Heat Increases the Editing Efficiency of Human Papillomavirus E2 Gene by Inducing Upregulation of APOBEC3A and 3G.

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

2017-04-01

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.

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

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

2014-01-01

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

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

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David J Stanley

2012-12-01

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

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

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Terumasa Ikeda

2018-04-01

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.

Inhibition of APOBEC3G Activity Impedes Double-Strand DNA Repair

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

2015-01-01

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

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

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Yuqing eFeng

2014-08-01

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.

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

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

2009-02-05

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.

Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

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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: kykangyi@163.com [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China)

2016-01-29

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.

Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

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

2016-01-01

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.

Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G.

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

2005-07-01

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.

Insights into the motif preference of APOBEC3 enzymes.

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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.

HBV/HIV co-infection and APOBEC3G polymorphisms in a population from Burkina Faso.

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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

2016-07-22

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.

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

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

2016-05-01

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

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

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

2014-07-29

Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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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.

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

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

2011-01-01

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.

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

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Monajemi Mahdis

2012-04-01

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.

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

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Cristina J Wittkopp

2016-10-01

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.

Multifaceted counter-APOBEC3G mechanisms employed by HIV-1 Vif.

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

2011-07-29

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.

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.

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

2003-11-07

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.

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

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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.

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

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Lucie Etienne

2015-09-01

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.

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

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Luis Apolonia

2015-01-01

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

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

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Wong Joseph K

2008-03-01

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.

A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

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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

2016-01-01

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

APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.

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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

2017-09-06

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.

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

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2012-01-01

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

APOBEC3 Interference during Replication of Viral Genomes

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Luc Willems

2015-06-01

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

Ubiquitin-fusion as a strategy to modulate protein half-life: A3G antiviral activity revisited

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Cadima-Couto, Iris; Freitas-Vieira, Acilino; Nowarski, Roni; Britan-Rosich, Elena; Kotler, Moshe; Goncalves, Joao

2009-01-01

The human APOBEC3G (A3G) is a potent inhibitor of HIV-1 replication and its activity is suppressed by HIV-1 virion infectivity factor (Vif). Vif neutralizes A3G mainly by inducing its degradation in the proteasome and blocking its incorporation into HIV-1 virions. Assessing the time needed for A3G incorporation into virions is, therefore, important to determine how quickly Vif must act to induce its degradation. We show that modelling the intracellular half-life of A3G can induce its Vif-independent targeting to the ubiquitin-proteasome system. By using various amino acids (X) in a cleavable ubiquitin-X-A3G fusion, we demonstrate that the half-life (t1/2) of X-A3G can be manipulated. We show that A3G molecules with a half-life of 13 min are incorporated into virions, whereas those with a half-life shorter than 5 min were not. The amount of X-A3G incorporated into virions increases from 13 min (Phe-A3G) to 85 min (Asn-A3G) and remains constant after this time period. Interestingly, despite the presence of similar levels of Arg-A3G (t1/2 = 28 min) and Asp-A3G (t1/2 = 65 min) into HIV-1 Δvif virions, inhibition of viral infectivity was only evident in the presence of A3G proteins with a longer half-life (t1/2 ≥ 65 min).

Effect of apolipoprotein B mRNA-editing catalytic polypeptide-like protein-3G in cervical cancer.

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Xu, Yanhua; Leng, Junhong; Xue, Fang; Dong, Ruiqian

2015-01-01

Cervical cancer is one of the most common gynecologic cancers. The role of apolipoprotein B mRNA-editing catalytic polypeptide-like protein-3G (APCBEC-3G) in cervical cancer has yet to be elucidated. This study intends to explore the effect of APCBEC-3G on cervical cancer cell proliferation and invasion. In vitro, the cervical cancer cell line Hela was transfected by APCBEC-3G plasmid. The mRNA and protein expression levels of APCBEC-3G were detected by Real-time PCR and Western blot, respectively. Cervical cancer cell proliferation was determined by MTT. Transwell assay was applied to measure the effect of APCBEC-3G on cell invasion. APCBEC-3G mRNA and protein increased significantly after transfection (P3G serves as a suppressor of cervical cancer cell proliferation and invasion. Our research provides theoretical basis for further investigation APOBEC-3G effect in cervical cancer occurrence and development.

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

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

2016-01-01

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...

Host apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G is an innate defensive factor and drug target against hepatitis C virus.

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Peng, Zong-Gen; Zhao, Zhi-Yun; Li, Yan-Ping; Wang, Yu-Ping; Hao, Lan-Hu; Fan, Bo; Li, Yu-Huan; Wang, Yue-Ming; Shan, Yong-Qiang; Han, Yan-Xing; Zhu, Yan-Ping; Li, Jian-Rui; You, Xue-Fu; Li, Zhuo-Rong; Jiang, Jian-Dong

2011-04-01

Host cellular factor apolipoprotein B messenger RNA (mRNA)-editing enzyme catalytic polypeptide-like 3G (hA3G) is a cytidine deaminase that inhibits a group of viruses including human immunodeficiency virus-1 (HIV-1). In the continuation of our research on hA3G, we found that hA3G stabilizing compounds significantly inhibited hepatitis C virus (HCV) replication. Therefore, this study investigated the role of hA3G in HCV replication. Introduction of external hA3G into HCV-infected Huh7.5 human hepatocytes inhibited HCV replication; knockdown of endogenous hA3G enhanced HCV replication. Exogenous HIV-1 virion infectivity factor (Vif) decreased intracellular hA3G and therefore enhanced HCV proliferation, suggesting that the presence of Vif might be an explanation for the HIV-1/HCV coinfection often observed in HIV-1(+) individuals. Treatment of the HCV-infected Huh7.5 cells with RN-5 or IMB-26, two known hA3G stabilizing compounds, increased intracellular hA3G and accordingly inhibited HCV replication. The compounds inhibit HCV through increasing the level of hA3G incorporated into HCV particles, but not through inhibiting HCV enzymes. However, G/A hypermutation in the HCV genome were not detected, suggesting a new antiviral mechanism of hA3G in HCV, different from that in HIV-1. Stabilization of hA3G by RN-5 was safe in vivo. hA3G appears to be a cellular restrict factor against HCV and could be a potential target for drug discovery. 2011 American Association for the Study of Liver Diseases.

Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity

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Strebel Klaus

2007-08-01

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

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

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Nowarski, Roni; Kotler, Moshe

2013-06-15

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

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

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

2016-01-01

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.

Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

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H. M. N. Iqbal

2015-09-01

Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

Natural resistance to HIV infection: The Vif-APOBEC interaction.

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Malim, Michael H

2006-11-01

Members of the APOBEC family of cellular polynucleotide cytidine deaminases (e.g., APOBEC3G) are potent inhibitors of HIV infection. Wild type viral infections are largely spared from APOBEC function through the action of the viral Vif protein. In Vif's absence, inhibitory APOBEC proteins are encapsidated by budding virus particles leading to excessive cytidine (C) to uridine (U) hypermutation of negative sense reverse transcripts in newly infected cells. This registers as guanosine (G) to adenosine (A) mutations in plus stranded cDNA. Because the functions of Vif and APOBEC proteins oppose each other, it is likely that fluctuations in the Vif/APOBEC balance can influence the natural history of HIV infection. Experimental support for this notion would further justify and stimulate drug discovery initiatives in this area.

An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G.

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Ejima, Tomohiko; Hirota, Mayuko; Mizukami, Tamio; Otsuka, Masami; Fujita, Mikako

2011-10-01

Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 µM SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 µM SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

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

2017-06-01

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

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

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Zeli Zhang

2018-04-01

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.

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

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

2018-01-01

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

Structural characterization of the Man5 glycoform of human IgG3 Fc

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Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan; Battaile, Kevin P.; Tolbert, Thomas J. (Kansas); (HWMRI)

2017-12-01

Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined the crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.

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

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Christopher Richards

2015-12-01

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

Serological blind spots for variants of human IgG3 and IgG4 by a commonly used anti-immunoglobulin reagent.

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Howie, Heather L; Delaney, Meghan; Wang, Xiaohong; Er, Lay See; Vidarsson, Gestur; Stegmann, Tamara C; Kapp, Linda; Lebedev, Jenna N; Wu, Yanyun; AuBuchon, James P; Zimring, James C

2016-12-01

Human immunoglobulin G (IgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4), and it is also now appreciated that there are genetic variations within IgG subtypes (called isoallotypes). Twenty-nine different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1, IgG2, IgG3, and IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized. A novel monoclonal anti-K antibody (PugetSound Monoclonal Antibody 1 [PUMA1]) was isolated and sequenced, and a panel of PUMA1 variants was expressed, consisting of the 29 known IgG isoallotypes. The resulting panel of antibodies was preincubated with K-positive red blood cells (RBCs) and then subjected to testing with currently approved anti-IgG by flow cytometry, solid phase systems, gel cards, and tube testing. A US Food and Drug Administration (FDA)-approved monoclonal anti-IgG (gamma-clone) failed to recognize 2 of 15 IgG3 isoallotypes (IgG3-03 and IgG3-13) and 3 of 3 IgG4 isoallotypes (IgG4-01, IgG4-02, and IgG4-03). In contrast, an FDA-approved rabbit polyclonal anti-IgG recognized each of the known human IgG isoallotypes. These findings demonstrate "blind spots" in isoalloantibody detection by a monoclonal anti-IgG. If a patient has anti-RBC antibodies predominantly of an IgG3 subtype (the IgG3-03 and/or IgG3-13 variety), then it is possible that a clinically significant alloantibody would be missed. IgG-03 and IgG-13 have an estimated frequency of 1% to 3% in Caucasian populations and 20% to 30% in certain African populations. Nonreactivity with IgG4 is a known characteristic of this monoclonal anti-IgG, but IgG4 isoallotypes have not been previously reported. © 2016 AABB.

Mass spectrometry detection of G3m and IGHG3 alleles and follow-up of differential mother and neonate IgG3.

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Célia Dechavanne

Full Text Available Mass spectrometry (MS analysis for detection of immunoglobulins (IG of the human IgG3 subclass is described that relies on polymorphic amino acids of the heavy gamma3 chains. IgG3 is the most polymorphic human IgG subclass with thirteen G3m allotypes located on the constant CH2 and CH3 domains of the gamma3 chain, the combination of which leads to six major G3m alleles. Amino acid changes resulting of extensive sequencing previously led to the definition of 19 IGHG3 alleles that have been correlated to the G3m alleles. As a proof of concept, MS proteotypic peptides were defined which encompass discriminatory amino acids for the identification of the G3m and IGHG3 alleles. Plasma samples originating from ten individuals either homozygous or heterozygous for different G3m alleles, and including one mother and her baby (drawn sequentially from birth to 9 months of age, were analyzed. Total IgG3 were purified using affinity chromatography and then digested by a combination of AspN and trypsin proteases, and peptides of interest were detected by mass spectrometry. The sensitivity of the method was assessed by mixing variable amounts of two plasma samples bearing distinct G3m allotypes. A label-free approach using the high-performance liquid chromatography (HPLC retention time of peptides and their MS mass analyzer peak intensity gave semi-quantitative information. Quantification was realized by selected reaction monitoring (SRM using synthetic peptides as internal standards. The possibility offered by this new methodology to detect and quantify neo-synthesized IgG in newborns will improve knowledge on the first acquisition of antibodies in infants and constitutes a promising diagnostic tool for vertically-transmitted diseases.

Differential evolution of antiretroviral restriction factors in pteropid bats as revealed by APOBEC3 gene complexity.

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

2018-03-29

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.

Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

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

2016-12-01

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

Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage.

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

2017-04-07

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.

Molecular Characterization of Echinococcus granulosus Cysts in North Indian Patients: Identification of G1, G3, G5 and G6 Genotypes

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Sharma, Monika; Sehgal, Rakesh; Fomda, Bashir Ahmad; Malhotra, Anil; Malla, Nancy

2013-01-01

Background Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India. Methodology/Principal Findings To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype. Conclusions/Significance These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis. PMID:23785531

3G Standards

DEFF Research Database (Denmark)

Saugstrup, Dan; Henten, Anders

2006-01-01

Purpose – The main purpose of this paper is to analyze which standard/technology will win the 3G mobile markets. In addition, two sub topics are examined. First, which kind of victory will it be – will one technological solution be all-dominating or is co-existence more likely? Second, which....... Originality/value – The paper is based on the understanding that a vast array of different factors in a complex dynamic environment goes into the determination of the outcome of such standardization games. However, the battle between 3G standards has already reached a level, where relatively certain...... predictions can be made. And, the paper contributes with a methodologically based discussion concerning the outcome of the battle between 3G standards....

Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes.

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Monika Sharma

Full Text Available BACKGROUND: Cystic echinococcosis (CE caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s of the parasite responsible for human hydatidosis in North India. METHODOLOGY/PRINCIPAL FINDINGS: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1 sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32 were found to be infected with hydatid cyst of either G3 (53.1% or G1 (40.62% genotype and one each of G5 (cattle strain and G6 (camel strain genotype. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate the zoonotic potential of G1 (sheep strain and G3 (buffalo strain genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain in an Asian country and presence of G6 genotype (camel strain in India. The results may have important implications in the planning of control strategies for human hydatidosis.

Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions.

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

2018-05-14

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.

Genetic-gonadal-genitals sex (3G-sex) and the misconception of brain and gender, or, why 3G-males and 3G-females have intersex brain and intersex gender.

