Sample records for apobec3 restriction factors

  1. Differential evolution of antiretroviral restriction factors in pteropid bats as revealed by APOBEC3 gene complexity. (United States)

    Hayward, Joshua A; Tachedjian, Mary; Cui, Jie; Cheng, Adam Z; Johnson, Adam; Baker, Michelle; Harris, Reuben S; Wang, Lin-Fa; Tachedjian, Gilda


    Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.

  2. HIV restriction by APOBEC3 in humanized mice.

    Directory of Open Access Journals (Sweden)

    John F Krisko


    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. Suppression of APOBEC3-mediated restriction of HIV-1 by Vif

    Directory of Open Access Journals (Sweden)

    Yuqing eFeng


    Full Text Available The APOBEC3 restriction factors are a family of deoxycytidine deaminases that are able to suppress replication of viruses with a single-stranded DNA intermediate by inducing mutagenesis and functional inactivation of the virus. Of the seven human APOBEC3 enzymes, only APOBEC3-D, -F, -G, and -H appear relevant to restriction of HIV-1 in CD4+ T cells and will be the focus of this review. The restriction of HIV-1 occurs most potently in the absence of HIV-1 Vif that induces polyubiquitination and degradation of APOBEC3 enzymes through the proteasome pathway. To restrict HIV-1, APOBEC3 enzymes must be encapsidated into budding virions. Upon infection of the target cell during reverse transcription of the HIV-1 RNA into (-DNA APOBEC3 enzymes deaminate cytosines to forms uracils in single-stranded (- DNA regions. Upon replication of the (-DNA to (+DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils thereby inducing C/G to T/A mutations that can functionally inactivate HIV-1. APOBEC3G is the most studied APOBEC3 enzyme and it is known that Vif attempts to thwart APOBEC3 function not only by inducing its proteasomal degradation but by several degradation-independent mechanisms such as inhibiting APOBEC3G virion encapsidation, mRNA translation, and for those APOBEC3G molecules that still become virion encapsidated, Vif can inhibit APOBEC3G mutagenic activity. Although most Vif variants can induce efficient degradation of APOBEC3-D, -F, and -G, there appears to be differential sensitivity to Vif-mediated degradation for APOBEC3H. This review examines APOBEC3-mediated HIV restriction mechanisms, how Vif acts as a substrate receptor for a Cullin5 ubiquitin ligase complex to induce degradation of APOBEC3s, and the determinants and functional consequences of the APOBEC3 and Vif interaction from a biological and biochemical perspective.

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

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


    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.

  5. Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.

    Directory of Open Access Journals (Sweden)

    Jennifer M Binning


    Full Text Available The lentiviral protein Viral Infectivity Factor (Vif counteracts the antiviral effects of host APOBEC3 (A3 proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs to the Vif complex. Two Fabs were found to inhibit Vif-mediated A3 neutralization through distinct mechanisms: shielding A3 from ubiquitin transfer and blocking Vif E3 assembly. Combined biochemical, cell biological and structural studies reveal that disruption of Vif E3 assembly inhibited A3 ubiquitination but was not sufficient to restore its packaging into viral particles and antiviral activity. These observations establish that Vif can neutralize A3 family members in a degradation-independent manner. Additionally, this work highlights the potential of Fabs as functional probes, and illuminates how Vif uses a multi-pronged approach involving both degradation dependent and independent mechanisms to suppress A3 innate immunity.

  6. Vif of Feline Immunodeficiency Virus from Domestic Cats Protects against APOBEC3 Restriction Factors from Many Felids▿ (United States)

    Zielonka, Jörg; Marino, Daniela; Hofmann, Henning; Yuhki, Naoya; Löchelt, Martin; Münk, Carsten


    To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Δvif FIV, felid A3Z2s did not show any antiviral activity against Δvif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether VifFIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.VifFIV was constructed. This HIV-1.VifFIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor. PMID:20444897

  7. Vif of feline immunodeficiency virus from domestic cats protects against APOBEC3 restriction factors from many felids. (United States)

    Zielonka, Jörg; Marino, Daniela; Hofmann, Henning; Yuhki, Naoya; Löchelt, Martin; Münk, Carsten


    To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Deltavif FIV, felid A3Z2s did not show any antiviral activity against Deltavif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether Vif(FIV) can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.Vif(FIV) was constructed. This HIV-1.Vif(FIV) was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

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

    Directory of Open Access Journals (Sweden)

    David J Stanley


    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.

  9. A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS) is aggravated in APOBEC3 deficient mice (United States)


    Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs). Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus. PMID:22691411

  10. A Single Nucleotide Polymorphism in Human APOBEC3C Enhances Restriction of Lentiviruses.

    Directory of Open Access Journals (Sweden)

    Cristina J Wittkopp


    Full Text Available Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution. Here, we describe a single nucleotide polymorphism in human APOBEC3C, a change from serine to isoleucine at position 188 (I188 that confers potent antiviral activity against HIV-1. The gain-of-function APOBEC3C SNP results in increased enzymatic activity and hypermutation of target sequences when tested in vitro, and correlates with increased dimerization of the protein. The I188 is widely distributed in human African populations, and is the ancestral primate allele, but is not found in chimpanzees or gorillas. Thus, while other hominids have lost activity of this antiviral gene, it has been maintained, or re-acquired, as a more active antiviral gene in a subset of humans. Taken together, our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses.

  11. Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases ▿ † (United States)

    Zielonka, Jörg; Bravo, Ignacio G.; Marino, Daniela; Conrad, Elea; Perković, Mario; Battenberg, Marion; Cichutek, Klaus; Münk, Carsten


    The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene. PMID:19458006

  12. Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

    Directory of Open Access Journals (Sweden)

    Zeli Zhang


    Full Text Available The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3 and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids.

  13. Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV? (United States)

    Zhang, Zeli; Gu, Qinyong; Marino, Daniela; Lee, Kyeong-Lim; Kong, Il-Keun; Häussinger, Dieter; Münk, Carsten


    The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids. PMID:29642583

  14. Molecular and functional interactions of cat APOBEC3 and feline foamy and immunodeficiency virus proteins: different ways to counteract host-encoded restriction. (United States)

    Chareza, Sarah; Slavkovic Lukic, Dragana; Liu, Yang; Räthe, Ann-Mareen; Münk, Carsten; Zabogli, Elisa; Pistello, Mauro; Löchelt, Martin


    Defined host-encoded feline APOBEC3 (feA3) cytidine deaminases efficiently restrict the replication and spread of exogenous retroviruses like Feline Immunodeficiency Virus (FIV) and Feline Foamy Virus (FFV) which developed different feA3 counter-acting strategies. Here we characterize the molecular interaction of FFV proteins with the diverse feA3 proteins. The FFV accessory protein Bet is the virus-encoded defense factor which is shown here to bind all feA3 proteins independent of whether they restrict FFV, a feature shared with FIV Vif that induces degradation of all feA3s including those that do not inactivate FIV. In contrast, only some feA3 proteins bind to FFV Gag, a pattern that in part reflects the restriction pattern detected. Additionally, one-domain feA3 proteins can homo- and hetero-dimerize in vitro, but a trans-dominant phenotype of any of the low-activity feA3 forms on FFV restriction by one of the highly-active feA3Z2 proteins was not detectable. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells. (United States)

    Wang, Yufei; Bergmeier, Lesley A; Stebbings, Richard; Seidl, Thomas; Whittall, Trevor; Singh, Mahavir; Berry, Neil; Almond, Neil; Lehner, Thomas


    APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.

  16. Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3. (United States)

    Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei


    The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3

  17. The inhibitory effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members on the activity of cellular microRNAs. (United States)

    Zhang, Hui


    The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or APOBEC3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. However, the cellular function of APOBEC3G remains to be further clarified. It has been reported that APOBEC3s can restrict the mobility of endogenous retroviruses and LTR-retrotransposons, suggesting that they can maintain stability in host genomes. However, APOBEC3G is normally cytoplasmic. Further studies have demonstrated that it is associated with an RNase-sensitive high molecular mass (HMM) and located in processing bodies (P-bodies) of replicating T-cells, indicating that the major cellular function of APOBEC3G seems to be related to P-body-related RNA processing and metabolism. As the function of P-body is closely related to miRNA activity, APOBEC3G could affect the miRNA function. Recent studies have demonstrated that APOBEC3G and its family members counteract miRNA-mediated repression of protein translation. Further, APOBEC3G enhances the association of miRNA-targeted mRNA with polysomes, and facilitates the dissociation of miRNA-targeted mRNA from P-bodies. As such, APOBEC3G regulate the activity of cellular miRNAs. Whether this function is related to its potent antiviral activity remains to be further determined.

  18. HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    Terumasa Ikeda


    Full Text Available HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which results in higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn enable faster virus DNA replication and protection from APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal that a moderate decrease in one essential viral activity, namely Env-mediated fusogenicity, enables the virus to change other activities, here, Gag-Pol packaging during particle production, and thereby escape restriction by the antiviral factor APOBEC3G. We propose a new paradigm in which alterations in viral homeostasis, through compensatory small changes, constitute a general mechanism used by HIV-1 and other viral pathogens to escape innate antiviral responses and other inhibitions including antiviral drugs.

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


    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.

  20. Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase. (United States)

    Nowarski, Roni; Britan-Rosich, Elena; Shiloach, Tamar; Kotler, Moshe


    Deamination of cytidine residues in single-stranded DNA (ssDNA) is an important mechanism by which apolipoprotein B mRNA-editing, catalytic polypeptide-like (APOBEC) enzymes restrict endogenous and exogenous viruses. The dynamic process underlying APOBEC-induced hypermutation is not fully understood. Here we show that enzymatically active APOBEC3G can be detected in wild-type Vif(+) HIV-1 virions, albeit at low levels. In vitro studies showed that single enzyme-DNA encounters result in distributive deamination of adjacent cytidines. Nonlinear translocation of APOBEC3G, however, directed scattered deamination of numerous targets along the DNA. Increased ssDNA concentrations abolished enzyme processivity in the case of short, but not long, DNA substrates, emphasizing the key role of rapid intersegmental transfer in targeting the deaminase. Our data support a model by which APOBEC3G intersegmental transfer via monomeric binding to two ssDNA segments results in dispersed hypermutation of viral genomes.

  1. Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation. (United States)

    Revathidevi, Sundaramoorthy; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Rajkumar, Kottayasamy Seenivasagam; Ramani, Rajendran; Rajaraman, Ramamurthy; Ajay, Chandrasekar; Munirajan, Arasambattu Kannan


    Breast cancer and cervical cancer are the leading causes of death in women worldwide as well as in India, whilst oral cancer is the top most common cancer among Asian especially in Indian men in terms of both incidence and mortality rate. Genetic factors determining the predisposition to cancer are being explored to identify the signature genetic variations associated with these cancers. Recently, a germline deletion polymorphism in APOBEC3 gene cluster which completely deletes APOBEC3B coding region has been studied for its association with cancer risk. We screened the germline deletion polymorphism in 409 cancer patients (224 breast cancer, 88 cervical cancer and 97 oral cancer samples), 478 controls and 239 cervical cancer tissue DNAs of South Indian origin. The results suggest that the APOBEC3A/3B deletion polymorphism is not significantly associated with cancer risk in our study population (OR 0.739, 95 % CI, p value 0.91457). Considering the viral restriction property of APOBEC3s, we also screened cervical cancer tissue DNAs for the human papilloma virus infection. We observed a gradual increase in the frequency of HPV16 infection from AA/BB cases (66.86 %) to AA/-- cases (71.43) which signifies the impact of this deletion polymorphism in HPV infection. In addition, we performed in silico analysis to understand the effect of this polymorphism on miRNA regulation of the APOBEC3A/3B fusion transcript. Only 8 APOBEC3B targeting miRNAs were observed to regulate the fusion transcript of which miR-34b-3p and miR-138-5p were found to be frequently downregulated in cancers suggesting miRNA-mediated deregulation of APOBEC3A expression in cancer patients harbouring this particular deletion polymorphism.

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

    Directory of Open Access Journals (Sweden)

    Lucie Etienne


    Full Text Available 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.

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


    Friew, Yeshitila N; Boyko, Vitaly; Hu, Wei-Shau; Pathak, Vinay K


    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-Ga...

  4. Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s. (United States)

    Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten


    Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z

  5. 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. (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


    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

  6. A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection. (United States)

    Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei


    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian

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

    Directory of Open Access Journals (Sweden)

    Kate N Bishop


    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.

  8. Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation. (United States)

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


    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

  9. Inhibition of APOBEC3G activity impedes double-stranded DNA repair. (United States)

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


    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. © 2015 FEBS.

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

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh


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

  11. Generation and characterization of APOBEC3G-positive 293T cells for HIV-1 Vif study


    Piroozmand, Ahmad; Yamamoto, Yoshihiko; Khamsri, Boonruang; Fujita, Mikako; Uchiyama, Tsuneo; Adachi, Akio


    We have established a number of 293T cell lines that express a human anti HIV-1 factor APOBEC3G. Out of seven cell clones examined, four were readily demonstrated to express APOBEC3G by immunoblotting analysis. In particular, two clones (A3G-C1 and -C4) were found to produce a much higher level of functional APOBEC3G relative to that by pooled cell clones. The transfection efficiency of all these cell clones were similar to that of the parental cells, producing a comparable level of virions u...

  12. APOBEC3G: a Double Agent in Defense


    Smith, Harold C.


    APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild type Vif targets A3G for proteasomal degradation and along with it, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In thi...

  13. Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV. (United States)

    Stieler, Kristin; Fischer, Nicole


    The human exogenous gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread. Here we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G. Our findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.

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

    Directory of Open Access Journals (Sweden)

    Luis Apolonia


    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.

  15. Retroviral restriction and dependency factors in primates and carnivores (United States)

    Fadel, Hind J.; Poeschla, Eric M.


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

  16. Cellular Restriction Factors of Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Carsten Münk


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

  17. Cellular Restriction Factors of Feline Immunodeficiency Virus (United States)

    Zielonka, Jörg; Münk, Carsten


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

  18. Insights into the motif preference of APOBEC3 enzymes.

    Directory of Open Access Journals (Sweden)

    Diako Ebrahimi

    Full Text Available We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome.

  19. Novel host restriction factors implicated in HIV-1 replication. (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu


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

  20. APOBEC3 Interference during Replication of Viral Genomes

    Directory of Open Access Journals (Sweden)

    Luc Willems


    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.

  1. Inhibition of APOBEC3G Activity Impedes Double-Strand DNA Repair (United States)

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


    The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor 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 dsDNA damage, such as ionizing irradiation (IR) and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases sensitivity of lymphoma cells to IR. In the current study, we show that additional peptides derived from Vif, A3G and A3F, which contain the LYYF motif, inhibit deamination activity. Each residue in the Vif25-39 sequence moderately contributes to the inhibitory effect, while, replacing a single amino acid in the LYYF motif completely abrogate inhibition of deamination. Treatment of A3G-expressing lymphoma cells exposed to ionizing radiation with the new inhibitory peptides reduces double-strand break (DSB) repair after radiation. Incubation of cultured irradiated lymphoma cells with peptides that inhibit DSB repair halts their propagation. These results suggest that A3G may be a potential therapeutic target amenable to peptide and peptidomimetic inhibition. PMID:26460502

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


    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.

  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. Vif Proteins from Diverse Primate Lentiviral Lineages Use the Same Binding Site in APOBEC3G


    Letko, Michael; Silvestri, Guido; Hahn, Beatrice H.; Bibollet-Ruche, Frederick; Gokcumen, Omer; Simon, Viviana; Ooms, Marcel


    APOBEC3G (A3G) is a cytidine deaminase that restricts human immunodeficiency virus type 1 (HIV-1) and other lentiviruses. Most of these viruses encode a Vif protein that directly binds A3G and leads to its proteasomal degradation. Both Vif proteins of HIV-1 and African green monkey simian immunodeficiency virus (SIVagm) bind residue 128 of A3G. However, this position does not control the A3G degradation by Vif variants derived from HIV-2 and SIVmac, which both originated from SIV of sooty man...

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

    International Nuclear Information System (INIS)

    Thangavelu, Pulari U.; Gupta, Vipul; Dixit, Narendra M.


    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 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

  6. Functions, structure, and read-through alternative splicing of feline APOBEC3 genes (United States)

    Münk, Carsten; Beck, Thomas; Zielonka, Jörg; Hotz-Wagenblatt, Agnes; Chareza, Sarah; Battenberg, Marion; Thielebein, Jens; Cichutek, Klaus; Bravo, Ignacio G; O'Brien, Stephen J; Lochelt, Martin; Yuhki, Naoya


    Background Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene. Results Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection. Conclusion Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher. PMID:18315870

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

    Directory of Open Access Journals (Sweden)

    Xiao-Liang ZHANG


    Full Text Available 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.

  8. Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yanli [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Li, Hui [The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science Technology, Wuhan, 430000 (China); Zhang, Xiaoju [Department of Respiratory Medicine, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Shang, Jia [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Kang, Yi, E-mail: [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China)


    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) exert antiviral defense as an important factor of innate immunity. A variety of cytokines such as IFN-γ,IL2,IL15,IL7 could induce the transcription of A3G. However, the regulation of other nuclear factor on the transcription of A3G have not been reported at the present. To gain new insights into the transcriptional regulation of this restriction factor, we cloned and characterized the promoter region of A3G and investigate the modulation of USF1 gene on the transcription of A3G. We identified a 232 bp region that was sufficient to regulate the activity of full promoter. Transcriptional start sites (TSS) were identified by the luciferase reporter assays of plasmids containing full or shorter fragments of the A3G promoter. The results demonstrated that the core promoter of A3G is located within the region -159/-84 relative to the TSS. Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position -91/-86 relative to the major TSS) and was abolished after mutation of this DNA element. USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte, and the identified E-box represented a binding site for the USF1. - Highlights: • The core promoter of A3G is located within the region −159/−84 relative to the TSS. • Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position −91/−86 relative to the major TSS). • USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte.

  9. Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

    International Nuclear Information System (INIS)

    Zeng, Yanli; Li, Hui; Zhang, Xiaoju; Shang, Jia; Kang, Yi


    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) exert antiviral defense as an important factor of innate immunity. A variety of cytokines such as IFN-γ,IL2,IL15,IL7 could induce the transcription of A3G. However, the regulation of other nuclear factor on the transcription of A3G have not been reported at the present. To gain new insights into the transcriptional regulation of this restriction factor, we cloned and characterized the promoter region of A3G and investigate the modulation of USF1 gene on the transcription of A3G. We identified a 232 bp region that was sufficient to regulate the activity of full promoter. Transcriptional start sites (TSS) were identified by the luciferase reporter assays of plasmids containing full or shorter fragments of the A3G promoter. The results demonstrated that the core promoter of A3G is located within the region -159/-84 relative to the TSS. Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position -91/-86 relative to the major TSS) and was abolished after mutation of this DNA element. USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte, and the identified E-box represented a binding site for the USF1. - Highlights: • The core promoter of A3G is located within the region −159/−84 relative to the TSS. • Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position −91/−86 relative to the major TSS). • USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte.

  10. Molecular evolution of the primate antiviral restriction factor tetherin.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

  11. New World feline APOBEC3 potently controls inter-genus lentiviral transmission. (United States)

    Konno, Yoriyuki; Nagaoka, Shumpei; Kimura, Izumi; Yamamoto, Keisuke; Kagawa, Yumiko; Kumata, Ryuichi; Aso, Hirofumi; Ueda, Mahoko Takahashi; Nakagawa, So; Kobayashi, Tomoko; Koyanagi, Yoshio; Sato, Kei


    The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals. Here we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved. To the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.

  12. APOBEC3G levels predict rates of progression to AIDS

    Directory of Open Access Journals (Sweden)

    Wu Hulin


    Full Text Available Abstract Background APOBEC3G (hA3G is a newly discovered cellular factor of innate immunity that inhibits HIV replication in vitro. Whether hA3G conferrs protection against HIV in vivo is not known. To investigate the possible anti-HIV activity of hA3G in vivo, we examined hA3G mRNA abundance in primary human cells isolated from either HIV-infected or HIV-uninfected individuals, and found that hA3G mRNA levels follow a hierarchical order of long-term nonprogressors>HIV-uninfected>Progressors; and, hA3G mRNA abundance is correlated with surrogates of HIV disease progression: viral load and CD4 count. Another group later confirmed that HIV-infected subjects have lower hA3G mRNA levels than HIV-uninfected controls, but did not find correlations between hA3G mRNA levels and viral load or CD4 count. These conflicing results indicate that a more comprehensive, conclusive investigation of hA3G expression levels in various patient cohorts is urgently needed. Presentation of the hypothesis For exploring whether hA3G abundance might influence HIV disease progression, we have formulated a hypothesis that inlcudes two parts: a in vivo, the basal hA3G mRNA expression level per PBMC is a constant – with minor physiologic fluctuations – determined by host genetic and epigenetic elements in a healthy individual; and that the basal hA3G mRNA expression levels in a population follow a Normal (or Gaussian distribution; b that although HIV infects randomly, it results in more rapid disease progression in those with lower hA3G mRNA levels, and slower disease progression in those with higher hA3G mRNA levels. Testing the hypothesis This hypothesis could be tested by a straighforward set of experiments to compare the distribution of hA3G mRNA levels in HIV-uninfected healthy individuals and that in HIV-infected, antiretroviral therapy-naïve subjects who are at early and late stages of infection. Implication of the hypothesis Testing this hypothesis will have

  13. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li


    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.

  14. Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population. (United States)

    Göhler, Stella; Da Silva Filho, Miguel Inacio; Johansson, Robert; Enquist-Olsson, Kerstin; Henriksson, Roger; Hemminki, Kari; Lenner, Per; Försti, Asta


    The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

  15. Host restriction factors in retroviral infection: promises in virus-host interaction

    Directory of Open Access Journals (Sweden)

    Zheng Yong-Hui


    Full Text Available Abstract Retroviruses have an intricate life cycle. There is much to be learned from studying retrovirus-host interactions. Among retroviruses, the primate lentiviruses have one of the more complex genome structures with three categories of viral genes: structural, regulatory, and accessory genes. Over time, we have gained increasing understanding of the lentivirus life cycle from studying host factors that support virus replication. Similarly, studies on host restriction factors that inhibit viral replication have also made significant contributions to our knowledge. Here, we review recent progress on the rapidly growing field of restriction factors, focusing on the antiretroviral activities of APOBEC3G, TRIM5, tetherin, SAMHD1, MOV10, and cellular microRNAs (miRNAs, and the counter-activities of Vif, Vpu, Vpr, Vpx, and Nef.

  16. Characterization of the relationship between APOBEC3B deletion and ACE Alu insertion.

    Directory of Open Access Journals (Sweden)

    Kang Wang

    Full Text Available The insertion/deletion (I/D polymorphism of the angiotensin converting enzyme (ACE, commonly associated with many diseases, is believed to have affected human adaptation to environmental changes during the out-of-Africa expansion. APOBEC3B (A3B, a member of the cytidine deaminase family APOBEC3s, also exhibits a variable gene insertion/deletion polymorphism across world populations. Using data available from published reports, we examined the global geographic distribution of ACE and A3B genotypes. In tracking the modern human dispersal routes of these two genes, we found that the variation trends of the two I/D polymorphisms were directly correlated. We observed that the frequencies of ACE insertion and A3B deletion rose in parallel along the expansion route. To investigate the presence of a correlation between the two polymorphisms and the effect of their interaction on human health, we analyzed 1199 unrelated Chinese adults to determine their genotypes and other important clinical characteristics. We discovered a significant difference between the ACE genotype/allele distribution in the A3B DD and A3B II/ID groups (P = 0.045 and 0.015, respectively, indicating that the ACE Alu I allele frequency in the former group was higher than in the latter group. No specific clinical phenotype could be associated with the interaction between the ACE and A3B I/D polymorphisms. A3B has been identified as a powerful inhibitor of Alu retrotransposition, and primate A3 genes have undergone strong positive selection (and expansion for restricting the mobility of endogenous retrotransposons during evolution. Based on these findings, we suggest that the ACE Alu insertion was enabled (facilitated by the A3B deletion and that functional loss of A3B provided an opportunity for enhanced human adaptability and survival in response to the environmental and climate challenges arising during the migration from Africa.

  17. Uracil DNA glycosylase counteracts APOBEC3G-induced hypermutation of hepatitis B viral genomes: excision repair of covalently closed circular DNA.

