Open Access Journals (Sweden)

    DD Motghare

    2014-01-01

    Full Text Available Objective: To study the maternal determinants of intrauterine growth restriction. Methods: A case-control study was conducted at a tertiary care Hospital in the year 2009. Ninety eight cases of intrauterine growth restriction were compared to 98 controls, matched for newborns sex and type of delivery. Data was collected by interviewing the mother using a structured pretested schedule and perusal of antenatal records. Intrauterine growth restriction was defined as occurring if birth weight of the newborn is below 10th percentile for gestational age on the intrauterine growth curve. Data was analyzed using SPSS software version 17 package. Percentages, odds ratios with 95% CI and multiple logistic regression analysis were used wherever appropriate. Results: Maternal age, education, socioeconomic status and number of antenatal visits were found to be the significant socio-demographic factors associated with Intrauterine growth restriction while, maternal height, parity, previous spontaneous abortion, direct obstetric morbidity, indirect obstetric morbidity and anemia were the maternal biological factors found to be significantly associated on bivariate analysis. Multiple logistic regression analysis identified parity, previous spontaneous abortion, direct obstetric morbidity, indirect obstetric morbidity and antenatal visits as significant maternal determinants of intrauterine growth restriction. Conclusions: A focus on good antenatal care, especially on high risk pregnancies would go a long way in reducing the problem of intrauterine growth restriction in the community thereby ensuring a safe and healthy future for our youngest generation.

  1. Characterization of RNA binding and chaperoning activities of HIV-1 Vif protein: Importance of the C-terminal unstructured tail

    OpenAIRE

    Sleiman, Dona; Bernacchi, Serena; Xavier Guerrero, Santiago; Brachet, Franck; Larue, Valéry; Paillart, Jean-Christophe; Tisné, Carine

    2014-01-01

    The viral infectivity factor (Vif) is essential for the productive infection and dissemination of HIV-1 in non-permissive cells, containing the cellular anti-HIV defense cytosine deaminases APOBEC3 (A3G and A3F). Vif neutralizes the antiviral activities of the APOBEC3G/F by diverse mechanisms including their degradation through the ubiquitin/proteasome pathway and their translational inhibition. In addition, Vif appears to be an active partner of the late steps of viral replication by interac...

  2. 7 CFR 322.28 - General requirements; restricted articles.

    Science.gov (United States)

    2010-01-01

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

  3. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

    Full Text Available BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y, overweight (body mass index, 27.8 +/- 0.7 kg/m(2 individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX, 12.5% CR + 12.5% increased energy expenditure (EE. In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008. Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05. In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005 and 21% +/- 4% in the CREX group (p < 0.004, with no change in the control group (2% +/- 2%. However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid cycle (citrate synthase, beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase, and electron transport chain (cytochrome C oxidase II was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003 and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011, but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content

  4. Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones

    OpenAIRE

    Yuen, William W.; Du, Nan R.; Chan, Chun H.; Silva, Eduardo A.; Mooney, David J.

    2010-01-01

    Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Furt...

  5. Restriction of dairy products: a reality in inflammatory bowel disease patients

    Directory of Open Access Journals (Sweden)

    Mirella Brasil Lopes

    2014-03-01

    Full Text Available Introduction: Calcium deficiency is considered a risk factor for the development of osteoporosis in inflammatory bowel disease (IBD patients. Various dietary restrictions, including milk products are reported by these patients. Objective: To evaluate dairy product and dietary calcium intake by IBD patients. Methods: This cross-sectional study enrolled 65 outpatients with IBD recruited from one reference center for IBD. A semi-structured questionnaire (to collect demographic, socioeconomic and clinical data and a quantitative food frequency questionnaire were administered. With regard to clinical data, we evaluated the anthropometric nutritional status, the disease classification, the disease activity index and the presence of gastrointestinal symptoms. Selfreported modifications in the use of dairy products were evaluated. Results: The IBD patients´ ages ranged from 20-75 years and 67.0% were diagnosed with ulcerative colitis. The majority (64.7% reported restricting dairy products. The frequency of gastrointestinal symptoms was higher among the Crohn´s disease patients who restricted dairy products than among those with no restrictions (100% vs 42.9%; p = 0.013; this result was not observed among the UC (ulcerative colitis patients. Disease activity was also more frequent in the IBD patients who restricted dairy products than in those with no restrictions (23.8% vs 4.5%; p = 0.031, and among the UC patients, extensive disease was more common in the patients who restricted dairy products than in those with no restrictions (42.9% vs 20.0%; p = 0.03. Conclusion: Restricting dairy products is common among IBD patients, possibly due to disease activity, the presence of gastrointestinal symptoms and the extension of the disease.

  6. Set identification via quantile restrictions in short panels

    OpenAIRE

    Rosen, Adam

    2012-01-01

    This paper studies the identifying power of conditional quantile restrictions in short panels with fixed effects. In contrast to classical fixed effects models with conditional mean restrictions, conditional quantile restrictions are not preserved by taking differences in the regression equation over time. This paper shows however that a conditional quantile restriction, in conjunction with a weak conditional independence restriction, provides bounds on quantiles of differences in time-varyin...

  7. A self-encoded capsid derivative restricts Ty1 retrotransposition in Saccharomyces.

    Science.gov (United States)

    Garfinkel, David J; Tucker, Jessica M; Saha, Agniva; Nishida, Yuri; Pachulska-Wieczorek, Katarzyna; Błaszczyk, Leszek; Purzycka, Katarzyna J

    2016-05-01

    Retrotransposons and retroviral insertions have molded the genomes of many eukaryotes. Since retroelements transpose via an RNA intermediate, the additive nature of the replication cycle can result in massive increases in copy number if left unchecked. Host organisms have countered with several defense systems, including domestication of retroelement genes that now act as restriction factors to minimize propagation. We discovered a novel truncated form of the Saccharomyces Ty1 retrotransposon capsid protein, dubbed p22 that inhibits virus-like particle (VLP) assembly and function. The p22 restriction factor expands the repertoire of defense proteins targeting the capsid and highlights a novel host-parasite strategy. Instead of inhibiting all transposition by domesticating the restriction gene as a distinct locus, Ty1 and budding yeast may have coevolved a relationship that allows high levels of transposition when Ty1 copy numbers are low and progressively less transposition as copy numbers rise. Here, we offer a perspective on p22 restriction, including its mode of expression, effect on VLP functions, interactions with its target, properties as a nucleic acid chaperone, similarities to other restriction factors, and future directions. PMID:26650614

  8. A Property Restriction Based Knowledge Merging Method

    Science.gov (United States)

    Che, Haiyan; Chen, Wei; Feng, Tie; Zhang, Jiachen

    Merging new instance knowledge extracted from the Web according to certain domain ontology into the knowledge base (KB for short) is essential for the knowledge management and should be processed carefully, since this may introduce redundant or contradictory knowledge, and the quality of the knowledge in the KB, which is very important for a knowledge-based system to provide users high quality services, will suffer from such "bad" knowledge. Advocates a property restriction based knowledge merging method, it can identify the equivalent instances, redundant or contradictory knowledge according to the property restrictions defined in the domain ontology and can consolidate the knowledge about equivalent instances and discard the redundancy and conflict to keep the KB compact and consistent. This knowledge merging method has been used in a semantic-based search engine project: CRAB and the effect is satisfactory.

  9. Competition and evolution in restricted space

    International Nuclear Information System (INIS)

    We study the competition and the evolution of nodes embedded in Euclidean restricted spaces. The population evolves by a branching process in which new nodes are generated when up to two new nodes are attached to the previous ones at each time unit. The competition in the population is introduced by considering the effect of overcrowding of nodes in the embedding space. The branching process is suppressed if the newborn node is closer than a distance ξ to the previous nodes. This rule may be relevant to describe a competition for resources, limiting the density of individuals and therefore the total population. This results in an exponential growth in the initial period, and, after some crossover time, approaching some limiting value. Our results show that the competition among the nodes associated with geometric restrictions can even, for certain conditions, lead the entire population to extinction. (paper)

  10. Affective tone of mothers' statements to restrict their children's eating.

    Science.gov (United States)

    Pesch, Megan H; Miller, Alison L; Appugliese, Danielle P; Rosenblum, Katherine L; Lumeng, Julie C