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Joel, Daphna

2012-12-17

The categorization of individuals as "male" or "female" is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the "female" form at all levels, or the "male" form at all levels). About 1% of the human population is identified as "intersex" because of either having an intermediate form at one or more levels, or having the "male" form at some levels and the "female" form at other levels. These two types of "intersex" reflect the facts, respectively, that the different levels of 3G-sex are not completely dimorphic nor perfectly consistent. Using 3G-sex as a model to understand sex differences in other domains (e.g., brain, behavior) leads to the erroneous assumption that sex differences in these other domains are also highly dimorphic and highly consistent. But parallel lines of research have led to the conclusion that sex differences in the brain and in behavior, cognition, personality, and other gender characteristics are for the most part not dimorphic and not internally consistent (i.e., having one brain/gender characteristic with the "male" form is not a reliable predictor for the form of other brain/gender characteristics). Therefore although only ~1% percent of humans are 3G-"intersex", when it comes to brain and gender, we all have an intersex gender (i.e., an array of masculine and feminine traits) and an intersex brain (a mosaic of "male" and "female" brain characteristics).

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

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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

2016-09-01

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.

Genetic-gonadal-genitals sex (3G-sex and the misconception of brain and gender, or, why 3G-males and 3G-females have intersex brain and intersex gender

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Joel Daphna

2012-12-01

Full Text Available Abstract The categorization of individuals as “male” or “female” is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the “female” form at all levels, or the “male” form at all levels. About 1% of the human population is identified as “intersex” because of either having an intermediate form at one or more levels, or having the “male” form at some levels and the “female” form at other levels. These two types of “intersex” reflect the facts, respectively, that the different levels of 3G-sex are not completely dimorphic nor perfectly consistent. Using 3G-sex as a model to understand sex differences in other domains (e.g., brain, behavior leads to the erroneous assumption that sex differences in these other domains are also highly dimorphic and highly consistent. But parallel lines of research have led to the conclusion that sex differences in the brain and in behavior, cognition, personality, and other gender characteristics are for the most part not dimorphic and not internally consistent (i.e., having one brain/gender characteristic with the “male” form is not a reliable predictor for the form of other brain/gender characteristics. Therefore although only ~1% percent of humans are 3G-“intersex”, when it comes to brain and gender, we all have an intersex gender (i.e., an array of masculine and feminine traits and an intersex brain (a mosaic of “male” and “female” brain characteristics.

The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer.

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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

2016-01-01

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

Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity.

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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

2017-04-28

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.

Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

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Lijuan He

Full Text Available Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

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He, Lijuan; Serrano, Christopher; Niphadkar, Nitish; Shobnam, Nadia; Hristova, Kalina

2012-01-01

Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

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

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

2016-09-15

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.

Irradiated graphite studies prior to decommissioning of G1, G2 and G3 reactors

International Nuclear Information System (INIS)

Bonal, J.P.; Vistoli, J.Ph.; Combes, C.

2005-01-01

G1 (46 MW th ), G2 (250 MW th ) and G3 (250 MW th ) are the first French plutonium production reactors owned by CEA (Commissariat a l'Energie Atomique). They started to be operated in 1956 (G1), 1959 (G2) and 1960 (G3); their final shutdown occurred in 1968, 1980 and 1984 respectively. Each reactor used about 1200 tons of graphite as moderator, moreover in G2 and G3, a 95 tons graphite wall is used to shield the rear side concrete from neutron irradiation. G1 is an air cooled reactor operated at a graphite temperature ranging from 30 C to 230 C; G2 and G3 are CO 2 cooled reactors and during operation the graphite temperature is higher (140 C to 400 C). These reactors are now partly decommissioned, but the graphite stacks are still inside the reactors. The graphite core radioactivity has decreased enough so that a full decommissioning stage may be considered. Conceming this decommissioning, the studies reported here are: (i) stored energy in graphite, (ii) graphite radioactivity measurements, (iii) leaching of radionuclide ( 14 C, 36 Cl, 63 Ni, 60 Co, 3 H) from graphite, (iv) chlorine diffusion through graphite. (authors)

Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies

Directory of Open Access Journals (Sweden)

Myrthe E. Sonneveld

2018-01-01

Full Text Available After albumin, immunoglobulin G (IgG are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγRIIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar.

Analysis on China 3G Development

Institute of Scientific and Technical Information of China (English)

Shen Zixin

2005-01-01

@@ Foreword: Forecast of 3G and 3G Evolution International Market Size According to UMTS forecast, by 2010, global annual 3G income could reach USD 320 billion, while that from Asia-Pacific region will be around USD 118 billion.China's selection of 3G standards will affect all global wireless equipment suppliers, while how to select TD-SCDMA most crucial.

Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside

International Nuclear Information System (INIS)

Hellstroem, I.; Brankovan, V.; Hellstroem, K.E.

1985-01-01

Three mouse monoclonal IgG3 antibodies, 2B2, IF4, and MG-21, recognize a G/sub D3/ ganglioside antigen that is expressed at the cell surface of most human melanomas. All three antibodies mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro when tested with human lymphocytes or effector cells in a 2-hr or 4-hr 51 Cr-release test, and one antibody, MG-21, also gives strong complement-dependent cytotoxicity with human serum. Antibody 2B2, which gives ADDC also in the presence of mouse lymphocytes, inhibited the outgrowth of a human melanoma in nude mice, but antibody IF4, which showed no ADCC with mouse lymphocyte effectors, did not

12 CFR 563g.3 - Exemptions.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Exemptions. 563g.3 Section 563g.3 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.3 Exemptions. The offering circular requirement of § 563g.2 of this part shall not apply to an issuer's offer or...

G2 and G3 reactors design; Description des reacteurs G2 et G3

Energy Technology Data Exchange (ETDEWEB)

Herreng,; Ertaud,; Pasquet, [Societe Alsacienne de Constructions Mecaniques (France)

1958-07-01

'FRANCE ATOME' Manufacturers Party has been entrusted with the G2 and G3 reactors engineering by the french A.E.C., for the first-five-year french project. Although these reactors are essentially plutonium generators, everyone has been linked with a power station which is supposed to supply with 40 MW, 'Electricite de France' has taken the liability upon itself. The reactor core includes most of G1 reactor parts (central gap excluded): horizontal channels, graphite parallelepipedic bricks stacking, steel thermal shield. The cooling is provided with CO{sub 2} under a 15 atmospheres pressure. This pressure is kept steady in a press-stressed concrete packing-case which is a cylinder horizontally shaped. Steel strips tightened encircle the concrete cylinder; itself protected by sole-plates. The cylinder bottom has brought about unusual problems which have been solved by the choice of an hemispheric shape. Packing-case tightness is provided by a 30 mm iron-plate connected with the inner wall of concrete. One of the reactor's special characteristics is the possibility of loading and unloading while operating. On loading side, barrel locks, each weighting 50 tons, allow new cans, at a pressure of 15 atmospheres, to pass. The cans process almost in a steady way through the channel, and finally drop down through bent spouts, then through spiral toboggans into a new lock. The cooling CO{sub 2} flow is provided with 3 turbo-bellows, these are actuated by average pressure-steam, obtained from exchangers. Every reactor supplies 4 exchangers which have been very difficult to build and to set up. The secondary cycle is standard and contains 3 stages (pressure 10,3: 2 and 0,5 kg/cm{sup 2}). Steam can be condensed in the event of a group turbo-generator stopping, with no modifion for the normal operating conditions of the reactor. Auxiliary circuits have to assure the continuous purifying of cooling CO{sub 2}, its storage and drain. 49 boron carbide rods are used to control the

DIDERO 3G: herramienta para la planificación estratégica de redes móviles híbridas 2G/3G

OpenAIRE

Portilla Figueras, José Antonio; Hackbarth Planeta, Klaus Dietrich; Fuente Cosío, Luis P. de la

2002-01-01

This paper presents the project DIDERO 3G that the Telematic Engineering Group of the University of Cantabria is going to develop. The aim of DIDERO is to perform strategic network planning for an hybrid 2G/3G Mobile network to provide as a result of this planning tecno-economical reports that could guide a mobile operator to take decissions about when and where to deploy 3G. DIDERO 3G can also serve the National Regulatory Atuhtorities as an objetvive basis to perform mo...

Presence of Tritium in the Cooling Circuits of the Reactors G2 and G3; Presence de tritium dans les circuits de refroidissement des reacteurs G2 et G3

Energy Technology Data Exchange (ETDEWEB)

Estournel, R [Commissariat a l' Energie Atomique. Centre de Production de Plutonium de Marcoule, 30 - Chusclan (France)

1962-07-01

In a reactor of the G 2-G 3 type, tritium can be formed by the neutronic bombardment of many elements present in the core. Tritium was found to be present in the cooling circuits of the reactors G 2 and G 3 in the water coming from the regeneration of the CO{sub 2} dehydrating columns. (author) [French] Dans un reacteur du type G 2 - G 3, le tritium peut etre forme par le bombardement. neutronique de nombreux elements existant dans le c r. La presence de tritium dans les circuits de refroidissement des reacteurs G 2 - G 3 a ete mis en evidence dans l'eau provenant de la regeneration des colonnes de deshydratation du CO{sub 2}. (auteur)

New World feline APOBEC3 potently controls inter-genus lentiviral transmission.

Science.gov (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

2018-04-10

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.

Vectronic's Power Macintosh G3 (B & W)

CERN Multimedia

1999-01-01

Apple introduced the Power Macintosh G3 Blue and White (B & W) on January 5, 1999. The Power Macintosh G3 line stayed in production until August 1999, and was replaced by the Power Macintosh G4, which used the same chassis. The Power Macintosh G3 originally cost between $1599 and $2900 depending on options. The three original Power Macintosh G3 models shipped with a 300 MHz, 350 MHz, or 400 MHz PowerPC 750 (G3) processor. Just pull on the small round handle on the side of the tower, and the entire side of the computer opens up. The G3's motherboard is mounted on that surface, giving you easy access for upgrading RAM or installed PCI cards. Apple added new ports (USB and the much-anticipated FireWire) that took the place of historic, and quickly becoming antiquated, Mac serial (printer and modem) ports. The Power Macintosh G3 has two USB (12 Mbps) ports, two FireWire (400 Mbps) ports, one 10/100BaseT Ethernet port, an RJ-11 jack for an optional 56K modem, a sound out and sound in jack, and one ADB (Apple D...

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.

An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures.

Science.gov (United States)

Peng, Weihai; Zheng, Wei; Shi, Kai; Wang, Wangshu; Shao, Ying; Zhang, Duo

2015-11-09

Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures.

An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures

International Nuclear Information System (INIS)

Peng, Weihai; Shi, Kai; Wang, Wangshu; Shao, Ying; Zhang, Duo; Zheng, Wei

2015-01-01

Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures. (paper)

The Vaporization of B2O3(l) to B2O3(g) and B2O2(g)

Science.gov (United States)

Jacobson, Nathan S.; Myers, Dwight L.

2011-01-01

The vaporization of B2O3 in a reducing environment leads to formation of both B2O3(g) and B2O2(g). While formation of B2O3(g) is well understood, many questions about the formation of B2O2(g) remain. Previous studies using B(s) + B2O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B2O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B2O2(g). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe2B. Both second and third law enthalpies of formation were measured for B2O2(g) and B2O3(g). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B2O2(g) and -833.4 +/- 13.1 kJ/mol for B2O3(g). Ab initio calculations to determine the enthalpies of formation of B2O2(g) and B2O3(g) were conducted using the W1BD composite method and show good agreement with the experimental values.

Sites of instability in the human TCF3 (E2A) gene adopt G-quadruplex DNA structures in vitro

Science.gov (United States)

Williams, Jonathan D.; Fleetwood, Sara; Berroyer, Alexandra; Kim, Nayun; Larson, Erik D.

2015-01-01

The formation of highly stable four-stranded DNA, called G-quadruplex (G4), promotes site-specific genome instability. G4 DNA structures fold from repetitive guanine sequences, and increasing experimental evidence connects G4 sequence motifs with specific gene rearrangements. The human transcription factor 3 (TCF3) gene (also termed E2A) is subject to genetic instability associated with severe disease, most notably a common translocation event t(1;19) associated with acute lymphoblastic leukemia. The sites of instability in TCF3 are not randomly distributed, but focused to certain sequences. We asked if G4 DNA formation could explain why TCF3 is prone to recombination and mutagenesis. Here we demonstrate that sequences surrounding the major t(1;19) break site and a region associated with copy number variations both contain G4 sequence motifs. The motifs identified readily adopt G4 DNA structures that are stable enough to interfere with DNA synthesis in physiological salt conditions in vitro. When introduced into the yeast genome, TCF3 G4 motifs promoted gross chromosomal rearrangements in a transcription-dependent manner. Our results provide a molecular rationale for the site-specific instability of human TCF3, suggesting that G4 DNA structures contribute to oncogenic DNA breaks and recombination. PMID:26029241

G2 - G3 inventive properties, the first french nuclear plants; Caracteristiques generales et aspects originaux des reacteurs G2 et G3

Energy Technology Data Exchange (ETDEWEB)

Pascal,; Horowitz,; Bussac,; Joatton,; de Meux, De Lagge; Martin, [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

This paper points out the inventive properties of the frenchctors G2 and G3. These are dual purpose reactors, i.e. designed for the production of both plutonium and energy (30 electrical MW); in this respect, they can be considered as the start point of the french electrical energy produced from nuclear fuel. The following points are specially discussed in this paper: the choice of the prestressed concrete pressure vessel, the horizontal arrangement of the channels, the interest of neutron flux flattening, the advantages of the charging and discharging device working during pile operation. (author)Fren. [French] Les caracteres originaux des reacteurs fran is G2 et G3 sont decrits dans ce rapport. Ce sont des reacteurs a double fin, plutonigenes et aussi producteurs d'energie (30 MW electriques); ils constituent a ce titre le point de depart de la production fran ise d'electricite d'origine nucleaire. Sont discutes, en particulier, dans ce rapport: le choix du caisson en beton precontraint pour tenir la pression, la disposition horizontale des canaux, l'interet de l'aplatissement du flux neutronique, les avantages de l'appareil permettant le chargement et le dechargement du combustible sans arreter la pile. (auteur)

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

2016-07-01

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.