    Directory of Open Access Journals (Sweden)

    Kouichi Kitamura

    Full Text Available The covalently closed circular DNA (cccDNA of the hepatitis B virus (HBV plays an essential role in chronic hepatitis. The cellular repair system is proposed to convert cytoplasmic nucleocapsid (NC DNA (partially double-stranded DNA into cccDNA in the nucleus. Recently, antiviral cytidine deaminases, AID/APOBEC proteins, were shown to generate uracil residues in the NC-DNA through deamination, resulting in cytidine-to-uracil (C-to-U hypermutation of the viral genome. We investigated whether uracil residues in hepadnavirus DNA were excised by uracil-DNA glycosylase (UNG, a host factor for base excision repair (BER. When UNG activity was inhibited by the expression of the UNG inhibitory protein (UGI, hypermutation of NC-DNA induced by either APOBEC3G or interferon treatment was enhanced in a human hepatocyte cell line. To assess the effect of UNG on the cccDNA viral intermediate, we used the duck HBV (DHBV replication model. Sequence analyses of DHBV DNAs showed that cccDNA accumulated G-to-A or C-to-T mutations in APOBEC3G-expressing cells, and this was extensively enhanced by UNG inhibition. The cccDNA hypermutation generated many premature stop codons in the P gene. UNG inhibition also enhanced the APOBEC3G-mediated suppression of viral replication, including reduction of NC-DNA, pre-C mRNA, and secreted viral particle-associated DNA in prolonged culture. Enhancement of APOBEC3G-mediated suppression by UNG inhibition was not observed when the catalytic site of APOBEC3G was mutated. Transfection experiments of recloned cccDNAs revealed that the combination of UNG inhibition and APOBEC3G expression reduced the replication ability of cccDNA. Taken together, these data indicate that UNG excises uracil residues from the viral genome during or after cccDNA formation in the nucleus and imply that BER pathway activities decrease the antiviral effect of APOBEC3-mediated hypermutation.

  18. Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA. (United States)

    Lada, Artem G; Waisertreiger, Irina S-R; Grabow, Corinn E; Prakash, Aishwarya; Borgstahl, Gloria E O; Rogozin, Igor B; Pavlov, Youri I


    Editing deaminases have a pivotal role in cellular physiology. A notable member of this superfamily, APOBEC3G (A3G), restricts retroviruses, and Activation Induced Deaminase (AID) generates antibody diversity by localized deamination of cytosines in DNA. Unconstrained deaminase activity can cause genome-wide mutagenesis and cancer. The mechanisms that protect the genomic DNA from the undesired action of deaminases are unknown. Using the in vitro deamination assays and expression of A3G in yeast, we show that replication protein A (RPA), the eukaryotic single-stranded DNA (ssDNA) binding protein, severely inhibits the deamination activity and processivity of A3G. We found that mutations induced by A3G in the yeast genomic reporter are changes of a single nucleotide. This is unexpected because of the known property of A3G to catalyze multiple deaminations upon one substrate encounter event in vitro. The addition of recombinant RPA to the oligonucleotide deamination assay severely inhibited A3G activity. Additionally, we reveal the inverse correlation between RPA concentration and the number of deaminations induced by A3G in vitro on long ssDNA regions. This resembles the "hit and run" single base substitution events observed in yeast. Our data suggest that RPA is a plausible antimutator factor limiting the activity and processivity of editing deaminases in the model yeast system. Because of the similar antagonism of yeast RPA and human RPA with A3G in vitro, we propose that RPA plays a role in the protection of the human genome cell from A3G and other deaminases when they are inadvertently diverged from their natural targets. We propose a model where RPA serves as one of the guardians of the genome that protects ssDNA from the destructive processive activity of deaminases by non-specific steric hindrance.

  19. Replication protein A (RPA hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA.

    Directory of Open Access Journals (Sweden)

    Artem G Lada

    Full Text Available Editing deaminases have a pivotal role in cellular physiology. A notable member of this superfamily, APOBEC3G (A3G, restricts retroviruses, and Activation Induced Deaminase (AID generates antibody diversity by localized deamination of cytosines in DNA. Unconstrained deaminase activity can cause genome-wide mutagenesis and cancer. The mechanisms that protect the genomic DNA from the undesired action of deaminases are unknown. Using the in vitro deamination assays and expression of A3G in yeast, we show that replication protein A (RPA, the eukaryotic single-stranded DNA (ssDNA binding protein, severely inhibits the deamination activity and processivity of A3G.We found that mutations induced by A3G in the yeast genomic reporter are changes of a single nucleotide. This is unexpected because of the known property of A3G to catalyze multiple deaminations upon one substrate encounter event in vitro. The addition of recombinant RPA to the oligonucleotide deamination assay severely inhibited A3G activity. Additionally, we reveal the inverse correlation between RPA concentration and the number of deaminations induced by A3G in vitro on long ssDNA regions. This resembles the "hit and run" single base substitution events observed in yeast.Our data suggest that RPA is a plausible antimutator factor limiting the activity and processivity of editing deaminases in the model yeast system. Because of the similar antagonism of yeast RPA and human RPA with A3G in vitro, we propose that RPA plays a role in the protection of the human genome cell from A3G and other deaminases when they are inadvertently diverged from their natural targets. We propose a model where RPA serves as one of the guardians of the genome that protects ssDNA from the destructive processive activity of deaminases by non-specific steric hindrance.

  20. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment

    Directory of Open Access Journals (Sweden)

    Monajemi Mahdis


    Full Text Available Abstract The enzyme APOBEC3G (A3G mutates the human immunodeficiency virus (HIV genome by converting deoxycytidine (dC to deoxyuridine (dU on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.

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

    Directory of Open Access Journals (Sweden)

    Weizi Liang

    Full Text Available 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.

  2. HBV/HIV co-infection and APOBEC3G polymorphisms in a population from Burkina Faso. (United States)

    Compaore, Tegwinde Rebeca; Diarra, Birama; Assih, Maleki; Obiri-Yeboah, Dorcas; Soubeiga, Serge Theophile; Ouattara, Abdoul Karim; Tchelougou, Damehan; Bisseye, Cyrille; Bakouan, Didier Romuald; Compaore, Issaka Pierre; Dembele, Augustine; Djigma, Wendkuuni Florencia; Simpore, Jacques


    Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) is a potent host defense factor, which interferes with HIV-1 and HBV. Our study had three objectives, to screen a population of HIV-1 infected and uninfected patients in Burkina Faso for HBV, to screen the population for APOBEC3G variants rs6001417, rs8177832, and rs35228531 previously described, and to analyze the effect of these three variants and their haplotypes on HIV-1/HBV co-infection in Burkina Faso. HBV detection was performed on samples from HIV-1 infected and uninfected subjects using rapid detection tests and real-time PCR. APOBEC3 genotyping was done by the TaqMan allelic discrimination method. Fisher Exact test, Odds ratio (OR), confidence intervals (CI) at 95 %, Linkage disequilibrium (LD) summary statistics and haplotype frequencies were calculated. The prevalence of HBV was 56.7 % among HIV-1 positive patients of our study while it was about 12.8 % among HIV-1 seronegative subjects. Genotype E was the genotype of HBV present in our hepatitis B positive samples. Minor allele frequencies of rs6001417, rs8177832, and rs35228531 were higher in seronegative subjects. The T minor allele of variant rs35228531 was protective against HIV-1/HBV co-infection with OR = 0.61, 95 % CI (0.42-0.90), p = 0.013. There was also an association between the GGT haplotype and protection against HIV-1/HBV co-infection, OR = 0.57, 95 % CI (0.33-0.99), p = 0.050. The other haplotypes present in the population were not statistically significant. There minor allele T of the rs35228531 was protective against HIV mono-infection OR = 0.53, 95 % CI (0.3-0.93), P = 0.030. But there was no effect of protection against HBV mono-infection. APOBEC3G through its variants rs6001417, rs8177832, and rs35228531, in this study interferes with HIV-1/HBV co-infection could be due the HIV-1 mono-infection in a population from Burkina Faso.

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

    Directory of Open Access Journals (Sweden)

    Joshua R. Kane


    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.

  4. The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer. (United States)

    Liu, Jingjing; Sieuwerts, Anieta M; Look, Maxime P; van der Vlugt-Daane, Michelle; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M


    Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90-1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first-line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69-1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71-1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist that may

  5. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. (United States)

    Chen, Ting-Wen; Lee, Chi-Ching; Liu, Hsuan; Wu, Chi-Sheng; Pickering, Curtis R; Huang, Po-Jung; Wang, Jing; Chang, Ian Yi-Feng; Yeh, Yuan-Ming; Chen, Chih-De; Li, Hsin-Pai; Luo, Ji-Dung; Tan, Bertrand Chin-Ming; Chan, Timothy En Haw; Hsueh, Chuen; Chu, Lichieh Julie; Chen, Yi-Ting; Zhang, Bing; Yang, Chia-Yu; Wu, Chih-Ching; Hsu, Chia-Wei; See, Lai-Chu; Tang, Petrus; Yu, Jau-Song; Liao, Wei-Chao; Chiang, Wei-Fan; Rodriguez, Henry; Myers, Jeffrey N; Chang, Kai-Ping; Chang, Yu-Sun


    Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B -/- :89A3B +/- :27A3B +/+ ), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

  6. APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion. (United States)

    Nowarski, Roni; Kotler, Moshe


    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. ©2013 AACR.

  7. Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage. (United States)

    Suspène, Rodolphe; Mussil, Bianka; Laude, Hélène; Caval, Vincent; Berry, Noémie; Bouzidi, Mohamed S; Thiers, Valérie; Wain-Hobson, Simon; Vartanian, Jean-Pierre


    Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A. By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal. The price to pay is chromosomal DNA damage in the form of CG→TA mutations and double stranded DNA breaks which, in the context of chronic inflammation, could drive cells down the path toward cancer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Directory of Open Access Journals (Sweden)

    Christopher Richards


    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.

  9. HIV-1 Vif promotes the formation of high molecular mass APOBEC3G complexes


    Goila-Gaur, Ritu; Khan, Mohammad A.; Miyagi, Eri; Kao, Sandra; Opi, Sandrine; Takeuchi, Hiroaki; Strebel, Klaus


    HIV-1 Vif inhibits the antiviral activity of APOBEC3G (APO3G) by inducing proteasomal degradation. Here, we studied the effects of Vif on APO3G in vitro. In this system, Vif did not cause APO3G degradation. Instead, Vif induced changes in APO3G that affected immunoprecipitation of the native protein. This effect required wt Vif and was reversed by heat-denaturation of APO3G. Sucrose gradient analysis demonstrated that wt Vif induced the gradual transition of APO3G translated in vitro or expre...

  10. The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. (United States)

    Shindo, Keisuke; Takaori-Kondo, Akifumi; Kobayashi, Masayuki; Abudu, Aierken; Fukunaga, Keiko; Uchiyama, Takashi


    Human immunodeficiency virus, type 1 (HIV-1) Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion. Vif functions to counteract an anti-HIV-1 cellular factor in non-permissive cells, CEM15/Apobec-3G, which shares a cytidine deaminase motif. CEM15/Apobec-3G deaminates dC to dU in the minus strand DNA of HIV-1, resulting in G to A hypermutation in the plus strand DNA. In this study, we have done the mutagenesis analysis on two cytidine deaminase motifs in CEM15/Apobec-3G and examined their antiviral functions as well as the DNA editing activity. Point mutations in the C-terminal active site such as E259Q and C291A almost completely abrogated the antiviral function, while those in the N-terminal active site such as E67Q and C100A retained this activity to a lesser extent as compared with that of the wild type. The DNA editing activities of E67Q and E259Q mutants were both retained but impaired to the same extent. This indicates that the enzymatic activity of this protein is essential but not a sole determinant of the antiviral activity. Furthermore, all the deletion mutants tested in this study lost the antiviral activity because of the loss of the activity for dimerization, suggesting that the entire protein structure is necessary for the antiviral function.

  11. 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


    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...... can inhibit this innate anti-viral defense through binding of the viral protein Vif to hA3G, but binding efficiency varies and hypermutation frequencies fluctuate in patients. A pivotal question is whether hA3G-induced G-to-A mutation is always lethal to the virus or if it may occur at sub......-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...

  12. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element. (United States)

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


    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. (United States)

    Kouno, Takahide; Silvas, Tania V; Hilbert, Brendan J; Shandilya, Shivender M D; Bohn, Markus F; Kelch, Brian A; Royer, William E; Somasundaran, Mohan; Kurt Yilmaz, Nese; Matsuo, Hiroshi; Schiffer, Celia A


    Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 Å. This structure not only visualizes the active site poised for catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards CC/TC motifs. The APOBEC3A-ssDNA complex defines the 5'-3' directionality and subtle conformational changes that clench the ssDNA within the binding groove, revealing the architecture and mechanism of ssDNA recognition that is likely conserved among all polynucleotide deaminases, thereby opening the door for the design of mechanistic-based therapeutics.

  14. Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population

    International Nuclear Information System (INIS)

    Marouf, Chaymaa; Göhler, Stella; Filho, Miguel Inacio Da Silva; Hajji, Omar; Hemminki, Kari; Nadifi, Sellama; Försti, Asta


    Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. Therefore, we investigated the potential association of several functional germline variants in the genes commonly mutated in sporadic breast cancer. In this case–control study, we examined 36 single nucleotide polymorphisms (SNPs) in 13 genes (APOBEC3A, APOBEC3B, ARID1B, ATR, MAP3K1, MLL2, MLL3, NCOR1, RUNX1, SF3B1, SMAD4, TBX3, TTN), which were located in the core promoter, 5’-and 3’UTR or which were nonsynonymous SNPs to assess their potential association with inherited predisposition to breast cancer development. Additionally, we identified a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B and explored possible associations with BC. A total of 226 Moroccan breast cancer cases and 200 matched healthy controls were included in this study. The analysis showed that12 SNPs in 8 driver genes, 4 SNPs in APOBEC3B gene and 1 SNP in APOBEC3A gene were associated with BC risk and/or clinical outcome at P ≤ 0.05 level. RUNX1-rs8130963 (odds ratio (OR) = 2.25; 95 % CI 1.42-3.56; P = 0.0005; dominant model), TBX3-rs8853 (OR = 2.04; 95 % CI 1.38-3.01; P = 0.0003; dominant model), TBX3-rs1061651 (OR = 2.14; 95 % CI1.43-3.18; P = 0.0002; dominant model), TTN-rs12465459 (OR = 2.02; 95 % confidence interval 1.33-3.07; P = 0.0009; dominant model), were the most significantly associated SNPs with BC risk. A strong association with clinical outcome were detected for the genes SMAD4 -rs3819122 with tumor size (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009) and TTN-rs2244492 with estrogen receptor (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009). Our results suggest that genetic variations in driver and APOBEC3 genes were associated with the risk of BC and may have impact on clinical outcome. However, the reported association between the

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

    Directory of Open Access Journals (Sweden)

    Manikandan Periyasamy


    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.

  16. Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. (United States)

    Rose, Kristine M; Marin, Mariana; Kozak, Susan L; Kabat, David


    APOBEC3G and 3F (A3G and A3F) cytidine deaminases incorporate into retroviral cores where they lethally hypermutate nascent DNA reverse transcripts. As substantiated here, the viral infectivity factor (Vif) encoded by human immunodeficiency virus type-1 (HIV-1) binds A3G and A3F and induces their degradation, thereby precluding their incorporation into viral progeny. Previous evidence suggested that A3G is expressed in H9 and other nonpermissive cells that contain this antiviral defense but not in several permissive cells, and that overexpression of A3G or A3F makes permissive cells nonpermissive. Using a broader panel of cell lines, we confirmed a correlation between A3G and cellular abilities to inactivate HIV-1(Deltavif). However, there was a quantitative discrepancy because several cells with weak antiviral activities had similar amounts of wild-type A3G mRNA and protein compared to H9 cells. Antiviral activity of H9 cells was also attenuated in some conditions. These quantitative discrepancies could not be explained by the presence of A3F or other A3G paralogs in some of the cell lines. Thus, A3A, A3B, and A3C had weak but significant anti-HIV-1 activities and did not dominantly interfere with A3G or A3F antiviral functions. Control of A3G synthesis by the protein kinase C/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway was also similar in permissive and nonpermissive cells. A3G in highly permissive cells is degraded by Vif, suggesting that it is not in a sequestered site, and is specifically incorporated in low amounts into HIV-1(Deltavif). Although A3G and/or A3F inactivate HIV-1(Deltavif) and are neutralized by Vif, the antiviral properties of cell lines are also influenced by other cellular and viral factors.

  17. Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions. (United States)

    Silvas, Tania V; Hou, Shurong; Myint, Wazo; Nalivaika, Ellen; Somasundaran, Mohan; Kelch, Brian A; Matsuo, Hiroshi; Kurt Yilmaz, Nese; Schiffer, Celia A


    The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH. We identified the A3A ssDNA binding motif as (T/C)TC(A/G), which correlated with enzymatic activity. We also validated that A3A binds RNA in a sequence specific manner. A3A bound tighter to substrate binding motif within a hairpin loop compared to linear oligonucleotide, suggesting A3A affinity is modulated by substrate structure. Based on these findings and previously published A3A-ssDNA co-crystal structures, we propose a new model with intra-DNA interactions for the molecular mechanism underlying A3A sequence preference. Overall, the sequence and structural preferences identified for A3A leads to a new paradigm for identifying A3A's involvement in mutation of endogenous or exogenous DNA.

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

    Directory of Open Access Journals (Sweden)

    Strebel Klaus


    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.

  19. 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.

  20. Turning up the volume on mutational pressure: Is more of a good thing always better? (A case study of HIV-1 Vif and APOBEC3

    Directory of Open Access Journals (Sweden)

    Wong Joseph K


    Full Text Available Abstract APOBEC3G and APOBEC3F are human cytidine deaminases that serve as innate antiviral defense mechanisms primarily by introducing C-to-U changes in the minus strand DNA of retroviruses during replication (resulting in G-to-A mutations in the genomic sense strand sequence. The HIV-1 Vif protein counteracts this defense by promoting the proteolytic degradation of APOBEC3G and APOBEC3F in the host cell. In the absence of Vif expression, APOBEC3 is incorporated into HIV-1 virions and the viral genome undergoes extensive G-to-A mutation, or "hypermutation", typically rendering it non-viable within a single replicative cycle. Consequently, Vif is emerging as an attractive target for pharmacological intervention and therapeutic vaccination. Although a highly effective Vif inhibitor may result in mutational meltdown of the viral quasispecies, a partially effective Vif inhibitor may accelerate the evolution of drug resistance and immune escape due to the codon structure and recombinogenic nature of HIV-1. This hypothesis rests on two principal assumptions which are supported by experimental evidence: a there is a dose response between intracellular APOBEC concentration and degree of viral hypermutation, and, b HIV-1 can tolerate an elevated mutation rate, and a true error or extinction threshold is as yet undetermined. Rigorous testing of this hypothesis will have timely and critical implications for the therapeutic management of HIV/AIDS, and delve into the complexities underlying the induction of lethal mutagenesis in a viral pathogen.

  1. Enzymatically Active APOBEC3G Is Required for Efficient Inhibition of Human Immunodeficiency Virus Type 1▿


    Miyagi, Eri; Opi, Sandrine; Takeuchi, Hiroaki; Khan, Mohammad; Goila-Gaur, Ritu; Kao, Sandra; Strebel, Klaus


    APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. Initial studies of the function of APO3G demonstrated extensive mutation of the viral genome, suggesting a model in which APO3G's antiviral activity is due to hypermutation of the viral genome. Recent studies, however, found that deaminase-defective APO3G mutants transiently expressed in virus-producing cells exhibited significant antiviral activity, suggesting that the antiviral activity of APO3G could be disso...

  2. Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells▿ (United States)

    Münk, Carsten; Zielonka, Jörg; Constabel, Hannelore; Kloke, Björn-Philipp; Rengstl, Benjamin; Battenberg, Marion; Bonci, Francesca; Pistello, Mauro; Löchelt, Martin; Cichutek, Klaus


    The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility of feline cells in order to evaluate the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that feline cell lines harbor multiple restrictions with respect to HIV-1 replication. The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA-1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase reporter activity and low expression of viral Gag-Pol proteins when pseudotyped vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4 and CCR5, were very permissive for viral entry and HIV-long terminal repeat-driven expression but failed to support spreading infection. KE-R cells displayed a profound block with respect to release of HIV-1 particles. In contrast, CrFK cells allowed very efficient particle production; however, the CrFK cell-derived HIV-1 particles had low specific infectivity. We subsequently identified feline apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity. CrFK cells express at least three different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A hypermutations of the viral cDNA and reduced the infectivity ∼10- to ∼40-fold. PMID:17459941

  3. Evolutionary genomics and HIV restriction factors. (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio


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

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

    DEFF Research Database (Denmark)

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


    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....

  5. Predictive factors for intrauterine growth restriction. (United States)

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


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

  6. High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from antiretroviral-naive patients. (United States)

    Bertine, Mélanie; Charpentier, Charlotte; Visseaux, Benoit; Storto, Alexandre; Collin, Gilles; Larrouy, Lucile; Damond, Florence; Matheron, Sophie; Brun-Vézinet, Françoise; Descamps, Diane


    In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.

  7. R Factor-Controlled Restriction and Modification of Deoxyribonucleic Acid: Restriction Mutants (United States)

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


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

  8. An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals (United States)


    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. PMID:22640020

  9. Multifaceted counter-APOBEC3G mechanisms employed by HIV-1 Vif. (United States)

    Britan-Rosich, Elena; Nowarski, Roni; Kotler, Moshe


    In the absence of human immunodeficiency virus type 1 (HIV-1) Vif protein, the host antiviral deaminase apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (A3G) restricts the production of infectious HIV-1 by deamination of dC residues in the negative single-stranded DNA produced by reverse transcription. The Vif protein averts the lethal threat of deamination by precluding the packaging of A3G into assembling virions by mediating proteasomal degradation of A3G. In spite of this robust Vif activity, residual A3G molecules that escape degradation and incorporate into newly assembled virions are potentially deleterious to the virus. We hypothesized that virion-associated Vif inhibits A3G enzymatic activity and therefore prevents lethal mutagenesis of the newly synthesized viral DNA. Here, we show that (i) Vif-proficient HIV-1 particles released from H9 cells contain A3G with lower specific activity compared with Δvif-virus-associated A3G, (ii) encapsidated HIV-1 Vif inhibits the deamination activity of recombinant A3G, and (iii) purified HIV-1 Vif protein and the Vif-derived peptide Vif25-39 inhibit A3G activity in vitro at nanomolar concentrations in an uncompetitive manner. Our results manifest the potentiality of Vif to control the deamination threat in virions or in the pre-integration complexes following entry to target cells. Hence, virion-associated Vif could serve as a last line of defense, protecting the virus against A3G antiviral activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Exposure to apoptotic activated CD4+ T cells induces maturation and APOBEC3G-mediated inhibition of HIV-1 infection in dendritic cells.

    Directory of Open Access Journals (Sweden)

    Venkatramanan Mohanram

    Full Text Available Dendritic cells (DCs are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4(+ T cells (ApoInf or apoptotic uninfected activated CD4(+ T cells (ApoAct induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4(+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4(+ T cells (ApoRest. Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection.

  11. Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.

    Directory of Open Access Journals (Sweden)

    Yanxing Han


    Full Text Available 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, TRIM5alpha, 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 by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies.In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons.These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s. Further characterization of this novel gene product(s will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1.

  12. Differential contributions of ubiquitin-modified APOBEC3G lysine residues to HIV-1 Vif-induced degradation


    Turner, Tiffany; Shao, Qiujia; Wang, Weiran; Wang, Yudi; Wang, Chenliang; Kinlock, Ballington; Liu, Bindong


    Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (A3G) is a host restriction factor that impedes HIV-1 replication. Viral integrity is salvaged by HIV-1 virion infectivity factor (Vif), which mediates A3G polyubiquitination and subsequent cellular depletion. Previous studies have implied that A3G polyubiquitination is essential for Vif-induced degradation. However, the contribution of polyubiquitination to the rate of A3G degradation remains unclear. Here we show that A3G po...

  13. Real moments of the restrictive factor

    Indian Academy of Sciences (India)

    To be more precise, we prove the following result. Theorem. Let λ be a real number such that 0 0. Also, define. Rλ(n) = k. ∏ ν=1 pλ(αν −1) ν. , where n = ∏k ν=1 pαν ν is the prime factorization of n. Then there exists a positive absolute constant c2 such that for all large x,. ∑ n≤x. Rλ(n). (. 1 − n x. ) = ζ(2 − λ).

  14. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier


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

  15. Heat Increases the Editing Efficiency of Human Papillomavirus E2 Gene by Inducing Upregulation of APOBEC3A and 3G. (United States)

    Yang, Yang; Wang, Hexiao; Zhang, Xinrui; Huo, Wei; Qi, Ruiqun; Gao, Yali; Zhang, Gaofeng; Song, Bing; Chen, Hongduo; Gao, Xinghua


    Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been identified as potent viral DNA mutators and have broad antiviral activity. In this study, we demonstrated that apolipoprotein B mRNA-editing catalytic polypeptide 3A (A3A) and A3G expression levels were significantly upregulated in human papillomavirus (HPV)-infected cell lines and tissues. Heat treatment resulted in elevated expression of A3A and A3G in a temperature-dependent manner in HPV-infected cells. Correspondingly, HPV-infected cells heat-treated at 44 °C showed accumulated G-to-A or C-to-T mutation in HPV E2 gene. Knockdown of A3A or A3G could promote cell viability, along with the lower frequency of A/T in HPV E2 gene. In addition, regressing genital viral warts also harbored high G-to-A or C-to-T mutation in HPV E2 gene. Taken together, we demonstrate that apolipoprotein B mRNA-editing catalytic polypeptide 3 expression and editing function was heat sensitive to a certain degree, partly explaining the mechanism of action of local hyperthermia to treat viral warts. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. In vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction.