    2016-08-01

    Maternal restrictive feeding behaviors have been associated with child weight status. The affective tone of mothers' statements intended to restrict their children's eating has not been examined. The objectives of this study were to describe the affective tone of mothers' restrictive feeding behaviors (positive or negative), and to test the association of child and mother characteristics with rates of Restriction with Positive Affect, Restriction with Negative Affect and Total Restriction. A total of 237 low-income child-mother dyads (mean child age 5.9 years) participated in a videotaped standardized laboratory eating protocol, during which mothers and children were both presented with large servings of cupcakes. A coding scheme was developed to count each restrictive statement with a positive affective tone and each restrictive statement with a negative affective tone. To establish reliability, 20% of videos were double-coded. Demographics and anthropometrics were obtained. Poisson regression models were used to test the association between characteristics of the child and mother with counts of Restriction with Positive Affect, Restriction with Negative Affect, and Total Restriction. Higher rates of Restriction with Positive Affect and Total Restriction were predicted by child obese weight status, and mother non-Hispanic white race/ethnicity. Higher rates of Restriction with Negative Affect were predicted by older child age, child obese weight status, mother non-Hispanic white race/ethnicity, and lower mother education level. In conclusion, in this study mothers of obese (vs. non-obese) children had higher rates of restriction in general, but particularly higher rates of Restriction with Negative Affect. Rather than being told not to restrict, mothers may need guidance on how to sensitively restrict their child's intake. Future studies should consider the contributions of maternal affect to children's responses to maternal restriction. PMID:27090342

  11. Restrictive atrial septum after the Fontan procedure.

    Science.gov (United States)

    Penford, Gemma; Quandt, Daniel; Stumper, Oliver

    2016-03-01

    In this study, three patients presenting with early or late postoperative Fontan complications were identified to suffer from restriction of the native atrial septum. This caused significant obstruction to pulmonary venous return and elevated systemic venous pressure. Dobutamine stress testing was used in one patient to identify this lesion. Transcatheter stenting was performed in the other two patients. Patients improved after relief of the obstruction. PMID:26175163

  12. Prior Restrictions on Bargaining Contract Curves

    OpenAIRE

    Brueckner, Jan K.

    2001-01-01

    It is well-known that the efficient-bargain model imposes no general restrictions on the slope of the contract curve. As a result, both upward- and downward-sloping curves are consistent with the theory. Less is known, however, about the effect on the contract curve of changes in the demand and supply variables that underlie employer and union indifference maps and help determine curve's position. To aid empirical researchers, this paper analyzes the effects of demand and supply variables on ...

  13. Nonparametric Option Pricing under Shape Restrictions

    OpenAIRE

    Yacine Ait-Sahalia; Jefferson Duarte

    2002-01-01

    Frequently, economic theory places shape restrictions on functional relationships between economic variables. This paper develops a method to constrain the values of the first and second derivatives of nonparametric locally polynomial estimators. We apply this technique to estimate the state price density (SPD), or risk-neutral density, implicit in the market prices of options. The option pricing function must be monotonic and convex. Simulations demonstrate that nonparametric estimates can b...

  14. Restriction endonuclease analysis of Aspergillus fumigatus DNA.

    OpenAIRE

    Burnie, J P; Coke, A.; Matthews, R. C.

    1992-01-01

    AIMS: To develop a genome based DNA fingerprinting system for Aspergillus fumigatus mould. METHODS: DNA was extracted from 21 isolates obtained from eight patients with an aspergilloma. This was with a freeze-dried mycelial extract fragmented in liquid nitrogen. DNA was subsequently purified by phenol-chloroform extraction followed by ultracentrifugation on a caesium chloride gradient. The DNA was restricted by EcoRI and Xba I. RESULTS: All isolates were identical when cut by EcoRI; Xba I del...

  15. Privacy-Preserving Restricted Boltzmann Machine

    OpenAIRE

    Yu Li; Yuan Zhang; Yue Ji

    2014-01-01

    With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM). The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provi...

  16. Epistemic Restrictions in Hilbert Space Quantum Mechanics

    OpenAIRE

    Griffiths, Robert B.

    2013-01-01

    A resolution of the quantum measurement problem(s) using the consistent histories interpretation yields in a rather natural way a restriction on what an observer can know about a quantum system, one that is also consistent with some results in quantum information theory. This analysis provides a quantum mechanical understanding of some recent work that shows that certain kinds of quantum behavior are exhibited by a fully classical model if by hypothesis an observer's knowledge of its state is...

  17. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis

    OpenAIRE

    Piccio, Laura; Stark, Jennifer L.; Cross, Anne H.

    2008-01-01

    Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antioxidant, and neuroprotective effects that may be beneficial in multiple sclerosis (MS). The present studies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for MS. SJL and C57BL/6 mice were subjected to 40% ...

  18. Intrauterine Growth Restriction and Cerebral Palsy

    OpenAIRE

    Kurjak, Asim; Predojevic, Maja; Stanojevic, Milan; Kadic, Aida Salihagic-; Miskovic, Berivoj; Badreldeen, Ahmed; Talic, Amira; Zaputovic, Sanja; Honemeyer, Ulrich

    2010-01-01

    Intrauterine growth restriction (IUGR) can be described as condition in which fetus fails to reach his potential growth. It is common diagnosis in obstetrics, and carries an increased risk of perinatal mortality and morbidity. Moreover, IUGR has lifelong implications on health, especially on neurological outcome. There is a need for additional neurological assessment during monitoring of fetal well-being, in order to better predict antenatally which fetuses are at risk for adverse neurologica...

  19. Free vs. Restricted Immigration: Bilateral Country Study

    OpenAIRE

    Razin, Assaf; Wahba, Jackline

    2011-01-01

    This paper tests the differential effects of the generosity of the welfare state under free migration and under policy-controlled migration, distinguishing between source developing and developed countries. We utilize free-movement within the EU to examine the free migration regime and compare that to immigration into the EU from two other groups, developed and developing source countries, to capture immigration-restricted regimes. We standardize cross-country education quality differences by...

  20. Caloric restriction improves memory in elderly humans

    OpenAIRE

    Witte, A. V.; Fobker, M; Gellner, R.; Knecht, S.; Flöel, A

    2009-01-01

    Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchange...

  1. Fasting or caloric restriction for Healthy Aging

    OpenAIRE

    Anton, Stephen; Leeuwenburgh, Christiaan

    2013-01-01

    Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prol...

  2. Restricted Conformal Property of Compressive Sensing

    OpenAIRE

    Cheng, Tao

    2014-01-01

    Energy and direction are tow basic properties of a vector. A discrete signal is a vector in nature. RIP of compressive sensing can not show the direction information of a signal but show the energy information of a signal. Hence, RIP is not complete. Orthogonal matrices can preserve angles and lengths. Preservation of length can show energies of signals like RIP do; and preservation of angle can show directions of signals. Therefore, Restricted Conformal Property (RCP) is proposed according t...

  3. Certifying the restricted isometry property is hard

    CERN Document Server

    Bandeira, Afonso S; Mixon, Dustin G; Sawin, William F

    2012-01-01

    This paper is concerned with an important matrix condition in compressed sensing known as the restricted isometry property (RIP). We demonstrate that testing whether a matrix satisfies RIP is hard for NP under randomized polynomial-time reductions. Our reduction is from the NP-complete clique decision problem, and it uses ideas from matroid theory. As a consequence of our result, it is impossible to efficiently test for RIP provided NP \

  4. Some Congruences of a Restricted Bipartition Function

    OpenAIRE

    Saikia, Nipen; Boruah, Chayanika

    2016-01-01

    Let $c_N(n)$ denotes the number of bipartitions $(\\lambda, \\mu)$ of a positive integer $n$ subject to the restriction that each part of $\\mu$ is divisible by $N$. In this paper, we prove some congruence properties of the function $c_N(n)$ for $N=7$, 11, and $5l$, for any integer $l\\ge 1$, by employing Ramanujan's theta-function identities.

  5. Sildenafil Citrate in Fetal Growth Restriction

    OpenAIRE

    Panda, Subrat; Das, Ananya; Md Nowroz, Hossain

    2014-01-01

    Background Pregnancies with early onset fetal growth restriction have poor perinatal outcome. Sildenafil citrate (PDE -5 inhibitor) as a vasodilator increases utero-placental blood flow and potentiates fetal growth. Case Presentation In this study, a case was examined and Sildenafil was administered for her. It was found that Sildenafil improved the uterine blood flow with a favorable fetal outcome at delivery. Conclusion Sildenafil, as a vasodilator has emerged as a potential management opti...

  6. Improved learning algorithms for restricted Boltzmann machines

    OpenAIRE

    Cho, Kyunghyun

    2011-01-01

    A restricted Boltzmann machine (RBM) is often used as a building block for constructing deep neural networks and deep generative models which have gained popularity recently as one way to learn complex and large probabilistic models. In these deep models, it is generally known that the layer-wise pretraining of RBMs facilitates finding a more accurate model for the data. It is, hence, important to have an efficient learning method for RBM. The conventional learning is mostly performed us...