The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

KAUST Repository

Abulfaraj, Aala A.; Mariappan, Kiruthiga; Bigeard, Jean; Manickam, Prabhu; Blilou, Ikram; Guo, Xiujie; Al-Babili, Salim; Pflieger, Delphine; Hirt, Heribert; Rayapuram, Naganand

2018-01-01

Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

KAUST Repository

Abulfaraj, Aala Abdulaziz Hussien

2018-05-31

Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

Molecular characterization of different equine-like G3 rotavirus strains from Germany.

Science.gov (United States)

Pietsch, Corinna; Liebert, Uwe G

2018-01-01

The genetic heterogeneity of rotaviruses constitutes a substantial burden to human and animal health. Occasional interspecies transmissions can generate novel virus strains in the human population. We detected equine-like G3P[8] strains in feces sampled from three children in Germany in 2015 and 2016, respectively. Thereof two showed a DS-1-like backbone. In one strain the NSP2 gene segment was of distinct genotype (G3-P[8]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Phylogenetic analyses of the German strains showed a relation to other equine-like G3 rotaviruses circulating in different countries. The reconstruction of reassortment events in the evolution of novel equine-like G3 rotaviruses suggests an independent introduction of the three strains into the local human rotavirus population. Copyright © 2017 Elsevier B.V. All rights reserved.

Health physics during work on the G. 2 and G. 3 reactor exchanges; La radioprotection des travaux sur les echangeurs des piles G. 2 et G. 3

Energy Technology Data Exchange (ETDEWEB)

Rodier, J; Chassany, J; Guillermin, P [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

1965-07-01

During this work and its preparation, which took place first at G. 2 and then at G. 3 over a period of 11 months, 15000 measurement results were obtained. Their analysis, together with a consideration of the organisation on the site and of the conclusions drawn from the experiment, shows the various factors which determine the importance of the radio-active dangers. (authors) [French] Au cours de ces travaux et de leur preparation, qui ont eu lieu successivement a G. 3 puis a G. 2, pendant 11 mois, 15 000 resultats de mesures ont ete obtenus. Leur etude, mise en parallele avec l'organisation du chantier et les enseignements tires de l'experience, met en evidence les divers facteurs conditionnant les niveaux de risques radioactifs. (auteurs)

Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells

Directory of Open Access Journals (Sweden)

Choi Hyun

2009-05-01

Full Text Available Abstract Background 3,3'-Diindolylmethane (DIM, an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 – 30 μmol/L inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells. Methods HT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK and cell division cycle (CDC2 were conducted. Results The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1. Conclusion Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells.

Science.gov (United States)

Choi, Hyun Ju; Lim, Do Young; Park, Jung Han Yoon

2009-05-29

3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 - 30 micromol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells. HT-29 cells were cultured with various concentrations of DIM (0 - 30 micromol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted. The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1. Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

Effects of electromagnetic waves emitted from 3G+wi-fi modems on human semen analysis.

Science.gov (United States)

Kamali, Koosha; Atarod, Mohammadmehdi; Sarhadi, Saeedeh; Nikbakht, Javad; Emami, Maryam; Maghsoudi, Robab; Salimi, Hormoz; Fallahpour, Bita; Kamali, Negar; Momtazan, Abdolreza; Ameli, Mojtaba

2017-10-25

The purpose of this study was to evaluate the effects of 3G+wifi modems on human sperm quality.A total of 40 semen specimens were gathered between March and September 2015, from healthy adult men. The sperm samples were divided into two groups - 3G+wi-fi exposed and unexposed groups. In the unexposed group, the specimens were shielded by aluminum foil in three layers and put into an incubator at a temperature of 37°C for 50 minutes. The exposed group was positioned in another room in an incubator at a temperature of 37°C for 50 minutes. A 3G+wi-fi modem was put into the same incubator and a laptop computer was connected to the modem and was downloading for the entire 50 minutes.Semen analysis was done for each specimen and comparisons between parameters of the two groups were done by using Kolmogorov-Smirnov study and a paired t-test. Mean percentage of sperm with class A and B motility were not significantly different in two groups (p = 0.22 and 0.54, respectively). In class C, it was significantly lower in the exposed group (p = 0.046), while in class D it was significantly higher (p = 0.022).Velocity curvilinear, velocity straight line, velocity average path, mean angular displacement, lateral displacement and beat cross frequency were significantly higher in the unexposed group. The limitation was the in vitro design. Electromagnetic waves (EMWs) emitted from 3G+wi-fi modems cause a significant decrease in sperm motility and velocity, especially in non-progressive motile sperms. Other parameters of semen analysis did not change significantly.EMWs, which are used in communications worldwide, are a suspected cause of male infertility. Many studies evaluated the effects of cell phones and wi-fi on fertility. To our knowledge, no study has yet been done to show the effects of EMWs emitted from 3G+wi-fi modems on fertility.Our study revealed a significant decrease in the quality of human semen after exposure to EMWs emitted from 3G+wi-fi modems.

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.

3-Nitrobenzanthrone (3-NBA) induced micronucleus formation and DNA damage in human hepatoma (HepG2) cells.

Science.gov (United States)

Lamy, Evelyn; Kassie, Fekadu; Gminski, Richard; Schmeiser, Heinz H; Mersch-Sundermann, Volker

2004-01-15

3-Nitrobenzanthrone (3-NBA), identified in diesel exhaust and in airborne particulate matter, is a potent mutagen in Salmonella, induces micronuclei formation in mice and in human cells and DNA adducts in rats. In the present study, we investigated the genotoxic potency of 3-NBA in human HepG2 cells using the micronucleus (MN) assay and the single cell gel electrophoresis (SCGE). 3-NBA caused a genotoxic effect at concentrations > or =12 nM in both assays. In the micronucleus assay, we found 98.7+/-10.3 MN/1000 BNC at a concentration of 100 nM 3-NBA in comparison to 27.3+/-0.6 MN/1000 BNC with the negative control. At the same concentration, the DNA-migration (SCGE) showed an Olive tail moment (OTM) of 2.7+/-0.45 and %DNA in the tail of 8.28+/-0.76; OTM and %DNA in the tail of cells treated with the negative control were 0.73+/-0.08 and 2.81+/-0.30, respectively. The results are discussed under consideration of former studies.

HLA-G 3′UTR Polymorphisms Predict Drug-Induced G3-4 Toxicity Related to Folinic Acid/5-Fluorouracil/Oxaliplatin (FOLFOX4) Chemotherapy in Non-Metastatic Colorectal Cancer

Science.gov (United States)

Garziera, Marica; Virdone, Saverio; De Mattia, Elena; Scarabel, Lucia; Cecchin, Erika; Polesel, Jerry; D’Andrea, Mario; Pella, Nicoletta; Buonadonna, Angela; Favaretto, Adolfo; Toffoli, Giuseppe

2017-01-01

Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC) that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4). Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4) toxicity related to FOLFOX4 therapy in patients with CRC. We retrospectively analyzed data for 144 patients with stages II-III CRC to identify HLA-G 3′ untranslated region (3′UTR) polymorphisms and related haplotypes and evaluate their impact on the risk of developing G3-4 toxicities (i.e., neutropenia, hematological/non-hematological toxicity, neurotoxicity) with logistic regression. The rs1610696-G/G polymorphism was associated with increased risk of G3-4 neutropenia (OR = 3.76, p = 0.015) and neurotoxicity (OR = 8.78, p = 0.016); rs371194629-Ins/Ins was associated with increased risk of neurotoxicity (OR = 5.49, p = 0.027). HLA-G 3′UTR-2, which contains rs1610696-G/G and rs371194629-Ins/Ins polymorphisms, was associated with increased risk of G3-4 neutropenia (OR = 3.92, p = 0.017) and neurotoxicity (OR = 11.29, p = 0.009). A bootstrap analysis confirmed the predictive value of rs1610696 and rs371194629, but the UTR-2 haplotype was validated only for neurotoxicity. This exploratory study identified new HLA-G 3′UTR polymorphisms/haplotypes as potential predictive markers of G3-4 toxicities in CRC. PMID:28653974

HLA-G 3′UTR Polymorphisms Predict Drug-Induced G3-4 Toxicity Related to Folinic Acid/5-Fluorouracil/Oxaliplatin (FOLFOX4 Chemotherapy in Non-Metastatic Colorectal Cancer

Directory of Open Access Journals (Sweden)

Marica Garziera

2017-06-01

Full Text Available Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4. Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G, a non-classical major histocompatibility complex (MHC class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4 toxicity related to FOLFOX4 therapy in patients with CRC. We retrospectively analyzed data for 144 patients with stages II-III CRC to identify HLA-G 3′ untranslated region (3′UTR polymorphisms and related haplotypes and evaluate their impact on the risk of developing G3-4 toxicities (i.e., neutropenia, hematological/non-hematological toxicity, neurotoxicity with logistic regression. The rs1610696-G/G polymorphism was associated with increased risk of G3-4 neutropenia (OR = 3.76, p = 0.015 and neurotoxicity (OR = 8.78, p = 0.016; rs371194629-Ins/Ins was associated with increased risk of neurotoxicity (OR = 5.49, p = 0.027. HLA-G 3′UTR-2, which contains rs1610696-G/G and rs371194629-Ins/Ins polymorphisms, was associated with increased risk of G3-4 neutropenia (OR = 3.92, p = 0.017 and neurotoxicity (OR = 11.29, p = 0.009. A bootstrap analysis confirmed the predictive value of rs1610696 and rs371194629, but the UTR-2 haplotype was validated only for neurotoxicity. This exploratory study identified new HLA-G 3′UTR polymorphisms/haplotypes as potential predictive markers of G3-4 toxicities in CRC.

Key technologies and concepts for beyond-3G networks

Science.gov (United States)

Pehkonen, Kari; Uskela, Sami; Kalliojarvi, Kari; Oksanen, Lauri; Rikkinen, Kari

2001-10-01

Standardization of 3rd Generation (3G) mobile communication systems has produced the first specification releases and the commercial deployment of the 3G systems has started. Whereas 1G and 2G focused on efficiently providing voice services, in 3G a lot of attention has been devoted to solutions that support both Circuit Switched (CS) and Packet Switched (PS) communication. That has called for very flexible air interface and network solutions. 3G will continue to evolve and there are already on-going standardization activities that will, for example, boost the peak data rates up to 5-10 Mbps and improve spectral efficiency by 2-4 times. In the future, 3G evolution will be going towards 10/100 Mbps peak data rates in wide/local are coverage, respectively. This will take place partly because of technical improvements of 3G radio interface solutions, but also due to network evolution which will allow the integration other radio access methods like radio LANs into the 3G system. In longer term the 3G network evolution will be going towards ALL-IP networks. As 3G evolution seems to be going towards 10 Mbps/100 Mbps peak data rates and ALL-IP networks any beyond 3G air interface or network solution should be clearly better in order to justify its technical and commercial feasibility. Given the long evolution time of 3G and integration of other radio access schemes with 3G radio we may not even see a new, complete beyond 3G system being developed. Maybe we will just witness the emergence of a new, more advanced radio access solution which will then be connected to the evolving 3G network. As 3G evolution will continue for several years to come the research targets for any beyond 3G solutions must be set very high. When it comes to air interface, we should aim at 100 Mbps peak data rates for wide area access with high mobility, and at 1 Gbps for local area access with low mobility. Regarding possible commercial launches of any beyond 3G systems or solutions they could then

Differential endothelial transcriptomics identifies semaphorin 3G as a vascular class 3 semaphorin.

Science.gov (United States)

Kutschera, Simone; Weber, Holger; Weick, Anja; De Smet, Frederik; Genove, Guillem; Takemoto, Minoru; Prahst, Claudia; Riedel, Maria; Mikelis, Constantinos; Baulande, Sylvain; Champseix, Catherine; Kummerer, Petra; Conseiller, Emmanuel; Multon, Marie-Christine; Heroult, Melanie; Bicknell, Roy; Carmeliet, Peter; Betsholtz, Christer; Augustin, Hellmut G

2011-01-01

To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]). Semaphorins have been identified as axon guidance molecules. Yet, they have more recently also been characterized as attractive and repulsive regulators of angiogenesis. Through a transcriptomic screen, we identified Sema3G as a molecule of angiogenic endothelial cells. Sema3G-deficient mice are viable and exhibit no overt vascular phenotype. Yet, LacZ expression in the Sema3G locus revealed intense arterial vascular staining in the angiogenic vasculature, starting at E9.5, which was detectable throughout adolescence and downregulated in adult vasculature. Sema3G is expressed as a full-length 100-kDa secreted molecule that is processed by furin proteases to yield 95- and a 65-kDa Sema domain-containing subunits. Full-length Sema3G binds to NP2, whereas processed Sema3G binds to NP1 and NP2. Expression profiling and cellular experiments identified autocrine effects of Sema3G on endothelial cells and paracrine effects on smooth muscle cells. Although the mouse knockout phenotype suggests compensatory mechanisms, the experiments identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners, respectively.