    Directory of Open Access Journals (Sweden)

    Kenji Ohba

    Full Text Available High prevalence of infection with high-risk human papilloma virus (HPV ranging from 25 to 100% (average 31% was observed in breast cancer (BC patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.

  17. Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins. (United States)

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


    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.

  18. Ifit2 Is a Restriction Factor in Rabies Virus Pathogenicity. (United States)

    Davis, Benjamin M; Fensterl, Volker; Lawrence, Tessa M; Hudacek, Andrew W; Sen, Ganes C; Schnell, Matthias J


    Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma cells in vitro This effect was replicated in vivo , where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type mice after intranasal inoculation of RABV. This increase in pathogenicity correlated to an increase in RABV mRNA and live viral load in the brain, as well as to an accelerated spread to brain regions normally affected by this RABV model. These results suggest that Ifit2 exerts its antiviral effect mainly at the level of viral replication, as opposed to functioning as a mechanism that restricts viral entry/egress or transports RABV particles through axons. IMPORTANCE Rabies is a fatal zoonotic disease with a nearly 100% case fatality rate. Although there are effective vaccines for rabies, this disease still takes the lives of about 50,000 people each year. Victims tend to be children living in regions without comprehensive medical infrastructure who present to health care workers too late for postexposure prophylaxis. The protein discussed in our report, Ifit2, is found to be an important restriction factor for rabies virus, acting directly or indirectly against viral replication. A more nuanced understanding of this interaction may reveal a step of a pathway or site at which the system could be exploited for the development of a targeted therapy. Copyright © 2017 American Society for Microbiology.

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

    Directory of Open Access Journals (Sweden)

    Andrésdóttir Valgerdur


    Full Text Available Abstract 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-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3, suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals. This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions were selected by ancient pathogenic retrovirus infections.

  20. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Fabio E. Leal


    Full Text Available HTLV-1-Associated Myelopathy (HAM/TSP is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this “IFN paradox” in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax, proviral load and 42 host genes with known antiretroviral (anti-HIV activity in purified CD4+ T cells. This revealed two major clusters (“antiviral/protective” vs. “proviral/deleterious”, as evidenced by significant negative (TRIM5/TRIM22/BST2 vs. positive correlation (ISG15/PAF1/CDKN1A with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H, underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2 were significantly

  1. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation. (United States)

    Leal, Fabio E; Menezes, Soraya Maria; Costa, Emanuela A S; Brailey, Phillip M; Gama, Lucio; Segurado, Aluisio C; Kallas, Esper G; Nixon, Douglas F; Dierckx, Tim; Khouri, Ricardo; Vercauteren, Jurgen; Galvão-Castro, Bernardo; Saraiva Raposo, Rui Andre; Van Weyenbergh, Johan


    HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4 + T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4 + T cells. This revealed two major clusters ("antiviral/protective" vs. "proviral/deleterious"), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN

  2. Cacao in México: Restrictive factors and productivity levels

    Directory of Open Access Journals (Sweden)

    Julio Díaz-José


    Full Text Available Cacao (Theobroma cacao L. represents one of the most important agricultural crops of the humid Mexican tropics. In the last 10 yr, approximately 23.000 t of this grain were no longer produced per cycle. The objective of this study was to identify characteristics and factors that restrict production in the states of Tabasco and Chiapas. A survey was applied to obtain information about 184 producers and their plantations by two-stage sampling. Descriptive statistics were calculated and multilevel models were adjusted to analyze the information. Results show that there are differences (P < 0.05 in cacao yield between municipalities (380 kg ha-1 + u,o j is the estimated residual for each municipality. Crop productivity levels are higher in the state of Tabasco than in Chiapas (644 and 344 kg ha-1, respectively. Incidence of frosty pod rot of cacoa, also known as moniliasis, induced by Moniliophthora roreri [(Cif H.C. Evans, Stalpers, Samson & Benny 1978] is significantly greater (P < 0.05 in the state of Chiapas (60% than in Tabasco (48%.Producers who carry out more crop management practices increase yields and decrease the pathogen's impact on their plantations. Results suggest the need to apply differentiated public policies to promote production within each region or municipality.

  3. Restricting Factors at Modification of Parameters of Associative Engineering Objects (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.

  4. Participation restrictions in ambulatory amyotrophic lateral sclerosis patients: Physical and psychological factors. (United States)

    Van Groenestijn, Annerieke C; Schröder, Carin D; Kruitwagen-Van Reenen, Esther T; Van Den Berg, Leonard H; Visser-Meily, Johanna M A


    The aim of this study was to assess the prevalence of participation restrictions in ambulatory patients with amyotrophic lateral sclerosis (ALS) and to identify physical and psychological contributory factors. In this cross-sectional study, self-reported participation restrictions of 72 ambulatory ALS patients were assessed using the social health status dimension (SIPSOC) of the Sickness Impact Profile (SIP-68). Associations between SIPSOC and physical functioning, psychological factors, and demographic factors were analyzed using hierarchical regression analyses. Ninety-two percent of the patients reported participation restrictions; 54.9% could be explained by physical functioning; psychological factors accounted for 8.1% of the variance. Lung capacity, functional mobility, fatigue, and helplessness were independently associated with participation restrictions. Ambulatory ALS patients have participation restrictions, which may be influenced if early ALS care is directed toward lung capacity, functional mobility, fatigue, and feelings of helplessness. Muscle Nerve 56: 912-918, 2017. © 2017 Wiley Periodicals, Inc.

  5. 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.


    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: 5.694, year: 2015

  6. Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor


    Giovannoni, Federico; Damonte, Elsa B.; Garc?a, Cybele C.


    The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity....

  7. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors. (United States)

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu


    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  8. Factors associated with prescribing restriction on oncology formulary drugs in Malaysia. (United States)

    Fatokun, Omotayo; Olawepo, Michael N


    Background Drugs listed on formularies are often subjected to a variety of utilization restriction measures. However, the degree of restriction is influenced by multiple factors, including the characteristics and attributes of the listed drugs. Objective To identify the factors that are associated with the levels of prescribing restriction on oncology formulary drugs in Malaysia. Setting Oncology formulary in Malaysia. Method The Malaysia Drug Code assigned to each of the drug products on the Malaysia Ministry of Health (MOH) drug formulary was used to identify oncology drugs belonging to WHO ATC class L (antineoplastic and immunomodulating agents). Main outcome measures Categories of prescribing restrictions, therapeutic class, drug type, administration mode, number of sources and the post-approval use period. Results Oncology drugs having a shorter post-approval use period (p Malaysia MOH drug formulary.

  9. Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans

    DEFF Research Database (Denmark)

    Heintz, Caroline; Doktor, Thomas K; Lanjuin, Anne


    via splicing factor 1 (SFA-1; the C. elegans homologue of SF1, also known as branchpoint binding protein, BBP). We show that SFA-1 is specifically required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also...... homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or subjected to dietary restriction, we find defects in global pre-mRNA splicing with age that are reduced by dietary restriction...

  10. Factors associated with parental use of restrictive feeding practices to control their children's food intake. (United States)

    Gray, Wendy N; Janicke, David M; Wistedt, Kristin M; Dumont-Driscoll, Marilyn C


    There is a critical need to identify risk factors that make parents more likely to restrict their child's food intake. Child weight and ethnicity, parent weight, parent body dissatisfaction, and parent concern of child weight were examined as correlates of parent use of restrictive feeding practices in a diverse sample of 191 youth (ages 7-17). Participants attending a pediatric outpatient visit completed the Child Feeding Questionnaire (parent feeding practices and beliefs), the Figure Rating Scale (body dissatisfaction) and a demographic form. Parent BMI and child degree of overweight were calculated. Parent use of restrictive feeding practices was positively associated with parent BMI and was moderated by parent body dissatisfaction. Parent concern of child weight mediated the relationship between increasing child degree of overweight and parent use of restrictive feeding practices. There were no differences by child gender or ethnicity in parent use of restrictive feeding practices. These preliminary findings highlight the importance of assessing for underlying parent motivations for utilizing restrictive feeding practices and may help to identify and intervene with families at-risk for engaging in counterproductive weight control strategies. Continued identification of correlates of parent use of restrictive feeding practices is needed across child development and among individuals from diverse backgrounds.

  11. Automobile driving in older adults: factors affecting driving restriction in men and women. (United States)

    Marie Dit Asse, Laetitia; Fabrigoule, Colette; Helmer, Catherine; Laumon, Bernard; Lafont, Sylviane


    To identify factors associated with driving restriction in elderly men and women. Prospective cohort study of French drivers from 2003 to 2009. The Three-City Cohort of Bordeaux, a prospective study of 2,104 people aged 65 and older. Five hundred twenty-three drivers with a mean age of 76 (273 male, 250 female). Sociodemographic characteristics, driving habits, health variables, cognitive evaluation and dementia diagnosis. Predementia was defined as no dementia at one follow-up and dementia at the next follow-up. Over the 6-year period, 54% of men and 63% of women stopped driving or reduced the distance they drove. Predementia, Parkinson's disease, older age, and a high number of kilometers previously driven were common restriction factors in both sexes. Prevalent dementia, depressive symptomatology, a decline in one or more instrumental activities of daily living, and poor visual working memory were specific factors in men. In women, low income, fear of falling, slow processing speed, and severe decline in global cognitive performance all affected driving restriction. Older women restricted their driving activity more than older men, regardless of the number of kilometers previously driven, physical health, and cognitive status. Factors affecting driving restriction differed according to sex, and women were more likely to stop driving than men in the period preceding a dementia diagnosis. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  12. Factor Structure of the Restricted Academic Situation Scale: Implications for ADHD (United States)

    Karama, Sherif; Amor, Leila Ben; Grizenko, Natalie; Ciampi, Antonio; Mbekou, Valentin; Ter-Stepanian, Marina; Lageix, Philippe; Baron, Chantal; Schwartz, George; Joober, Ridha


    Background: To study the factor structure of the Restricted Academic Situation Scale (RASS), a psychometric tool used to assess behavior in children with ADHD, 117 boys and 21 girls meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.; "DSM-IV") criteria for ADHD and aged between 6 and 12 years were recruited. Assessments were…

  13. Inter-organizational relationships: promoters and restrictive factors in the formation of cooperation network

    Directory of Open Access Journals (Sweden)

    Marcos Antonio Gaspar


    Full Text Available The present paper had as aim to identify factors of inter-organizational relationships which promotes and restricts the formation of companies’ cooperation network, from two levels of analysis (organizational and inter-organizational. To achieve this goal, it was developed a descriptive-qualitative study, with prospecting for primary and secondary data on a cooperation network. The universe was composed by 41 participating companies associated to the analyzed network. The sampling procedure was for researcher’s accessibility and convenience. As a result, it was identified that the network is guided by goals of cooperation among the participating companies, in addition to representing the sector and provide services in the interests of the associates. The main factors influencing the formation of the network were: business center, marketing and training; but only training has been achieved satisfactorily. The business center and marketing factors have not yet been fully developed, being both identified as restrictive factors.

  14. [Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction]. (United States)

    Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László


    Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

  15. Two genetic determinants acquired late in Mus evolution regulate the inclusion of exon 5, which alters mouse APOBEC3 translation efficiency.

    Directory of Open Access Journals (Sweden)

    Jun Li


    Full Text Available Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3, an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6 mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5 mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.

  16. Adherence to diet and fluid restriction of individuals on hemodialysis treatment and affecting factors in Turkey. (United States)

    Efe, Dilek; Kocaöz, Semra


    This study was conducted to determine adherence to diet and fluid restriction in hemodialysis-treated individuals and the affecting factors in Turkey. This descriptive study was conducted between 15 October 2010 and 15 January 2011 in subjects who voluntarily agreed to participate in the study from three dialysis centers in a city located in the Central Anatolia Region of Turkey. One hundred and twenty-one individuals treated with hemodialysis made up the study sample. The data were collected using a questionnaire consisting of 41 questions and the Dialysis Diet and Fluid Non-adherence Questionnaire. The data were evaluated with percentage, median, Mann-Whitney U-test, Kruskal-Wallis test, Student's t-test in independent samples and Spearman's rank correlation coefficient. The authors found that 98.3% of the individuals experienced non-adherence to diet and 95.0% with fluid restriction. The authors found a weak and negative relationship between calcium levels and non-adherence to fluid restriction, a weak relationship between phosphorus levels and diet non-adherence frequency and degree and the fluid non-adherence frequency scores, and a moderate positive relationship between phosphorus levels and fluid restriction non-adherence degree scores (P < 0.05). Based on these results, regular training and information regarding diet and fluid restriction must be provided to individuals aged 21-35 years with no one in the family to help with their care, those who consumed salted food, or had interdialytic weight gain of 4.5 kg or more. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

  17. Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction. (United States)

    Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László


    We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

  18. [Study on restriction factors and countermeasures of influence of China medical devices competitiveness]. (United States)

    Zhang, Zhijun


    Recent years, China medical devices industry has been a sunrise industry with widely-ranged products, high-tech innovation, and booming market demands. But with the globalization of market economy, China industry is still in the inferior position of competition. How to promote the industrial structure transition, increase scientific and technological level, speed up the updating of products, enhance the international competitiveness is one of the major tasks to maintain the healthy development of industry. This article makes a study on current situation of China medical devices industry, analyses the new opportunities, challenges and restriction factors, provides the countermeasures of strengthening industry competitiveness as well.

  19. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction. (United States)

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan


    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  20. Regulatory role of neuron-restrictive silencing factor in expression of TRPC1

    International Nuclear Information System (INIS)

    Ohba, Takayoshi; Watanabe, Hiroyuki; Takahashi, Yoichiro; Suzuki, Takashi; Miyoshi, Ichiro; Nakayama, Shinnsuke; Satoh, Eisaku; Iino, Kenji; Sasano, Hironobu; Mori, Yasuo; Kuromitsu, Sadao; Imagawa, Keiichi; Saito, Yoshihiko; Iijima, Toshihiko; Ito, Hiroshi; Murakami, Manabu


    Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca 2+ channel (SOCC)-mediated Ca 2+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings strongly suggest that NRSF regulates TRP1 gene expression and causes changes in the levels of calcium entry through SOCCs

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

    DEFF Research Database (Denmark)

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


    electric power consumption, local price and meteorological data collected from 1900 customers. The households are equipped with local generation and smart appliances capable of responding to realtime pricing signals. The results show that for the short-term (5 minute to 1 day ahead) prediction problems......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...... 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...

  2. SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV

    Directory of Open Access Journals (Sweden)

    Gracia Viviana Gonzalez-Enriquez


    Full Text Available The serine incorporator 5 (SERINC5 is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef, S2, and glycosylated Gag (glycoGag. These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

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

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari


    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.

  4. Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis. (United States)

    Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent


    To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.

  5. Cultural factors influencing dietary and fluid restriction behaviour: perceptions of older Chinese patients with heart failure. (United States)

    Rong, Xiaoshan; Peng, Youqing; Yu, Hai-Ping; Li, Dan


    To explore the cultural factors related to dietary and fluid restriction behaviours among older Chinese patients. Excess dietary sodium and fluid intake are risk factors contributing to the worsening and rehospitalisation for heart failure in older patients. Managing the complex fluid and diet requirements of heart failure patients is challenging and is made more complicated by cultural variations in self-management behaviours in response to a health threat. Qualitative study using semi-structured in interviews and framework analysis. The design of this study is qualitative descriptive. Semi-structured in-depth interviews were conducted with 15 heart failure patients. Data were analysed through content analysis. Seven cultural themes emerged from the qualitative data: the values placed on health and illness, customary way of life, preference for folk care and the Chinese healthcare system, and factors related to kinship and social ties, religion, economics and education. Dietary change and management in response to illness, including heart failure, is closely related to individuals' cultural background. Healthcare providers should have a good understanding of cultural aspects that can influence patients' conformity to medical recommendations. Heart failure patients need support that considers their cultural needs. Healthcare providers must have a good understanding of the experiences of people from diverse cultural backgrounds. © 2016 John Wiley & Sons Ltd.

  6. The association between measurement sites of visceral adipose tissue and cardiovascular risk factors after caloric restriction in obese Korean women. (United States)

    Lee, Hye-Ok; Yim, Jung-Eun; Lee, Jeong-Sook; Kim, Young-Seol; Choue, Ryowon


    Quantities as well as distributions of adipose tissue (AT) are significantly related to cardiovascular disease (CVD) risk factors and can be altered with caloric restriction. This study investigated which cross-sectional slice location of AT is most strongly correlated with changes in CVD risk factors after caloric restriction in obese Korean women. Thirty-three obese pre-menopausal Korean women (32.4 ± 8.5 yrs, BMI 27.1 ± 2.3 kg/m(2)) participated in a 12 weeks caloric restriction program. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using computed tomography (CT) scans at the sites of L2-L3, L3-L4, and L4-L5. Fasting serum levels of glucose, insulin, triglyceride, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), leptin and homeostasis model assessment-insulin resistance (HOMA-IR) were observed. Pearson's partial correlation coefficients were used to assess the relationship between AT measurement sites and changes in CVD risk factors after calorie restriction. When calories were reduced by 350 kcal/day for 12 weeks, body weight (-2.7%), body fat mass (-8.2%), and waist circumference (-5.8%) all decreased (P restriction, serum levels of glucose (-4.6%), TC (-6.2%), LDL-C (-5.3%), leptin (-17.6%) and HOMA-IR (-18.2%) decreased significantly (P restriction.

  7. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study. (United States)

    Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline


    The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

  8. Determination of the growth restriction factor and grain size for aluminum alloys by a quasi-binary equivalent method

    International Nuclear Information System (INIS)

    Mitrašinović, A.M.; Robles Hernández, F.C.


    Highlights: ► A new method to determine the growth restricting factor. (Q) is proposed ► The proposed method is highly accurate (R 2 = 0.99) and simple. ► A major novelty of this method is the determination of Q for non-dilute samples. ► The method proposed herein is based on quasi-binary phase diagrams and composition. ► This method can be easily implemented industrially or as a research tool. - Abstract: In the present research paper is suggested a new methodology to determine the growth restricting factor (Q) and grain size (GS) for various Al-alloys. The present method combines a thermodynamical component based on the liquidus behavior of each alloying element that is later incorporated into the well known growth restricting models for multi-component alloys. This approach that can be used to determine Q and/or GS based on the chemical composition and the slope of the liquidus temperature of any Al-alloy solidified in close to equilibrium conditions. This method can be modified further in order to assess the effect of cooling rate or thermomechanical processing on growth restricting factor and grain size. In the present paper is proposed a highly accurate (R 2 = 0.99) and validated model for Al–Si alloys, but it can be modified for any other Al–X alloying system. The present method can be used for alloys with relatively high solute content and due to the use of the thermodynamics of liquidus this system considers the poisoning effects of single and multi-component alloying elements.

  9. Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries. (United States)

    Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T


    The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

  10. Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction. (United States)

    Szentpéteri, Imre; Rab, Attila; Kornya, László; Kovács, Péter; Joó, József Gábor


    In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)β-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α) 37 weeks: 1.35). Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.

  11. 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.

  12. Assessment of Attention to Clothing and Impact of Its Restrictive Factors in Iranian Patients with Traumatic Spinal Cord Injury (ACIRF-SCI): Introduction of a New Questionnaire. (United States)

    Laleh, Leila; Latifi, Sahar; Koushki, Davood; Matin, Marzieh; Javidan, Abbas Norouzi; Yekaninejad, Mir Saeed


    Patients with spinal cord injury (SCI) deal with various restrictive factors regarding their clothing, such as disability and difficulty with access to shopping centers. We designed a questionnaire to assess attention to clothing and impact of its restrictive factors among Iranian patients with SCI (ACIRF-SCI). The ACIRF-SCI has 5 domains: functional, medical, attitude, aesthetic, and emotional. The first 3 domains reflect the impact of restrictive factors (factors that restrict attention to clothing), and the last 2 domains reflect attention to clothing and fashion. Functional restrictive factors include disability and dependence. Medical restrictive factors include existence of specific medical conditions that interfere with clothing choice. Construct validity was assessed by factorial analysis, and reliability was expressed by Cronbach's alpha. A total of 100 patients (75 men and 25 women) entered this study. Patients with a lower injury level had a higher total score (P SCI who have greater ability and independence experience a lower impact of restrictive factors related to clothing. The ACIRF-SCI reveals that this assumption is statistically significant, which shows its admissible discriminant validity. The measured construct validity (0.97) and reliability (internal consistency expressed by alpha = 0.61) are acceptable.

  13. NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P


    The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5...

  14. Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy. (United States)

    Kuo, Shu-Ming; Chen, Chi-Jene; Chang, Shih-Cheng; Liu, Tzu-Jou; Chen, Yi-Hsiang; Huang, Sheng-Yu; Shih, Shin-Ru


    Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2 627 E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2 627 K (human signature) and PB2 627 E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2 627 E than PB2 627 K in transfected human cells. Stronger binding of TUFM to avian-signature PB2 590 G/ 591 Q and PB2 627 E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2 627 E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2 627 E viruses, but not PB2 627 K viruses. In addition, enhanced levels of interaction between TUFM and PB2 627 E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2 627 E virus; however, autophagy remained consistent in PB2 627 K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy. IMPORTANCE An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both

  15. Exposure to tobacco secondhand smoke and its associated factors among non-smoking adults in smoking-restricted and non-restricted areas: findings from a nationwide study in Malaysia. (United States)

    Lim, Kuang Hock; Teh, Chien Huey; Nik Mohamed, Mohamad Haniki; Pan, Sayan; Ling, Miaw Yn; Mohd Yusoff, Muhammad Fadhli; Hassan, Noraryana; Baharom, Nizam; Dawam, Netty Darwina; Ismail, Norliana; Ghazali, Sumarni Mohd; Cheong, Kee Chee; Chong, Kar Hon; Lim, Hui Li


    Secondhand smoke (SHS) has been associated with increased morbidity and mortality. Therefore, the aims of the paper are to assess SHS exposure among non-smoking adults in Malaysia attending various smoking-restricted and non-restricted public areas according to the Control of Tobacco Product Regulations (CTPR) as well as its relationship with various sociodemographic variables. Data were extracted from a cross-sectional study, the Global Adults Tobacco Survey (GATS) 2011 which involved 3269 non-smokers in Malaysia. Data was obtained through face-to-face interviews using a validated pre-tested questionnaire. Factors associated with exposure to SHS were identified via multivariable analysis. The study revealed that almost two-thirds of respondents were exposed to SHS in at least one public area in the past 1 month, with a significantly higher exposure among males (70.6%), those with higher educational attainment (81.4%) and higher income (quintile 1%-73.9%). Besides, the exposure to SHS was almost four times higher in non-restricted areas compared with restricted areas under the CTPR (81.9% vs 22.9). Multivariable analysis revealed that males and younger adults at non-restricted areas were more likely to be exposed to SHS while no significant associated factors of SHS exposure was observed in restricted areas. The study revealed the prevalence of SHS exposure was higher among Malaysian adults. Although smoke-free laws offer protection to non-smokers from exposure to SHS, enforcement activities in restricted areas should be enhanced to ensure strict public abidance. In addition, legislation of restricted areas should also be extended to greatly reduce the SHS exposure among non-smokers in Malaysia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins. (United States)

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan


    Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

  17. Analysis on the restriction factors of the green building scale promotion based on DEMATEL (United States)

    Wenxia, Hong; Zhenyao, Jiang; Zhao, Yang


    In order to promote the large-scale development of the green building in our country, DEMATEL method was used to classify influence factors of green building development into three parts, including green building market, green technology and macro economy. Through the DEMATEL model, the interaction mechanism of each part was analyzed. The mutual influence degree of each barrier factor that affects the green building promotion was quantitatively analysed and key factors for the development of green building in China were also finally determined. In addition, some implementation strategies of promoting green building scale development in our country were put forward. This research will show important reference value and practical value for making policies of the green building promotion.

  18. Analysis of key hardware factors and countermeasure for restricting 49-2 swimming pool reactor lifetime

    International Nuclear Information System (INIS)

    Zhang Yadong; Guo Yue; Yang Xiao; Wang Yiwei; Wang Zhanwen


    Safe operation is the most important factor to determine the lifetime of aged 49-2 swimming pool reactor. In this paper, the hardware factors of lifetime were analyzed, such as the pool concrete aging, corrosion of aluminum container and primary coolant system, and graphite swelling etc., and then the corresponding measures such as surveillance, prevention and maintenance were purposed. The results show that 49-2 swimming pool reactor can continue to operate safely due to that container is safe under 8 degree earthquake, the reactor is safe on flood level of once per millennium, adding dam break, and the ageing condition of primary coolant system and container is acceptable. (authors)

  19. KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia


    Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characte......Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly...... characterized, but represent a decisive moment in establishing a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin associated transcription factor regulates the dynamic organization of host chromatin structure via its ability to influence epigenetic marks...

  20. Enhancing maya women's development through cooperative associations : what factors support or restrict the contribution of cooperatives?