  7. Towards Bayesian filtering on restricted support

    Czech Academy of Sciences Publication Activity Database

    Pavelková, Lenka; Kárný, Miroslav; Šmídl, Václav

    Cambridge : University of Cambridge, 2006, s. 1-4. ISBN 978-1-4244-0579-4. [Nonlinear Statistical Siganl Processing Workshop 2006. Cambridge (GB), 13.09.2006-15.09.2006] R&D Projects: GA MŠk 1M0572; GA AV ČR 1ET100750401; GA MŠk 2C06001 Institutional research plan: CEZ:AV0Z10750506 Keywords : bayesian estimation * state model * restricted support Subject RIV: BC - Control Systems Theory

  8. Blood flow-restricted exercise in space

    OpenAIRE

    Hackney, Kyle J; Everett, Meghan; Scott, Jessica M; Ploutz-Snyder, Lori

    2012-01-01

    Prolonged exposure to microgravity results in chronic physiological adaptations including skeletal muscle atrophy, cardiovascular deconditioning, and bone demineralization. To attenuate the negative consequences of weightlessness during spaceflight missions, crewmembers perform moderate- to high-load resistance exercise in conjunction with aerobic (cycle and treadmill) exercise. Recent evidence from ground-based studies suggests that low-load blood flow-restricted (BFR) resistance exercise tr...

  9. Team Formation and Communication Restrictions in Collectives

    Science.gov (United States)

    Agogino, Adrian K.; Turner, Kagan

    2003-01-01

    A collective of agents often needs to maximize a "world utility" function which rates the performance of an entire system, while subject to communication restrictions among the agents. Such communication restrictions make it difficult for agents which try to pursue their own "private" utilities to take actions that also help optimize the world utility. Team formation presents a solution to this problem, where by joining other agents, an agent can significantly increase its knowledge about the environment and improve its chances of both optimizing its own utility and that its doing so will contribute to the world utility. In this article we show how utilities that have been previously shown to be effective in collectives can be modified to be more effective in domains with moderate communication restrictions resulting in performance improvements of up to 75%. Additionally we show that even severe communication constraints can be overcome by forming teams where each agent of a team shares the same utility, increasing performance an additional 25%. We show that utilities and team sizes can be manipulated to form the best compromise between how "aligned" an agent s utility is with the world utility and how easily an agent can learn that utility.

  10. Mechanistic insight into Type I restriction endonucleases.

    Science.gov (United States)

    Youell, James; Firman, Keith

    2012-01-01

    Restriction and modification are two opposing activities that are used to protect bacteria from cellular invasion by DNA (e.g. bacteriophage infection). Restriction activity involves cleavage of the DNA; while modification activity is the mechanism used to "mark" host DNA and involves DNA methylation. The study of Type I restriction enzymes has often been seen as an esoteric exercise and this reflects some of their more unusual properties - non-stoichiometric (non-catalytic) cleavage of the DNA substrate, random cleavage of DNA, a massive ATPase activity, and the ability to both cleave DNA and methylate DNA. Yet these enzymes have been found in many bacteria and are very efficient as a means of protecting bacteria against bacteriophage infection, indicating they are successful enzymes. In this review, we summarise recent work on the mechanisms of action, describe switching of function and review their mechanism of action. We also discuss structural rearrangements and cellular localisation, which provide powerful mechanisms for controlling the enzyme activity. Finally, we speculate as to their involvement in recombination and discuss their relationship to helicase enzymes. PMID:22652768

  11. Emergency building temperature restrictions. Final evaluation

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-11-01

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

  12. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2005-11-01

    conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  13. Universal Restrictions on Syllable Structure: Evidence From Mandarin Chinese.

    Science.gov (United States)

    Zhao, Xu; Berent, Iris

    2016-08-01

    Across languages, certain onset clusters are systematically preferred (e.g., [Formula: see text], "[Formula: see text]" indicates preference), and speakers extend these preferences even to onsets that are unattested in their language. All such demonstrations, however, come from cluster-rich languages, so the observed preferences could reflect not universal linguistic restrictions but lexical analogy. To address this possibility, here, we turn to Mandarin Chinese-a cluster-poor language. We reasoned that, if people are sensitive to the onset hierarchy, then they should repair ill-formed onsets as better-formed ones [Formula: see text]-the worse formed the onset, the more likely its repair, hence, its misidentification. Results were consistent with this hypothesis, and they obtained irrespective of participants' experience with their second language (English). Nonetheless, the effect of syllable structure was strongly modulated by phonetic cues and task demands. These findings suggest that speakers might share broad phonological restrictions, but phonetic factors play a major role in their detection. PMID:25980969

  14. Classical simulation of restricted quantum computations

    OpenAIRE

    Nebhwani, Mrityunjaya

    2013-01-01

    Treball final de màster oficial fet en col·laboració amb Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB) i Institut de Ciències Fotòniques (ICFO) [ANGLÈS] We study restricted models of measurement-based quantum computation; and we investigate whether their output probability distributions can be sampled from efficiently on a classical computer. We find that even for non-adaptive models of MBQC, if this task were feasible then a major conjecture of computational compl...

  15. Privacy-Preserving Restricted Boltzmann Machine

    Directory of Open Access Journals (Sweden)

    Yu Li

    2014-01-01

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

  16. Privacy-preserving restricted boltzmann machine.

    Science.gov (United States)

    Li, Yu; Zhang, Yuan; Ji, Yue

    2014-01-01

    With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM). The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provide a correctness and efficiency analysis of our algorithms. The comparative experiment shows that the accuracy is very close to the original RBM model. PMID:25101139

  17. The Monetary Policy – Restrictive or Expansive?

    Directory of Open Access Journals (Sweden)

    Adam Szafarczyk

    2007-10-01

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

  18. Diophantine exponents for mildly restricted approximation

    DEFF Research Database (Denmark)

    Bugeaud, Yann; Kristensen, Simon

    takes all values in the interval , with the value attained for almost all . We calculate the Hausdorff dimension of the set of vectors with for . Finally, letting denote the exponent obtained by removing the restrictions on , we show that there are vectors for which the gaps in the increasing sequence......We are studying the Diophantine exponent defined for integers and a vector by letting , where is the scalar product and denotes the distance to the nearest integer and is the generalised cone consisting of all vectors with the height attained among the first coordinates. We show that the exponent...

  19. Approximate Message Passing with Restricted Boltzmann Machine Priors

    CERN Document Server

    Tramel, Eric W; Krzakala, Florent

    2015-01-01

    Approximate Message Passing (AMP) has been shown to be an excellent statistical approach to signal inference and compressed sensing problem. The AMP framework provides modularity in the choice of signal prior; here we propose a hierarchical form of the Gauss-Bernouilli prior which utilizes a Restricted Boltzmann Machine (RBM) trained on the signal support to push reconstruction performance beyond that of simple iid priors for signals whose support can be well represented by a trained binary RBM. We present and analyze two methods of RBM factorization and demonstrate how these affect signal reconstruction performance within our proposed algorithm. Finally, using the MNIST handwritten digit dataset, we show experimentally that using an RBM allows AMP to approach oracle-support performance.

  20. 77 FR 24760 - Safety Advisory 2012-02; Restricted Speed

    Science.gov (United States)

    2012-04-25

    ... Federal Railroad Administration Safety Advisory 2012-02; Restricted Speed AGENCY: Federal Railroad... speed. This safety advisory contains a preliminary discussion of recent train accidents involving a failure to operate at restricted speed and makes recommendations to railroads to ensure...

  1. Soil seed banks in restrictive environments: dynamics and response to human disturbance.

    OpenAIRE

    Martínez Duro, Esmeralda

    2009-01-01

    Gypsum steppes and saline steppes are restrictive environments, on which factors controlling seedling recruitment and establishment in early stages are little known. Information on the factors controlling recruitment and establishment of the gypsophytes and halophytes will improve our limited knowledge on arid edaphic endemism and provide a basic tool for the management and conservation of protected ecosystems, such as gypsum outcrops and saline steppes. Abandonment of agricultural lands in l...

  2. Food restriction affects energy metabolism in rat liver mitochondria.

    OpenAIRE

    Dumas, Jean-François; Roussel, Damien; Simard, Gilles; Douay, Olivier; Foussard, Françoise; Malthiery, Yves; Ritz, Patrick

    2004-01-01

    To examine the effect of 50% food restriction over a period of 3 days on mitochondrial energy metabolism, liver mitochondria were isolated from ad libitum and food-restricted rats. Mitochondrial enzyme activities and oxygen consumption were assessed spectrophotometrically and polarographically. With regard to body weight loss (-5%), food restriction decreased the liver to body mass ratio by 7%. Moreover, in food-restricted rats, liver mitochondria displayed diminished state 3 (-30%), state 4-...