Indirect radioiodination of human IgG with N-succinimidyl-3-iodo[125I] benzoate

International Nuclear Information System (INIS)

Liu Zhenfeng; Wang Yongxian; Dong Mo; Zhou Wei; Xia Jiaoyun; Yin Duanzhi; Li Linfa

2007-01-01

The objective of this study was to develop an acylation method for the radioiodination of monoclonal antibodies that could decrease the loss of radioiodine in vivo. Preparation of N- succinimidyl-3-iodobenzoate(S 125 IB) from the organoth precursor, N-succinimidyl-3-(tri-n-bu- tylstannyl)benzoate(ATE) proceeds in more than 95% labelling yield, when the mass of ATE and NCS are respectively 25-100 μg and 10-20 μg, and the volume of PBS is 10-20 μL, and reaction time is 5 min. IgG is labeled using S 125 IB in up to 75% conjugation efficiency and with well retained immunoreactivity to sheep anti-human IgG. Hepama-1 is also labeled using S 125 IB in more than 75% conjugation efficiency. Paired-label biodistribution studies in normal mice demonstrate that thyroid uptake(a monitor of dehalogenation) of Hepama-1 labeled by S 125 IB method is up to 87.9 times lower than that of Hepama-1 labeled with Iodogen. This result suggests that S 125 IB offers significant advantages for labeling proteins, antibodies over other conventional methods for protein radioiodination. (authors)

Indoor radio planning a practical guide for 2G, 3G and 4G

CERN Document Server

Tolstrup, Morten

2015-01-01

Why is high performance indoor wireless service needed, and how is it best implemented? As the challenge of providing better service and higher data speeds and quality for mobile applications intensifies, ensuring adequate in-building and tunnel coverage and capacity is increasingly important. A unique, single-source reference on the theoretical and practical knowledge behind indoor and tunnel radio planning, this book provides a detailed overview of mobile networks systems, coverage and capacity solutions with 2G, 3G and 4G cellular system technologies as a backdrop.  All of the available s

Effects of 2G and 3G mobile phones on performance and electrophysiology in adolescents, young adults and older adults.

Science.gov (United States)

Leung, S; Croft, R J; McKenzie, R J; Iskra, S; Silber, B; Cooper, N R; O'Neill, B; Cropley, V; Diaz-Trujillo, A; Hamblin, D; Simpson, D

2011-11-01

This study examined sensory and cognitive processing in adolescents, young adults and older adults, when exposed to 2nd (2G) and 3rd (3G) generation mobile phone signals. Tests employed were the auditory 3-stimulus oddball and the N-back. Forty-one 13-15 year olds, forty-two 19-40 year olds and twenty 55-70 year olds were tested using a double-blind cross-over design, where each participant received Sham, 2G and 3G exposures, separated by at least 4 days. 3-Stimulus oddball task: Behavioural: accuracy and reaction time of responses to targets were not affected by exposure. Electrophysiological: augmented N1 was found in the 2G condition (independent of age group). N-back task: Behavioural: the combined groups performed less accurately during the 3G exposure (compared to Sham), with post hoc tests finding this effect separately in the adolescents only. Electrophysiological: delayed ERD/ERS responses of the alpha power were found in both 3G and 2G conditions (compared to Sham; independent of age group). Employing tasks tailored to each individual's ability level, this study provides support for an effect of acute 2G and 3G exposure on human cognitive function. The subtlety of mobile phone effect on cognition in our study suggests that it is important to account for individual differences in future mobile phone research. Copyright © 2011 International Federation of Clinical Neurophysiology. All rights reserved.

The CO{sub 2} cooling gas for the reactors G2/G3 (leaking, analysis, activity); Le CO{sub 2} de refroidissement des reacteurs G2/G3 (fuites, analyse, activite)

Energy Technology Data Exchange (ETDEWEB)

Meiffren, J; Dupay, F [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

1965-07-01

The main objective of this study is to publicise the data obtained during five years operation of the reactor G2 and G3 at Marcoule as far as the cooling gas is concerned, from storage of reserves up to its slow escape into the atmosphere, and including all the stages of its practical use, its chemical examination, its nuclear behaviour and its possible physicochemical transformation. This work can not only yield information about the operations carried out at Marcoule but can also provide useful suggestions for improving the sealing and for decreasing the activity of the pressurized gas circuits in reactors similar to G2/G3. (authors) [French] Le but principal de cette etude est de diffuser les connaissances acquises au cours de cinq annees d'exploitation des reacteurs G2 et G3 de Marcoule en ce qui concerne le gaz de refroidissement, depuis son stockage d'appoint jusqu'a son echappement lent dans l'atmosphere, en passant par tous les stades de son utilisation pratique, de son etude chimique, de son comportement nucleaire, eventuellement de ses transformations physico-chimiques. Cette etude peut, non seulement renseigner sur les operations effectuees couramment a Marcoule, mais egalement donner des suggestions interessantes pour l'amelioration de l'etancheite et la diminution de l'activite des circuits de gaz en pression dans des reacteurs analogues a G2/G3. (auteurs)

G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.

Science.gov (United States)

Bidet, Katell; Dadlani, Dhivya; Garcia-Blanco, Mariano A

2014-07-01

Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV). We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs), and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA), which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.

3G Bet

Institute of Scientific and Technical Information of China (English)

DAN; STEINBOCK

2006-01-01

Since the late 1990s, Chinese mobile players have caught up rapidly with cutting-edge mobile services, while the Chinese marketplace has become an R&D hub for multinational companies and a test laboratory for large-scale ad campaigns by global marketers. As China prepares to enter the third-generation (3G) industry, it is faced with both great challenges and great opportunities. Scale and mobile services In late summer 2002, Coca-Cola ran a short message service (SMS) ad campaign, featuring

Wigner effect in graphite stack: G2 and G3 reactors

International Nuclear Information System (INIS)

Artozoul, M.; L'Homme, M.

1982-11-01

This text describes work carried out between 1978 and 1980 by a COGEMA/CEA team responsible for a report on the feasibility, effectiveness and possible hazards likely to be encountered in the nuclear annealing of G2 and in changing the operating conditions of G3 [fr

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

2016-01-01

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

Downlink power distributions for 2G and 3G mobile communication networks.

Science.gov (United States)

Colombi, Davide; Thors, Björn; Persson, Tomas; Wirén, Niklas; Larsson, Lars-Eric; Jonsson, Mikael; Törnevik, Christer

2013-12-01

Knowledge of realistic power levels is key when conducting accurate EMF exposure assessments. In this study, downlink output power distributions for radio base stations in 2G and 3G mobile communication networks have been assessed. The distributions were obtained from network measurement data collected from the Operations Support System, which normally is used for network monitoring and management. Significant amounts of data were gathered simultaneously for large sets of radio base stations covering wide geographical areas and different environments. The method was validated with in situ measurements. For the 3G network, the 90th percentile of the averaged output power during high traffic hours was found to be 43 % of the maximum available power. The corresponding number for 2G, with two or more transceivers installed, was 65 % or below.

G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.

Directory of Open Access Journals (Sweden)

Katell Bidet

2014-07-01

Full Text Available Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV. We examined three conserved host RNA-binding proteins (RBPs G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2 infection and found them to be novel regulators of the interferon (IFN response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs, and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA, which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.

Dynamics of Inter-heavy Chain Interactions in Human Immunoglobulin G (IgG) Subclasses Studied by Kinetic Fab Arm Exchange

NARCIS (Netherlands)

Rispens, Theo; Davies, Anna M.; Ooijevaar-de Heer, Pleuni; Absalah, Samira; Bende, Onno; Sutton, Brian J.; Vidarsson, Gestur; Aalberse, Rob C.

2014-01-01

Background: Fab arm exchange requires weak interactions between CH3 domains, such as in human IgG4. Results: CH3-CH3 interactions differ >1,000,000-fold between human subclasses and allotypes due to variations Lys/Asn-392, Val/Met-397, and Lys/Arg-409. Conclusion: For IgG2 and IgG3, but not IgG1,

3-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-1,2,5-selenadiazole (G-1103), a novel combretastatin A-4 analog, induces G2/M arrest and apoptosis by disrupting tubulin polymerization in human cervical HeLa cells and fibrosarcoma HT-1080 cells.

Science.gov (United States)

Zuo, Daiying; Guo, Dandan; Jiang, Xuewei; Guan, Qi; Qi, Huan; Xu, Jingwen; Li, Zengqiang; Yang, Fushan; Zhang, Weige; Wu, Yingliang

2015-02-05

Microtubule is a popular target for anticancer drugs. In this study, we describe the effect 3-(3-hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-1,2,5-selenadiazole (G-1103), a newly synthesized analog of combretastatin A-4 (CA-4), showing a strong time- and dose-dependent anti-proliferative effect on human cervical cancer HeLa cells and human fibrosarcoma HT-1080 cells. We demonstrated that the growth inhibitory effects of G-1103 in HeLa and HT-1080 cells were associated with microtubule depolymerization and proved that G-1103 acted as microtubule destabilizing agent. Furthermore, cell cycle analysis revealed that G-1103 treatment resulted in cell cycle arrest at the G2/M phase in a time-dependent manner with subsequent apoptosis induction. Western blot analysis revealed that down-regulation of cdc25c and up-regulation of cyclin B1 was related with G2/M arrest in HeLa and HT-1080 cells treatment with G-1103. In addition, G-1103 induced HeLa cell apoptosis by up-regulating cleaved caspase-3, Fas, cleaved caspase-8 expression, which indicated that G-1103 induced HeLa cell apoptosis was mainly associated with death receptor pathway. However, G-1103 induced HT-1080 cell apoptosis by up-regulating cleaved caspase-3, Fas, cleaved caspase-8, Bax and cleaved caspase-9 expression and down-regulating anti-apoptotic protein Bcl-2 expression, which indicated that G-1103 induced HT-1080 cell apoptosis was associated with both mitochondrial and death receptor pathway. Taken together, all the data demonstrated that G-1103 exhibited its antitumor activity through disrupting the microtubule assembly, causing cell cycle arrest and consequently inducing apoptosis in HeLa and HT-1080 cells. Therefore, the novel compound G-1103 is a promising microtubule inhibitor that has great potentials for therapeutic treatment of various malignancies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neutron flux determinations in the reactors G2 and G3 during operation; Releves du flux neutronique dans les reacteurs G2 et G3 en puissance

Energy Technology Data Exchange (ETDEWEB)

Boulinier, C; Faurot, P; Sagot, M; Teste du Bailler, A [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

After demonstrating the sensitivity of the distribution of power in a production reactor to a deformation caused by dissymmetries of reactivity in the reactor, the authors describe the method of neutron flux determination devised for the reactors G2 and G3 under working conditions; the detector used is a tungsten or nickel wire, the {gamma} activity of which is measured with an ionisation chamber. Several flux determinations are given as examples to illustrate the sensitivity of the method. (author) [French] Apres avoir mis en evidence la sensibilite de la repartition de la puissance dans un reacteur de production a une deformation provoquee par de faibles dissymetries de reactivite dans le reacteur, les auteurs decrivent la methode de releve du flux neutronique mise au point pour les reacteurs G2 et G3 en puissance; le detecteur utilise est un fil de tungstene ou de nickel dont l'activite {gamma} est mesuree a l'aide d'une chambre d'ionisation. Quelques releves de flux illustrant la sensibilite de la methode sont donnes a titre d'exemple. (auteur)

Effects of 2G and 3G mobile phones on human alpha rhythms: Resting EEG in adolescents, young adults, and the elderly.

Science.gov (United States)

Croft, R J; Leung, S; McKenzie, R J; Loughran, S P; Iskra, S; Hamblin, D L; Cooper, N R

2010-09-01

The present study was conducted to determine whether adolescents and/or the elderly are more sensitive to mobile phone (MP)-related bioeffects than young adults, and to determine this for both 2nd generation (2G) GSM, and 3rd generation (3G) W-CDMA exposures. To test this, resting alpha activity (8-12 Hz band of the electroencephalogram) was assessed because numerous studies have now reported it to be enhanced by MP exposure. Forty-one 13-15 year olds, forty-two 19-40 year olds, and twenty 55-70 year olds were tested using a double-blind crossover design, where each participant received Sham, 2G and 3G exposures, separated by at least 4 days. Alpha activity, during exposure relative to baseline, was recorded and compared between conditions. Consistent with previous research, the young adults' alpha was greater in the 2G compared to Sham condition, however, no effect was seen in the adolescent or the elderly groups, and no effect of 3G exposures was found in any group. The results provide further support for an effect of 2G exposures on resting alpha activity in young adults, but fail to support a similar enhancement in adolescents or the elderly, or in any age group as a function of 3G exposure. 2010 Wiley-Liss, Inc.

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

2015-05-01

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

AFA 2G and AFA 3G fuel rod performance analysis

International Nuclear Information System (INIS)

Lu Huaquan; Liu Tong; Jiao Yongjun; Pang Hua

2002-01-01

For 18-months fuel cycle strategy in GNPJVC DAYA BAY unit 1/2, by means of COCCINEL, the fuel rod performance for AFA 3G and AFA 2G in transition cycle is analyzed. The design criteria which should be respected in fuel rod design are included and the design methodology is introduced. All the criteria mentioned are verified and met

COMPARATIVE STUDY OF 3G / 4G NETWORK SERVICE

OpenAIRE

Gulshan Kumar; Sheenam Bhola; Manisha Batra

2015-01-01

Modern technology is evolving so fast, that it can be very difficult to keep follow everything new. Cellular Communication is one of the most recent areas which is developing tremendously fast at present times, it is only due to the advancement of technology in all the fields of cellular and wireless communications. Networks are used basically in business and home applications, mobile users, and in all social concerns. At the present time, the use of 3rd Generation (3G) cellular communication...