    NARCIS (Netherlands)

    Osorio Vazquez, Maria Cristina


    With the aim of contributing to the development of Mayan women living in the Yucatan Peninsula, this research focused on determine the factors that support or inhibit the sustainability of micro-businesses cooperatives, which are organizations with innovative elements that allow Mayan women to work

  1. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

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

    International Nuclear Information System (INIS)

    Noguchi, M.; Onoe, K.; Ogasawara, M.; Iwabuchi, K.; Geng, L.; Ogasawara, K.; Good, R.A.; Morikawa, K.


    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

  3. 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


    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.

  4. A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

    Directory of Open Access Journals (Sweden)

    Mohamed Lamine Hafirassou


    Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

  5. KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces intrauterine growth restriction in mice. (United States)

    Abe, Naomichi; Nakahara, Tsutomu; Morita, Akane; Wada, Yoshiko; Mori, Asami; Sakamoto, Kenji; Nagamitsu, Tohru; Ishii, Kunio


    We previously reported that treatment with KRN633, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, during mid-pregnancy caused intrauterine growth restriction resulting from impairment of blood vessel growth in the labyrinthine zone of the placenta and fetal organs. However, the relative sensitivities of blood vessels in the placenta and fetal organs to vascular endothelial growth factor (VEGF) inhibitors have not been determined. In this study, we aimed to examine the effects of KRN633 on the vasculatures of organs in mother mice and their newborn pups by immunohistochemical analysis. Pregnant mice were treated daily with KRN633 (5 mg/kg) either from embryonic day 13.5 (E13.5) to E17.5 or from E13.5 to the day of delivery. The weights of the pups of KRN633-treated mice were lower than those of the pups of vehicle-treated mothers. However, no significant difference in body weight was observed between the vehicle- and KRN633-treated mice. The vascular development in the organs (the pancreas, kidney, and intestine) and intestinal lymphatic formation of the pups of KRN633-treated mothers was markedly impaired. In contrast, the KRN633 treatment showed no significant effect on the vascular beds in the organs, including the labyrinthine zone of the placenta, of the mother mice. These results suggest that blood vessels in fetal organs are likely to be more sensitive to reduced VEGF signaling than those in the mother. A partial loss of VEGF function during pregnancy could suppress vascular growth in the fetus without affecting the vasculature in the mother mouse, thereby increasing the risk of intrauterine growth restriction. © 2013 Wiley Periodicals, Inc.

  6. Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers. (United States)

    Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi


    Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine

  7. HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor

    Directory of Open Access Journals (Sweden)

    Tsukahara Tomohide


    Full Text Available Abstract Background To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2. Methods Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201+ patients with osteosarcoma using limiting dilution (LD/mixed lymphocyte peptide culture (MLPC followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by 51Cr release assay. Results Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 × 10-7 to 5 × 10-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2. Conclusion These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.

  8. Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

    International Nuclear Information System (INIS)

    HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.


    Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

  9. Factors associated with fear of falling and associated activity restriction in community-dwelling older adults: a systematic review. (United States)

    Denkinger, Michael D; Lukas, Albert; Nikolaus, Thorsten; Hauer, Klaus


    Fear of falling (FOF) is an important threat to autonomy. Current interventions to reduce FOF have yielded conflicting results. A possible reason for this discrepancy could be its multicausality. Some risk factors may not have been identified and addressed in recent studies. The last systematic review included studies until 2006. To identify additional risk factors for FOF and to test those mentioned previously, we conducted a systematic literature review. Studies examining FOF in community-dwelling older adults between 2006 and October 2013 were screened. Outcomes are summarized with respect to different constructs such as FOF, fall-related self-efficacy/balance confidence, and FOF-related activity restriction. Odds ratios and p values are reported. There is no clear pattern with regard to the different FOF-related constructs studied. The only parameters robustly associated across all constructs were female gender, performance-based and questionnaire-based physical function, the use of a walking aid, and, less robust, a history of falls and poor self-rated health. Conflicting results were identified for depression and anxiety, multiple drugs, and psychotropic drugs. Other potentially modifiable risk factors were only mentioned in one or two studies and warrant further investigation. Parameters with mainly negative results are also presented. Only few risk factors identified were robustly associated across all FOF-related constructs and should be included in future studies on FOF. Some newer factors have to be tested again in different cohorts. The comprehensive overview might assist in the conceptualization of future studies. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses. (United States)

    Tse, J Y; Lao, T T; Chan, C C; Chiu, P M; Cheung, A N


    Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.

  11. Prediction of Fetal Growth Restriction by Analyzing the Messenger RNAs of Angiogenic Factor in the Plasma of Pregnant Women. (United States)

    Takenaka, Shin; Ventura, Walter; Sterrantino, Anna Freni; Kawashima, Akihiro; Koide, Keiko; Hori, Kyoko; Farina, Antonio; Sekizawa, Akihiko


    To predict the occurrence of fetal growth restriction (FGR) by analyzing messenger RNA (mRNA) expression levels of vascular endothelial growth factor receptor 1 (fms-like tyrosine kinase 1 [Flt-1]) in maternal blood. Eleven women with FGR were matched with 88 controls. Plasma samples were obtained during each trimester. The Flt-1 mRNA expression levels were compared between groups. Predicted probabilities were calculated, and sensitivity-specificity (receiver-operating characteristic [ROC]) curves were assessed based on regression models for each trimester measurement and possible combinations of measurements. The mRNA levels of the FGR group during all trimesters were significantly higher than those of the control group. The ROC curve of combined first and second trimester data yielded a detection rate of 60% at a 10% false-positive rate, with an area under curve of 0.79. The Flt-1 mRNA expression in maternal blood can be used as a marker to predict the development of FGR, long before a clinical diagnosis is made. © The Author(s) 2014.

  12. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. (United States)

    Xu, Lei; Zhou, Xinying; Wang, Wenshi; Wang, Yijin; Yin, Yuebang; Laan, Luc J W van der; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei


    IFN regulatory factor 1 (IRF1) is one of the most important IFN-stimulated genes (ISGs) in cellular antiviral immunity. Although hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, how ISGs counteract HEV infection is largely unknown. This study was conducted to investigate the effect of IRF1 on HEV replication. Multiple cell lines were used in 2 models that harbor HEV. In different HEV cell culture systems, IRF1 effectively inhibited HEV replication. IRF1 did not trigger IFN production, and chromatin immunoprecipitation sequencing data analysis revealed that IRF1 bound to the promoter region of signal transducers and activators of transcription 1 (STAT1). Functional assay confirmed that IRF1 could drive the transcription of STAT1, resulting in elevation of total and phosphorylated STAT1 proteins and further activating the transcription of a panel of downstream antiviral ISGs. By pharmacological inhibitors and RNAi-mediated gene-silencing approaches, we revealed that antiviral function of IRF1 is dependent on the JAK-STAT cascade. Furthermore, induction of ISGs and the anti-HEV effect of IRF1 overlapped that of IFNα, but was potentiated by ribavirin. We demonstrated that IRF1 effectively inhibits HEV replication through the activation of the JAK-STAT pathway, and the subsequent transcription of antiviral ISGs, but independent of IFN production.-Xu, L., Zhou, X., Wang, W., Wang, Y., Yin, Y., van der Laan, L. J. W., Sprengers, D., Metselaar, H. J., Peppelenbosch, M. P., Pan, Q. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. © FASEB.

  13. Hypoxia activates muscle-restricted coiled-coil protein (MURC) expression via transforming growth factor-β in cardiac myocytes. (United States)

    Shyu, Kou-Gi; Cheng, Wen-Pin; Wang, Bao-Wei; Chang, Hang


    The expression of MURC (muscle-restricted coiled-coil protein), a hypertrophy-regulated gene, increases during pressure overload. Hypoxia can cause myocardial hypertrophy; however, how hypoxia affects the regulation of MURC in cardiomyocytes undergoing hypertrophy is still unknown. The aim of the present study was to test the hypothesis that hypoxia induces MURC expression in cardiomyocytes during hypertrophy. The expression of MURC was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia and in an in vivo model of AMI (acute myocardial infarction) to induce myocardial hypoxia in adult rats. MURC protein and mRNA expression were significantly enhanced by hypoxia. MURC proteins induced by hypoxia were significantly blocked after the addition of PD98059 or ERK (extracellular-signal-regulated kinase) siRNA 30 min before hypoxia. Gel-shift assay showed increased DNA-binding activity of SRF (serum response factor) after hypoxia. PD98059, ERK siRNA and an anti-TGF-β (transforming growth factor-β) antibody abolished the SRF-binding activity enhanced by hypoxia or exogenous administration of TGF-β. A luciferase promoter assay demonstrated increased transcriptional activity of SRF in cardiomyocytes by hypoxia. Increased βMHC (β-myosin heavy chain) and BNP (B-type natriuretic peptide) protein expression and increased protein synthesis was identified after hypoxia with the presence of MURC in hypertrophic cardiomyocytes. MURC siRNA inhibited the hypertrophic marker protein expression and protein synthesis induced by hypoxia. AMI in adult rats also demonstrated increased MURC protein expression in the left ventricular myocardium. In conclusion, hypoxia in cultured rat neonatal cardiomyocytes increased MURC expression via the induction of TGF-β, SRF and the ERK pathway. These findings suggest that MURC plays a role in hypoxia-induced hypertrophy in cardiomyocytes.

  14. Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats. (United States)

    Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki


    Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

  15. Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups (United States)

    Sveinsdóttir, Kristbjörg; Länsberg, John-Kalle; Sveinsdóttir, Snjólaug; Garwicz, Martin; Ohlsson, Lennart; Hellström, Ann; Smith, Lois; Gram, Magnus; Ley, David


    Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population. PMID:28972955

  16. Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G. (United States)

    Radwan, Mohamed O; Sonoda, Sachiko; Ejima, Tomohiko; Tanaka, Ayumi; Koga, Ryoko; Okamoto, Yoshinari; Fujita, Mikako; Otsuka, Masami


    Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G, A3G), is a human anti-virus restriction protein which works deaminase-dependently and -independently. A3G is known to be ubiquitinated by HIV-1 viral infectivity factor (Vif) protein, leading to proteasomal degradation. A3G contains two zinc ions at the N-terminal domain and the C-terminal domain. Four lysine residues, K(297), K(301), K(303), and K(334), are known to be required for Vif-mediated A3G ubiquitination and degradation. Previously, we reported compound SN-1, a zinc chelator that increases steady-state expression level of A3G in the presence of Vif. In this study, we prepared Biotin-SN-1, a biotinylated derivative of SN-1, to study the SN-1-A3G interaction. A pull-down assay revealed that Biotin-SN-1 bound A3G. A zinc-abstraction experiment indicated that SN-1 binds to the zinc site of A3G. We carried out a SN-1-A3G docking study using molecular operating environment. The calculations revealed that SN-1 binds to the C-terminal domain through Zn(2+), H(216), P(247), C(288), and Y(315). Notably, SN-1-binding covers the H(257), E(259), C(288), and C(291) residues that participate in zinc-mediated deamination, and the ubiquitination regions of A3G. The binding of SN-1 presumably perturbs the secondary structure between C(288) and Y(315), leading to less efficient ubiquitination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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.


    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

  18. Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men

    NARCIS (Netherlands)

    Velthuis-te Wierik, E.J.M.; Meijer, P.; Kluft, C.; Berg, H. van den


    Impaired fibrinolytic activity has been reported in the elderly and is thought to play a role in the etiology of cardiovascular disease, one of the leading causes of death in most Western countries. Since restriction of energy intake has been demonstrated to act beneficially on the aging process in

  19. HLA-E-Restricted Cross-Recognition of Allogeneic Endothelial Cells by CMV-Associated CD8 T Cells: A Potential Risk Factor following Transplantation (United States)

    Allard, Mathilde; Tonnerre, Pierre; Nedellec, Steven; Oger, Romain; Morice, Alexis; Guilloux, Yannick; Houssaint, Elisabeth; Charreau, Béatrice; Gervois, Nadine


    Although association between CMV infection and allograft rejection is well admitted, the precise mechanisms involved remain uncertain. Here, we report the characterization of an alloreactive HLA-E-restricted CD8 T cell population that was detected in the PBL of a kidney transplant patient after its CMV conversion. This monoclonal CD8 T cell population represents a sizable fraction in the blood (3% of PBL) and is characterized by an effector-memory phenotype and the expression of multiple NK receptors. Interestingly, these unconventional T cells display HLA-E-dependent reactivity against peptides derived from the leader sequences of both various HCMV-UL40 and allogeneic classical HLA-I molecules. Consequently, while HLA-E-restricted CD8 T cells have potential to contribute to the control of CMV infection in vivo, they may also directly mediate graft rejection through recognition of peptides derived from allogeneic HLA-I molecules on graft cells. Therefore, as HLA-E expression in nonlymphoid organs is mainly restricted to endothelial cells, we investigated the reactivity of this HLA-E-restricted T cell population towards allogeneic endothelial cells. We clearly demonstrated that CMV-associated HLA-E-restricted T cells efficiently recognized and killed allogeneic endothelial cells in vitro. Moreover, our data indicate that this alloreactivity is tightly regulated by NK receptors, especially by inhibitory KIR2DL2 that strongly prevents TCR-induced activation through recognition of HLA-C molecules. Hence, a better evaluation of the role of CMV-associated HLA-E-restricted T cells in transplantation and of the impact of HLA-genotype, especially HLA-C, on their alloreactivity may determine whether they indeed represent a risk factor following organ transplantation. PMID:23226431

  20. A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction. (United States)

    Kwiatkowski, Sebastian; Dołęgowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Torbè, Andrzej; Bednarek-Jędrzejek, Magdalena


    Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing

  1. Restrictive cardiomyopathy (United States)

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

  2. Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors. (United States)

    Candel-Pau, Júlia; Perapoch López, Josep; Castillo Salinas, Félix; Sánchez Garcia, Olga; Pérez Hoyos, Santiago; Llurba Olivé, Elisa


    Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.

  3. Restrictive Cardiomyopathy (United States)

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

  4. 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


    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.

  5. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins


    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan


    Productive viral replication requires overcoming many barriers posed by the host innate immune system. Human sterile alpha motif domain-containing 9 (SAMD9) is a newly identified antiviral factor that is specifically targeted by poxvirus proteins belonging to the C7 family of host-range factors. Here we provide the first, to our knowledge, atomic view of two functionally divergent proteins from the C7 family and determine the molecular basis that dictates whether they can target SAMD9 effecti...

  6. Association of sociodemographic factors, smoking-related beliefs, and smoking restrictions with intention to quit smoking in Korean adults: findings from the ITC Korea Survey. (United States)

    Myung, Seung-Kwon; Seo, Hong Gwan; Cheong, Yoo-Seock; Park, Sohee; Lee, Wonkyong B; Fong, Geoffrey T


    Few studies have reported the factors associated with intention to quit smoking among Korean adult smokers. This study aimed to examine sociodemographic characteristics, smoking-related beliefs, and smoking-restriction variables associated with intention to quit smoking among Korean adult smokers. We used data from the International Tobacco Control Korea Survey, which was conducted from November through December 2005 by using random-digit dialing and computer-assisted telephone interviewing of male and female smokers aged 19 years or older in 16 metropolitan areas and provinces of Korea. We performed univariate analysis and multiple logistic regression analysis to identify predictors of intention to quit. A total of 995 respondents were included in the final analysis. Of those, 74.9% (n = 745) intended to quit smoking. In univariate analyses, smokers with an intention to quit were younger, smoked fewer cigarettes per day, had a higher annual income, were more educated, were more likely to have a religious affiliation, drank less alcohol per week, were less likely to have self-exempting beliefs, and were more likely to have self-efficacy beliefs regarding quitting, to believe that smoking had damaged their health, and to report that smoking was never allowed anywhere in their home. In multiple logistic regression analysis, higher education level, having a religious affiliation, and a higher self-efficacy regarding quitting were significantly associated with intention to quit. Sociodemographic factors, smoking-related beliefs, and smoking restrictions at home were associated with intention to quit smoking among Korean adults.

  7. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb. (United States)

    Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L


    Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

  8. The critical role of personality and organizational factors as determinants of reactions to restricted and stressful environments. [undersea habitats (United States)

    Helmreich, Robert L.


    Research into the impact of personality factors on groups in various settings is reviewed as an introduction to a brief discussion of personality and group behavior research needs relevant to the space program. Significant findings of some earlier research are summarized, and methodological problems are touched on. The study of intergroup and intragroup conflict in a stressful environment, as exemplified particularly by undersea habitats, is seen as being of consequence for long-term space missions. It is concluded that adequate research can only be conducted as an adjunct to data collection from operational stressful environments, and not from laboratory experiments.

  9. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus


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

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

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


    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.

  11. 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


    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...... while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). Conclusions: Under energy restriction, participants on a low-fat diet who had...... 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....

  12. Association of Sociodemographic Factors, Smoking-Related Beliefs, and Smoking Restrictions With Intention to Quit Smoking in Korean Adults: Findings From the ITC Korea Survey (United States)

    Myung, Seung-Kwon; Seo, Hong Gwan; Cheong, Yoo-Seock; Park, Sohee; Lee, Wonkyong B; Fong, Geoffrey T


    Background Few studies have reported the factors associated with intention to quit smoking among Korean adult smokers. This study aimed to examine sociodemographic characteristics, smoking-related beliefs, and smoking-restriction variables associated with intention to quit smoking among Korean adult smokers. Methods We used data from the International Tobacco Control Korea Survey, which was conducted from November through December 2005 by using random-digit dialing and computer-assisted telephone interviewing of male and female smokers aged 19 years or older in 16 metropolitan areas and provinces of Korea. We performed univariate analysis and multiple logistic regression analysis to identify predictors of intention to quit. Results A total of 995 respondents were included in the final analysis. Of those, 74.9% (n = 745) intended to quit smoking. In univariate analyses, smokers with an intention to quit were younger, smoked fewer cigarettes per day, had a higher annual income, were more educated, were more likely to have a religious affiliation, drank less alcohol per week, were less likely to have self-exempting beliefs, and were more likely to have self-efficacy beliefs regarding quitting, to believe that smoking had damaged their health, and to report that smoking was never allowed anywhere in their home. In multiple logistic regression analysis, higher education level, having a religious affiliation, and a higher self-efficacy regarding quitting were significantly associated with intention to quit. Conclusions Sociodemographic factors, smoking-related beliefs, and smoking restrictions at home were associated with intention to quit smoking among Korean adults. PMID:22186157

  13. [Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction]. (United States)

    Li, Xiang-Wen; Li, Fang; Liu, Jing; Wang, Yan; Fu, Wei


    To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (Ptaurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (Ptaurine group had significantly higher mRNA expression of Rac than the FGR and control groups (Ptaurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (Ptaurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

  14. Formation of the embryonic organizer is restricted by the competitive influences of Fgf signaling and the SoxB1 transcription factors.

    Directory of Open Access Journals (Sweden)

    Cheng-Liang Kuo

    Full Text Available The organizer is one of the earliest structures to be established during vertebrate development and is crucial to subsequent patterning of the embryo. We have previously shown that the SoxB1 transcription factor, Sox3, plays a central role as a transcriptional repressor of zebrafish organizer gene expression. Recent data suggest that Fgf signaling has a positive influence on organizer formation, but its role remains to be fully elucidated. In order to better understand how Fgf signaling fits into the complex regulatory network that determines when and where the organizer forms, the relationship between the positive effects of Fgf signaling and the repressive effects of the SoxB1 factors must be resolved. This study demonstrates that both fgf3 and fgf8 are required for expression of the organizer genes, gsc and chd, and that SoxB1 factors (Sox3, and the zebrafish specific factors, Sox19a and Sox19b can repress the expression of both fgf3 and fgf8. However, we also find that these SoxB1 factors inhibit the expression of gsc and chd independently of their repression of fgf expression. We show that ectopic expression of organizer genes induced solely by the inhibition of SoxB1 function is dependent upon the activation of fgf expression. These data allow us to describe a comprehensive signaling network in which the SoxB1 factors restrict organizer formation by inhibiting Fgf, Nodal and Wnt signaling, as well as independently repressing the targets of that signaling. The organizer therefore forms only where Nodal-induced Fgf signaling overlaps with Wnt signaling and the SoxB1 proteins are absent.

  15. Simulating Spatial-Temporal Changes of Land-Use Based on Ecological Redline Restrictions and Landscape Driving Factors: A Case Study in Beijing

    Directory of Open Access Journals (Sweden)

    Zimu Jia


    Full Text Available A change in the usage of land is influenced by a variety of driving factors and policies on spatial constraints. On the basis of considering the conventional natural and socio-economic indicators, the landscape pattern indicators were considered as new driving forces in the conversion of land use and its effects at small regional extent (CLUE-S model to simulate spatial and temporal changes of land-use in Beijing. Compared with traditional spatial restrictions characterized by small and isolated areas, such as forest parks and natural reserves, the ecological redline areas increase the spatial integrity and connectivity of ecological and environmental functions at a regional scale, which were used to analyze the distribution patterns and behaviors of land use conversion in the CLUE-S model. The observed results indicate that each simulation scenario has a Kappa coefficient of more than 0.76 beyond the threshold value of 0.6 and represents high agreements between the actual and simulated land use maps. The simulation scenarios including landscape pattern indicators are more accurate than those without consideration of these new driving forces. The simulation results from using ecological redline areas as space constraints have the highest precision compared with the unrestricted and traditionally restricted scenarios. Therefore, the CLUE-S model based on the restriction of ecological redline and the consideration of landscape pattern factors has shown better effectiveness in simulating the future land use change. The conversion of land use types mainly occurred between construction land and cropland during the period from 2010 to 2020. Meanwhile, a large number of grasslands are being changed to construction lands in the mountain towns of northwest Beijing and large quantities of water bodies have disappeared and been replaced by construction lands due to rapid urbanization in the eastern and southern plains. To improve the sustainable use of

  16. Rice Ethylene-Response AP2/ERF Factor OsEATB Restricts Internode Elongation by Down-Regulating a Gibberellin Biosynthetic Gene1[W][OA (United States)

    Qi, Weiwei; Sun, Fan; Wang, Qianjie; Chen, Mingluan; Huang, Yunqing; Feng, Yu-Qi; Luo, Xiaojin; Yang, Jinshui


    Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops. PMID:21753115

  17. Rice ethylene-response AP2/ERF factor OsEATB restricts internode elongation by down-regulating a gibberellin biosynthetic gene. (United States)

    Qi, Weiwei; Sun, Fan; Wang, Qianjie; Chen, Mingluan; Huang, Yunqing; Feng, Yu-Qi; Luo, Xiaojin; Yang, Jinshui


    Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops.

  18. What Do We Know about Risk Factors for Fetal Growth Restriction in Africa at the Time of Sustainable Development Goals? A Scoping Review. (United States)

    Accrombessi, Manfred; Zeitlin, Jennifer; Massougbodji, Achille; Cot, Michel; Briand, Valérie


    The reduction in the under-5 year mortality rate to at least as low as 25 per 1000 livebirths by 2030 has been implemented as one of the new Sustainable Development Goals. Fetal growth restriction (FGR) is one of the most important determinants of infant mortality in developing countries. In this review, we assess the extent of the literature and summarize its findings on the main preventable factors of FGR in Africa. A scoping review was conducted using the Arksey and O'Malley framework. Five bibliographic databases and grey literature were used to identify studies assessing at least one risk factor for FGR. Aggregate risk estimates for the main factors associated with FGR were calculated. Forty-five of a total of 671 articles were selected for the review. The prevalence of FGR varied between 2.6 and 59.2% according to both the African region and the definition of FGR. The main preventable factors reported were a low maternal nutritional status (aggrerate odds ratio [OR]: 2.28, 95% confidence interval [CI] 1.59, 3.25), HIV infection (aOR 1.86, 95% CI 1.38, 2.50), malaria (aOR 1.95, 95% CI 1.04, 3.66), and gestational hypertension (aOR 2.61, 95% CI 2.42, 2.82). FGR is, to a large extent, preventable through existing efficacious interventions dedicated to malaria, HIV and nutrition. Further studies are still needed to assess the influence of risk factors most commonly documented in high-income countries. Improving research on FGR in Africa requires a consensual and standardized definition of FGR-for a higher comparability-between studies and settings. © 2017 John Wiley & Sons Ltd.

  19. Characterization of insulin-like growth factor I receptors in the median eminence of the brain and their modulation by food restriction

    International Nuclear Information System (INIS)

    Bohannon, N.J.; Corp, E.S.; Wilcox, B.J.; Figlewicz, D.P.; Dorsa, D.M.; Baskin, D.G.