  3. Respiratory Conditions Update: Restrictive Lung Disease.

    Science.gov (United States)

    Robinson, H Coleman

    2016-09-01

    Restrictive lung diseases are a heterogeneous group of conditions characterized by a restrictive pattern on spirometry and confirmed by a reduction in total lung volume. Patients with more severe symptoms may have a reduced diffusing capacity of the lung for carbon monoxide. Etiologies can be intrinsic with lung parenchymal involvement, as in interstitial lung diseases, or extrinsic to the lung, as in obesity and neuromuscular disorders. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia with fibrosis for which treatment is primarily supportive with oxygen therapy, pulmonary rehabilitation, and management of comorbid conditions. Newer drugs for idiopathic pulmonary fibrosis, such as pirfenidone and nintedanib, can slow disease progression. Referral for evaluation for lung transplantation is recommended for appropriate patients. Obstructive sleep apnea and obesity hypoventilation syndrome increasingly are common health issues, with symptoms that can include snoring, daytime somnolence, difficulty concentrating, fatigue, witnessed apneas, and morning headaches. Serum bicarbonate may serve as a biomarker in screening for subclinical obesity hypoventilation syndrome. Preoperative evaluations should assess pulmonary risk in addition to cardiac risk with a thorough history, laboratory tests, and functional capacity assessments. Optimization of management may include weight loss, pulmonary rehabilitation, oxygen therapy, and respiratory support. PMID:27576233

  4. Columbus Closure Project Released without Radiological Restrictions

    International Nuclear Information System (INIS)

    The Columbus Closure Project (CCP), a historic radiological research complex, was cleaned up for future use without radiological restriction in 2006. The CCP research and development site contributed to national defense, nuclear fuel fabrication, and the development of safe nuclear reactors in the United States until 1988 when research activities were concluded for site decommissioning. In November of 2003, the Ohio Field Office of the U.S. Department of Energy contracted ECC/E2 Closure Services, LLC (Closure Services) to complete the removal of radioactive contamination from of a 1955 era nuclear sciences area consisting of a large hot cell facility, research reactor building and underground piping. The project known as the Columbus Closure Project (CCP) was completed in 27 months and brought to a close 16 years of D and D in Columbus, Ohio. This paper examines the project innovations and challenges presented during the Columbus Closure Project. The examination of the CCP includes the project regulatory environment, the CS safety program, accelerated clean up innovation, project execution strategies and management of project waste issues and the regulatory approach to site release 'without radiological restrictions'. (authors)

  5. 20 CFR 332.3 - Mileage and work restrictions.

    Science.gov (United States)

    2010-04-01

    ... INSURANCE ACT MILEAGE OR WORK RESTRICTIONS AND STAND-BY OR LAY-OVER RULES § 332.3 Mileage and work... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Mileage and work restrictions. 332.3 Section... solely because of the application to him of a mileage or work restriction agreed upon in a...

  6. 14 CFR 1274.929 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... WITH COMMERCIAL FIRMS Other Provisions and Special Conditions § 1274.929 Restrictions on lobbying. Restrictions on Lobbying July 2002 This award is subject to the provisions of 14 CFR part 1271 “New... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Restrictions on lobbying. 1274.929...

  7. 7 CFR 1710.125 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... and Basic Policies § 1710.125 Restrictions on lobbying. Borrowers are required to comply with certain requirements with respect to restrictions on lobbying activities. See 7 CFR part 3018. ... 7 Agriculture 11 2010-01-01 2010-01-01 false Restrictions on lobbying. 1710.125 Section...

  8. 7 CFR 1724.8 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Restrictions on lobbying. 1724.8 Section 1724.8 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF... Restrictions on lobbying. Borrowers shall comply with the restrictions and requirements in connection...

  9. 36 CFR 13.1174 - Whale water restrictions.

    Science.gov (United States)

    2010-07-01

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

  10. 75 FR 9860 - Release, Handling, and Protection of Restricted Information

    Science.gov (United States)

    2010-03-04

    ... the restricted information and did not require the Contractor to hold it in confidence; or (iv) Is... Protection of Restricted Information AGENCY: National Aeronautics and Space Administration. ACTION: Proposed...) to clarify the policy and procedures regarding the release of contractors' restricted information...

  11. 50 CFR 648.51 - Gear and crew restrictions.

    Science.gov (United States)

    2010-10-01

    ... Atlantic Sea Scallop Fishery § 648.51 Gear and crew restrictions. (a) Trawl vessel gear restrictions. Trawl... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear and crew restrictions. 648.51 Section 648.51 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND...

  12. 49 CFR 215.303 - Stenciling of restricted cars.

    Science.gov (United States)

    2010-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Sudhir S Shetkar

    2015-01-01

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

  14. Gender differences in the rate of restriction to room among Ontario forensic patients.

    Science.gov (United States)

    Mathias, Krista; Hirdes, John P

    2015-07-01

    Gender can have separate and interacting effects on mental health. Gender-based analysis provides insight into these effects on mental health, and it can provide evidence to inform policy and practice to meet these gender-specific needs among persons in forensic mental health settings. Both individual and facility-level characteristics play a role in restriction to room as a form of control intervention in forensic mental health. Understanding the gender differences associated with the factors that increase a person's risk of restriction to room can allow for more targeted interventions and provide insight into policies that will help reduce these types of control interventions. PMID:26015491

  15. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

    OpenAIRE

    Szu-Chieh Mei; Charles Brenner

    2015-01-01

    In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we develop...

  16. Contribution of MxB Oligomerization to HIV-1 Capsid Binding and Restriction

    OpenAIRE

    Buffone, Cindy; Schulte, Bianca; OPP, Silvana; Diaz-Griffero, Felipe

    2015-01-01

    The alpha interferon (IFN-α)-inducible restriction factor myxovirus B (MxB) blocks HIV-1 infection after reverse transcription but prior to integration. MxB binds to the HIV-1 core, which is composed of capsid protein, and this interaction leads to inhibition of the uncoating process of HIV-1. Previous studies suggested that HIV-1 restriction by MxB requires binding to capsid. This work tests the hypothesis that MxB oligomerization is important for the ability of MxB to bind to the HIV-1 core...

  17. Prevalence of Spirometrically-defined Restrictive Ventilatory Defect in Korea: The Fourth-2, 3, and Fifth Korean National Health and Nutrition Examination Survey, 2008-2012

    OpenAIRE

    Lee, Jung Yeon; Hwang, Yong Il; Park, Yong Bum; Park, Jae Yong; Kim, Ki Uk; Oh, Yeon-Mok; Yoon, Hyoung Kyu; Yoon, Ho Il; Sheen, Sueng Su; Lee, Sang Yeub; Lee, Chang-Hoon; Lee, Heung Bum; Lim, Sung Chul; Jung, Sung Soo; Oh, Kyungwon

    2015-01-01

    The aim of the study was to evaluate the prevalence of restrictive ventilatory defect and to determine the risk factors in subjects with spirometrically-defined restrictive ventilatory defect. We used the population-based, fourth-2, 3 (2008, 2009) and fifth (2010-2012) Korea National Health and Nutrition Examination Survey (KNHANES) to analyze 15,073 subjects, aged ≥40 yr who underwent spirometry. Chest radiographs were also analyzed to identify restrictive lung disease. Spirometrically-defin...

  18. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    Science.gov (United States)

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

  19. Restricted Edge Connectivity of BinaryUndirected Kautz Graphs

    Institute of Scientific and Technical Information of China (English)

    OUJian-ping

    2004-01-01

    A restricted edge cut is an edge cut of a connected graph whose removal resultsin a disconnected graph without isolated vertices. The size of a minimum restricted edge cutof a graph G is called its restricted edge connectivity, and is denoted by λ′(G). Let ξ(G) bethe minimum edge degree of graph G. It is known that λ′(G) ≤ξ(G) if G contains restrictededge cuts. Graph G is called maximal restricted edge connected if the equality holds in thethe preceding inequality. In this paper, undirected Kautz graph UK(2, n) is proved to bemaximal restricted edge connected if n ≥ 2.

  20. A FORTRAN Program for Correcting Correlation Coefficients for Restriction in Range for Explicit or Implicit Restriction.

    Science.gov (United States)

    Lewis, Mary A.; Boone, James O.

    1979-01-01

    Restriction in range is a measurement problem frequently encountered in research studies that utilize correlation coefficients. A FORTRAN program is described that can compute the estimated unrestricted correlation coefficient in either the explicit or implicit case. The user selects the appropriate formula to be employed from five that are…

  1. Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

    Directory of Open Access Journals (Sweden)

    Woods Matthew W

    2011-11-01

    Full Text Available Abstract Background The identification and characterization of several interferon (IFN-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5 that blocks a unique late stage of the HIV-1 life cycle. Results HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. Conclusions HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

  2. What are the social impacts of land use restrictions on local communities? Empirical evidence from Costa Rica

    OpenAIRE

    Andam, Kwaw S.; Ferraro, Paul J.; Holland, Margaret B.