Comparative Study of 3G / 4G Network Service

OpenAIRE

Gulshan Kumar; Sheenam Bhola; Manisha Batra

2014-01-01

Modern technology is evolving so fast, that it can be very difficult to keep follow everything new. Cellular Communication is one of the most recent areas which is developing tremendously fast at present times, it is only due to the advancement of technology in all the fields of cellular and wireless communications. Networks are used basically in business and home applications, mobile users, and in all social concerns. At the present time, the use of 3 rd Generation (3G) cel...

Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

2013-01-01

Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

Supersymmetric M3-branes and G2 manifolds

International Nuclear Information System (INIS)

Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

2002-01-01

We obtain a generalisation of the original complete Ricci-flat metric of G 2 holonomy on (R 4 xS 3 to a family with a nontrivial parameter λ. For generic λ the solution is singular, but it is regular when λ={-1,0,+1}. The case λ=0 corresponds to the original G 2 metric, and λ={-1,1} are related to this by an S 3 automorphism of the SU(2) 3 isometry group that acts on the S 3 xS 3 principal orbits. We then construct explicit supersymmetric M3-brane solutions in D=11 supergravity, where the transverse space is a deformation of this class of G 2 metrics. These are solutions of a system of first-order differential equations coming from a superpotential. We also find M3-branes in the deformed backgrounds of new G 2 holonomy metrics that include one found by A. Brandhuber, J. Gomis, S. Gubser and S. Gukov, and show that they also are supersymmetric

Supersymmetric M3-branes and G2 manifolds

Science.gov (United States)

Cvetič, M.; Gibbons, G. W.; Lü, H.; Pope, C. N.

2002-01-01

We obtain a generalisation of the original complete Ricci-flat metric of G2 holonomy on R4×S 3 to a family with a nontrivial parameter λ. For generic λ the solution is singular, but it is regular when λ={-1,0,+1}. The case λ=0 corresponds to the original G2 metric, and λ={-1,1} are related to this by an S3 automorphism of the SU(2) 3 isometry group that acts on the S3× S3 principal orbits. We then construct explicit supersymmetric M3-brane solutions in D=11 supergravity, where the transverse space is a deformation of this class of G2 metrics. These are solutions of a system of first-order differential equations coming from a superpotential. We also find M3-branes in the deformed backgrounds of new G2 holonomy metrics that include one found by A. Brandhuber, J. Gomis, S. Gubser and S. Gukov, and show that they also are supersymmetric.

Coexistence of 3G repeaters with LTE base stations.

Science.gov (United States)

Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

2013-01-01

Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

Avaliação das subclasses IgG1 e IgG3 na doença hemolítica perinatal Assessment of IgG1 and IgG3 subclasses in perinatal hemolytic disease

Directory of Open Access Journals (Sweden)

Maria A. Araújo

2003-01-01

Full Text Available A doença hemolítica perinatal (DHPN ainda é um problema clínico. Nenhum teste isolado prediz, com segurança, a gravidade do quadro hemolítico. O objetivo do presente estudo foi determinar as subclasses de anticorpos IgG1 e IgG3 por citometria de fluxo no soro de 42 gestantes isoimunizadas e correlacionar os dados obtidos com a gravidade da DHPN. A distribuição dos fetos ou neonatos segundo a gravidade do quadro hemolítico evidenciou 13 casos com doença leve, 16 casos com doença moderada e 13 com doença grave. As subclasses foram detectadas em 33/42 (79% amostras. A subclasse IgG1, isoladamente, foi evidenciada em 14/33 (42,4% casos. Na relação entre gravidade da doença e subclasses de IgG, observou-se que IgG1 isolada foi encontrada em todos os grupos, e os valores da mediana de intensidade de fluorescência (MIF foram significativamente mais altos nas formas mais graves da DHPN (pThe hemolytic disease of the newborn (HDN continues to be a clinical problem in spite of prophylaxis. To date, none of the available tests, developed to predict the severity of HDN, has provided complete reliability. The objective of the present study was to determine the IgG1 and IgG3 subclasses in 42 isoimmunized pregnant women, and to correlate them with clinical severity of hemolytic disease. The IgG subclasses were determined employing flow cytometry. According to the clinical severity of HDN, fetuses and newborn babies were classified as 13 mild, 16 moderate and 13 severe cases. The IgG subclasses were detected in 33 of the 42 pregnant women. Of these, IgG1 was predominant in 72.7% of the cases; either isolated (42.4% or in association with IgG3 (30.3%. IgG1 was present in all the three clinical severity categories, however, its values were significantly higher in cases with greater clinical severity of HDN (p<0.01. On the other hand, the distribution of IgG3 values within each group was not statistically significant (p=0.11. IgG3 seems to be more

Conjugation of hydroxyapatite nanocrystals with human immunoglobulin G for nanomedical applications.

Science.gov (United States)

Iafisco, Michele; Varoni, Elena; Di Foggia, Michele; Pietronave, Stefano; Fini, Milena; Roveri, Norberto; Rimondini, Lia; Prat, Maria

2012-02-01

Inorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specific and selective recognition ability of the antibodies to antigens. Biomimetic carbonate-hydroxyapatite (HA) nanoparticles were synthesized and fully characterized; human IgGs, used as model antibodies, were coupled to these nanocrystals. The maximum loading amount, the interaction modelling, the preferential orientation and the secondary structure modifications were evaluated using theoretical models (Langmuir, Freundlich and Langmuir-Freundlich) spectroscopic (UV-Vis, Raman), calorimetric (TGA), and immunochemical techniques (ELISA, Western Blot). HA nanoparticles of about 30 nm adsorbed human IgGs, in a dose-dependent, saturable and stable manner with micromolar affinity and adsorption capability around 2.3 mg/m(2). Adsorption isotherm could be described by Langmuir-Freundlich model, and was due to both energetically homogeneous and heterogeneous binding sites on HA surface, mainly of electrostatic nature. Binding did not induce secondary structure modification of IgGs. A preferential IgG end-on orientation with the involvement of IgG Fc moiety in the adsorption seems most probable due to the steric hindrance of their Fab domains. Biomimetic HA nanocrystals are suitable substrates to produce nanoparticles which can be functionalized with antibodies for efficient targeted drug delivery to tumours. Copyright © 2011 Elsevier B.V. All rights reserved.

Mobile telephones: a comparison of radiated power between 3G VoIP calls and 3G VoCS calls.

Science.gov (United States)

Jovanovic, Dragan; Bragard, Guillaume; Picard, Dominique; Chauvin, Sébastien

2015-01-01

The purpose of this study is to assess the mean RF power radiated by mobile telephones during voice calls in 3G VoIP (Voice over Internet Protocol) using an application well known to mobile Internet users, and to compare it with the mean power radiated during voice calls in 3G VoCS (Voice over Circuit Switch) on a traditional network. Knowing that the specific absorption rate (SAR) is proportional to the mean radiated power, the user's exposure could be clearly identified at the same time. Three 3G (High Speed Packet Access) smartphones from three different manufacturers, all dual-band for GSM (900 MHz, 1800 MHz) and dual-band for UMTS (900 MHz, 1950 MHz), were used between 28 July and 04 August 2011 in Paris (France) to make 220 two-minute calls on a mobile telephone network with national coverage. The places where the calls were made were selected in such a way as to describe the whole range of usage situations of the mobile telephone. The measuring equipment, called "SYRPOM", recorded the radiation power levels and the frequency bands used during the calls with a sampling rate of 20,000 per second. In the framework of this study, the mean normalised power radiated by a telephone in 3G VoIP calls was evaluated at 0.75% maximum power of the smartphone, compared with 0.22% in 3G VoCS calls. The very low average power levels associated with use of 3G devices with VoIP or VoCS support the view that RF exposure resulting from their use is far from exceeding the basic restrictions of current exposure limits in terms of SAR.

α/sub i/-3 cDNA encodes the α subunit of G/sub k/, the stimulatory G protein of receptor-regulated K+ channels

International Nuclear Information System (INIS)

Codina, J.; Olate, J.; Abramowitz, J.; Mattera, R.; Cook, R.G.; Birnbaumer, L.

1988-01-01

cDNA cloning has identified the presence in the human genome of three genes encoding α subunits of pertussis toxin substrates, generically called G/sub i/. They are named α/sub i/-1, α/sub i/-2 and α/sub i/-3. However, none of these genes has been functionally identified with any of the α subunits of several possible G proteins, including pertussis toxin-sensitive G/sub p/'s, stimulatory to phospholipase C or A 2 , G/sub i/, inhibitory to adenylyl cyclase, or G/sub k/, stimulatory to a type of K + channels. The authors now report the nucleotide sequence and the complete predicted amino acid sequence of human liver α/sub i/-3 and the partial amino acid sequence of proteolytic fragments of the α subunit of human erythrocyte G/sub k/. The amino acid sequence of the proteolytic fragment is uniquely encoded by the cDNA of α/sub i/-3, thus identifying it as α/sub k/. The probable identity of α/sub i/-1 with α/sub p/ and possible roles for α/sub i/-2, as well as additional roles for α/sub i/-1 and α/sub i/-3 (α/sub k/) are discussed

Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging

International Nuclear Information System (INIS)

Goldstein, Robert; Livanos, Maria; Bhavsar, Gaurav; Rashid, Mohammed; Miranda, Enrique; Tolner, Berend; Meyer, Tim; Chester, Kerry; Sosabowski, Jane; Leyton, Julius; Mather, Stephen; Vigor, Kim; Nagy-Davidescu, Gabriela; Plueckthun, Andreas; Yeung, Jenny

2015-01-01

Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. G3 DARPins tagged with hexahistidine (His 6 ) or with histidine glutamate (HE) 3 and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with 125 I, or with 111 In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE) 3 -G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. For both isotopes, (HE) 3 -G3 had significantly lower liver uptake than His 6 -G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His 6 -G3 and untagged G3. (HE) 3 -G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from 111 In-(HE) 3 -G3 was better maintained in tumours and cleared faster from serum than radioactivity from 125 I-(HE) 3 -G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, 111 In-labelled and 125 I-labelled (HE) 3 -G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of radioactivity with 111 In-(HE) 3 -G3. Preadministration of trastuzumab did not

Tumor Necrosis Factor (TNF -308G>A, Nitric Oxide Synthase 3 (NOS3 +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis.

Directory of Open Access Journals (Sweden)

Min Chen

Full Text Available Conflicting data have been reported on the association between tumor necrosis factor (TNF -308G>A and nitric oxide synthase 3 (NOS3 +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the TNF -308G>A and NOS3 +894G>T polymorphisms confer genetic susceptibility to migraine.We performed an updated meta-analysis for TNF -308G>A and a meta-analysis for NOS3 +894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR and 95% confidence intervals (95% CI assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates.Eleven studies in 6682 migraineurs and 22591 controls for TNF -308G>A and six studies in 1055 migraineurs and 877 controls for NOS3 +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the "A" allele of the TNF -308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 - 2.87. The risk of migraine with aura (MA was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the "T" allele of the NOS3 +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 - 3.88.Our findings appear to support the hypothesis that the TNF -308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the NOS3 +894G>T polymorphism may modulate the risk of migraine among non-Caucasians.

Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but G0/G1 arrest

International Nuclear Information System (INIS)

Dan, Shingo; Yoshimi, Hisashi; Okamura, Mutsumi; Mukai, Yumiko; Yamori, Takao

2009-01-01

Phosphoinositide 3-kinase (PI3K) is a potential target in cancer therapy. Inhibition of PI3K is believed to induce apoptosis. We recently developed a novel PI3K inhibitor ZSTK474 with antitumor efficacy. In this study, we have examined the underlying mode of action by which ZSTK474 exerts its antitumor efficacy. In vivo, ZSTK474 effectively inhibited the growth of human cancer xenografts. In parallel, ZSTK474 treatment suppressed the expression of phospho-Akt, suggesting effective PI3K inhibition, and also suppressed the expression of nuclear cyclin D1 and Ki67, both of which are hallmarks of proliferation. However, ZSTK474 treatment did not increase TUNEL-positive apoptotic cells. In vitro, ZSTK474 induced marked G 0 /G 1 arrest, but did not increase the subdiploid cells or activate caspase, both of which are hallmarks of apoptosis. These results clearly indicated that inhibition of PI3K by ZSTK474 did not induce apoptosis but rather induced strong G 0 /G 1 arrest, which might cause its efficacy in tumor cells.

The expression and functional activity of membrane-bound human leukocyte antigen-G1 are influenced by the 3'-untranslated region

DEFF Research Database (Denmark)

Svendsen, Signe Goul; Hantash, Basil M; Zhao, Longmei

2013-01-01

Human Leukocyte Antigen (HLA)-G is an immunosuppressive molecule acting on both the innate and adaptive immune system. A 14 bp insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region (3'UTR) of the HLA-G gene has been associated with a number of diseases, pregnancy complication...

CERTIFICATION REPORT The certification of the mass concentration of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA) in human serum: ERM® - DA483/IFCC

OpenAIRE

MONOGIOUDI EVANTHIA; HUTU DANA PETRONELA; CHAROUD-GOT JEAN; SHELDON JOANNA; SCHIMMEL HEINZ; TRAPMANN STEFANIE; MERONI PIERLUIGI; EMONS HENDRIK; ZEGERS INGRID

2017-01-01

This report describes the production and certification of ERM-DA483/IFCC, a serum protein reference material intended for the standardisation of measurements of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA). The material was produced according to ISO Guide 34:2009 [ ] and is certified in accordance with ISO Guide 35:2006. The raw material used to prepare ERM-DA483/IFCC was a plasmapheresis material containing a high concentration of IgG PR3 ANCA. A...