    High affinity binding sites for 125I-labeled [Thr59]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slide-mounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr59]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h. Densitometry by computer digital image analysis of autoradiographic images indicated that specific binding of iodo-[Thr59]IGF-I to the median eminence was reversible. The specificity of binding was evaluated with competition of iodo-[Thr59]IGF-I with unlabeled [Thr59]IGF-I, rat IGF-II (multiplication-stimulating activity), and porcine insulin. All were recognized by the binding site, but the rank order of potency was [Thr59]IGF-I greater than IGF-II greater than insulin. Somatostatin was completely ineffective. Further, an antibody against the rat IGF-II receptor did not block binding of iodo-[Thr59]IGF-I to the median eminence. Fourteen days of food restriction (75% of food intake of controls) resulted in significant weight loss and reduction of plasma immunoreactive IGF-I in six food-restricted rats (0.9 +/- 0.1 U/ml) compared with values in six controls (2.6 +/- 0.5 U/ml; P less than 0.001). Binding of 125I-labeled [Thr59]IGF-I in the median eminence was significantly increased in the food-restricted rats, primarily due to an increase in the concentration of iodo-[Thr59]IGF-I-binding sites in the median eminence; the affinity (Kd) of binding was unchanged. The results indicate that the median eminence has type I IGF-I receptors, which become more numerous under metabolic conditions associated with decreased caloric intake and lowered plasma IGF-I levels

  20. [Intra-uterine growth restriction impact on maternal serum concentration of PlGF (placental growth factor): A case control study]. (United States)

    Margossian, A; Boisson-Gaudin, C; Subtil, F; Rudigoz, R-C; Dubernard, G; Allias, F; Huissoud, C


    Placental growth factor (PlGF) is a pro-angiogenic factor mainly assessed in preeclampsia in which its blood concentration is decreased. The aim of this study was to dose the blood concentration of PlGF in women with fetal intra-uterine growth restriction (IUGR) without associated preeclampsia at the time of diagnosis. Case/control study: IUGR was defined by a fetal biometry with abnormal uterine and/or umbilical doppler (n=23). This group was compared to a control group of fetuses (n=25) matched for gestational age at blood sampling for the dosage of maternal seric PlGF. Women with preeclampsia were not included. The plasma PlGF concentration was 11pg/mL (IQR [11-42,8]) in the IUGR group vs 287pg/mL [135-439] in the control group (P<0.001) and this difference was available after adjustment for gestational age at the time of blood sampling (P<0.001). PlGF sensitivity and specificity for discrimination were respectively 87% (CI 95% [66-97]) and 88% (CI 95% [69-97]). Maternal serum PlGF concentrations were very low in IUGR group compared with those of the control group. Copyright © 2015. Published by Elsevier SAS.

  1. 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.

  2. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. (United States)

    Brehm, Bonnie J; Seeley, Randy J; Daniels, Stephen R; D'Alessio, David A


    Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors. Therefore, we designed a randomized, controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors. Subjects were randomized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30% of the calories as fat. Anthropometric and metabolic measures were assessed at baseline, 3 months, and 6 months. Fifty-three healthy, obese female volunteers (mean body mass index, 33.6 +/- 0.3 kg/m(2)) were randomized; 42 (79%) completed the trial. Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months. The very low carbohydrate diet group lost more weight (8.5 +/- 1.0 vs. 3.9 +/- 1.0 kg; P fat (4.8 +/- 0.67 vs. 2.0 +/- 0.75 kg; P low fat diet group. Mean levels of blood pressure, lipids, fasting glucose, and insulin were within normal ranges in both groups at baseline. Although all of these parameters improved over the course of the study, there were no differences observed between the two diet groups at 3 or 6 months. beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months (P = 0.001). Based on these data, a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on important cardiovascular risk factors in healthy women.

  3. A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction. (United States)

    Ormesher, L; Johnstone, E D; Shawkat, E; Dempsey, A; Chmiel, C; Ingram, E; Higgins, L E; Myers, J E


    To evaluate the use of plasma Placental Growth Factor (PlGF), recommended by the recent NICE guidance, in women with suspected pre-eclampsia (PE) and/or fetal growth restriction (FGR). Non-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit. PlGF testing was performed in addition to routine clinical assessment in 260 women >20 weeks' gestation with chronic disease (hypertension, renal disease ± diabetes) with a change in maternal condition or in women with suspected FGR to determine the impact on clinical management. Results were revealed and standardised care pathways followed. Outcome of pregnancies with a low PlGF (women had an adverse outcome (PE/birthweight women with PlGF 14 days. The PlGF result altered clinical management (surveillance or timing of birth) in 196/260 (75.4%) cases. Alternative PlGF thresholds did not significantly improve diagnostic performance. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice. Copyright © 2018. Published by Elsevier B.V.

  4. Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages (United States)

    Mastrogiannis, Dimitrios S.; Wang, Xu; Dai, Min; Li, Jieliang; Wang, Yizhong; Zhou, Yu; Sakarcan, Selin; Peña, Juliet Crystal; Ho, Wenzhe


    Alcohol consumption or alcohol abuse is common among pregnant HIV+ women and has been identified as a potential behavioral risk factor for the transmission of HIV. In this study, we examined the impact of alcohol on HIV infection of cord blood monocyte-derived macrophages (CBMDM). We demonstrated that alcohol treatment of CBMDM significantly enhanced HIV infection of CBMDM. Investigation of the mechanisms of alcohol action on HIV demonstrated that alcohol inhibited the expression of several HIV restriction factors, including anti-HIV microRNAs, APOBEC3G and APOBEC3H. Additionally, alcohol also suppressed the expression of IFN regulatory factor 7 (IRF-7) and retinoic acid-inducible gene I (RIG-I), an intracellular sensor of viral infection. The suppression of these IFN regulatory factors was associated with reduced expression of type I IFN. These experimental findings suggest that maternal alcohol consumption may facilitate HIV infection, promoting vertical transmission of HIV. PMID:25053361

  5. Effects of parturition and feed restriction on concentrations and distribution of the insulin-like growth factor-binding proteins in plasma and cerebrospinal fluid of dairy cows. (United States)

    Laeger, T; Wirthgen, E; Piechotta, M; Metzger, F; Metges, C C; Kuhla, B; Hoeflich, A


    Hormones and metabolites act as satiety signals in the brain and play an important role in the control of feed intake (FI). These signals can reach the hypothalamus and brainstem, 2 major centers of FI regulation, via the blood stream or the cerebrospinal fluid (CSF). During the early lactation period of high-yielding dairy cows, the increase of FI is often insufficient. Recently, it has been demonstrated that insulin-like growth factors (IGF) may control FI. Thus, we asked in the present study if IGF-binding proteins (IGFBP) are regulated during the periparturient period and in response to feed restriction and therefore might affect FI as well. In addition, we specifically addressed conditional distribution of IGFBP in plasma and CSF. In one experiment, 10 multiparous German Holstein dairy cows were fed ad libitum and samples of CSF and plasma were obtained before morning feeding on d -20, -10, +1, +10, +20, and +40 relative to calving. In a second experiment, 7 cows in second mid-lactation were sampled for CSF and plasma after ad libitum feeding and again after feeding 50% of the previous ad libitum intake for 4 d. Intact IGFBP-2, IGFBP-3, and IGFBP-4 were detected in plasma by quantitative Western ligand blot analysis. In CSF, we were able to predominantly identify intact IGFBP-2 and a specific IGFBP-2 fragment containing detectable binding affinities for biotinylated IGF-II. Whereas plasma concentrations of IGFBP-2 and IGFBP-4 increased during the periparturient period, IGFBP-3 was unaffected over time. In CSF, concentrations of IGFBP-2, both intact and fragmented, were not affected during the periparturient period. Plasma IGF-I continuously decreased until calving but remained at a lower concentration in early lactation than in late pregnancy. Food restriction did not affect concentrations of IGF components present in plasma or CSF. We could show that the IGFBP profiles in plasma and CSF are clearly distinct and that changes in IGFBP in plasma do not simply

  6. Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-β/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction. (United States)

    Alcázar, Miguel Angel Alejandre; Dinger, Katharina; Rother, Eva; Östreicher, Iris; Vohlen, Christina; Plank, Christian; Dötsch, Jörg


    Intrauterine growth restriction (IUGR) is intimately linked with postnatal catch-up growth, leading to impaired lung structure and function. However, the impact of catch-up growth induced by early postnatal hyperalimentation (HA) on the lung has not been addressed to date. The aim of this study was to investigate whether prevention of HA subsequent to IUGR protects the lung from 1) deregulation of the transforming growth factor-β(TGF-β)/bone morphogenetic protein (BMP) pathway, 2) activation of interleukin (IL)-6 signaling, and 3) profibrotic processes. IUGR was induced in Wistar rats by isocaloric protein restriction during gestation by feeding a control (Co) or a low-protein diet with 17% or 8% casein, respectively. On postnatal day 1 (P1), litters from both groups were randomly reduced to 6 pups per dam to induce HA or adjusted to 10 pups and fed with standard diet: Co, Co with HA (Co-HA), IUGR, and IUGR with HA (IUGR-HA). Birth weights in rats after IUGR were lower than in Co rats (P < 0.05). HA during lactation led to accelerated body weight gain from P1 to P23 (Co vs. Co-HA, IUGR vs. IUGR-HA; P < 0.05). At P70, prevention of HA after IUGR protected against the following: 1) activation of both TGF-β [phosphorylated SMAD (pSMAD) 2; plasminogen activator inhibitor 1 (Pai1)] and BMP signaling [pSMAD1; inhibitor of differentiation (Id1)] compared with Co (P < 0.05) and Co or IUGR (P < 0.05) rats, respectively; 2) greater mRNA expression of interleukin (Il) 6 and Il13 (P < 0.05) as well as activation of signal transducer and activator of transcription 3 (STAT3) signaling (P < 0.05) after IUGR-HA; and 3) greater gene expression of collagen Iα1 and osteopontin (P < 0.05) and increased deposition of bronchial subepithelial connective tissue in IUGR-HA compared with Co and IUGR rats. Moreover, HA had a significant additive effect (P < 0.05) on the increased enhanced pause (indicator of airway resistance) in the IUGR group (P < 0.05) at P70. This study demonstrates

  7. 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.

  8. Establishment of an intermittent cold stress model using Tupaia belangeri and evaluation of compound C737 targeting neuron-restrictive silencer factor (United States)

    Hai-Ying, Chi; Nagano, Kiori; Ezzikouri, Sayeh; Yamaguchi, Chiho; Kayesh, Mohammad Enamul Hoque; Rebbani, Khadija; Kitab, Bouchra; Nakano, Hirohumi; Kouji, Hiroyuki; Kohara, Michinori; Tsukiyama-Kohara, Kyoko


    Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins. Based on these similarities, we hypothesized that induction of ICS in Tupaia would provide a useful animal model of stress responses. We exposed young adult Tupaia to ICS and observed decreases in body temperature and body weight in both female and male Tupaia, suggesting that Tupaia are an appropriate animal model for ICS studies. We further examined the efficacy of a new small-molecule compound, C737, against the effects of ICS. C737 mimics the helical structure of neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of target genes involved in neuronal function and pain modulation. Treatment with C737 significantly reduced stress-induced weight loss in female Tupaia; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that Tupaia represents a useful non-rodent ICS model. Our data also provide new insights into the function of NRSF/REST in stress-induced depression and other disorders with epigenetic influences or those with high prevalence in women. PMID:27041457

  9. Aging, adiposity, and calorie restriction. (United States)

    Fontana, Luigi; Klein, Samuel


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

  10. Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1

    International Nuclear Information System (INIS)

    Nogueira, Leticia M; Lavigne, Jackie A; Chandramouli, Gadisetti V R; Lui, Huaitian; Barrett, J Carl; Hursting, Stephen D


    The prevalence of obesity, an established risk and progression factor for breast and many other cancer types, remains very high in the United States and throughout the world. Calorie restriction (CR), a reduced-calorie dietary regimen typically involving a 20–40% reduction in calorie consumption, prevents or reverses obesity, and inhibits mammary and other types of cancer in multiple tumor model systems. Unfortunately, the mechanisms underlying the tumor inhibitory effects of CR are poorly understood, and a better understanding of these mechanisms may lead to new intervention targets and strategies for preventing or controlling cancer. We have previously shown that the anticancer effects of CR are associated with decreased systemic levels of insulin-like growth factor-1 (IGF-1), the primary source of which is liver. We have also reported that CR strongly suppresses tumor development and growth in multiple mammary cancer models. To identify CR-responsive genes and pathways, and to further characterize the role of IGF-1 as a mediator of the anticancer effects of CR, we assessed hepatic and mammary gland gene expression, hormone levels and growth of orthotopically transplanted mammary tumors in control and CR mice with and without exogenous IGF-1. C57BL/6 mice were fed either control AIN-76A diet ad libitum (AL), subjected to 20%, 30%, or 40% CR plus placebo timed-release pellets, or subjected to 30% or 40% CR plus timed-release pellets delivering murine IGF-1 (mIGF-1, 20 μg/day). Compared with AL-fed controls, body weights were decreased 14.3% in the 20% CR group, 18.5% in the 30% CR group, and 38% in the 40% CR group; IGF-1 infusion had no effect on body weight. Hepatic transcriptome analyses indicated that compared with 20% CR, 30% CR significantly modulated more than twice the number of genes and 40% CR more than seven times the number of genes. Many of the genes specific to the 40% CR regimen were hepatic stress-related and/or DNA damage-related genes

  11. Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction. (United States)

    Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner


    Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

  12. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction (United States)

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


    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…

  13. 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.


    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.

  14. A Traffic Restriction Scheme for Enhancing Carpooling

    Directory of Open Access Journals (Sweden)

    Dong Ding


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

  15. Feed restriction and insulin-like growth factor-I (IGF-I) affect the oocyte maturation in matrinxã Brycon amazonicus. (United States)

    Montrezor, Luís Henrique; Urbinati, Elisabeth Criscuolo


    The feeding and nutrition of breeders are crucial aspects in the reproductive process. During the maturation period, metabolic changes occur aiming at mobilizing energy for growth and follicular development. The involvement of IGF-1 in metabolic and reproductive events is important. The aim of this work was to evaluate if alternate feed restriction and re-feeding have permissive effects on in vitro actions of IGF-1 on oocytes development of matrinxã. In vivo experiments were performed during vitellogenesis period. Females (n = 60) were fed with a commercial feed (2% of biomass) and they were divided into two treatments: fish receiving food daily (control - fed), and fish submitted to cycles of 3 days of feed restriction and 2 days of re-feeding (no-fed group). For the in vitro experiments, oocytes (n = 20) were obtained from the ovaries removed at the end of the in vivo experiment and were divided into four groups: fed -IGF-1; fed +IGF-1; no-fed -IGF-1 and no-fed +IGF-1. Fish under restriction had lower body weights, decreased plasma glucose, increased triglycerides levels, and their final maturation and mature oocyte were reduced and the atresic ones were in higher number. Moreover, IGF-1, in vitro, increased the percentage of mature oocytes in fed females and decreased the atresic ones. In no-fed females, IGF-1 increased the final maturation and mature oocytes and reduced the atresic ones. This study demonstrates the importance of the feeding management of female breeders of matrinxã during the vitellogenesis period.

  16. 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)

    Noguchi, M.; Ogasawara, M.; Iwabuchi, K.; Osgasawara, K.; Ishihara, T.; Good, R.A.; Morikawa, K.; Onoe, K.


    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

  17. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik


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

  18. Restricting wolves risks escape (United States)

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


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

  19. The welfare effects of mobility restrictions

    Czech Academy of Sciences Publication Activity Database

    Jeong, Byeongju


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

  20. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S


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

  1. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S


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

  2. Mutation of Breast Cancer Cell Genomic DNA by APOBEC3B (United States)


    Future work is needed to understand A3B regulation and the potential interaction with other oncogenes and tumour suppressors . For example, although...Limited. All rights reserved©2013 METHODS SUMMARY Flash -frozen tissues were obtained from the University of Minnesota Tissue Procurement Facility...used for RNA isolation, cDNA synthesis and qPCR as described14. Tissue RNA was from 100mg flash -frozen tissue disrupted by a 2-h water bath sonication in

  3. Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation.

    Directory of Open Access Journals (Sweden)

    Vanessa C McFadden


    Full Text Available The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma.

  4. 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


    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

  5. Care-Related and Maternal Risk Factors Associated with the Antenatal Nondetection of Intrauterine Growth Restriction: A Case-Control Study from Bremen, Germany

    Directory of Open Access Journals (Sweden)

    Sinja Alexandra Ernst


    Full Text Available Objective. To identify care-related and maternal risk factors for the antenatal nondetection of IUGR. Methods. In this hospital-based case-control study we compared antenatally undetected IUGR neonates (cases to detected IUGR neonates (controls. Data were collected using newborn documentation sheets and standardized personal interviews with the mothers. We calculated antenatal detection rates and used uni- and multivariable logistic regression models to assess the association of antenatal nondetection of IUGR and maternal and care-related factors. Results. A total of 161 neonates from three hospitals were included in the study. Suboptimal fetal growth was identified antenatally in n=77 pregnancies while in n=84 it was not detected antenatally (antenatal detection rate: 47.8%. Severity of IUGR, maternal complications, and a Doppler examination during the course of pregnancy were associated with IUGR detection. We did not find statistically significant differences regarding parental socioeconomic status and maternal migration background. Conclusions. In our study, about half of all pregnancies affected by suboptimal growth remained undetected. Future in-depth studies with larger study populations should further examine factors that could increase antenatal detection rates for IUGR.

  6. Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction. (United States)

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo


    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. Copyright © 2014 the authors 0270-6474/14/3411316-09$15.00/0.

  7. Transcription Factors Synergistically Activated at the Crossing of the Restriction Point between G1 and S Cell Cycle Phases. Pathologic Gate Opening during Multi-Hit Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Nicoletta Castagnino


    Full Text Available Transcription factors (TFs represent key regulators of gene-expression patterns controlling cell behavior. TFs are active at nuclear – chromatin levels. TFs do not act in isolation; small sets of TFs cooperate toward the transcription of sets of mRNAs and consequently the translation of new proteins (the molecular phenotypes of a cell. Most TFs are activated through a cascade of biochemical reactions mediated by receptors expressed on the target cell surface. Nuclear Receptors (NRs are transcription factors activated instead by small hydrophobic molecules capable of crossing the plasma membrane. The convergence of different pathways on TFs and their posttranslational modifications ensure that the external stimuli generate appropriate and integrated responses. The reconstruction of the molecular anatomy of these pathways through Molecular Interactions Maps (MIMs can depict these intricate interactions. A mathematical modeling approach simulates/mimics their mechanism of action in normal and pathological conditions. We can simulate the effect of virtual hits in neoplastic transformation as mutations/alterations in these pathways. We can also simulate the effect of targeted inhibitors on these deregulated pathways. This strategy can help to guide an appropriate combination of targeted drugs in the treatment of a cancer patient, a major innovative perspective of incoming years.

  8. Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors

    Directory of Open Access Journals (Sweden)

    Diego Santa-Cruz


    Full Text Available Heme oxygenase-1 (HO-1 plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs in soybean plants subjected to ultraviolet-B (UV-B radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15 kJ m-2 UV-B. A 304 bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%. Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Keywords: Heme oxygenase, DNA methylation, Transcription factors, Ultraviolet-B radiation, Glycine max

  9. Decoding restricted participation in sequential electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Knaut, Andreas; Paschmann, Martin


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

  10. Long-term weight maintenance and cardiovascular risk factors are not different following weight loss on carbohydrate-restricted diets high in either monounsaturated fat or protein in obese hyperinsulinaemic men and women. (United States)

    Keogh, Jennifer B; Luscombe-Marsh, Natalie D; Noakes, Manny; Wittert, Gary A; Clifton, Peter M


    The aim of this study was to determine after 52 weeks whether advice to follow a lower carbohydrate diet, either high in monounsaturated fat or low fat, high in protein had differential effects in a free-living community setting. Following weight loss on either a high monounsaturated fat, standard protein (HMF; 50 % fat, 20 % protein (67 g/d), 30 % carbohydrate) or a high protein, moderate fat (HP) (40 % protein (136 g/d), 30 % fat, 30 % carbohydrate) energy-restricted diet (6000 kJ/d) subjects were asked to maintain the same dietary pattern without intensive dietary counselling for the following 36 weeks. Overall weight loss was 6.2 (SD 7.3) kg (P loss at the end of the study were sex, age and reported percentage energy from protein (R2 0.22, P loss and improvement in cardiovascular risk factors with no adverse effects of a high monounsaturated fat diet.

  11. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. (United States)

    Cowans, Nicholas J; Spencer, Kevin


    PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and

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


    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.

  13. HIV-1 Vpu Blocks Recycling and Biosynthetic Transport of the Intrinsic Immunity Factor CD317/Tetherin To Overcome the Virion Release Restriction (United States)

    Schmidt, Sarah; Fritz, Joëlle V.; Bitzegeio, Julia; Fackler, Oliver T.; Keppler, Oliver T.


    ABSTRACT The intrinsic immunity factor CD317 (BST-2/HM1.24/tetherin) imposes a barrier to HIV-1 release at the cell surface that can be overcome by the viral protein Vpu. Expression of Vpu results in a reduction of CD317 surface levels; however, the mechanism of this Vpu activity and its contribution to the virological antagonism are incompletely understood. Here, we characterized the influence of Vpu on major CD317 trafficking pathways using quantitative antibody-based endocytosis and recycling assays as well as a microinjection/microscopy-based kinetic de novo expression approach. We report that HIV-1 Vpu inhibited both the anterograde transport of newly synthesized CD317 and the recycling of CD317 to the cell surface, while the kinetics of CD317 endocytosis remained unaffected. Vpu trapped trafficking CD317 molecules at the trans-Golgi network, where the two molecules colocalized. The subversion of both CD317 transport pathways was dependent on the highly conserved diserine S52/S56 motif of Vpu; however, it did not require recruitment of the diserine motif interactor and substrate adaptor of the SCF-E3 ubiquitin ligase complex, β-TrCP. Treatment of cells with the malaria drug primaquine resulted in a CD317 trafficking defect that mirrored that induced by Vpu. Importantly, primaquine could functionally replace Vpu as a CD317 antagonist and rescue HIV-1 particle release. PMID:21610122

  14. Protein restriction and cancer. (United States)

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


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

  15. Intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales


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

  16. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

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


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

  17. Restricted Variance Interaction Effects

    DEFF Research Database (Denmark)

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


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

  18. The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators (United States)

    Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna


    The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

  19. Levels of serum-circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre-eclampsia, gestational hypertension, and/or fetal growth restriction. (United States)

    Nanjo, Sakiko; Minami, Sawako; Mizoguchi, Mika; Yamamoto, Madoka; Yahata, Tamaki; Toujima, Saori; Shiro, Michihisa; Kobayashi, Aya; Muragaki, Yasuteru; Ino, Kazuhiko


    We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE]). All sera were obtained within 1 week prior to delivery, and soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured with enzyme-linked immunosorbent assay. (i) In PE, a significantly increased sFlt-1, sEng, and sFlt-1 to PlGF ratio (sFlt-1/PlGF) and significantly decreased PlGF were observed compared with GH and Term control, whereas in GH, only sFlt-1/PlGF was significantly higher than Term control. (ii) In PE + FGR, similar changes were more markedly shown compared with PE alone. The FGR alone group exhibited similar tendencies as PE, although significant differences were found in PlGF and sEng levels. (iii) In EO PE, significant changes were observed in all factors compared with LO PE or Term control, while no significant change in PlGF levels was observed between LO PE and Term control. We demonstrated that the levels of circulating angiogenic factors just before delivery are correlated with the severity of hypertensive disorders of pregnancy and FGR. Profiling these specific markers may contribute to better understanding of the clinical conditions in individual patients and their pathogenesis. © 2017 Japan Society of Obstetrics and Gynecology.

  20. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

    Directory of Open Access Journals (Sweden)

    Michael S Harper

    Full Text Available HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8 and weak (IFNα1 subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

  1. On restricted context-free grammars

    Czech Academy of Sciences Publication Activity Database

    Dassow, J.; Masopust, Tomáš


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

  2. Rat Neutrophil Phagocytosis Following Feed Restriction

    Czech Academy of Sciences Publication Activity Database

    Slapničková, Martina; Berger, J.


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

  3. Placental Adaptations in Growth Restriction (United States)

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


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

  4. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

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

  5. Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction. (United States)

    Shinohara, Satoshi; Uchida, Yuzo; Kasai, Mayuko; Sunami, Rei


    To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). Thirty-four women with FGR diagnosed at Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

  6. Metabolic Regulation of Methionine Restriction in Diabetes. (United States)

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


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

  7. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

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

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

    DEFF Research Database (Denmark)

    Werlauff, Erik


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

  9. Host Specificity of Salmonella typhimurium Deoxyribonucleic Acid Restriction and Modification (United States)

    Slocum, Harvey; Boyer, Herbert W.


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

  10. Restricting uniformly open surjections

    Czech Academy of Sciences Publication Activity Database

    Kania, Tomasz; Rmoutil, M.


    Roč. 355, č. 9 (2017), s. 925-928 ISSN 1631-073X Institutional support: RVO:67985840 Keywords : Banach space * uniform spaces Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.396, year: 2016

  11. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

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

  12. Epigenetic regulation of caloric restriction in aging

    Directory of Open Access Journals (Sweden)

    Daniel Michael


    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.

  13. Nutrigenetics and nutrigenomics of caloric restriction. (United States)

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


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

  14. Activity restriction among women with a short cervix. (United States)

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


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

  15. Can early protein restriction induce the development of binge eating? (United States)

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


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

  16. How Harmful are Adaptation Restrictions


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


    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...

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

    Directory of Open Access Journals (Sweden)

    Jaime Eduardo Bernal Villegas


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

  18. Telomere Restriction Fragment (TRF) Analysis. (United States)

    Mender, Ilgen; Shay, Jerry W


    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

  19. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

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

  20. 49 CFR 215.203 - Restricted cars. (United States)


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

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

    Directory of Open Access Journals (Sweden)

    Wood Richard J


    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.