    2009-01-01

    Global efforts to reduce deforestation rely heavily on protected areas and land use restrictions. The effect of these restrictions on local communities is currently the subject of heated debate among conservation and development experts. Measuring the social impacts of protected areas is difficult because the effects cannot be isolated from other factors, given the nonrandom placement of protection. We address this problem by applying a quasi-experimental approach to establish the counterfact...

  3. THE TSC COMPLEX IS REQUIRED FOR THE BENEFITS OF DIETARY PROTEIN RESTRICTION ON STRESS RESISTANCE IN VIVO

    OpenAIRE

    Eylul Harputlugil; Christopher Hine; Dorathy Vargas; Lauren Robertson; Brendan D. Manning; James R. Mitchell

    2014-01-01

    Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for the evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repre...

  4. Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Richard C Grandison

    Full Text Available BACKGROUND: Outcomes of lifespan studies in model organisms are particularly susceptible to variations in technical procedures. This is especially true of dietary restriction, which is implemented in many different ways among laboratories. PRINCIPAL FINDINGS: In this study, we have examined the effect of laboratory stock maintenance, genotype differences and microbial infection on the ability of dietary restriction (DR to extend life in the fruit fly Drosophila melanogaster. None of these factors block the DR effect. CONCLUSIONS: These data lend support to the idea that nutrient restriction genuinely extends lifespan in flies, and that any mechanistic discoveries made with this model are of potential relevance to the determinants of lifespan in other organisms.

  5. Training Restricted Boltzmann Machines on Word Observations

    CERN Document Server

    Dahl, George E; Larochelle, Hugo

    2012-01-01

    The restricted Boltzmann machine (RBM) is a flexible tool for modeling complex data, however there have been significant computational difficulties in using RBMs to model high-dimensional multinomial observations. In natural language processing applications, words are naturally modeled by K-ary discrete distributions, where K is determined by the vocabulary size and can easily be in the hundred thousands. The conventional approach to training RBMs on word observations is limited because it requires sampling the states of K-way softmax visible units during block Gibbs updates, an operation that takes time linear in K. In this work, we address this issue by employing a more general class of Markov chain Monte Carlo operators on the visible units, yielding updates with computational complexity independent of K. We demonstrate the success of our approach by training RBMs on hundreds of millions of word n-grams using larger vocabularies than previously feasible with RBMs and using the learned features to improve p...

  6. Epitaxial growth by monolayer restricted galvanic displacement

    Directory of Open Access Journals (Sweden)

    Vasilić Rastko

    2012-01-01

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

  7. Classes of graphs with restricted interval models

    Directory of Open Access Journals (Sweden)

    Andrzej Proskurowski

    1999-12-01

    Full Text Available We introduce q-proper interval graphs as interval graphs with interval models in which no interval is properly contained in more than q other intervals, and also provide a forbidden induced subgraph characterization of this class of graphs. We initiate a graph-theoretic study of subgraphs of q-proper interval graphs with maximum clique size k+1 and give an equivalent characterization of these graphs by restricted path-decomposition. By allowing the parameter q to vary from 0 to k, we obtain a nested hierarchy of graph families, from graphs of bandwidth at most k to graphs of pathwidth at most k. Allowing both parameters to vary, we have an infinite lattice of graph classes ordered by containment.

  8. Formation reconfiguration in restricted three body problem

    Institute of Scientific and Technical Information of China (English)

    Shengping Gong; Junfeng Li; Hexi Baoyin; Yunfeng Gao

    2007-01-01

    Reconfiguration of formation flying around a halo orbit of the Sun-Earth restricted three body system is investigated with impulse maneuvers. For a short time reconfiguration, the two-impulse maneuver is investigated with both analytical and numerical methods and the BeginningEnding (BE) method is proven to be an energy-optimal one of all two-impulse (TI) reconfigurations, and the energy consumption of BE is independent of the position of the chief spacecraft, and decreases with the reconfiguration time.Then, genetic algorithm is adopted to optimize the energy consumption. The results show that the optimal energy increases with radius difference between the initial and final orbits, and decreases with the reconfiguration time.

  9. Membrane barriers for radon gas flow restrictions

    International Nuclear Information System (INIS)

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

  10. A Survey of Geographic Restriction Mobility Models

    Directory of Open Access Journals (Sweden)

    Ibrahim Khider

    2007-01-01

    Full Text Available In this study, we present and visit the limitation of Random mobility model, the unconstraint motion of mobile node. Mobile nodes, in the Random Waypoint and Random walk mobility models, are allowed to move freely and randomly anywhere in the simulation field. However, in most real life applications, we observe that a node’s movement is subject to the environment. In particular, the motions of vehicles are bounded to the freeways or local streets in the urban area and on campus the pedestrians may be blocked by the buildings and other obstacles. Therefore, the nodes may move in a pseudo-random way on predefined pathways in the simulation field. Some recent works address this characteristic and integrate the paths and obstacles into mobility models. We call this kind of mobility model a mobility model with geographic restriction.

  11. Autotagging music with conditional restricted Boltzmann machines

    CERN Document Server

    Mandel, Michael; Larochelle, Hugo; Bengio, Yoshua

    2011-01-01

    This paper describes two applications of conditional restricted Boltzmann machines (CRBMs) to the task of autotagging music. The first consists of training a CRBM to predict tags that a user would apply to a clip of a song based on tags already applied by other users. By learning the relationships between tags, this model is able to pre-process training data to significantly improve the performance of a support vector machine (SVM) autotagging. The second is the use of a discriminative RBM, a type of CRBM, to autotag music. By simultaneously exploiting the relationships among tags and between tags and audio-based features, this model is able to significantly outperform SVMs, logistic regression, and multi-layer perceptrons. In order to be applied to this problem, the discriminative RBM was generalized to the multi-label setting and four different learning algorithms for it were evaluated, the first such in-depth analysis of which we are aware.

  12. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  13. Restriction modification systems as engines of diversity.

    Science.gov (United States)

    Sneppen, Kim; Semsey, Szabolcs; Seshasayee, Aswin S N; Krishna, Sandeep

    2015-01-01

    Restriction modification (RM) systems provide protection against a broad spectrum of phages. However, the likelihood of a phage permanently bypassing this can be as high as 0.1 per infection (Korona et al., 1993) which makes for a relatively weak defense. Here we argue that, apart from providing such transient defenses, RM systems can facilitate long-term coexistence of many bacterial strains. We show that this diversity can be as large as the burst size of the phage but no larger-a curious correspondence between a number at the level of species and another number at the level of individuals. Such a highly diverse and stably coexisting ecosystem is robust to substantial variation in both bacterial growth rates and strength of their RM systems, which might be one reason why quite weak RM systems exist in the wild. PMID:26082758

  14. Restriction Modification Systems as Engines of Diversity

    Directory of Open Access Journals (Sweden)

    Kim eSneppen

    2015-06-01

    Full Text Available Restriction modification (RM systems provide protection against a broad spectrum of phages. However, the likelihood of a phage permanently bypassing this can be as high as 0.1 per infection (Korona et al., J. Gen. Microbiol. 139: 1283-1290, 1993 which makes for a relatively weak defence. Here we argue that, apart from providing such transient defences, RM systems can facilitate long-term coexistence of many bacterial strains. We show that this diversity can be as large as the burst size of the phage but no larger -- a curious correspondence between a number at the level of species and another number at the level of individuals. Such a highly diverse and stably coexisting ecosystem is robust to substantial variation in both bacterial growth rates and strength of their RM systems, which might be one reason why quite weak RM systems exist in the wild.

  15. Capture in restricted four body problem

    CERN Document Server

    Rosaev, Alexey

    2011-01-01

    A number of irregular moons of the Jovian planets have recently been discovered. Most adequate way of their origin is capture, but detailed mechanism is unknown. A few possibilities are discussed: collisions, gas drag, tidal destruction of a binary asteroid. In this paper the capture process in restricted four body problem (RFBP) is researched. The interaction with regular satellite can be studied by this way as well as binary asteroid destruction in Hill sphere of planet. The energetic criteria of ballistic capture are studied and some numerical experiments are developed. It is confirmed, that capture in four body problem is more probable on retrograde than on prograde orbit. In according with our results, encounter with regular satellites is more effective mechanism to create an irregular satellite population, than a binary asteroid flyby.