Down-link power distributions for 2G and 3G mobile communication networks

International Nuclear Information System (INIS)

Colombi, D.; Thors, B.; Persson, T.; Wiren, N.; Larsson, L. E.; Jonsson, M.; Toernevik, C.

2013-01-01

Knowledge of realistic power levels is key when conducting accurate EMF exposure assessments. In this study, down-link output power distributions for radio base stations in 2G and 3G mobile communication networks have been assessed. The distributions were obtained from network measurement data collected from the Operations Support System, which normally is used for network monitoring and management. Significant amounts of data were gathered simultaneously for large sets of radio base stations covering wide geographical areas and different environments. The method was validated with in situ measurements. For the 3G network, the 90. percentile of the averaged output power during high traffic hours was found to be 43 % of the maximum available power. The corresponding number for 2G, with two or more transceivers installed, was 65 % or below. (authors)

Mobile Technology Waiting for the 3G Rush

Institute of Scientific and Technical Information of China (English)

HAYET SELLAMI

2006-01-01

@@ China is potentially the biggest third generation (3G) mobile market in the world, and everyone is eager to grab a piece of the pie. Foreign carriers are still not allowed to apply for licences since China's decision regarding licensing and adoption of 3G mobile services is still pending, but the waiting list is long. Both Chinese officials and industry executives have stated that they want 3G in place in time for the August 2008 Olympic Games held in Beijing. This tight deadline leaves no room for failure.

Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging

Energy Technology Data Exchange (ETDEWEB)

Goldstein, Robert; Livanos, Maria; Bhavsar, Gaurav; Rashid, Mohammed; Miranda, Enrique; Tolner, Berend; Meyer, Tim; Chester, Kerry [UCL Cancer Institute, London (United Kingdom); Sosabowski, Jane; Leyton, Julius; Mather, Stephen [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom); Vigor, Kim [Clare Hall Laboratories, Biotherapeutics Development Unit, Cancer Research UK, South Mimms (United Kingdom); Nagy-Davidescu, Gabriela; Plueckthun, Andreas [Universitaet Zuerich, Biochemisches Institut, Zuerich (Switzerland); Yeung, Jenny [UCL Cancer Institute, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom)

2014-11-13

Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. G3 DARPins tagged with hexahistidine (His{sub 6}) or with histidine glutamate (HE){sub 3} and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with {sup 125}I, or with {sup 111}In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE){sub 3}-G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. For both isotopes, (HE){sub 3}-G3 had significantly lower liver uptake than His{sub 6}-G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His{sub 6}-G3 and untagged G3. (HE){sub 3}-G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from {sup 111}In-(HE){sub 3}-G3 was better maintained in tumours and cleared faster from serum than radioactivity from {sup 125}I-(HE){sub 3}-G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, {sup 111}In-labelled and {sup 125}I-labelled (HE){sub 3}-G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of

EIF3G is associated with narcolepsy across ethnicities

DEFF Research Database (Denmark)

Holm, Anja; Lin, Ling; Faraco, Juliette

2015-01-01

conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could...... be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT......1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus...

Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase.

Science.gov (United States)

Stoyanov, B; Volinia, S; Hanck, T; Rubio, I; Loubtchenkov, M; Malek, D; Stoyanova, S; Vanhaesebroeck, B; Dhand, R; Nürnberg, B

1995-08-04

Phosphoinositide-3 kinase activity is implicated in diverse cellular responses triggered by mammalian cell surface receptors and in the regulation of protein sorting in yeast. Receptors with intrinsic and associated tyrosine kinase activity recruit heterodimeric phosphoinositide-3 kinases that consist of p110 catalytic subunits and p85 adaptor molecules containing Src homology 2 (SH2) domains. A phosphoinositide-3 kinase isotype, p110 gamma, was cloned and characterized. The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85. A potential pleckstrin homology domain is located near its amino terminus. The p110 gamma isotype may link signaling through G protein-coupled receptors to the generation of phosphoinositide second messengers phosphorylated in the D-3 position.

Antibody response in vaccinated pregnant mares to recent G3BP[12] and G14P[12] equine rotaviruses

Directory of Open Access Journals (Sweden)

Nemoto Manabu

2012-11-01

Full Text Available Abstract Background Both the G3P[12] and the G14P[12] type of equine group A rotavirus (RVA have recently become predominant in many countries, including Japan. G3 types are classified further into G3A and G3B. The G3A viruses have been circulating in Europe, Australia, and Argentina, and the G3B viruses have been circulating in Japan. However, only an inactivated vaccine containing a single G3BP[12] strain is commercially available in Japan. To assess the efficacy of the current vaccine against recently circulating equine RVA strains, we examined antibody responses in pregnant mares to recent G3BP[12] and G14P[12] strains by virus neutralization test. Findings After vaccination in five pregnant mares, the geometric mean serum titers of virus-neutralizing antibody to recent G3BP[12] strains increased 5.3- to 7.0-fold and were similar to that against homologous vaccine strain. Moreover, antibody titers to recent G14P[12] strains were also increased 3.0- to 3.5-fold. Conclusions These results suggest that inoculation of mares with the current vaccine should provide foals with virus-neutralizing antibodies against not only the G3BP[12] but also the G14P[12] RVA strain via the colostrum.

Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft

International Nuclear Information System (INIS)

Nelson, H.; Ramsey, P.S.; Kerr, L.A.; McKean, D.J.; Donohue, J.H.

1990-01-01

Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature

Tumor Necrosis Factor (TNF) –308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis

Science.gov (United States)

Chen, Min; Tang, Wenjing; Hou, Lei; Liu, Ruozhuo; Dong, Zhao; Han, Xun; Zhang, Xiaofei; Wan, Dongjun; Yu, Shengyuan

2015-01-01

Background and Objective Conflicting data have been reported on the association between tumor necrosis factor (TNF) –308G>A and nitric oxide synthase 3 (NOS3) +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the TNF –308G>A and NOS3 +894G>T polymorphisms confer genetic susceptibility to migraine. Method We performed an updated meta-analysis for TNF –308G>A and a meta-analysis for NOS3 +894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR) and 95% confidence intervals (95% CI) assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates. Results Eleven studies in 6682 migraineurs and 22591 controls for TNF –308G>A and six studies in 1055 migraineurs and 877 controls for NOS3 +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the “A” allele of the TNF –308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 – 2.87). The risk of migraine with aura (MA) was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the “T” allele of the NOS3 +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 – 3.88). Conclusions Our findings appear to support the hypothesis that the TNF –308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the NOS3 +894G>T polymorphism may modulate the risk of migraine among non-Caucasians. PMID:26098763

Security aspects of 3G-WLAN interworking

DEFF Research Database (Denmark)

Køien, Geir M.

2003-01-01

to roaming and mobility support. In short, WLAN systems are great for hot spot coverage, while 3G systems provide global coverage and the necessary network and management infrastructure to cater for security, roaming, and charging requirements. The focus of the article is on security aspects of 3GPP......Third-generation cellular systems will provide wide coverage and nearly universal roaming, but will not realistically live up to the bit rate expectations placed on them. On the other hand, WLAN systems already offer bit rates surpassing those of 3G systems, but are often found lacking with respect...

Preparation of WO3/g-C3N4 composites and their application in oxidative desulfurization

International Nuclear Information System (INIS)

Zhao, Rongxiang; Li, Xiuping; Su, Jianxun; Gao, Xiaohan

2017-01-01

Highlights: • The WO 3 /g-C 3 N 4 was successfully synthesized through simple calcination. • The process is simple and the cost raw materials is cheap. • The WO 3 /g-C 3 N 4 firstly applied to ODS. • The desulpurization rate of WO 3 /g-C 3 N 4 may attach to 91.2%. • Five recycles of WO 3 /g-C 3 N 4 still attach to 89.5% due to heterogeneous catalysis. - Abstract: WO 3 /graphitic carbon nitride (g-C 3 N 4 ) composites were successfully synthesized through direct calcining of a mixture of WO 3 and g-C 3 N 4 at 400 °C for 2 h. The WO 3 was prepared by calcination of phosphotungstic acid at 550 °C for 4 h, and the g-C 3 N 4 was obtained by calcination of melamine at 520 °C for 4 h. The WO 3 /g-C 3 N 4 composites were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and Brunner−Emmett−Teller analysis (BET). The WO 3 /g-C 3 N 4 composites exhibited stronger XRD peaks of WO 3 and g-C 3 N 4 than the WO 3 and pure g-C 3 N 4 . In addition, two WO 3 peaks at 25.7° and 26.6° emerged for the 36% −WO 3 /g-C 3 N 4 composite. This finding indicated that WO 3 was highly dispersed on the surface of the g-C 3 N 4 nanosheets and interacted with the nanosheets, which resulted in the appearance of (012) and (022) planes of WO 3 . The WO 3 /g-C 3 N 4 composite also exhibited a larger specific surface area and higher degree of crystallization than WO 3 or pure g-C 3 N 4 , which resulted in high catalytic activity of the catalyst. Desulfurization experiments demonstrated that the desulfurization rate of dibenzothiophene (DBT) in model oil reached 91.2% under optimal conditions. Moreover, the activity of the catalyst was not significantly decreased after five recycles.

Congenital Chloride-Losing Diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W

Directory of Open Access Journals (Sweden)

Fabian R. Reimold

2015-06-01

Full Text Available Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl-/HCO3- exchanger, SLC26A3.We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent intracellular distribution. The WT protein is similarly localized in LLCPK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting.

Preparation of WO3/g-C3N4 composites and their application in oxidative desulfurization

Science.gov (United States)

Zhao, Rongxiang; Li, Xiuping; Su, Jianxun; Gao, Xiaohan

2017-01-01

WO3/graphitic carbon nitride (g-C3N4) composites were successfully synthesized through direct calcining of a mixture of WO3 and g-C3N4 at 400 °C for 2 h. The WO3 was prepared by calcination of phosphotungstic acid at 550 °C for 4 h, and the g-C3N4 was obtained by calcination of melamine at 520 °C for 4 h. The WO3/g-C3N4 composites were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and Brunner-Emmett-Teller analysis (BET). The WO3/g-C3N4 composites exhibited stronger XRD peaks of WO3 and g-C3N4 than the WO3 and pure g-C3N4. In addition, two WO3 peaks at 25.7° and 26.6° emerged for the 36% -WO3/g-C3N4 composite. This finding indicated that WO3 was highly dispersed on the surface of the g-C3N4 nanosheets and interacted with the nanosheets, which resulted in the appearance of (012) and (022) planes of WO3. The WO3/g-C3N4 composite also exhibited a larger specific surface area and higher degree of crystallization than WO3 or pure g-C3N4, which resulted in high catalytic activity of the catalyst. Desulfurization experiments demonstrated that the desulfurization rate of dibenzothiophene (DBT) in model oil reached 91.2% under optimal conditions. Moreover, the activity of the catalyst was not significantly decreased after five recycles.

LLNL-G3Dv3: Global P wave tomography model for improved regional and teleseismic travel time prediction: LLNL-G3DV3---GLOBAL P WAVE TOMOGRAPHY

Energy Technology Data Exchange (ETDEWEB)

Simmons, N. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Myers, S. C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Johannesson, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Matzel, E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2012-10-06

[1] We develop a global-scale P wave velocity model (LLNL-G3Dv3) designed to accurately predict seismic travel times at regional and teleseismic distances simultaneously. The model provides a new image of Earth's interior, but the underlying practical purpose of the model is to provide enhanced seismic event location capabilities. The LLNL-G3Dv3 model is based on ∼2.8 millionP and Pnarrivals that are re-processed using our global multiple-event locator called Bayesloc. We construct LLNL-G3Dv3 within a spherical tessellation based framework, allowing for explicit representation of undulating and discontinuous layers including the crust and transition zone layers. Using a multiscale inversion technique, regional trends as well as fine details are captured where the data allow. LLNL-G3Dv3 exhibits large-scale structures including cratons and superplumes as well numerous complex details in the upper mantle including within the transition zone. Particularly, the model reveals new details of a vast network of subducted slabs trapped within the transition beneath much of Eurasia, including beneath the Tibetan Plateau. We demonstrate the impact of Bayesloc multiple-event location on the resulting tomographic images through comparison with images produced without the benefit of multiple-event constraints (single-event locations). We find that the multiple-event locations allow for better reconciliation of the large set of direct P phases recorded at 0–97° distance and yield a smoother and more continuous image relative to the single-event locations. Travel times predicted from a 3-D model are also found to be strongly influenced by the initial locations of the input data, even when an iterative inversion/relocation technique is employed.

iMac G3 Blueberry 350MHz

CERN Multimedia

2000-01-01

The iMac G3 is an all-in-one personal computer, encompassing both the monitor and the computer in one package. It allowed to revitalize the Apple brand that was in decline and close to financial ruin. Originally released in striking bondi blue and later a range of other translucent plastic envelopes in bright colors. The iMac comes with a keyboard and mouse matching the color of the case. The iMac G3 was sold from 1998 to 2003 and has been updated many times.