  2. Absence of A3Z3-Related Hypermutations in the env and vif Proviral Genes in FIV Naturally Infected Cats

    Directory of Open Access Journals (Sweden)

    Lucía Cano-Ortiz


    Full Text Available Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3 proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 activity. Seven haplotypes of APOBEC3Z3 (A3Z3 were described in domestic cats (hap I–VII, and in-vitro studies have demonstrated that these proteins reduce infectivity of vif-defective feline immunodeficiency virus (FIV. Moreover, hap V is resistant to vif-mediated degradation. However, studies on the effect of A3Z3 in FIV-infected cats have not been developed. Here, the correlation between APOBEC A3Z3 haplotypes in domestic cats and the frequency of hypermutations in the FIV vif and env genes were assessed in a retrospective cohort study with 30 blood samples collected between 2012 and 2016 from naturally FIV-infected cats in Brazil. The vif and env sequences were analyzed and displayed low or undetectable levels of hypermutations, and could not be associated with any specific A3Z3 haplotype.

  3. Targeting Virus-host Interactions of HIV Replication. (United States)

    Weydert, Caroline; De Rijck, Jan; Christ, Frauke; Debyser, Zeger


    Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research efforts have led to the validation of different cofactors and some successes in therapeutic applications. Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs) have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase- LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.

  4. HIV-related travel restrictions: trends and country characteristics. (United States)

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


    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.

  5. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli


    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.

  6. Parenting and restrictions in childhood epilepsy

    NARCIS (Netherlands)

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


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

  7. Restricted Social Engagement among Adults Living with Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Kayla P. Meek


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

  8. 49 CFR 383.95 - Restrictions. (United States)


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

  9. 9 CFR 92.3 - Movement restrictions. (United States)


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

  10. 21 CFR 203.20 - Sales restrictions. (United States)


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

  11. Restricted Predicates for Hypothetical Datalog

    Directory of Open Access Journals (Sweden)

    Fernando Sáenz-Pérez


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

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

    Directory of Open Access Journals (Sweden)

    Anjan Mukherjee


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

  13. Hypercaloric diet prevents sexual impairment induced by maternal food restriction. (United States)

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


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

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

    International Nuclear Information System (INIS)

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


    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

  15. 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


    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)

  16. Evaluation of placenta in foetal demise and foetal growth restriction. (United States)

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


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

  17. Maternal restrictive feeding and eating in the absence of hunger among toddlers: a cohort study. (United States)

    Bauer, Katherine W; Haines, Jess; Miller, Alison L; Rosenblum, Katherine; Appugliese, Danielle P; Lumeng, Julie C; Kaciroti, Niko A


    Restrictive feeding by parents has been associated with greater eating in the absence of hunger (EAH) among children, a risk factor for obesity. However, few studies have examined the association between restrictive feeding and EAH longitudinally, raising questions regarding the direction of associations between restrictive feeding and child EAH. Our objective was to examine the bidirectional prospective associations between restrictive feeding and EAH among toddlers. Low-income mother-child dyads (n = 229) participated when children were 21, 27, and 33 months old. Restriction with regard to food amount and food quality were measured with the Infant Feeding Styles Questionnaire. EAH was measured as kilocalories of food children consumed after a satiating meal. A cross-lagged analysis adjusting for child sex and weight-for-length z-score was used to simultaneously test cross-sectional and bidirectional prospective associations between each type of restriction and children's EAH. At 21 months, mothers of children with greater EAH reported higher restriction with regard to food amount (b = 0.17, p < .05). Restriction with regard to food amount at age 21 months was inversely associated with EAH at 27 months (b = -0.20, p < .05). Restriction with regard to food amount at 27 months was not associated with EAH at 33 months and restriction with regard to food quality was not associated with EAH. EAH did not prospectively predict maternal restriction. Neither restriction with regard to food amount nor food quality increased risk for EAH among toddlers. Current US clinical practice recommendations for parents to avoid restrictive feeding, and the potential utility of restrictive feeding with regard to food amount in early toddlerhood, deserve further consideration.

  18. Intrauterine growth restriction - part 2. (United States)

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


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

  19. 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: [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)


    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.

  20. Assessing restrictiveness of national alcohol marketing policies. (United States)

    Esser, Marissa B; Jernigan, David H


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

  1. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS


    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

  2. Curves of restricted type in euclidean spaces

    Directory of Open Access Journals (Sweden)

    Bengü Kılıç Bayram


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

  3. Inherited thrombophilia in pregnant women with intrauterine growth restriction. (United States)

    Coriu, Letitia; Copaciu, Elena; Tulbure, Dan; Talmaci, Rodica; Secara, Diana; Coriu, Daniel; Cirstoiu, Monica


    Intrauterine growth restriction (IUGR) is a major cause of fetal morbidity and mortality during pregnancy. The role of mutation in the factor V gene, prothrombin gene, MTHFR gene, as risk factors for intrauterine growth restriction during pregnancy, is not very well known so far. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: intrauterine growth restriction, preeclampsia, recurrent pregnancy loss or maternal venous thromboembolism, who were admitted in Bucharest Emergency University Hospital, during the period January 2010 to July 2014. Genetic testing was performed for all the cases to detect: factor V Leiden mutation, G20210A mutation in the prothrombin gene, C677T mutation and A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. Blood samples were obtained as soon as the diagnosis of intrauterine growth restriction was established with ultrasonography. The following gene mutations were associated with increased risk of IUGR: G20210A prothrombin gene mutation (OR 4.81, 95% CI 1.05 - 2.22, p= 0.043), G1691A factor V gene mutation (factor V Leiden) (OR 1.58, 95% CI 0.61 - 4.080, p= 0.347), C677T MTHFR gene mutation (OR 1.61, 95% CI 0.79 to 3.26, p= 0.186), compound heterozygous MTHFR C677T and A1298C (OR 1.66, 95% CI 0.81- 3.42, p= 0.169). Particularly, for G20210A prothrombin gene mutation we found statistically significant risk (p≤0.05) of IUGR.

  4. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome. (United States)

    Ohtsuka, Hokuto; Takinami, Masahiro; Shimasaki, Takafumi; Hibi, Takahide; Murakami, Hiroshi; Aiba, Hirofumi


    Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1 + gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner. © 2017 John Wiley & Sons Ltd.

  5. Activity restriction induced by fear of falling and objective and subjective measures of physical function: a prospective cohort study. (United States)

    Deshpande, Nandini; Metter, E Jeffrey; Lauretani, Fulvio; Bandinelli, Stefania; Guralnik, Jack; Ferrucci, Luigi


    To examine whether activity restriction specifically induced by fear of falling (FF) contributes to greater risk of disability and decline in physical function. Prospective cohort study. Population-based older cohort. Six hundred seventy-three community-living elderly (> or = 65) participants in the Invecchiare in Chianti Study who reported FF. FF, fear-induced activity restriction, cognition, depressive symptoms, comorbidities, smoking history, and demographic factors were assessed at baseline. Disability in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and performance on the Short Performance Physical Battery (SPPB) were evaluated at baseline and at the 3-year follow-up. One-quarter (25.5%) of participants did not report any activity restriction, 59.6% reported moderate activity restriction (restriction or avoidance of or = 3 activities). The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups. Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up. Severe and moderate activity restriction were independent predictors of worsening IADL disability. Results were consistent even after adjusting for multiple potential confounders. In an elderly population, activity restriction associated with FF is an independent predictor of decline in physical function. Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons.

  6. Work-hour restrictions as an ethical dilemma for residents. (United States)

    Carpenter, Robert O; Austin, Mary T; Tarpley, John L; Griffin, Marie R; Lomis, Kimberly D


    We propose that the standardized work-hour limitations have created an ethical dilemma for residents. A survey tool was designed to assess factors that influence the number of hours residents work and report. The program directors of pediatrics, internal medicine, and general surgery at our institution supported their residents' participation. A voluntary, anonymous survey of these residents was performed. One hundred seventy of 265 eligible residents were surveyed. Eighty-one percent of residents surveyed responded. Eighty percent of respondents reported exceeding work-hour restrictions at least once within the past 6 months. The factor of greatest influence measured was concern for patient care (80%). Forty-nine percent of respondents admitted underreporting their work hours. The Accreditation Council for Graduate Medical Education work-hour restrictions have created an ethical dilemma for residents. Our data show that a significant number of residents feel compelled to exceed work-hour regulations and report those hours falsely.

  7. Universal Cycles of Restricted Classes of Words


    Leitner, Arielle; Godbole, Anant


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

  8. Freedom and Restrictions in Language Use. (United States)

    O'Donnell, Roy C.

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

  9. Protein restriction in chronic renal failure

    NARCIS (Netherlands)


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

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

    African Journals Online (AJOL)

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

  11. Eclampsia despite strict dietary sodium restriction.

    NARCIS (Netherlands)

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


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

  12. 7 CFR 3430.205 - Funding restrictions. (United States)


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

  13. 28 CFR 804.3 - Restrictions. (United States)


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

  14. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction (United States)

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularl...

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

    International Nuclear Information System (INIS)

    Cho, Y.M.


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

  16. The influence of food restriction on the small bowel: Does intensive short‑term food restriction lead to weight loss?

    Czech Academy of Sciences Publication Activity Database

    Makovický, Peter; Tůmová, E.; Volek, Z.; Makovický, P.; Arnone, J.M.; Švecová, Ivana; Samasca, G.


    Roč. 118, č. 6 (2017), s. 361-365 ISSN 0006-9248 R&D Projects: GA MŠk(CZ) LM2015040; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : experimental medicine * food restriction * rabbit * slimming * small bowel weight loss Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Pathology Impact factor: 0.667, year: 2016

  17. Urban water restrictions: Attitudes and avoidance (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin


    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.

  18. 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.

  19. Investigation of restricted baby Skyrme models

    International Nuclear Information System (INIS)

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


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


    Boyer, Herbert


    Boyer, Herbert (Yale University, New Haven, Conn.). Genetic control of restriction and modification in Escherichia coli. J. Bacteriol. 88:1652–1660. 1964.—Bacterial crosses with K-12 strains of Escherichia coli as Hfr donors (Hfr Hayes, Hfr Cavalli, and Hfr P4X-6) and B/r strains of E. coli as F− recipients were found to differ from crosses between K-12 Hfr donors and K-12 F− recipients in two ways: (i) recombinants (leu, pro, lac, and gal) did not appear at discrete time intervals but did appear simultaneously 30 min after matings were initiated, and (ii) the linkage of unselected markers to selected markers was reduced. Integration of a genetic region linked to the threonine locus of K-12 into the B/r genome resulted in a hybrid which no longer gave anomalous results in conjugation experiments. A similar region of the B strain was introduced into the K-12 strain, which then behaved as a typical B F− recipient. These observations are interpreted as the manifestation of host-controlled modification and restriction on the E. coli chromosome. This was verified by experiments on the restriction and modification of the bacteriophage lambda, F-lac, F-gal, and sex-factor, F1. It was found that the genetic region that controlled the mating responses of the K-12 and B/r strains also controlled the modification and restriction properties of these two strains. The genes responsible for the restricting and modifying properties of the K-12 and B strains of E. coli were found to be allelic, linked to each other, and linked to the threonine locus. PMID:14240953

  1. The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats. (United States)

    Freije, William A; Thamotharan, Shanthie; Lee, Regina; Shin, Bo-Chul; Devaskar, Sherin U


    Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation. © 2014 Wiley Periodicals, Inc.

  2. distribution, abundance and properties of restriction enzymes

    African Journals Online (AJOL)

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

  3. Health Benefits of Fasting and Caloric Restriction. (United States)

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


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

  4. Compensatory mechanisms activated with intermittent energy restriction

    DEFF Research Database (Denmark)

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


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

  5. Restricted Coherent Risk Measures and Actuarial Solvency

    Directory of Open Access Journals (Sweden)

    Christos E. Kountzakis


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

  6. Avoidant/Restrictive Food Intake Disorder (United States)

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

  7. A topological insight into restricted Boltzmann machines

    NARCIS (Netherlands)

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

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

  8. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S


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

  9. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S


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

  10. Public Investment, Revenue Shocks, and Borrowing Restrictions


    Büttner, Thiess; Wildasin, David E.


    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...

  11. Restrictive extraocular myopathy: A presenting feature of acromegaly

    Directory of Open Access Journals (Sweden)

    Steven Heireman


    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.

  12. Social-cognitive predictors of low-income parents' restriction of screen time among preschool-aged children. (United States)

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


    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 < .001) were associated with greater restriction of 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.

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

    Directory of Open Access Journals (Sweden)

    Changhan Lee


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

  14. The family context of low-income parents who restrict child screen time. (United States)

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


    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. 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. 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. 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.

  15. Vsx2 in the zebrafish retina: restricted lineages through derepression

    Directory of Open Access Journals (Sweden)

    Higashijima Shin-ichi


    Full Text Available Abstract Background The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs. It is not clear, however, which progenitors are multipotent or why they are multipotent. Results In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2. Conclusion Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

  16. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction. (United States)

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


    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal 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 cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  17. Fasting or caloric restriction for healthy aging. (United States)

    Anton, Stephen; Leeuwenburgh, Christiaan


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

  18. Newer antidiabetic drugs and calorie restriction mimicry

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra


    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.

  19. 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 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.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.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.

  20. Model of adipose tissue cellularity dynamics during food restriction. (United States)

    Soula, H A; Géloën, A; Soulage, C O


    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Francine Einstein


    Full Text Available Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  2. Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction (United States)

    Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.


    Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

  3. Aging, neurogenesis, and caloric restriction in different model organisms. (United States)

    Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M


    Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

  4. Optimizing Restriction Site Placement for Synthetic Genomes (United States)

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

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

  5. Sight Restrictions in Maghrib Muslim Architecture

    Directory of Open Access Journals (Sweden)

    Mustapha Ben Hamouche


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

  6. Optimal Policy under Restricted Government Spending

    DEFF Research Database (Denmark)

    Sørensen, Anders


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

  7. Effects of restricted and free suckling


    Fröberg, Sofie


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

  8. Strong dietary restrictions protect Drosophila against anoxia/reoxygenation injuries.

    Directory of Open Access Journals (Sweden)

    Paul Vigne

    Full Text Available Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2 for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside, an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling

  9. Learning to overeat: maternal use of restrictive feeding practices promotes girls' eating in the absence of hunger. (United States)

    Birch, Leann L; Fisher, Jennifer Orlet; Davison, Kirsten Krahnstoever


    Experimental findings causally link restrictive child-feeding practices to overeating in children. However, longitudinal data are needed to determine the extent to which restrictive feeding practices promote overeating. Our objectives were to determine whether restrictive feeding practices foster girls' eating in the absence of hunger (EAH) and whether girls' weight status moderates the effects of restrictive feeding practices. Longitudinal data were used to create a study design featuring 2 maternal restriction factors (low and high), 2 weight-status factors (nonoverweight and overweight), and 3 time factors (ages 5, 7, and 9 y). Mean EAH increased significantly (P responsive to environmental cues. These findings are not expected to be generalized to boys or to other racial and ethnic groups.

  10. Time of Day When Type 1 Diabetes Patients With Eating Disorder Symptoms Most Commonly Restrict Insulin. (United States)

    Merwin, Rhonda M; Moskovich, Ashley A; Honeycutt, Lisa K; Lane, James D; Feinglos, Mark; Surwit, Richard S; Zucker, Nancy L; Dmitrieva, Natalia O; Babyak, Michael A; Batchelder, Heather; Mooney, Jan

    Restricting insulin to lose weight is a significant problem in the clinical management of type 1 diabetes (T1D). Little is known about this behavior or how to effectively intervene. Identifying when insulin restriction occurs could allow clinicians to target typical high-risk times or formulate hypotheses regarding factors that influence this behavior. The current study investigated the frequency of insulin restriction by time of day. Fifty-nine adults with T1D and eating disorder symptoms completed 72 hours of real-time reporting of eating and insulin dosing with continuous glucose monitoring. We used a generalized estimating equation model to test the global hypothesis that frequency of insulin restriction (defined as not taking enough insulin to cover food consumed) varied by time of day, and examined frequency of insulin restriction by hour. We also examined whether patterns of insulin restriction for 72 hours corresponded with patients' interview reports of insulin restriction for the past 28 days. Frequency of insulin restriction varied as a function of time (p = .016). Insulin restriction was the least likely in the morning hours (6:00-8:59 AM), averaging 6% of the meals/snacks consumed. Insulin restriction was more common in the late afternoon (3:00-5:59 PM), peaking at 29%. Insulin was restricted for 32% of the meals/snacks eaten overnight (excluding for hypoglycemia); however, overnight eating was rare. Insulin restriction was associated with higher 120-minute postprandial blood glucose (difference = 44.4 mg/dL, 95% confidence interval = 22.7-68.5, p < .001) and overall poorer metabolic control (r = 0.43-0.62, p's < .01). Patients reported restricting insulin for a greater percentage of meals and snacks for the past 28 days than during the 72 hour real-time assessment; however, the reports were correlated (Spearman's ρ = 0.46, p < .001) and accounted for similar variance in HbA1c (34% versus 35%, respectively). Findings suggest that insulin restriction

  11. 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


    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

  12. 47 CFR 64.1200 - Delivery restrictions. (United States)


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

  13. Review: Neuroinflammation in intrauterine growth restriction. (United States)

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


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

  14. 7 CFR 3430.905 - Funding restrictions. (United States)


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

  15. Determination of genotype differences through restriction ...

    African Journals Online (AJOL)

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

  16. 9 CFR 166.2 - General restrictions. (United States)


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

  17. A new restriction endonuclease from Citrobacter freundii (United States)

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


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

  18. A new restriction endonuclease from Citrobacter freundii


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


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

  19. Strategies in intrauterine growth restriction at term

    NARCIS (Netherlands)

    Boers, Kim Esther


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

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

    African Journals Online (AJOL)

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

  1. 18 CFR 35.39 - Affiliate restrictions. (United States)


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

  2. An Adjustment Restriction on Fish Quota

    NARCIS (Netherlands)

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


    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

  3. Periodic Solutions for Circular Restricted -Body Problems

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Zhao


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

  4. Sleep restriction progress to cardiac autonomic imbalance

    African Journals Online (AJOL)

    Arbind Kumar Choudhary


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

  5. Employees, Trade Secrets and Restrictive Covenants

    NARCIS (Netherlands)

    Kamperman Sanders, Anselm; Heath, C.


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

  6. Restricted Choice in the Management of Change. (United States)

    North, R. F. J.


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

  7. 32 CFR 701.44 - Restrictions. (United States)


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

  8. 50 CFR 648.164 - Possession restrictions. (United States)


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

  9. 38 CFR 1.462 - Confidentiality restrictions. (United States)


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

  10. Intrauterine growth restriction: screening, diagnosis, and management. (United States)

    Lausman, Andrea; Kingdom, John


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

  11. The influence of cognitive impairment with no dementia on driving restriction and cessation in older adults. (United States)

    Kowalski, Kristina; Love, Janet; Tuokko, Holly; MacDonald, Stuart; Hultsch, David; Strauss, Esther


    Cognitively impaired older adults may be at increased risk of unsafe driving. Individuals with insight into their own impairments may minimize their risk by restricting or stopping driving. The purpose of this study was to examine the influence of cognitive impairment on driving status and driving habits and intentions. Participants were classified as cognitively impaired, no dementia single (CIND-single), CIND-multiple, or not cognitively impaired (NCI) and compared on their self-reported driving status, habits, and intentions to restrict or quit driving in the future. The groups differed significantly in driving status, but not in whether they restricted their driving or reduced their driving frequency. CIND-multiple group also had significantly higher intention to restrict/stop driving than the NCI group. Reasons for restricting and quitting driving were varied and many individuals reported multiple reasons, both external and internal, for their driving habits and intentions. Regardless of cognitive status, none of the current drivers were seriously thinking of restricting or quitting driving in the next 6 months. It will be important to determine, in future research, how driving practices change over time and what factors influence decisions to restrict or stop driving for people with cognitive impairment. Copyright © 2011. Published by Elsevier Ltd.

  12. 7 CFR 322.28 - General requirements; restricted articles. (United States)


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

  13. 7 CFR 319.75-2 - Restricted articles. 1 (United States)


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

  14. Variants of early-onset restrictive eating disturbances in middle childhood. (United States)

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja


    This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben


    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 mean...... residual lifetime as target parameter. We account for confounding factors using the Aalen additive hazards model. Large sample property of the proposed estimator is established and simulation studies are conducted in order to assess small sample performance of the resulting estimator. The method is also......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...

  16. Calorie restriction reduces the incidence of radiation-induced myeloid leukemia and spontaneous tumor

    International Nuclear Information System (INIS)

    Yoshida, Kazuko


    The host-defense mechanisms against cancers are known to be modulated by changing the environmental factor(s). The spontaneous incidence of myeloid leukemia is about 1% in C3H/He mice, and the incidence increases up to 23.3% when a single dose of radiation, 3 Gy X-ray, is exposed to a whole-body. Since calorie restriction was known to reduce the incidence of spontaneous tumors, a question as to whether such radiation induced-increase of myeloid leukemia would be also decreased by calorie restriction, was aimed to answer to elucidate possible mechanism of radiation-induced myeloid leukemia. By the calorie restriction, the incidence of myeloid leukemia was significantly decreased; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the latent period of the myeloid leukemia in the groups for calorie restriction was significantly extended at a greater extent as compared with the control diet groups. Number of hematopoietic stem cells, the possible target cells for radiation-induced leukemias, in the groups for the calorie restriction demonstrated a significant decrease, especially in the spleen, as compared with that in the control, when the evaluation was made at the time of radiation exposure. Then, we examined whether the decreased number of target cells at the time of exposure is caused by the reduction of radiation-induced myeloid leukemia with caloric restriction. The third restricted groups were fed 65 kcal diet (restricted diet) for the first 4 weeks i.e. from 6 weeks to 10 weeks old, then, the mice were fed with control diet after radiation. The incidence of myeloid leukemia in this group was slightly decreased but did not show statistically significance. Therefore, the caloric restriction seems to be more effective in the promotion stage than the initiation stage on radiation-induced leukemogenesis. It is well known that C3H/He mice develop hepatoma spontaneously

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

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese


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

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

    Directory of Open Access Journals (Sweden)

    DD Motghare


    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.

  19. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

    Directory of Open Access Journals (Sweden)

    Malene Hansen


    Full Text Available In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin. TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

  20. Evolution of the retroviral restriction gene Fv1: inhibition of non-MLV retroviruses.

    Directory of Open Access Journals (Sweden)

    Melvyn W Yap


    Full Text Available Fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus (MLV. It was first identified in cells that were derived from laboratory mice and was found to be homologous to the gag gene of an endogenous retrovirus (ERV. To understand the evolution of the host restriction gene from its retroviral origins, Fv1s from wild mice were isolated and characterized. Most of these possess intact open reading frames but not all restricted N-, B-, NR-or NB-tropic MLVs, suggesting that other viruses could have played a role in the selection of the gene. The Fv1s from Mus spretus and Mus caroli were found to restrict equine infectious anemia virus (EIAV and feline foamy virus (FFV respectively, indicating that Fv1 could have a broader target range than previously thought, including activity against lentiviruses and spumaviruses. Analyses of the Fv1 sequences revealed a number of residues in the C-terminal region that had evolved under positive selection. Four of these selected residues were found to be involved in the novel restriction by mapping studies. These results strengthen the similarities between the two capsid binding restriction factors, Fv1 and TRIM5α, which support the hypothesis that Fv1 defended mice against waves of retroviral infection possibly including non-MLVs as well as MLVs.

  1. The nature and nurture of cell heterogeneity: accounting for macrophage gene-environment interactions with single-cell RNA-Seq. (United States)

    Wills, Quin F; Mellado-Gomez, Esther; Nolan, Rory; Warner, Damien; Sharma, Eshita; Broxholme, John; Wright, Benjamin; Lockstone, Helen; James, William; Lynch, Mark; Gonzales, Michael; West, Jay; Leyrat, Anne; Padilla-Parra, Sergi; Filippi, Sarah; Holmes, Chris; Moore, Michael D; Bowden, Rory


    Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome's limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic 'snapshots' of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic ('nature') and environmental ('nurture') modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages. We introduce the programmable Polaris™ microfluidic lab-on-chip for single-cell sequencing, which performs live-cell imaging while controlling for the culture microenvironment of each cell. Using gene-edited macrophages we demonstrate how previously unappreciated knockout effects of SAMHD1, such as an altered oxidative stress response, have a large paracrine signaling component. Furthermore, we demonstrate single-cell pathway enrichments for cell cycle arrest and APOBEC3G degradation, both associated with the oxidative stress response and altered proteostasis. Interestingly, SAMHD1 and APOBEC3G are both HIV-1 inhibitors ('restriction factors'), with no known co-regulation. As single-cell methods continue to mature, so will the ability to move beyond simple 'snapshots' of cell populations towards studying the determinants of population dynamics. By combining single-cell culture, live-cell imaging, and single-cell sequencing, we have demonstrated the ability to study cell phenotypes and microenvironmental influences. It's these microenvironmental components - ignored by standard single-cell workflows - that likely determine how macrophages, for example, react to inflammation and form treatment resistant HIV reservoirs.