  16. Restrictions on the transnational movement of uranium

    International Nuclear Information System (INIS)

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

  17. Mining for Restriction Endonucleases in Nicaragua

    Directory of Open Access Journals (Sweden)

    Suyén S. Espinoza-Miranda

    2012-12-01

    Full Text Available The Molecular Biology Center at the University of Central America in Nicaragua (CBM-UCA was founded in 1999 to strengthen biotechnology research capacity and education in Nicaragua and the Central American region. One of the first projects launched by the CBM-UCA was bio-prospecting for key industrial enzymes. This ongoing study seeks to discover and characterize restriction enzymes (RE in bacteria, and to create a database of microorganisms isolated and identified by 16S rDNA sequencing methodology. In this paper we highlight the importance of studying the extreme environmental conditions for building knowledge of Nicaraguan biodiversity through modern molecular biology techniques such as metagenomics. The isolation of prototype enzymes such as EcoRV and ClaI is presented as an update and extension of previously undertaken work.

  18. Diophantine exponents for mildly restricted approximation

    DEFF Research Database (Denmark)

    Bugeaud, Yann; Kristensen, S.

    2009-01-01

    that the exponent takes all values in the interval [l+1,∞), with the value n attained for almost all α. We calculate the Hausdorff dimension of the set of vectors α with μ n,l (α)=μ for μ≥n. Finally, letting w n denote the exponent obtained by removing the restrictions on , we show that there are vectors α......We are studying the Diophantine exponent μ n,l defined for integers 1≤lvector α∈ℝ n by letting where is the scalar product, denotes the distance to the nearest integer and is the generalised cone consisting of all vectors with the height attained among the first l coordinates. We show...

  19. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells

    International Nuclear Information System (INIS)

    The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors

  20. Effects of selenium supply and dietary restriction on maternal and fetal body weight, visceral organ mass, cellularity estimates, and jejeunal vascularity in pregnant ewe lambs.

    Science.gov (United States)

    To examine effects of nutrient restriction and dietary Se on maternal and fetal visceral tissues, 36 pregnant Targhee-cross ewe lambs were allotted randomly to one of four treatments in a 2 x 2 factorial design. Factors were nutrition [control nutrition (CON, 100% of requirements) vs. restricted nu...

  1. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.

    Science.gov (United States)

    Hine, Christopher; Mitchell, James R

    2015-08-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action. PMID:25523462

  2. Near BPS Skyrmions and Restricted Harmonic Maps

    CERN Document Server

    Speight, J M

    2014-01-01

    Motivated by a class of near BPS Skyrme models introduced by Adam, S\\'anchez-Guill\\'en and Wereszczy\\'nski, the following variant of the harmonic map problem is introduced: a map $\\phi:(M,g)\\rightarrow (N,h)$ between Riemannian manifolds is restricted harmonic (RH) if it locally extremizes $E_2$ on its $SDiff(M)$ orbit, where $SDiff(M)$ denotes the group of volume preserving diffeomorphisms of $(M,g)$, and $E_2$ denotes the Dirichlet energy. It is conjectured that near BPS skyrmions tend to RH maps in the BPS limit. It is shown that $\\phi$ is RH if and only if $\\phi^*h$ has exact divergence, and a linear stability theory of RH maps is developed, whence it follows that all weakly conformal maps, for example, are stable RH. Examples of RH maps in every degree class $R^3\\to SU(2)$ and $R^2\\to S^2$ are constructed. It is shown that the axially symmetric BPS skyrmions on which all previous analytic studies of near BPS Skyrme models have been based, are not RH, so each such field can be deformed along $SDiff(R^3)$ ...

  3. Restricted meniscus convective self-assembly.

    Science.gov (United States)

    Chen, Kai; Stoianov, Stefan V; Bangerter, Justin; Robinson, Hans D

    2010-04-15

    Convective (or evaporation-induced) self-assembly is a standard technique for depositing uniform, poly-crystalline coatings of nanospheres across multiple square centimeters on the timescale of minutes. In this paper, we present a variation of this technique, where the drying meniscus is restricted by a straight-edge located approximately 100 microm above the substrate adjacent to the drying zone. Surprisingly, we find this technique to yield films at roughly twice the growth rate compared to the standard technique. We attribute this to differing rates of diffusion of vapor from the drying crystal in the two cases. We also investigate the crystal growth rate dependence on ambient relative humidity and find, contrary to some previous reports, that the growth rate depends strongly on the humidity. We introduce a model which indicates that while the length of the drying zone may increase with humidity, this alone cannot compensate for the simultaneous reduction in evaporation rate, so a lower humidity must always lead to a higher growth speed. Comparing the model to our experimental results, we find that the length of the drying zone is constant and mostly independent of parameters such as humidity and surface tension. PMID:20132947

  4. Restriction-modification systems in Mycoplasma spp

    Directory of Open Access Journals (Sweden)

    Marcelo Brocchi

    2007-01-01

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

  5. Second law of thermodynamics under control restrictions

    Science.gov (United States)

    Wilming, H.; Gallego, R.; Eisert, J.

    2016-04-01

    The second law of thermodynamics, formulated as an ultimate bound on the maximum extractable work, has been rigorously derived in multiple scenarios. However, the unavoidable limitations that emerge due to the lack of control on small systems are often disregarded when deriving such bounds, which is specifically important in the context of quantum thermodynamics. Here we study the maximum extractable work with limited control over the working system and its interaction with the heat bath. We derive a general second law when the set of accessible Hamiltonians of the working system is arbitrarily restricted. We then apply our bound to particular scenarios that are important in realistic implementations: limitations on the maximum energy gap and local control over many-body systems. We hence demonstrate in what precise way the lack of control affects the second law. In particular, contrary to the unrestricted case, we show that the optimal work extraction is not achieved by simple thermal contacts. Our results not only generalize the second law to scenarios of practical relevance, but also take first steps in the direction of local thermodynamics.

  6. Migration policy: from restriction to regulation.

    Science.gov (United States)

    Wu, Z

    1996-12-01

    This article describes the extent of rural-urban migration, the flows by province in 1992, and social policies relating to migration in China. Population movements followed several patterns: increased flows from rural-urban areas during 1945-66, reversed flows back to rural areas during the Cultural Revolution of 1966-77, and relaxed controls during 1978-87 and increased rural-urban migration. Migration policy began on a strict household registration system. Restrictions were eased to allow for regulation and allocation of surplus rural workers. Rapid industrial development helped China recover from the war. Peak movements were in 1958 during the "Great Leap Forward." An estimated 19 million rural workers were recruited during 1958-60. Supply of labor exceeded needs, and urban governments reversed this strategy in 1961. During the 1960s, the household registration system was strictly enforced. Urban population declined during 1965-76. Youth were required to reeducate themselves in farming areas. During 1978-87, China's central leadership established the household land-contract responsibility system and grain production increased. Limits on arable land resulted in surplus labor. In the mid-1980s, policy focused on nonagricultural wage labor in local factories. After 1988, the government encouraged development of cities and towns and village enterprises under the socialist market economy. It is likely that now the labor market rather than the household registration system will control the size, direction, and selectivity of migration. PMID:12320642

  7. How restriction enzymes became the workhorses of molecular biology

    OpenAIRE

    Roberts, Richard J.

    2005-01-01

    Restriction enzymes have proved to be invaluable for the physical mapping of DNA. They offer unparalleled opportunities for diagnosing DNA sequence content and are used in fields as disparate as criminal forensics and basic research. In fact, without restriction enzymes, the biotechnology industry would certainly not have flourished as it has. The first experiments demonstrating the utility of restriction enzymes were carried out by Danna and Nathans and reported in 1971. This pioneering stud...

  8. What you should know about restrictive covenants in health care.

    Science.gov (United States)

    Austin, Michael G; Grosack, Matthew

    2013-01-01

    In recent years, many states have shown a greater inclination to enforce restrictive covenant provisions in contracts involving healthcare organizations and their employees, physicians, or other contacting parties. In general, an enforceable restrictive covenant is one that is deemed to have been reasonably drafted to do no more than to protect the company's legitimate business interest. Key areas of concern in health care that often fall under the protection of restrictive covenants include patient referral sources and relationships with patients. PMID:23360060

  9. Self and non-self discrimination by "restriction proteases".

    OpenAIRE

    Lefkovits, I

    1986-01-01

    I propose that an organism possesses a set of specific enzymes ("restriction proteases") that cleave self proteins at defined amino acid sequences unless these sequences are rendered inaccessible by glycosylation. Intracellular proteins are degraded by restriction proteases when cells die. In this way, intracellular proteins remain undetected by the immune system. I propose that some autoimmune diseases are caused by the absence of a specific restriction protease.