Synthesis of g-C3N4/Ag3PO4 heterojunction with enhanced photocatalytic performance

International Nuclear Information System (INIS)

He, Peizhi; Song, Limin; Zhang, Shujuan; Wu, Xiaoqing; Wei, Qingwu

2014-01-01

Graphical abstract: g-C 3 N 4 /Ag 3 PO 4 heterojunction photocatalyst with visible-light response was prepared by a facile coprecipitation method. The results show that g-C 3 N 4 /Ag 3 PO 4 possesses a much higher activity for the decomposition of RhB than that of the pure Ag 3 PO 4 particles. The most mechanism is that g-C 3 N 4 /Ag 3 PO 4 heterojunction photocatalyst can efficiently separate the photogenerated electron–hole pairs, enhancing the photocatalytic activity of g-C 3 N 4 /Ag 3 PO 4 composites. - Highlights: • g-C 3 N 4 /Ag 3 PO 4 heterojunction showed much higher activity than that of Ag 3 PO 4 . • The high activity could be attributed to g-C 3 N 4 for modifying Ag 3 PO 4 . • More ·OH radicals may be significant reason to improve Ag 3 PO 4 activity. - Abstract: g-C 3 N 4 /Ag 3 PO 4 heterojunction photocatalyst with visible-light response was prepared by a facile coprecipitation method. The photocatalysts were characterized by X-ray powder diffraction, transmission electron microscopy, UV–vis absorption spectroscopy and Fourier transform infrared spectroscopy. The photocatalytic activities of the obtained samples were tested by using Rhodamine B (RhB) as the degradation target under visible light irradiation. g-C 3 N 4 /Ag 3 PO 4 decomposed RhB more effectively than the pure Ag 3 PO 4 particles did, and 2 wt.% g-C 3 N 4 had the highest activity. Furthermore, 2 wt.% g-C 3 N 4 /Ag 3 PO 4 degraded high-concentration RhB more potently than unmodified Ag 3 PO 4 did, probably because g-C 3 N 4 /Ag 3 PO 4 heterojunction photocatalyst enhanced the photocatalytic activity by efficiently separating the photogenerated electron–hole pairs

Liquid Robotics Wave Glider, Honey Badger (G3), 2015, C3

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Liquid Robotics Wave Glider, Honey Badger (G3), 2015, C3. C3 board number 8215 (not coated) appears as board_id=32, task_id=23. C3 board number 771 (coated) appears...

Web Services in 3G Service Platforms

NARCIS (Netherlands)

Lagerberg, Ko; Plas, Dirk-Jaap; Wegdam, M.

2002-01-01

In third-generation (3G) networks, third-party service developers will have access to the mobile network resources using open network interfaces, such as the 3rd Generation Partnership Project's (3GPP's) Open Service Access (OSA). The service platforms that offer these interfaces provide

Molecular epidemiology and genetic evolution of the whole genome of G3P[8] human rotavirus in Wuhan, China, from 2000 through 2013.

Directory of Open Access Journals (Sweden)

Yuan-Hong Wang

Full Text Available Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as "new variant G3" have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated.The complete genomes of 33 G3P[8] human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences.Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted throughout the study period.Chinese G3P[8] rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P[8] in an Asian country.

Direct G-code manipulation for 3D material weaving

Science.gov (United States)

Koda, S.; Tanaka, H.

2017-04-01

The process of conventional 3D printing begins by first build a 3D model, then convert to the model to G-code via a slicer software, feed the G-code to the printer, and finally start the printing. The most simple and popular 3D printing technique is Fused Deposition Modeling. However, in this method, the printing path that the printer head can take is restricted by the G-code. Therefore the printed 3D models with complex pattern have structural errors like holes or gaps between the printed material lines. In addition, the structural density and the material's position of the printed model are difficult to control. We realized the G-code editing, Fabrix, for making a more precise and functional printed model with both single and multiple material. The models with different stiffness are fabricated by the controlling the printing density of the filament materials with our method. In addition, the multi-material 3D printing has a possibility to expand the physical properties by the material combination and its G-code editing. These results show the new printing method to provide more creative and functional 3D printing techniques.

In vitro cytotoxicity of the ternary PAMAM G3–pyridoxal–biotin bioconjugate

Directory of Open Access Journals (Sweden)

Uram Ł

2013-12-01

Full Text Available Łukasz Uram, Magdalena Szuster, Krzysztof Gargasz, Aleksandra Filipowicz, Elżbieta Wałajtys-Rode, Stanisław Wołowiec Cosmetology Department, University of Information Technology and Management in Rzeszów, Rzeszów, Poland Abstract: A third-generation polyamidoamine dendrimer (PAMAM G3 was used as a macromolecular carrier for pyridoxal and biotin. The binary covalent bioconjugate of G3, with nine molecules of biotin per one molecule of G3 (G39B, and the ternary covalent bioconjugate of G3, with nine biotin and ten pyridoxal molecules (G39B10P, were synthesized. The biotin and pyridoxal residues of the bioconjugate were available for carboxylase and transaminase enzymes, as demonstrated in the conversion of pyruvate to oxaloacetate and alanine to pyruvate, respectively, by in vitro monitoring of the reactions, using 1H nuclear magnetic resonance spectroscopy. The toxicity of the ternary bioconjugate (BC-PAMAM was studied in vitro on BJ human normal skin fibroblasts and human squamous cell carcinoma (SCC-15 cell cultures in comparison with PAMAM G3, using three cytotoxicity assays (XTT, neutral red, and crystal violet and an estimation of apoptosis by confocal microscopy detection. The tests have shown that BC-PAMAM has significantly lower cytotoxicity compared with PAMAM. Nonconjugated PAMAM was not cytotoxic at concentrations up to 5 µM (NR and 10 µM (XTT, and BC-PAMAM was not cytotoxic up to 50 µM (both assays for both cell lines. It has been also found that normal fibroblasts were more sensitive than SCC to both PAMAM and BC-PAMAM. The effect of PAMAM and BC-PAMAM on the initiation of apoptosis (PAMAM in fibroblasts at 5 µM and BC-PAMAM at 10 µM in both cell lines corresponded with cytotoxicity assays for both cell lines. We concluded that normal fibroblasts are more sensitive to the cytotoxic effects of the PAMAM G3 dendrimer and that modification of its surface cationic groups by substitution with biologically active molecules

Isolation and expression of a novel chick G-protein cDNA coding for a G alpha i3 protein with a G alpha 0 N-terminus.

OpenAIRE

Kilbourne, E J; Galper, J B

1994-01-01

We have cloned cDNAs coding for G-protein alpha subunits from a chick brain cDNA library. Based on sequence similarity to G-protein alpha subunits from other eukaryotes, one clone was designated G alpha i3. A second clone, G alpha i3-o, was identical to the G alpha i3 clone over 932 bases on the 3' end. The 5' end of G alpha i3-o, however, contained an alternative sequence in which the first 45 amino acids coded for are 100% identical to the conserved N-terminus of G alpha o from species such...

Mercury-Induced Externalization of Phosphatidylserine and Caspase 3 Activation in Human Liver Carcinoma (HepG2 Cells

Directory of Open Access Journals (Sweden)

Paul B. Tchounwou

2006-03-01

Full Text Available Apoptosis arises from the active initiation and propagation of a series of highly orchestrated specific biochemical events leading to the demise of the cell. It is a normal physiological process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. Diverse groups of molecules are involved in the apoptosis pathway and it functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early and late-stage apoptosis in human liver carcinoma (HepG2 cells. The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG2 cells. Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 ± 0.6 μg/mL for mercury in HepG2 cells. The study data indicated a dose response relationship between mercury exposure and the degree of early and late-stage apoptosis in HepG2 cells. The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0

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

Science.gov (United States)

2012-01-01

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

Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

International Nuclear Information System (INIS)

Hu, Tao; Zhang, Chunhua; Tang, Qiongling; Su, Yanan; Li, Bo; Chen, Long; Zhang, Zheng; Cai, Tianchi; Zhu, Yuechun

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown. HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (A375-WT), G6PD deficiency (A375-G6PD∆), G6PD cDNA overexpression (A375-G6PD∆-G6PD-WT), and mutant G6PD cDNA (A375-G6PD∆-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot. Delayed formation and slowed growth were apparent in A375-G6PD∆ cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD∆, along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD∆-G6PD-WT and A375-G6PD∆-G6PD-G487A cells. G6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications

Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

Science.gov (United States)

Bai, Xiaoxia; Tian, Ting; Wang, Peng; Yang, Xiaofu; Wang, Zhengping; Dong, Minyue

2015-03-01

Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV. © 2014 Wiley Periodicals, Inc.

Uus 3G mobiilivõrk maksab 2-3 miljardit / Raigo Neudorf

Index Scriptorium Estoniae

Neudorf, Raigo

2003-01-01

Kolmanda põlvkonna (3G) ehk UMTS mobiilsidevõrgu loomine läheb kohalikele mobiilioperaatoritele maksma hinnanguliselt 2-3 miljardit krooni. Litsentsi eest riigi nõutavat 70 miljonit krooni peetakse kalliks

3G toob EMT-le praegu veel kahjumikroone / Mikk Salu

Index Scriptorium Estoniae

Salu, Mikk, 1975-

2006-01-01

Mobiilsidefirmal EMT on ligi 6000 3G klienti, sobivate telefonimudelite arv on kasvanud viieteistkümnele, 3G võrgutehnoloogia hind on hüppeliselt langenud - EMT investeerib 3G arendamisse vaid mõnikümmend miljonit krooni, samas kui mõni aasta tagasi kulutasid suured välismaised firmad miljardeid dollareid

A review on g-C3N4-based photocatalysts

International Nuclear Information System (INIS)

Wen, Jiuqing; Xie, Jun; Chen, Xiaobo; Li, Xin

2017-01-01

Graphical abstract: The photocatalytic fundamentals, versatile properties, design strategies and potential applications of g-C 3 N 4 -based photocatalysts were systematically summarized and addressed. - Highlights: • The photocatalytic fundamentals of g-C 3 N 4 were systematically summarized. • The versatile properties of g-C 3 N 4 photocatalysts were highlighted. • The different design strategies of g-C 3 N 4 photocatalysts were reviewed. • The important photocatalytic applications of g-C 3 N 4 were also addressed. - Abstract: As one of the most appealing and attractive technologies, heterogeneous photocatalysis has been utilized to directly harvest, convert and store renewable solar energy for producing sustainable and green solar fuels and a broad range of environmental applications. Due to their unique physicochemical, optical and electrical properties, a wide variety of g-C 3 N 4 -based photocatalysts have been designed to drive various reduction and oxidation reactions under light irradiation with suitable wavelengths. In this review, we have systematically summarized the photocatalytic fundamentals of g-C 3 N 4 -based photocatalysts, including fundamental mechanism of heterogeneous photocatalysis, advantages, challenges and the design considerations of g-C 3 N 4 -based photocatalysts. The versatile properties of g-C 3 N 4 -based photocatalysts are highlighted, including their crystal structural, surface phisicochemical, stability, optical, adsorption, electrochemical, photoelectrochemical and electronic properties. Various design strategies are also thoroughly reviewed, including band-gap engineering, defect control, dimensionality tuning, pore texture tailoring, surface sensitization, heterojunction construction, co-catalyst and nanocarbon loading. Many important applications are also addressed, such as photocatalytic water splitting (H 2 evolution and overall water splitting), degradation of pollutants, carbon dioxide reduction, selective organic

Magneto-optical and catalytic properties of Fe{sub 3}O{sub 4}@HA@Ag magnetic nanocomposite

Energy Technology Data Exchange (ETDEWEB)

Amir, Md., E-mail: mdamir01031001@gmail.com [Department of Chemistry, Fatih University, 34500 B.Çekmece-İstanbul, Turkey (Turkey); Bio & Nanotechnology Engineering, Faculty of Engineering, Istanbul University, 34452 Beyazıt/Fatih-İstanbul (Turkey); Güner, S. [Department of Physics, Fatih University, 34500 B.Çekmece-İstanbul, Turkey (Turkey); Yıldız, A. [Department of Textile Engineering, Namık Kemal University, 59860 Çorlu-Tekirdağ, Turkey (Turkey); Baykal, A. [Department of Chemistry, Fatih University, 34500 B.Çekmece-İstanbul, Turkey (Turkey)

2017-01-01

Fe{sub 3}O{sub 4}@HA@Ag magnetic nanocomposites (MNCs) were successfully synthesized by the simple reflux method for the removal of azo dyes from the industrial aqueous media. Fe{sub 3}O{sub 4}@HA@AgMNCs exhibited high catalytic activity to reduce MB within 20 min from the waste water. The obtained materials were characterized by the means of different techniques. Powder X-ray diffraction (XRD) analysis confirmed the single-phase of Fe{sub 3}O{sub 4} spinel structure. SEM and TEM analysis indicated that Fe{sub 3}O{sub 4}@HA@AgMNCs were nanoparticles like structure with small agglomeration. TG result showed that the products contained 9% of HA. The characteristic peaks of HA at 1601 cm{sup −1} and 1703 cm{sup −1} was observed by the means of FT-IR spectra of Fe{sub 3}O{sub 4}@HA@AgMNCs. The hysteresis (σ–H) curves revealed Fe{sub 3}O{sub 4}@HA@Ag MNCs exhibit a typical superparamagnetic characteristic with a saturation magnetization of 59.11 emu/g and measured magnetic moment is 2.45 µ{sub B}. The average magnetic particle dimension (D{sub mag}) is 13.25 nm. In accordance, the average crystallite and particle dimensions were obtained as 11.50 nm and 13.10 nm from XRD and TEM measurements, respectively. Magnetocrystalline anisotropy was offered as uniaxial and calculated effective anisotropy constant (K{sub eff}) is 2.96×10{sup 5} Erg/g. The blocking temperature was estimated as 522 K. The size-dependent saturation magnetization suggests the existence of a magnetically dead layer as 0.793 nm for Fe{sub 3}O{sub 4}@HA@Ag MNCs. The UV–vis diffuse reflectance spectroscopy (DRS) and Kubelka–Munk theory were applied to determine the optical properties of powder samples. The direct optical energy band gap (E{sub g}) values were estimated from Tauc plots between 1.62 eV and 2.12 eV. - Graphical abstract: An illustration for the fabrication of Fe{sub 3}O{sub 4}@HA@Ag MNCs. - Highlights: • The reduction of azo dye such Methylene Blue was instantly completed with

Functional interaction between type III-secreted protein IncA of Chlamydophila psittaci and human G3BP1.