  2. Accessory genes confer a high replication rate to virulent feline immunodeficiency virus. (United States)

    Troyer, Ryan M; Thompson, Jesse; Elder, John H; VandeWoude, Sue


    Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between two FIV molecular clones with divergent disease potentials: a highly pathogenic isolate that replicates rapidly in vitro and is associated with significant immunopathology in vivo, FIV-C36 (referred to here as high-virulence FIV [HV-FIV]), and a less-pathogenic strain, FIV-PPR (referred to here as low-virulence FIV [LV-FIV]). Using PCR-driven overlap extension, we produced viruses in which vif, orfA, or both genes from virulent HV-FIV replaced equivalent genes in LV-FIV. The generation of these chimeras is more straightforward in FIV than in primate lentiviruses, since FIV accessory gene open reading frames have very little overlap with other genes. All three chimeric viruses exhibited increased replication kinetics in vitro compared to the replication kinetics of LV-FIV. Chimeras containing HV-Vif or Vif/OrfA had replication rates equivalent to those of the virulent HV-FIV parental virus. Furthermore, small interfering RNA knockdown of feline APOBEC3 genes resulted in equalization of replication rates between LV-FIV and LV-FIV encoding HV-FIV Vif. These findings demonstrate that Vif-APOBEC interactions play a key role in controlling the replication and pathogenicity of this immunodeficiency-inducing virus in its native host species and that accessory genes act as mediators of lentiviral strain-specific virulence.

  3. The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Sakiko Honjoh


    Full Text Available Organismal lifespan is highly plastic in response to environmental cues, and dietary restriction (DR is the most robust way to extend lifespan in various species. Recent studies have shown that sex also is an important factor for lifespan regulation; however, it remains largely unclear how these two factors, food and sex, interact in lifespan regulation. The nematode Caenorhabditis elegans has two sexes, hermaphrodite and male, and only the hermaphrodites are essential for the short-term succession of the species. Here, we report an extreme sexual dimorphism in the responsiveness to DR in C. elegans; the essential hermaphrodites show marked longevity responses to various forms of DR, but the males show few longevity responses and sustain reproductive ability. Our analysis reveals that the sex determination pathway and the steroid hormone receptor DAF-12 regulate the sex-specific DR responsiveness, integrating sex and environmental cues to determine organismal lifespan.

  4. Avoidant/Restrictive Food Intake Disorder (ARFID). (United States)

    Zimmerman, Jacqueline; Fisher, Martin


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

  5. Sizing of high-pressure restriction orifices

    International Nuclear Information System (INIS)

    Casado Flores, E.


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

  6. Octreotide therapy and restricted fetal growth

    DEFF Research Database (Denmark)

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


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

  7. Investment Restrictions and Contagion in Emerging Markets


    Anna Ilyina


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

  8. Optimal Detection under the Restricted Bayesian Criterion

    Directory of Open Access Journals (Sweden)

    Shujun Liu


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

  9. Meeting licensing restrictions from a regulator's perspective

    International Nuclear Information System (INIS)

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


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

  10. Emergency building temperature restrictions. Final evaluation

    Energy Technology Data Exchange (ETDEWEB)



    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.

  11. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients (United States)

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank


    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

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

    Volek, Jeff S; Feinman, Richard D


    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. 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


    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.

  14. Restrictive annuloplasty to treat functional mitral regurgitation: optimize the restriction to improve the results? (United States)

    Totaro, Pasquale; Adragna, Nicola; Argano, Vincenzo


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

  15. [Restricted motion after total knee arthroplasty]. (United States)

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


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

  16. Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring. (United States)

    Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi


    Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Restrictive educational placements increase adolescent risks for students with early-starting conduct problems. (United States)

    Powers, Christopher J; Bierman, Karen L; Coffman, Donna L


    Students with early-starting conduct problems often do poorly in school; they are disproportionately placed in restrictive educational placements outside of mainstream classrooms. Although intended to benefit students, research suggests that restrictive placements may exacerbate the maladjustment of youth with conduct problems. Mixed findings, small samples, and flawed designs limit the utility of existing research. This study examined the impact of restrictive educational placements on three adolescent outcomes (high school noncompletion, conduct disorder, depressive symptoms) in a sample of 861 students with early-starting conduct problems followed longitudinally from kindergarten (age 5-6). Causal modeling with propensity scores was used to adjust for confounding factors associated with restrictive placements. Analyses explored the timing of placement (elementary vs. secondary school) and moderation of impact by initial problem severity. Restrictive educational placement in secondary school (but not in elementary school) was iatrogenic, increasing the risk of high school noncompletion and the severity of adolescent conduct disorder. Negative effects were amplified for students with conduct problem behavior with less cognitive impairment. To avoid harm to students and to society, schools must find alternatives to restrictive placements for students with conduct problems in secondary school, particularly when these students do not have cognitive impairments that might warrant specialized educational supports. © 2015 Association for Child and Adolescent Mental Health.

  18. Rhabdomyolysis After Performing Blood Flow Restriction Training: A Case Report. (United States)

    Tabata, Shogo; Suzuki, Yukio; Azuma, Koichiro; Matsumoto, Hideo


    Tabata, S, Suzuki, Y, Azuma, K, and Matsumoto, H. Rhabdomyolysis after performing blood flow restriction training: a case report. J Strength Cond Res 30(7): 2064-2068, 2016-Rhabdomyolysis is a serious and potentially life-threatening condition related to resistance training. Despite numerous reports of low-intensity blood flow restriction (BFR) training inducing muscle hypertrophy and increasing strength, few reports of rhabdomyolysis related to BFR training have been published. Here, we report a 30-year-old obese Japanese man admitted to our hospital the day after his first BFR training session with complaints of severe muscle pain in his upper and lower extremities, high fever, and pharyngeal pain. He was diagnosed with acute rhabdomyolysis based on a serum creatine phosphokinase level of 56,475 U·L and a urine myoglobin level of >3,000 ng·ml, and with acute tonsillitis based on a white blood cell count of 17,390 and C-reactive protein level of 10.43 mg·dl. A number of factors are suspected to be related to the onset and exacerbation of rhabdomyolysis, including excessive muscular training with BFR, bacterial infection, and medication. After 10 days of hospitalization with intravenous fluids and antibacterial drugs, he recovered without complications. This case indicates that BFR training should be conducted with careful consideration of the physical condition and strength of the individual to prevent serious complications, such as rhabdomyolysis.

  19. Third sound in a restricted geometry

    International Nuclear Information System (INIS)

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


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

  20. Identifying product order with restricted Boltzmann machines (United States)

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


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

  1. Privacy-Preserving Restricted Boltzmann Machine

    Directory of Open Access Journals (Sweden)

    Yu Li


    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.

  2. The Monetary Policy – Restrictive or Expansive?

    Directory of Open Access Journals (Sweden)

    Adam Szafarczyk


    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.

  3. Criminal Protection Orders for Women Victims of Domestic Violence: Explicating Predictors of Level of Restrictions Among Orders Issued. (United States)

    Sullivan, Tami P; Weiss, Nicole H; Price, Carolina; Pugh, Nicole E


    Criminal protection orders (POs), with varying degrees of restrictions, are issued by the criminal justice system to enhance the safety of victims of domestic violence (DV). Limited research exists to elucidate factors associated with their issuance. Therefore, the purpose of this study was to investigate how demographic, relationship, parenting, and court-process-related factors are related to the level of restriction the PO places on the offender. Two-hundred ninety-eight women who were victims in a criminal DV case ( M age 36.4, 50.0% African American) participated in a structured interview approximately 12 to 15 months following the offenders' arraignment. Results revealed that psychological DV severity and fear of the offender in the 30 days prior to arraignment significantly predicted PO level of restriction issued. In addition, level of restriction requested by the victim significantly predicted level of restriction issued by the judge (though closer examination of the data revealed that many orders were issued at a different level of restriction than the victim requested). Other demographic, relationship, parenting, and court-process-related factors did not predict PO level of restriction issued. Findings are discussed with respect to practice and policy in the criminal justice system.

  4. A statistical mechanical approach to restricted integer partition functions (United States)

    Zhou, Chi-Chun; Dai, Wu-Sheng


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

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


    Boccard, Nicolas; Wauthy, Xavier


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

  6. Restrictive pattern on spirometry: association with cardiovascular risk and level of physical activity in asymptomatic adults

    Directory of Open Access Journals (Sweden)

    Evandro Fornias Sperandio


    Full Text Available Objective : To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL, as well as with cardiovascular disease (CVD risk factors, in asymptomatic adults. Methods : A total of 374 participants (mean age, 41 ± 14 years underwent spirometry, which included the determination of FVC and FEV1. A restrictive pattern on spirometry was defined as an FEV1/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer. Results : A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness, the following variables retained significance (OR; 95% CI as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8, smoking (11.6; 1.56-87.5, physical inactivity (8.1; 1.43-46.4, larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71; and dyslipidemia (1.89; 1.12-1.98. Conclusions : A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies.

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

    International Nuclear Information System (INIS)

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


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

  8. A placenta clinic approach to the diagnosis and management of fetal growth restriction. (United States)

    Kingdom, John C; Audette, Melanie C; Hobson, Sebastian R; Windrim, Rory C; Morgen, Eric


    Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening

  9. Maternal nutrient restriction in early gestation upregulates myogenic genes in cattle fetal muscle tissue (United States)

    Prenatal myogenesis is a critical factor in determining the muscle growth potential of cattle. We hypothesized that maternal nutrient restriction during early gestation would alter the transcriptome of fetal primordial muscle tissue in cattle. A total of 14 Angus-cross heifers were estrus synchroniz...

  10. Cleavage of DNA containing 5-fluorocytosine or 5-fluorouracil by type II restriction endonucleases

    Czech Academy of Sciences Publication Activity Database

    Olszewska, Agata; Daďová, Jitka; Mačková, Michaela; Hocek, Michal


    Roč. 23, č. 21 (2015), s. 6885-6890 ISSN 0968-0896 R&D Projects: GA ČR GA14-04289S Institutional support: RVO:61388963 Keywords : modified nucleotides * DNA * restriction endonucleases * DNA polymerase * pyrimidine nucleosides Subject RIV: CC - Organic Chemistry Impact factor: 2.923, year: 2015

  11. Childhood and adolescent energy restriction and subsequent colorectal cancer risk: Results from The Netherlands cohort study

    NARCIS (Netherlands)

    Hughes, L.A.E.; Brandt, P.A. van den; Goldbohm, R.A.; Goeij, A.F.P.M. d; Bruïne, A.P. de; Engeland, M. van; Weijenberg, M.P.


    Background: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study. Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were

  12. Postnatal food restriction in the rat as a model for a low nephron endowment

    DEFF Research Database (Denmark)

    Schreuder, Michiel F.; Nyengaard, Jens Randel; Remmers, Floor


    A low nephron endowment may be associated with hypertension. Nephrogenesis is the process that leads to the formation of nephrons until week 36 of gestation in humans and may be inhibited by many factors like intrauterine growth restriction and premature birth. To study the consequences of a low ...

  13. Transient and Switchable (Triethylsilyl)ethynyl Protection of DNA against Cleavage by Restriction Endonucleases

    Czech Academy of Sciences Publication Activity Database

    Kielkowski, Pavel; Macíčková-Cahová, Hana; Pohl, Radek; Hocek, Michal


    Roč. 50, č. 37 (2011), s. 8727-8730 ISSN 1433-7851 R&D Projects: GA ČR GA203/09/0317 Institutional research plan: CEZ:AV0Z40550506 Keywords : alkynes * DNA * protecting groups * nucleotides * restriction endonucleases Subject RIV: CC - Organic Chemistry Impact factor: 13.455, year: 2011

  14. Effects of moderate energy restriction on physical performance and substrate utilization in non-obese men

    NARCIS (Netherlands)

    Velthuis-te Wierik, E.J.M.; Hoogzaad, L.V.; Berg, H. van den; Schaafsma, G.


    Energy restriction (ER) has shown to be an effective 'anti-aging' factor in rodents, resulting in an increased life span and preventing or delaying the occurrence of many age-related diseases in rodents. As a part of a feasibility study on the potential application of ER in humans, we studied the

  15. Novel analogues of bradykinin conformationally restricted in the C-terminal part of the molecule

    Czech Academy of Sciences Publication Activity Database

    Sleszynska, M.; Wierzba, T. H.; Malinowski, K.; Borovičková, Lenka; Maluch, I.; Sobolewski, D.; Lammek, B.; Slaninová, Jiřina; Prahl, A.


    Roč. 17, č. 5 (2011), s. 366-372 ISSN 1075-2617 Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin analogues * B2 receptor antagonists * sterically restricted residue * in vivo rat blood pressure test * in vitro rat uterus Subject RIV: CC - Organic Chemistry Impact factor: 1.799, year: 2011

  16. Restricting the vertical and horizontal extent of the Field-of-View: Effects on manoeuvring performance

    NARCIS (Netherlands)

    Jansen, S.E.M.; Toet, A.; Delleman, N.J.


    It is known that Field-of-view restrictions affect distance estimation, postural equilibrium, and the ability to control heading. These are all important factors when manoeuvring on foot through complex structured environments. Although considerable research has been devoted to the horizontal

  17. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J. W. R.; Blankenstein, M. A.; Heijboer, A. C.; van Vugt, J. M. G.


    To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). PlGF concentration was retrospectively measured in first trimester serum specimens of 23

  18. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J.W.; Blankenstein, M.A.; Heijboer, A.C.; van Vugt, J.M.


    Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: PlGF concentration was retrospectively measured in first trimester

  19. The Acquisition of English Restrictive Relative Clauses by Arab Adult EFL Learners (United States)

    Alroudhan, Hayat Eid


    This study investigates the challenges faced by Arab adult learners of English as a foreign language (EFL) in acquiring English restrictive relative clauses (RRCs), as well as the factors that affect the process of acquisition. This issue has received considerable attention in second language (L2) research. The present study discusses the…

  20. Can we restrict the health care menu? (United States)

    Klein, R


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

  1. Cardiorespiratory effects of inelastic chest wall restriction. (United States)

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


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

  2. Restricted Interval Guelph permeameter: Theory and application

    International Nuclear Information System (INIS)

    Freifeld, Barry M.; Oldenburg, Curtis M.


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

  3. Caloric Restriction Promotes Structural and Metabolic Changes in the Skin

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Forni


    Full Text Available Caloric restriction (CR is the most effective intervention known to enhance lifespan, but its effect on the skin is poorly understood. Here, we show that CR mice display fur coat remodeling associated with an expansion of the hair follicle stem cell (HFSC pool. We also find that the dermal adipocyte depot (dWAT is underdeveloped in CR animals. The dermal/vennule annulus vasculature is enlarged, and a vascular endothelial growth factor (VEGF switch and metabolic reprogramming in both the dermis and the epidermis are observed. When the fur coat is removed, CR mice display increased energy expenditure associated with lean weight loss and locomotion impairment. Our findings indicate that CR promotes extensive skin and fur remodeling. These changes are necessary for thermal homeostasis and metabolic fitness under conditions of limited energy intake, suggesting a potential adaptive mechanism.

  4. Restrictive Diet Control as a Means of Child Abuse. (United States)

    Kudek, Matthew R; Luyet, Francois; Herringa, Ryan J; Knox, Barbara L


    We have recently encountered a series of cases where an obese caretaker is juxtaposed to a severely starved, malnourished dependent. The cases described all share a common characteristic: that the primary perpetrator was an obese caretaker who tried to exert absolute control over their victim's daily life in a way that included either a severe restriction or complete denial of food. Because the pathophysiology of both child abuse and obesity are incredibly complex and multifactorial, these cases are presented to encourage further discussion and more rigorous investigation into the validity of a hypothesis that has been derived from this set of cases: that the obesity of a child's caretaker may be an additional risk factor for child maltreatment by starvation.

  5. 36 CFR 1275.58 - Deletion of restricted portions. (United States)


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

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

    Directory of Open Access Journals (Sweden)

    Sudhir S Shetkar


    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.

  7. 10 CFR 1016.34 - Accountability for Secret Restricted Data. (United States)


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

  8. 36 CFR 13.1174 - Whale water restrictions. (United States)


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

  9. 48 CFR 552.203-71 - Restriction on Advertising. (United States)


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

  10. 50 CFR 697.23 - Restricted gear areas. (United States)


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

  11. 49 CFR 215.303 - Stenciling of restricted cars. (United States)


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

  12. 5 CFR 1304.4605 - Post-employment restrictions. (United States)


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


    Directory of Open Access Journals (Sweden)

    Alan Kacin


    Full Text Available Blood flow restricted resistance (BFRR training with pneumatic tourniquet has been suggested as an alternative for conventional weight training due to the proven benefits for muscle strength and hypertrophy using relatively low resistance, hence reducing the mechanical stress across a joint. As such, it has become an important part of rehabilitation programs used in either injured or operated athletes. Despite a general consensus on effectiveness of BFRR training for muscle conditioning, there are several uncertainties regarding the interplay of various extrinsic and intrinsic factors on its safety and efficiency, which are being reviewed from a clinical perspective. Among extrinsic factors tourniquet cuff pressure, size and shape have been identified as key for safety and efficiency. Among intrinsic factors, limb anthropometrics, patient history and presence of cardiac, vascular, metabolic or peripheral neurologic conditions have been recognized as most important. Though there are a few potential safety concerns connected to BFRR training, the following have been identified as the most probable and health-hazardous: (a mechanical injury to the skin, muscle, and peripheral nerves, (b venous thrombosis due to vascular damage and disturbed hemodynamics and (c augmented arterial blood pressure responses due to combined high body exertion and increased peripheral vascular resistance. Based on reviewed literature and authors’ personal experience with the use of BFRR training in injured athletes, some guidelines for its safe application are outlined. Also, a comprehensive risk assessment tool for screening of subjects prior to their inclusion in a BFRR training program is being introduced.

  14. Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations. (United States)

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


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

  15. Membrane barriers for radon gas flow restrictions

    International Nuclear Information System (INIS)

    Archibald, J.F.


    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

  16. Restricted fish feeding reduces cod otolith opacity

    DEFF Research Database (Denmark)

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


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

  17. Restrictions on the transnational movement of uranium

    International Nuclear Information System (INIS)

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


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

  18. Nonequilibrium thermodynamics of restricted Boltzmann machines (United States)

    Salazar, Domingos S. P.


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

  19. Epitaxial growth by monolayer restricted galvanic displacement

    Directory of Open Access Journals (Sweden)

    Vasilić Rastko


    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.

  20. Nonequilibrium thermodynamics of restricted Boltzmann machines. (United States)

    Salazar, Domingos S P


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

  1. Botulinum toxin for treatment of restrictive strabismus. (United States)

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

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

  2. The resurgence of selective contracting restrictions. (United States)

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


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


    Directory of Open Access Journals (Sweden)

    Student Claudia MOISĂ


    Full Text Available Youth travel is an important part of global tourism, consequently, getting to know the evolution of this form of tourism requires an approach of the aspects regarding the permissive and restrictive factors that influence the youth travel dynamic worldwide. In terms of the factors that influence youth travel, we highlighted these two categories of factors (permissive and restrictive and, within each category, we tried to singularize the influence of every factor over youth travel.

  4. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous (United States)

    Mei, Szu-Chieh; Brenner, Charles


    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 developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell. PMID:25633578

  5. Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

    Directory of Open Access Journals (Sweden)

    Szu-Chieh Mei


    Full Text Available 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 developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

  6. 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)

    Bradley, S.M.; Kruisbeek, A.M.; Singer, A.


    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

  7. Caloric restriction in the presence of attractive food cues: external cues, eating, and weight. (United States)

    Polivy, Janet; Herman, C Peter; Coelho, Jennifer S


    A growing body of research on caloric restriction (CR) in many species of laboratory animals suggests that underfeeding leads to better health and longevity in the calorically-restricted animal (e.g., see [[34]. J.P. Pinel, S. Assanand and D.R. Lehman, (2000). Hunger, eating and ill health. Am Psychol, 55, 1105-1116.], for a review). Although some objections have been raised by scientists concerned about negative psychological and behavioral sequelae of such restriction, advocates of CR continue to urge people to adopt sharply reduced eating regimes in order to increase their longevity. Yet very few people are even attempting to reap the benefits of such restriction. The present paper explores one factor that may deter many humans from drastically reducing their food consumption--the presence of abundant, attractive food cues in the environment. Research on the influence of food cues on food-related behaviors is reviewed to demonstrate that the presence of food cues makes restriction of intake more difficult.

  8. Maintainability of manpower system with restricted recruitment ...

    African Journals Online (AJOL)

    The maintainability of a manpower system is studied under a Markov framework. The classical method of controlling only one factor of flow is extended to highlight the case in which two factors are under control simultaneously. One special case of this extension, where recruitment of units faces partial embargo, is given, ...

  9. Cofactor requirement of HpyAV restriction endonuclease.

    Directory of Open Access Journals (Sweden)

    Siu-Hong Chan

    Full Text Available BACKGROUND: Helicobacter pylori is the etiologic agent of common gastritis and a risk factor for gastric cancer. It is also one of the richest sources of Type II restriction-modification (R-M systems in microorganisms. PRINCIPAL FINDINGS: We have cloned, expressed and purified a new restriction endonuclease HpyAV from H. pylori strain 26695. We determined the HpyAV DNA recognition sequence and cleavage site as CCTTC 6/5. In addition, we found that HpyAV has a unique metal ion requirement: its cleavage activity is higher with transition metal ions than in Mg(++. The special metal ion requirement of HpyAV can be attributed to the presence of a HNH catalytic site similar to ColE9 nuclease instead of the canonical PD-X-D/EXK catalytic site found in many other REases. Site-directed mutagenesis was carried out to verify the catalytic residues of HpyAV. Mutation of the conserved metal-binding Asn311 and His320 to alanine eliminated cleavage activity. HpyAV variant H295A displayed approximately 1% of wt activity. CONCLUSIONS/SIGNIFICANCE: Some HNH-type endonucleases have unique metal ion cofactor requirement for optimal activities. Homology modeling and site-directed mutagenesis confirmed that HpyAV is a member of the HNH nuclease family. The identification of catalytic residues in HpyAV paved the way for further engineering of the metal binding site. A survey of sequenced microbial genomes uncovered 10 putative R-M systems that show high sequence similarity to the HpyAV system, suggesting lateral transfer of a prototypic HpyAV-like R-M system among these microorganisms.


    Directory of Open Access Journals (Sweden)

    Endang Sri P Ningsih


    Full Text Available Introduction: Nonadherence is a rampant problem among patients undergoing dialysis and can impact multiple aspects of patient care, including medications, and treatment regimens as well as dietary and fluid restriction. The purpose of this descriptive correlative research, on hemodyalysa patient with chronic renal failure was to know the influencing factors of compliance patient to fluid restriction. Method: This study used descriptive correlative design, Data was analysed by using distibution frequency and chi square for analysys relation between variable. Result: The result revealed there were nor significant statistic difference at p > 0.05 between age, gender, education level, frequency of hemodyalysa and health education from nurse to compliance patient to fluid restriction (p = 0.647; p = 0.717; p = 0.345; p = 0.774; p = 0.273. Discussion: Level of patient adherence to therapy not influenced by demographi factor but by the quality of interaction health workers and other factors. This study recommended for further analysis of the factors that influence the level of compliance of the patient as psychological factors (belieft , motivation, socio-economic, and social support.

  11. Left ventricular dimensions, systolic functions, and mass in term neonates with symmetric and asymmetric intrauterine growth restriction. (United States)

    Cinar, Bahar; Sert, Ahmet; Gokmen, Zeynel; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun


    Previous studies have demonstrated structural changes in the heart and cardiac dysfunction in foetuses with intrauterine growth restriction. There are no available data that evaluated left ventricular dimensions and mass in neonates with symmetric and asymmetric intrauterine growth restriction. Therefore, we aimed to evaluate left ventricular dimensions, systolic functions, and mass in neonates with symmetric and asymmetric intrauterine growth restriction. We also assessed associated maternal risk factors, and compared results with healthy appropriate for gestational age neonates. In all, 62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine growth restriction neonates, and 50 healthy appropriate for gestational age neonates were evaluated by transthoracic echocardiography. The asymmetric intrauterine growth restriction group had significantly lower left ventricular end-systolic and end-diastolic diameters and posterior wall diameter in systole and diastole than the control group. The symmetric intrauterine growth restriction group had significantly lower left ventricular end-diastolic diameter than the control group. All left ventricular dimensions were lower in the asymmetric intrauterine growth restriction neonates compared with symmetric intrauterine growth restriction neonates (p>0.05), but not statistically significant except left ventricular posterior wall diameter in diastole (3.08±0.83 mm versus 3.54 ±0.72 mm) (pintrauterine growth restriction groups had significantly lower relative posterior wall thickness (0.54±0.19 versus 0.48±0.13 versus 0.8±0.12), left ventricular mass (9.8±4.3 g versus 8.9±3.4 g versus 22.2±5.7 g), and left ventricular mass index (63.6±29.1 g/m2 versus 54.5±24.4 g/m2 versus 109±28.8 g/m2) when compared with the control group. Our study has demonstrated that although neonates with both symmetric and asymmetric intrauterine growth restriction had lower left ventricular dimensions, relative

  12. Molecular mechanisms of intrauterine growth restriction. (United States)

    Gurugubelli Krishna, Rao; Vishnu Bhat, B


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

  13. Intrauterine Growth Restriction: Hungry for an Answer (United States)

    Chu, Alison


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

  14. Estimation of fluctuation in restricted energy loss

    International Nuclear Information System (INIS)

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


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

  15. Restriction-modification systems in Mycoplasma spp

    Directory of Open Access Journals (Sweden)

    Marcelo Brocchi


    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.