  10. Thermodynamic restrictions on the constitutive equations of electromagnetic theory

    Science.gov (United States)

    Coleman, B. D.; Dill, E. H.

    1971-01-01

    Thermodynamics second law restrictions on constitutive equations of electromagnetic theory for nonlinear materials with long-range gradually fading memory, considering dissipation principle consequences

  11. Health promotion by dietary restriction--a focus.

    Science.gov (United States)

    Ramkumar, K M

    2006-01-01

    Food restriction, although long popular among gerontologists, has emerged as a new challenge in public health in postindustrial societies because this is the only intervention that repeatedly and strikingly increases maximum life span. The practice of food restriction is widespread for cosmetic, health, and economic reasons. The beneficial effects and the molecular mechanism of food restriction have been well established. The present review summarizes the rapidly accumulating evidence on the involvement of food restriction in various diseases and focuses on good dietary practices for health promotion in modern life style. PMID:16910315

  12. Restriction alleviation by bacteriophages lambda and lambda reverse.

    OpenAIRE

    Toothman, P

    1981-01-01

    Deletion analysis indicated that the phage lambda restriction alleviation gene(s) ral resides between the cIII and N genes. The Ral+ phenotype was expressed only when lambda ral+ carried a modification such that it was resistant to restriction by the host specificity system. Under these conditions, Ral function protected superinfecting unmodified phages from restriction by EcoK or EcoB but not from restriction by EcoP1. Ral-protected phage DNA was not concomitantly K and B modified, but rathe...

  13. Acute sleep restriction reduces insulin sensitivity in adolescent boys

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

    International Nuclear Information System (INIS)

    In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5α with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain

  15. Dietary restriction: could it be considered as speed bump on tumor progression road?

    Science.gov (United States)

    Cangemi, Antonina; Fanale, Daniele; Rinaldi, Gaetana; Bazan, Viviana; Galvano, Antonio; Perez, Alessandro; Barraco, Nadia; Massihnia, Daniela; Castiglia, Marta; Vieni, Salvatore; Bronte, Giuseppe; Mirisola, Mario; Russo, Antonio

    2016-06-01

    Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes. PMID:27043958

  16. Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

    Institute of Scientific and Technical Information of China (English)

    TIE Zuo-Xiu; QIN Meng; ZOU Da-Wei; CAO Yi; WANG Wei

    2011-01-01

    @@ The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels.In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by n - TT stacking among the phenyl groups.Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions.Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous.%The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π - π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive “smart”materials.

  17. Determinants of participation restriction among community dwelling stroke survivors: A path analysis

    Directory of Open Access Journals (Sweden)

    Chang Anne M

    2009-09-01

    Full Text Available Abstract Background Apart from promoting physical recovery and assisting in activities of daily living, a major challenge in stroke rehabilitation is to minimize psychosocial morbidity and to promote the reintegration of stroke survivors into their family and community. The identification of key factors influencing long-term outcome are essential in developing more effective rehabilitation measures for reducing stroke-related morbidity. The aim of this study was to test a theoretical model of predictors of participation restriction which included the direct and indirect effects between psychosocial outcomes, physical outcome, and socio-demographic variables at 12 months after stroke. Methods Data were collected from 188 stroke survivors at 12 months following their discharge from one of the two rehabilitation hospitals in Hong Kong. The settings included patients' homes and residential care facilities. Path analysis was used to test a hypothesized model of participation restriction at 12 months. Results The path coefficients show functional ability having the largest direct effect on participation restriction (β = 0.51. The results also show that more depressive symptoms (β = -0.27, low state self-esteem (β = 0.20, female gender (β = 0.13, older age (β = -0.11 and living in a residential care facility (β = -0.12 have a direct effect on participation restriction. The explanatory variables accounted for 71% of the variance in explaining participation restriction at 12 months. Conclusion Identification of stroke survivors at risk of high levels of participation restriction, depressive symptoms and low self-esteem will assist health professionals to devise appropriate rehabilitation interventions that target improving both physical and psychosocial functioning.

  18. Comparison of a Restricted and Unrestricted Vegan Diet Plan with a Restricted Omnivorous Diet Plan on Health-Specific Measures

    OpenAIRE

    Bloomer, Richard J; Gunnels, Trint A; Schriefer, JohnHenry M

    2015-01-01

    Background: We have previously noted beneficial health outcomes when individuals follow a dietary restriction plan in accordance with the Daniel Fast (DF). This is true whether individuals eliminate all animal products or include small amounts of meat and dairy in their plan. The present study sought to compare anthropometric and biochemical measures of health in individuals following a traditional DF (i.e., restricted vegan) or modified DF (i.e., restricted omnivorous; inclusive of ad libitu...

  19. Impact of Six-Month Caloric Restriction on Autonomic Nervous System Activity in Healthy, Overweight, Individuals

    OpenAIRE

    de Jonge, Lillian; Moreira, Emilia AM; Martin, Corby K.; Ravussin, Eric

    2009-01-01

    Caloric restriction (CR) increases maximum lifespan but the mechanisms are unclear. Dominance of the sympathetic nervous System (SNS) over the Parasympathetic Nervous System (PNS) has been shown to be a strong risk factor for cardiovascular disease. Obesity and aging are associated with increased SNS activity and weight loss and/or exercise seem to have positive effects on this balance. We therefore evaluated the effect of different approaches of CR on autonomic function in 48 overweight indi...

  20. Alterations induced by juvenile obesity on the renal tissue of nutrient restricted offspring

    OpenAIRE

    Fainberg, Hernan Pablo

    2010-01-01

    Human epidemiological studies have indentified obesity as an independent risk factor for renal disease. In addition, maternal nutrient restriction (MNR) during gestation results in a series of adaptations that may predispose those offspring to obesity and hypertension. Recent reports demonstrated that obese sheep exposed to MNR during early to mid gestation have a predisposition to ectopic lipid deposition in the heart and a rise in necrotic adipocytes, which are markers of severe metabolic d...

  1. Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

    OpenAIRE

    Guido Carlomagno; Valentina Mercurio; Antonio Ruvolo; Ignazio Senatore; Irina Halinskaya; Valeria Fazio; Flora Affuso; Serafino Fazio

    2011-01-01

    Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for...

  2. The role and regulation of IGFBP-1 phosphorylation in fetal growth restriction

    OpenAIRE

    Gupta, Madhulika B.

    2015-01-01

    Fetal growth restriction (FGR) increases the risk of perinatal complications and predisposes the infant to developing metabolic, cardiovascular, and neurological diseases in childhood and adulthood. The pathophysiology underlying FGR remains poorly understood and there is no specific treatment available. Biomarkers for early detection are also lacking. The insulin-like growth factor (IGF) system is an important regulator of fetal growth. IGF-I is the primary regulator of fetal growth, and fet...

  3. Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

    Science.gov (United States)

    Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K

    2015-02-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. PMID:24916330

  4. The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells.

    Science.gov (United States)

    Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M; Vives-Pi, Marta; Esté, José A; Ballana, Ester

    2016-08-01

    Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

  5. Alteration of the Specificity of PstⅠRestriction Endonuclease

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The influence of factors on the substrate-specificity of Pst Ⅰ restriction endonuclease has been studied with the method of electrophoresis. The results show that, the specificity of Pst Ⅰ almost can not be influenced by the single alteration of the concentration of Tris*HCl, Mg2+ or Na+ in the reaction system, but it can be altered by the reduction of any two of them. The specificity can not be altered by the single alteration of pH or the replacement of Mg2+ with Mn2+. The addition of glycerol or dimethylsulphoxide (DMSO) to the reaction system results in the relaxation of the substrate-specificity of Pst Ⅰ , but dimethylmethylformide, glycol and ethyl alcohol can not bring about the alteration of Pst Ⅰ specificity. Through the method of cloning and sequencing, the nucleotides of No.1 and 6 in the recognition sequence of Pst Ⅰ have changed (1C→A or 6G→T). Used with the enzyme analysis of an artificially synthetic DNA segment containing a special sequence, the nucleotides of No.1 and 6 have both changed (1C→A and 6G→T). The recognition sequence of Pst Ⅰ is speculated to be changed from CTGCA↓G to TGCA↓.

  6. Tetherin restricts productive HIV-1 cell-to-cell transmission.

    Directory of Open Access Journals (Sweden)

    Nicoletta Casartelli

    Full Text Available The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24 impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.

  7. 29 CFR 530.2 - Restriction of homework.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Restriction of homework. 530.2 Section 530.2 Labor... OF HOMEWORKERS IN CERTAIN INDUSTRIES General § 530.2 Restriction of homework. Except as provided in... special homework certificate issued and in effect pursuant to this part has been obtained for...