  16. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep


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

  17. [Sodium restriction during pregnancy: an outdated advice]. (United States)

    de Leeuw, P W; Peeters, L L


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

  18. An ontology for major histocompatibility restriction. (United States)

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


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

  19. Calorie Restriction, Stem Cells, and Rejuvenation Approach

    Directory of Open Access Journals (Sweden)

    Taufiqurrachman Nasihun


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

  20. Calorie restriction in rodents: Caveats to consider. (United States)

    Ingram, Donald K; de Cabo, Rafael


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

  1. Effect on Caries of Restricting Sugars Intake (United States)

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


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

  2. Origins and Consequences of Religious Restrictions: A Global Overview (United States)

    Finke, Roger


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

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

    DEFF Research Database (Denmark)

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


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

  4. Reshuffling and Relocating: The Gendered and Income-Related Differential Effects of Restricting Smoking Locations

    Directory of Open Access Journals (Sweden)

    Natalie Hemsing


    Full Text Available This study investigates secondhand smoke (SHS exposure and management in the context of smoking location restrictions, for nonsmokers, former, and current smokers. A purposive sample of 47 low income and non-low-income men and women of varied smoking statuses was recruited to participate in a telephone interview or a focus group. Amidst general approval of increased restrictions there were gendered patterns of SHS exposure and management, and effects of SHS policies that reflect power, control, and social roles that need to be considered as policies are developed, implemented and monitored. The experience of smoking restrictions and the management of SHS is influenced by the social context (relationship with a partner, family member, or stranger, the space of exposure (public or private, worksite, the social location of individuals involved (gender, income, and differential tolerance to SHS. This confluence of factors creates differing unintended and unexpected consequences to the social and physical situations of male and female smokers, nonsmokers, and former smokers. These factors deserve further study, in the interests of informing the development of future interventions and policies restricting SHS.

  5. Consequences in Infants That Were Intrauterine Growth Restricted

    Directory of Open Access Journals (Sweden)

    Erich Cosmi


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

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

    Directory of Open Access Journals (Sweden)

    Ashraf A. Foda


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

  7. Restricted mass energy absorption coefficients for use in dosimetry

    International Nuclear Information System (INIS)

    Brahme, A.


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

  8. 33 CFR 106.265 - Security measures for restricted areas. (United States)


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

  9. Attitudes toward smoking restrictions in work sites, restaurants, and bars among North Carolinians. (United States)

    Maguire, Rachel Loflin; Brinkley, Jason; Mansfield, Christopher


    Public support for smoking restrictions has increased in recent years, but support varies among groups and according to where restrictions should apply. National studies show that Americans are less likely to favor smoking restrictions in restaurants and bars than at other work sites but that the support varies across segments of the population. A full examination of the changes and status of attitudes toward smoking restrictions by site and across subgroups in North Carolina has not been undertaken. Data from US Census Bureau Current Population Surveys conducted during 2001-2002 and 2006-2007 were analyzed. Trends in attitudes toward smoke-free policies at indoor work sites, restaurants, and bars are presented overall and by occupation, smoking status, income, race/ethnicity, workplace smoking policy, age, sex, and education. Logistic regression was used to identify key factors predicting support for smoke-free policies at work sites. Support for smoke-free policies increased by at least 7.4 percentage points at each venue between 2001-2002 and 2006-2007. In 2006-2007, the strongest public support for smoking restrictions was reported for work sites (69.6%), followed by restaurants (52.3%) and bars (36.1%). Whether a person smokes is the strongest predictor of their attitude about smoking restrictions in indoor work sites. Data are self-reported, from independent samples, and lack county identifiers. There is substantial and increasing public support for smoke-free policies in North Carolina. These findings show extensive support for extending smoking bans to all indoor work sites, with nearly 70% of respondents in 2006-2007 favoring smoke-free work sites.

  10. Determinants of participation restriction among community dwelling stroke survivors: A path analysis

    Directory of Open Access Journals (Sweden)

    Chang Anne M


    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.

  11. Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction. (United States)

    Sanchez-Roman, Ines; Barja, Gustavo


    Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Effects of house type and early feed restriction on performance and fat deposition in unsexed broilers

    Directory of Open Access Journals (Sweden)

    U Santoso


    Full Text Available The present experiment was conducted to evaluate the effects of house type and early feed restriction on performance and fat deposition of unsexed broilers. Four hundreds seven-day old unsexed broilers (Arbor Acres CP 707 were distributed into eight treatment groups. Each treatment group was represented by five replicates of ten broilers each. Two types of house (cage vs litter and four levels of feeding (ad lib., 75% ad lib., 50% ad lib. and 25% ad lib. were tested as treatment factors. Broilers were feed-restricted for 6 days from 7 to 13 days of age and thereafter they were fed ad lib. Feed intake of restricted broilers during restriction period was calculated from feed consumed by ad lib. group in the previous day. Results showed that unsexed broilers raised in litter had higher body weight (P<0.05, lower abdominal fat and higher triglyceride concentration at 42 days of age (P<0.05, and lower liver fat and higher carcass percentage at 56 days of age (P<0.05. Early feed restriction reduced body weight of 42-day old unsexed broilers except for broilers fed 75% ad lib. At 56 days of age, restricted broilers had similar body weight to those fed ad lib. At 56 days of age, broilers fed 25% ad lib. had lower FCR (P<0.05, lower abdominal fat (P<0.05 and lower triglyceride concentration (P<0,05. In conclusion, unsexed broilers fed 25% ad lib. showed compensatory growth with better FCR and lower fat accumulation at 56 days of age. Broilers raised in litter had higher body weight and lower abdominal and liver fat deposition.

  13. Ferritin and body mass index predict cardiac dysfunction in female adolescents with anorexia of the restrictive type. (United States)

    Docx, Martine K F; Weyler, Joost; Simons, Annik; Ramet, José; Mertens, Luc


    Decreased left ventricular mass index in anorexia nervosa is amply reported. The aim of this study is to identify non-burdensome predictors of reduced left yentricular mass/height (cLVM) in a cohort of adolescent restrictive anorexic girls. This is a retrospective study of all anorexic girls of the restrictive type referred to our tertiary eating disorder unit between September 2002 and December 2012, for somatic assessment of weig ht loss. All subjects fulfilled DMS-IV criteria, without a family history of cardiac or cardiovascular diseases. In all, 283 restrictive anorexic girls (age: 14.63 +/- 1.65 y; body mass index: 15.72 +/- 1.81 kg/m2) were included. Ferritin and body mass index were independent, statistically significant predictors of the corrected left ventricular mass (P anorexia nervosa of the restrictive type. Two factors predicted decreased cLVM in our population: ferritin and BMI.

  14. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

    International Nuclear Information System (INIS)

    Diaz-Griffero, Felipe; Vandegraaff, Nick; Li Yuan; McGee-Estrada, Kathleen; Stremlau, Matthew; Welikala, Sohanya; Si Zhihai; Engelman, Alan; Sodroski, Joseph


    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. Niche restriction and conservatism in a neotropical psittacine: the case of the Puerto Rican parrot (United States)

    White, Thomas H.; Collazo, Jaime A.; Dinsmore, Stephen J.; Llerandi-Roman, I. C.


    The factors which govern species‘ distribution and abundance are myriad, and together constitute the ecological niche of a given species. Because abiotic factors are arguably the most profound of the factors influencing niche boundaries and thus, species distributions, substantial changes in either climatic or habitat-related parameters can be expected to produce interrelated and profound niche shifts. Habitat loss and degradation can also effectively induce a de facto climate change by forcing populations to relocate to environmentally suboptimal habitats. Populations experiencing niche shifts due to range restrictions and geographic isolation become subject to a suite of factors that may act synergistically to amplify deleterious ecological effects of habitat loss. These factors tend to exert a greater influence on populations of rare or endemic species with inherently restricted ranges. The Puerto Rican parrot (Amazona vittata) is an example of a tropical, insular, endemic and critically-endangered species that has suffered from extensive habitat loss and degradation over the past century, resulting in a single relict wild population restricted for more than 70 years to the montane rainforest of the Luquillo Mountains in northeastern Puerto Rico. In this chapter, we examine the current ecological situation of this geographically and demographically isolated parrot population by reviewing the history of landscape-level changes in and around the Luquillo Mountains, and concurrent biotic and abiotic limiting factors in relation to both historical population trajectory and current prognosis for species recovery. We used a decade (2000-2009) of empirical data on parrot fledgling survival together with long-term climatological data to model effects of local climate on fledgling survival and gain insights into its influence on population growth. We also modeled hypothetical survival of parrot fledglings in the lowlands surrounding the Luquillo Mountains, areas

  16. Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats. (United States)

    Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D


    Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    African Journals Online (AJOL)

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

  18. Acute sleep restriction reduces insulin sensitivity in adolescent boys

    DEFF Research Database (Denmark)

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


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

  19. 30 CFR 57.4461 - Gasoline use restrictions underground. (United States)


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

  20. 32 CFR 1903.16 - Restriction on animals. (United States)


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

  1. 32 CFR 234.12 - Restriction on animals. (United States)


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

  2. 32 CFR 228.15 - Restriction regarding animals. (United States)


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

  3. 25 CFR 141.14 - Trade in livestock restricted. (United States)


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

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

    DEFF Research Database (Denmark)

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


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

  5. Cardiovascular adaptation to extrauterine life after intrauterine growth restriction. (United States)

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


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

  6. Consequences of intrauterine growth restriction for the kidney

    NARCIS (Netherlands)

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


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

  7. 49 CFR 236.813a - State, most restrictive. (United States)


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

  8. ECO-generation for some restricted classes of compositions

    Directory of Open Access Journals (Sweden)

    Jean-Luc Baril


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

  9. 30 CFR 77.1502 - Auger holes; restriction against entering. (United States)


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

  10. Synthesis of conformationally restricted beta-turn mimics

    NARCIS (Netherlands)

    IJsselstijn, M.


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

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

    NARCIS (Netherlands)

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

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

  12. 7 CFR 301.92 - Restrictions on interstate movement. (United States)


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

  13. Growth throughout childhood of children born growth restricted

    NARCIS (Netherlands)

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


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

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

    African Journals Online (AJOL)



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

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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


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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  19. 75 FR 11620 - Waiver of Restriction on Assistance to Cambodia (United States)


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

  20. 48 CFR 1403.570 - Restrictions on contractor advertising. (United States)


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

  1. 12 CFR 615.5462 - Restrictive endorsement of bearer securities. (United States)


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

  2. 9 CFR 590.800 - Identification of restricted eggs. (United States)


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

  3. 50 CFR 635.21 - Gear operation and deployment restrictions. (United States)


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

  4. 50 CFR 665.127 - Allowable gear and gear restrictions. (United States)


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

  5. 50 CFR 665.627 - Allowable gear and gear restrictions. (United States)


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

  6. 50 CFR 665.227 - Allowable gear and gear restrictions. (United States)


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

  7. 50 CFR 640.22 - Gear and diving restrictions. (United States)


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

  8. 50 CFR 665.427 - Allowable gear and gear restrictions. (United States)


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

  9. 37 CFR 1.144 - Petition from requirement for restriction. (United States)


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

  10. 37 CFR 1.142 - Requirement for restriction. (United States)


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

  11. 21 CFR 1314.20 - Restrictions on sales quantity. (United States)


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

  12. Electricity system planning under the CO2 emission restriction

    International Nuclear Information System (INIS)

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


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

  13. [Restrictions for ICD patients in daily life]. (United States)

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


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

  14. Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring. (United States)

    Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K


    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. © The Author(s) 2014.

  15. Role of uteroplacental and fetal Doppler in identifying fetal growth restriction at term.


    Khalil, A; Thilaganathan, B


    Identification of the fetus at risk of adverse outcome at term is a challenge to both clinicians and researchers alike. Despite the fact that fetal growth restriction (FGR) is a known risk factor for stillbirth, at least two thirds of the stillbirth cases at term are not small for gestational age (SGA) - a commonly used proxy for FGR. However, the majority of SGA fetuses are constitutionally small babies and do not suffer from adverse perinatal outcome. The cerebroplacental ratio (CPR) is eme...

  16. The Acquisition of English Restrictive Relative Clauses by Arab Adult EFL Learners


    Hayat Eid Alroudhan


    This study investigates the challenges faced by Arab adult learners of English as a foreign language (EFL) in acquiring English restrictive relative clauses (RRCs), as well as the factors that affect the process of acquisition. This issue has received considerable attention in second language (L2) research. The present study discusses the syntactic structure of RRCs in English and Arabic with regard to the use of resumptive pronouns and the use of overt versus covert relative markers as relat...

  17. Restrictions in Availability of Drugs Used for Suicide

    DEFF Research Database (Denmark)

    Nordentoft, Merete


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

  18. Impact of intrauterine growth restriction on preterm lung disease. (United States)

    Sasi, Arun; Abraham, Vinita; Davies-Tuck, Miranda; Polglase, Graeme R; Jenkin, Graham; Miller, Suzanne L; Malhotra, Atul


    Intrauterine growth restriction (IUGR) is an important cause for prematurity and adversely influences prematurity-related morbidities. This study evaluates the impact of IUGR on respiratory outcomes in infants CLD), CLD or death, and need for home oxygen at discharge. Subgroup analysis by gestation-based stratification (CLD (45% vs. 17%, p = 0.0001), death (16% vs. 4.6%, p = 0.0001), CLD or death (46% vs. 21.5%, p = 0.0001), home oxygen rates (13.7% vs. 6.5%, p = 0.01) and duration of respiratory support was significantly higher in the IUGR group. IUGR emerged as the strongest predictor of CLD (adjusted OR, 95%CI: (8.4 [2, 35]) and CLD or death (12.7 [3, 54]) across all gestation. IUGR is a major risk factor for adverse short-term pulmonary outcomes as reflected by higher rates of CLD, CLD or death, and oxygen dependency at discharge in preterm infants. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. 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.

  20. Insurance loss coverage under restricted risk classification


    Hao, Mingjie; Radfall Charitable Trust


    Insurers hope to make profit through pooling policies from a large number of individuals. Unless the risk in question is similar for all potential customers, an insurer is exposed to the possibility of adverse selection by attracting only high-risk individuals. To counter this, insurers have traditionally employed underwriting principles, identifying suitable risk factors to subdivide their potential customers into homogeneous risk groups, based on which risk-related premiums can be charged. ...

  1. Does SIRT-1 Mediate Calorie Restriction and Prolong Life? – A Mini Review

    Directory of Open Access Journals (Sweden)

    Kordala Anna


    Full Text Available Calorie restriction is the only intervention proved to prolong both average and maximum lifespan in yeast, worms, fish, rodents and possibly primates. Not only does the regimen prolong life, but it also reduces the incident of numerous age-related diseases like diabetes, atherosclerosis or cancer and slows down ageing. Mechanisms by which that is thought to occur have not yet been elucidated, but they probably involve reactive oxygen species signaling, insulin growth factor and transcriptional factors. Here, special emphasis is given to SIRT1 - silent information regulator. There is sound evidence showing that SIRT1 is a key player in mediating physiological response to calorie restriction and that its overexpression is correlated with extended lifespan. The possible mechanism leading to its elevated levels is high NAD/NADH ratio, observed in Sir2 in yeast. SIRT1 increases glucose production, enhances fat mobilization, stimulates angiogenesis, prevents neuronal degeneration and rises insulin sensitivity. Therefore, it seems to be a very beneficial factor activated by such a simple intervention that is calorie restriction.

  2. The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells (United States)

    Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester


    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

  3. 7 CFR 57.905 - Importation of restricted eggs or eggs containing more restricted eggs than permitted in the... (United States)


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

  4. 9 CFR 590.905 - Importation of restricted eggs or eggs containing more restricted eggs than permitted in the... (United States)


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

  5. Appetite Regulatory Hormones in Women With Anorexia Nervosa: Binge-Eating/Purging Versus Restricting Type (United States)

    Eddy, Kamryn T.; Lawson, Elizabeth A.; Meade, Christina; Meenaghan, Erinne; Horton, Sarah E.; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.


    Objective Anorexia nervosa is a psychiatric illness characterized by low weight, disordered eating, and hallmark neuroendocrine dysfunction. Behavioral phenotypes are defined by predominant restriction or bingeing/purging; binge-eating/purging type anorexia nervosa is associated with poorer outcome. The pathophysiology underlying anorexia nervosa types is unknown, but altered hormones, known to be involved in eating behaviors, may play a role. Method To examine the role of anorexigenic hormones in anorexia nervosa subtypes, we examined serum levels of peptide YY (PYY; total and active [3-36] forms), brain-derived neurotrophic factor (BDNF), and leptin as primary outcomes in women with OSM-5 restricting type anorexia nervosa (n=50), binge-eating/purging type anorexia nervosa (n = 22), and healthy controls (n = 22).1n addition, women completed validated secondary outcome measures of eating disorder psychopathology (Eating Disorder Examination-Questionnaire) and depression and anxiety symptoms (Hamilton Rating Scales for Depression [HDRS] and Anxiety [HARS]). The study samples were collected from May 22, 2004, to February 7, 2012. Results Mean PYY 3-36 and leptin levels were lower and BDNF levels higher in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa (all Pvalues anorexia nervosa types were significant (Panorexia nervosa, the anorexigenic hormones PYY, BDNF, and leptin are differentially regulated between the restricting and binge/purge types. Whether these hormone pathways play etiologic roles with regard to anorexia nervosa behavioral types or are compensatory merits further study. PMID:25098834

  6. Identification of genes differentially expressed by calorie restriction in the rotifer (Brachionus plicatilis). (United States)

    Oo, Aung Kyaw Swar; Kaneko, Gen; Hirayama, Makoto; Kinoshita, Shigeharu; Watabe, Shugo


    A monogonont rotifer Brachionus plicatilis has been widely used as a model organism for physiological, ecological studies and for ecotoxicology. Because of the availability of parthenogenetic mode of reproduction as well as its versatility to be used as live food in aquaculture, the population dynamic studies using the rotifer have become more important and acquired the priority over those using other species. Although many studies have been conducted to identify environmental factors that influence rotifer populations, the molecular mechanisms involved still remain to be elucidated. In this study, gene(s) differentially expressed by calorie restriction in the rotifer was analyzed, where a calorie-restricted group was fed 3 h day(-1) and a well-fed group fed ad libitum. A subtracted cDNA library from the calorie-restricted rotifer was constructed using suppression subtractive hybridization (SSH). One hundred sixty-three expressed sequence tags (ESTs) were identified, which included 109 putative genes with a high identity to known genes in the publicly available database as well as 54 unknown ESTs. After assembling, a total of 38 different genes were obtained among 109 ESTs. Further validation of expression by semi-quantitative reverse transcription-PCR showed that 29 out of the 38 genes obtained by SSH were up regulated by calorie restriction.

  7. Do driving restriction policies effectively motivate commuters to use public transportation?

    International Nuclear Information System (INIS)

    Liu, Yunxia; Hong, Zaisheng; Liu, Yong


    Driving restriction policies have been implemented in some large Chinese cities to cope with severe urban smog pollution. We explored the roles of policy acceptance and other factors in commuters' transport mode decisions, based on the Theory of Planned Behavior. A questionnaire survey was conducted in Tianjin, China. A structural equation model was developed to test eight hypotheses, two of which were rejected. The results indicate that a driving restriction policy alone cannot effectively motivate commuters to use public transport if the policymakers fail to improve public transport, enhance commuters' awareness of consequences, increase commuters' perceived behavior control, and encourage car owners to change driving behavior. Comparisons between car owners and non-owners indicated that car owners view driving restriction policy and public transport more negatively. These negative views could be a barrier for the promotion of public transport among car owners. In addition, attitude toward public transport was found to have positive correlation with commuting time. - Highlights: • Attitude towards public transport has an impact on policy acceptance. • Driving habit indirectly affects policy acceptance and perceived behavior control. • Driving restriction policy and public transport are not popular among car owners. • Attitude towards public transport correlates positively with commuting time.

  8. Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

    International Nuclear Information System (INIS)

    Tie Zuo-Xiu; Qin Meng; Zou Da-Wei; Cao Yi; Wang Wei


    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. (cross-disciplinary physics and related areas of science and technology)

  9. Photo-crosslinking induced geometric restriction controls the self-assembly of diphenylalanine based peptides

    International Nuclear Information System (INIS)

    Tie Zuoxiu; Qin Meng; Zou Dawei; Cao Yi; Wang Wei


    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. (authors)

  10. Quantitative Analysis Method of Output Loss due to Restriction for Grid-connected PV Systems (United States)

    Ueda, Yuzuru; Oozeki, Takashi; Kurokawa, Kosuke; Itou, Takamitsu; Kitamura, Kiyoyuki; Miyamoto, Yusuke; Yokota, Masaharu; Sugihara, Hiroyuki

    Voltage of power distribution line will be increased due to reverse power flow from grid-connected PV systems. In the case of high density grid connection, amount of voltage increasing will be higher than the stand-alone grid connection system. To prevent the over voltage of power distribution line, PV system's output will be restricted if the voltage of power distribution line is close to the upper limit of the control range. Because of this interaction, amount of output loss will be larger in high density case. This research developed a quantitative analysis method for PV systems output and losses to clarify the behavior of grid connected PV systems. All the measured data are classified into the loss factors using 1 minute average of 1 second data instead of typical 1 hour average. Operation point on the I-V curve is estimated to quantify the loss due to the output restriction using module temperature, array output voltage, array output current and solar irradiance. As a result, loss due to output restriction is successfully quantified and behavior of output restriction is clarified.

  11. Protein restriction does not affect body temperature pattern in female mice. (United States)

    Kato, Goro A; Shichijo, Hiroki; Takahashi, Toshihiro; Shinohara, Akio; Morita, Tetsuo; Koshimoto, Chihiro


    Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.

  12. Effect of dietary protein restriction on renal ammonia metabolism (United States)

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


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

  13. Life on Mars? II. Physical restrictions (United States)

    Mancinelli, R. L.; Banin, A.


    The primary physical factors important to life's evolution on a planet include its temperature, pressure and radiation regimes. Temperature and pressure regulate the presence and duration of liquid water on the surface of Mars. The prolonged presence of liquid water is essential for the evolution and sustained presence of life on a planet. It has been postulated that Mars has always been a cold dry planet; it has also been postulated that early mars possessed a dense atmosphere of CO2 (> or = 1 bar) and sufficient water to cut large channels across its surface. The degree to which either of these postulates is true correlates with the suitability of Mars for life's evolution. Although radiation can destroy living systems, the high fluxes of UV radiation on the martian surface do not necessarily stop the origin and early evolution of life. The probability for life to have arisen and evolved to a significant degree on Mars, based on the postulated ranges of early martian physical factors, is almost solely related to the probability of liquid water existing on the planet for at least hundreds of millions to billions of years.

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

    Directory of Open Access Journals (Sweden)

    Joshua M Epstein


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

  15. Predicting support for restricting food marketing to youth. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. Company Law as a Restriction to Free Movement

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig


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

  18. p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development. (United States)

    Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro


    Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

  19. Feeding period restriction alters the expression of peripheral circadian rhythm genes without changing body weight in mice.

    Directory of Open Access Journals (Sweden)

    Hagoon Jang

    Full Text Available Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD or a high-fat diet (HFD. In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.

  20. New Economic Geography: the Possibilities and Restrictions

    Directory of Open Access Journals (Sweden)

    Dmitry Alexandrovich Izotov


    Full Text Available The article analyzes scientific publications on the new economic geography (NEG relevance. On the basis of the publications array the author determined characteristic features of the simulation and the central idea of this research direction. Analysis showed that modeling in the terms of NEG is based on the approach of general equilibrium under monopolistic competition, endogenous factors and homogeneous space. The NEG central idea can be presented as follows: the increasing economy of scale is the main force for factors migration in homogeneous space. The theoretical studies analysis revealed that the development of NEG models is carried out by consideration of different options for the migration behavior of the agglomeration subjects and inclusion of theoretical constructs from adjacent areas, in particular, new economic growth theory and urban economics models. The article shows that empirical papers mainly test the NEG provisions in the terms of the model “core- periphery”. The extremely rare cases of testing other NEG models are apparently due to the absence of statistical data; the difficulty of obtaining reliable estimates of the elasticity of substitution of goods by different countries, regions and cities. Systematization of the scientific community criticism has allowed identifying the main problems of NEG: identification in the system of socio- economic researches, spatial characteristics ignoring, research object limitations, simplicity of the backgrounds, problems with empirical evidence. Further NEG development, according to experts, depends on obtaining of its specific place in the system of socio-economic researches or NEG may remain as one of the modeling approaches in the general equilibrium framework