  8. 7 CFR 319.75-2 - Restricted articles. 1

    Science.gov (United States)

    2010-01-01

    ... other provisions of 7 CFR part 319. For example, fresh whole chilies (Capsicum spp.) and fresh whole red... be subject to additional restrictions under the provisions in 7 CFR 319.8 et seq. (6) Used jute or... 7 Agriculture 5 2010-01-01 2010-01-01 false Restricted articles. 1 319.75-2 Section...

  9. 32 CFR 234.12 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

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

  10. 32 CFR 1903.16 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

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

  11. 32 CFR 228.15 - Restriction regarding animals.

    Science.gov (United States)

    2010-07-01

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

  12. 7 CFR 800.76 - Prohibited services; restricted services.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Prohibited services; restricted services. 800.76..., PACKERS AND STOCKYARD ADMINISTRATION (FEDERAL GRAIN INSPECTION SERVICE), DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS Kinds of Official Services § 800.76 Prohibited services; restricted services. (a)...

  13. Reverse triple I method of restriction for fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A theory of reverse triple I method of restriction for implication operator R0 is proposed.And the general computation formulas of infimum for fuzzy modus ponens and supremum for fuzzy modus tollens of a-reverse triple I method of restriction are obtained respectively.

  14. 13 CFR 400.108 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Restrictions on lobbying. 400.108 Section 400.108 Business Credit and Assistance EMERGENCY STEEL GUARANTEE LOAN BOARD EMERGENCY STEEL GUARANTEE LOAN PROGRAM Board Procedures § 400.108 Restrictions on lobbying. (a) No funds received through...

  15. 7 CFR 1726.17 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Restrictions on lobbying. 1726.17 Section 1726.17 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES General § 1726.17 Restrictions on...

  16. 13 CFR 500.108 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Restrictions on lobbying. 500.108 Section 500.108 Business Credit and Assistance EMERGENCY OIL AND GAS GUARANTEED LOAN BOARD EMERGENCY OIL AND GAS GUARANTEED LOAN PROGRAM Board Procedures § 500.108 Restrictions on lobbying. (a) No...

  17. 7 CFR 1944.657 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Restrictions on lobbying. 1944.657 Section 1944.657...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants § 1944.657 Restrictions on lobbying... funds for lobbying the Federal Government in connection with a specific grant....

  18. 7 CFR 2200.10 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Restrictions on lobbying. 2200.10 Section 2200.10 Agriculture Regulations of the Department of Agriculture (Continued) LOCAL TELEVISION LOAN GUARANTEE BOARD... Restrictions on lobbying. (a) No funds received through a Loan guaranteed under this Program in this...

  19. 7 CFR 761.5 - Restrictions on lobbying.

    Science.gov (United States)

    2010-01-01

    ... lobbying. A person who applies for or receives a loan made or guaranteed by the Agency must comply with the restrictions on lobbying in 7 CFR part 3018. ... 7 Agriculture 7 2010-01-01 2010-01-01 false Restrictions on lobbying. 761.5 Section...

  20. On some Frobenius Restriction Theorems for Semistable Sheaves

    Indian Academy of Sciences (India)

    V B Mehta; V Trivedi

    2009-02-01

    We prove a version of an effective Frobenius restriction theorem for semistable bundles in characteristic . The main novelty is in restricting the bundle to the -fold thickening of a hypersurface section. The base variety is /, an abelian variety or a smooth projective toric variety.

  1. 9 CFR 121.13 - Restricted experiments. 10

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Restricted experiments. 10 121.13... TRANSFER OF SELECT AGENTS AND TOXINS § 121.13 Restricted experiments. 10 10 For guidance, see the NIH publication, “NIH Guidelines for Research Involving Recombinant DNA Molecules.” This document is available...

  2. 50 CFR 697.17 - Non-trap harvest restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Non-trap harvest restrictions. 697.17... MANAGEMENT Management Measures § 697.17 Non-trap harvest restrictions. (a) Non-trap landing limits. In... non-trap gear on board capable of catching lobsters, or, that fishes for, takes, catches, or...

  3. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665.127 Section 665.127 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may...

  4. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665.627 Section 665.627 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may...

  5. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665.427 Section 665.427 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS...

  6. 50 CFR 697.23 - Restricted gear areas.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Restricted gear areas. 697.23 Section 697.23 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... Measures § 697.23 Restricted gear areas. (a) Resolution of lobster gear conflicts with fisheries...

  7. 50 CFR 648.296 - Gear restricted areas.

    Science.gov (United States)

    2010-10-01

    ... Tilefish Fishery § 648.296 Gear restricted areas. No vessel of the United States may fish with bottom... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restricted areas. 648.296 Section 648.296 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND...

  8. 50 CFR 648.264 - Gear requirements/restrictions.

    Science.gov (United States)

    2010-10-01

    ... Measures for the Atlantic Deep-Sea Red Crab Fishery § 648.264 Gear requirements/restrictions. (a) Limited... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear requirements/restrictions. 648.264 Section 648.264 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC...

  9. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Allowable gear and gear restrictions. 665.227 Section 665.227 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be...

  10. 50 CFR 648.234 - Gear restrictions. [Reserved

    Science.gov (United States)

    2010-10-01

    ... Fishery § 648.234 Gear restrictions. ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.234 Section 648.234 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  11. Restriction endonuclease EcaI from Enterobacter cloacae

    OpenAIRE

    Hobom, G.; Schwarz, E; Melzer, M.; Mayer, H

    1981-01-01

    Restriction endonuclease EcaI obtained from Enterobacter cloacae DSM30056 recognizes the group of heptanucleotide palindromes 5′-G[unk]G-T-N-A-C-C-3′, and on cleavage (arrow) produces fragments with 5′-terminal pentanucleotide extensions. It is identical in specificity with restriction endonuclease BstEII from Bacillus stearothermophilus ET.

  12. 30 CFR 57.4461 - Gasoline use restrictions underground.

    Science.gov (United States)

    2010-07-01

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

  13. 12 CFR 563.36 - Tying restriction exception.

    Science.gov (United States)

    2010-01-01

    ...-OPERATIONS Operation and Structure § 563.36 Tying restriction exception. (a) Safe harbor for combined-balance... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Tying restriction exception. 563.36 Section 563.... (b) Limitations on exception. This exception shall terminate upon a finding by the OTS that...

  14. Supporting several levels of restriction in the UML

    DEFF Research Database (Denmark)

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

    The emergence of the Unified Modeling Language (UML) has provided software developers with an effective and efficient shared language. However, UML is often too restrictive in initial, informal, and creative modelling, and it is in some cases not restrictive enough, e.g., for code generation. Based...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  16. 40 CFR 152.175 - Pesticides classified for restricted use.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pesticides classified for restricted...) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Classification of Pesticides § 152.175 Pesticides classified for restricted use. The following uses of pesticide products containing...

  17. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

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

    2016-01-01

    The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive-multiplicative restricte...

  18. 32 CFR 516.5 - Restriction on contact with DOJ.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Restriction on contact with DOJ. 516.5 Section 516.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION General § 516.5 Restriction on contact with DOJ. (a) General...

  19. Access to Minerals: WTO Export Restrictions and Climate Change Considerations

    Directory of Open Access Journals (Sweden)

    Stephanie Switzer

    2015-09-01

    Full Text Available In the past few years, the Chinese government opted to restrict the export of selected minerals on environmental and health grounds, subsequently leading to an uproar in countries and regions that rely heavily on imports from China to develop their renewable industry sector. This paper places the focus on the law and policy of the Chinese export restrictions of critical minerals, and its implications for the global renewables energy industry. The paper critically assesses how such export restrictions have been dealt with under the dispute settlement system of the World Trade Organisation (WTO. Drawing on this WTO jurisprudence, we posit that litigation on export restrictions of the kind imposed by China poses a threat to the legitimacy of the WTO. We therefore conclude by exploring whether there are any alternatives to litigation as a means to deal with countries choosing to impose mineral export restrictions.

  20. Quadratic Loss of Isotonic Normal Means Under Simultaneous Order Restrictions

    Institute of Scientific and Technical Information of China (English)

    马艳萍; 史宁中

    2002-01-01

    For two normal populations with unknown means μ and unknown variances σ2,assume that there are simple order restrictions among the means and variances:μ1≤μ2 and σ12≥σ22>0,This case is said to be simultaneous order restriction by Shi (Maximum likelihood estimation of means and variances from normal populations under simultaneous order restrictions.J.Multivariate,Anal.50(1994),282-293.)and an iterative algorithm of computing the order restricted maximum likelihood estimates of μi and σi2 was given in that paper,This paper shows that the restricted maximum likelihood estimate of μi has smaller mean square loss than the usual estimate xi under some conditions.