Science.gov (United States)

Borth, Nicole; Litsche, Katrin; Franke, Claudia; Sachse, Konrad; Saluz, Hans Peter; Hänel, Frank

2011-01-31

Chlamydophila (Cp.) psittaci, the causative agent of psittacosis in birds and humans, is the most important zoonotic pathogen of the family Chlamydiaceae. These obligate intracellular bacteria are distinguished by a unique biphasic developmental cycle, which includes proliferation in a membrane-bound compartment termed inclusion. All Chlamydiaceae spp. possess a coding capacity for core components of a Type III secretion apparatus, which mediates specific delivery of anti-host effector proteins either into the chlamydial inclusion membrane or into the cytoplasm of target eukaryotic cells. Here we describe the interaction between Type III-secreted protein IncA of Cp. psittaci and host protein G3BP1 in a yeast two-hybrid system. In GST-pull down and co-immunoprecipitation experiments both in vitro and in vivo interaction between full-length IncA and G3BP1 were shown. Using fluorescence microscopy, the localization of G3BP1 near the inclusion membrane of Cp. psittaci-infected Hep-2 cells was demonstrated. Notably, infection of Hep-2 cells with Cp. psittaci and overexpression of IncA in HEK293 cells led to a decrease in c-Myc protein concentration. This effect could be ascribed to the interaction between IncA and G3BP1 since overexpression of an IncA mutant construct disabled to interact with G3BP1 failed to reduce c-Myc concentration. We hypothesize that lowering the host cell c-Myc protein concentration may be part of a strategy employed by Cp. psittaci to avoid apoptosis and scale down host cell proliferation.

Investigation of Load Sharing in Hybrid (2G/3G) Mobile Networks

OpenAIRE

Martynas Stirbys; Karolis Žvinys

2015-01-01

The main purpose of this work is to investigate load sharing methods for 2G/3G cellular networks in order to determine their impact on the network and users. One of the study aims is to analyze the performance of the methods. Moreover the paper provides an overview of the methods circumstances, limitations. Directed Retry and Load Based Handover methods were chosen. Data was obtained from real Lithuanian mobile operator’s network. The paper also discusses the changes in Key Performance Indica...

Supersymmetric M3-branes and G{sub 2} manifolds

Energy Technology Data Exchange (ETDEWEB)

Cvetic, M. E-mail: cvetic@cvetic.hep.upenn.edu; Gibbons, G.W.; Lue, H.; Pope, C.N

2002-01-07

We obtain a generalisation of the original complete Ricci-flat metric of G{sub 2} holonomy on R{sup 4}xS{sup 3} to a family with a nontrivial parameter {lambda}. For generic {lambda} the solution is singular, but it is regular when {lambda}={l_brace}-1,0,+1{r_brace}. The case {lambda}=0 corresponds to the original G{sub 2} metric, and {lambda}={l_brace}-1,1{r_brace} are related to this by an S{sub 3} automorphism of the SU(2){sup 3} isometry group that acts on the S{sup 3}xS{sup 3} principal orbits. We then construct explicit supersymmetric M3-brane solutions in D=11 supergravity, where the transverse space is a deformation of this class of G{sub 2} metrics. These are solutions of a system of first-order differential equations coming from a superpotential. We also find M3-branes in the deformed backgrounds of new G{sub 2} holonomy metrics that include one found by A. Brandhuber, J. Gomis, S. Gubser and S. Gukov, and show that they also are supersymmetric.

78 FR 958 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof Notice of Receipt...

Science.gov (United States)

2013-01-07

... INTERNATIONAL TRADE COMMISSION [DN 2929] Certain Wireless Devices With 3G and/or 4G Capabilities... with 3G and/or 4G Capabilities and Components Thereof, DN 2929; the Commission is soliciting comments... importation of certain wireless devices with 3g and/or 4g capabilities and components thereof. The complaint...

Evolution to 3G Mobile Communication

Indian Academy of Sciences (India)

introduced to allow for high-speed data packet transmission. IS-. 9SB supports .... tors not only to expand the wireless data market in preparation for the introduction of 3G ... A mobile terminal can save power by supporting. 8PSK only when RF ...

Health physics during work on the G. 2 and G. 3 reactor exchanges

International Nuclear Information System (INIS)

Rodier, J.; Chassany, J.; Guillermin, P.

1965-01-01

During this work and its preparation, which took place first at G. 2 and then at G. 3 over a period of 11 months, 15000 measurement results were obtained. Their analysis, together with a consideration of the organisation on the site and of the conclusions drawn from the experiment, shows the various factors which determine the importance of the radio-active dangers. (authors) [fr

Highly specific detection of muscarinic M3 receptor, G protein interaction and intracellular trafficking in human detrusor using Proximity Ligation Assay (PLA).

Science.gov (United States)

Berndt-Paetz, Mandy; Herbst, Luise; Weimann, Annett; Gonsior, Andreas; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

2018-05-01

Muscarinic acetylcholine receptors (mAChRs) regulate a number of important physiological functions. Alteration of mAChR expression or function has been associated in the etiology of several pathologies including functional bladder disorders (e.g bladder pain syndrome/interstitial cystitis - BPS/IC). In a previous study we found specific mAChR expression patterns associated with BPS/IC, while correlation between protein and gene expression was lacking. Posttranslational regulatory mechanisms, e.g. altered intracellular receptor trafficking, could explain those differences. In addition, alternative G protein (GP) coupling could add to the pathophysiology via modulation of muscarinic signaling. In our proof-of-principle study, we addressed these questions in situ. We established PLA in combination with confocal laserscanning microscopy (CLSM) and 3D object reconstruction for highly specific detection and analysis of muscarinic 3 receptors (M3), G protein (GP) coupling and intracellular trafficking in human detrusor samples. Paraffin sections of formalin-fixed bladder tissue (FFPE) of BPS/IC patients receiving transurethral biopsy were examined by Cy3-PLA for M3 expression, coupling of M3 to GPs (G αq/11 , G αs , G αi ) and interaction of M3 with endocytic regulator proteins. Membranes were labeled with wheat germ agglutinin-Alexa Fluor ® 488, nuclei were stained with DAPI. Object density and co-localization were analyzed in 3D-reconstruction of high resolution confocal z-stacks. Confocal image stack processing resulted in well demarcated objects. Calculated receptor densities correlated significantly with existing confocal expression data, while significantly improved specificity of M3 detection by PLA was verified using bladder tissue samples from transgenic mice. 50-60% of the M3 receptor complexes were plasma membrane associated in human bladder detrusor. Application of PLA for M3 and GPs allowed visualization of M3-GP interactions and revealed individual GP

Investigation of Load Sharing in Hybrid (2G/3G Mobile Networks

Directory of Open Access Journals (Sweden)

Martynas Stirbys

2015-07-01

Full Text Available The main purpose of this work is to investigate load sharing methods for 2G/3G cellular networks in order to determine their impact on the network and users. One of the study aims is to analyze the performance of the methods. Moreover the paper provides an overview of the methods circumstances, limitations. Directed Retry and Load Based Handover methods were chosen. Data was obtained from real Lithuanian mobile operator’s network. The paper also discusses the changes in Key Performance Indicators.

Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment

DEFF Research Database (Denmark)

Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

2002-01-01

A cancer patient receiving long-term oral sustained-release morphine treatment and periodically presenting with unusually high plasma M3G/M6G ratios is described. We found the patient's formation of M6G more unstable and perhaps delayed compared to the formation of M3G. There is no apparent...... explanation for this phenomenon and the high M3G/M6G ratios had no implications for the patient's pain experience or side effects from the morphine treatment....

Investigating the Role of the Arabidopsis Homologue of the Human G3BP in RNA Metabolism, Cellular Stress Responses and Innate Immunity

KAUST Repository

Abulfaraj, Aala A.

2018-04-01

Mitogen-activated protein kinases (MAPKs) belong to the most conserved signaling pathways and are found in all eukaryotes, including humans where they play important roles in various diseases and cancer. Stimulation of this signal transduction pathway by microbe-associated molecular patterns (MAMP) results in a multitude of events to regulate innate immune responses in Arabidopsis thaliana stimulating large-scale changes in gene expression. Starting from a phosphoproteomic screen in Arabidopsis thaliana wild type and mpk3, mpk4 and mpk6 mutants following microbe-associated molecular pattern (MAMP) treatment, several novel chromatin-associated proteins were identified that are differentially phosphorylated by stress-induced protein kinases. Arabidopsis Ras GTPase-activating protein SH3-domain-binding protein (AtG3BP-1) is a downstream putative substrate of the MAMP-stimulated MAPK pathway that is phosphorylated by MPK3, 4 and 6 in in vitro kinase assays. AtG3BP1 belongs to a highly conserved family of RNA-binding proteins in eukaryotes that link kinase receptormediated signaling to RNA metabolism. Here, we report the characterization of the Arabidopsis homolog of human G3BP1 in plant innate immunity. AtG3BP1 negatively regulates plant immunity and defense immune responses. Atg3bp1 mutant lines show constitutive stomata closure, expression of a number of key defense marker genes, and accumulate salicylic acid but not jasmonic acid. Furthermore, Atg3bp1 plants exhibit enhanced resistance to the biotrophic pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated by stomatal and apoplastic immunity in Atg3bp1. More generally, our data reinforce that AtG3BP1 is a key mediator of plant defense responses and transient expression of AtG3BP1 delivered striking disease resistance in the absence of yield penalty, highlighting a potential application of this gene in crop protection.

78 FR 8191 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof; Institution of...

Science.gov (United States)

2013-02-05

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-868] Certain Wireless Devices With 3G and... importation, and the sale within the United States after importation of certain wireless devices with 3G and... devices with 3G and/or 4G capabilities and components thereof by reason of infringement of one or more of...

Novel gene PUS3 c.A212G mutation in Ukrainian family with intellectual disability

Directory of Open Access Journals (Sweden)

Gulkovskyi R. V.

2015-04-01

Full Text Available Aim. To evaluate a possible role of a novel c.A212G substitution in the PUS3 gene at intellectual disability (ID. Methods. The observed group consisted of the ID Ukrainian family members (parents and two affected children and the control group – of 300 healthy individuals from general population of Ukraine. Sanger sequencing of the PUS3 gene exon 1 was performed for the family members. Polymorphic variants of c.A212G were analyzed using ARMS PCR. The homology models of wild type and p.Y71C mutant catalytic domains of human Pus3 were generated using the crystal structure of the human Pus1 catalytic domain (PDB ID: 4NZ6 as a template. Results. It was shown that the father of the affected siblings was the c.A212G substitution heterozygous carrier whereas the mother was a wild type allele homozygote, and the exom sequencing result was confirmed – the affected children are 212G homozygotes. We supposed de novo mutation in the maternal germ line. A low frequency of 212G allele (0.0017 was shown in the population of Ukraine. Homology modelling of the wild type and p.Y71C mutant catalytic domain of human Pus3 revealed that substitution p.Y71C is located in close proximity to its active site. Conclusions. The absence of hypoproteinemia in our patients, homozygous for the 212C allele allows us to assume that the mutation c.A212G PUS3 is rather neutral and cannot be the major cause of ID. However, considering a low frequency of the 212G allele in the population and close localization of p.Y71C substitution to the active site of hPus3 we cannot exclude that the c.A212G mutation in PUS3 may be a modifier for some pathologies including syndromic ID.

Clad failure detection in G 3 - operational feedback; Detection de rupture de gaines G 3 - experience d'exploitation

Energy Technology Data Exchange (ETDEWEB)

Plisson, J [CEA Marcoule, Centre de Production de Plutonium, 30 (France)

1964-07-01

After briefly reviewing the role and the principles of clad failure detection, the author describes the working conditions and the conclusions reached after 4 years operation of this installation on the reactor G 3. He mentions also the modifications made to the original installation as well as the tests carried out and the experiments under way. (author) [French] Apres un rappel succinct du role et des principes de la detection de rupture de gaines, l'auteur fait un expose des conditions de fonctionnement et de l'experience tiree de 4 annees d'exploitation de cette installation sur le reacteur G 3. Il signale au passage les modifications apportees a l'installation d'origine, ainsi que les essais effectues, et les experiences en cours.

Experiences in transferring of AFA 3G fuel assembly fabrication

International Nuclear Information System (INIS)

Yang Xiaodong; Wu Zhiming; Luo Jiankang

2002-01-01

Implementation program is developed for the transferring of AFA 3G technology, together with the project management experts designated by Framatome Company, to facilitate the technology import under the guidance of strict program. Technical documents and quality insurance management documents are developed based on the full understanding of the information provided by Framatome to guide the fabrication of AFA 3G fuel elements. Technical requirement suggested by Framatome is adopted as much as possible, considering the practical process capability of YFP. The focus is the technology about fabrication difficulties in the AFA 3G technology, to insure the successful transfer of the AFA 3G fabrication technology

Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways

Directory of Open Access Journals (Sweden)

Gina-Maria Lilienthal

2018-05-01

Full Text Available IgG antibodies (Abs mediate their effector functions through the interaction with Fcγ receptors (FcγRs and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated complement activation in a hemolytic assay in an antigen-dependent and IgG subclass-specific manner. From this perspective, we discuss the potential of murine IgG1 and human IgG4 to block the complement activation as well as suppressive effects of sialylated IgG subclass Abs on FcγR-mediated immune cell activation. Accumulating evidence suggests that both mechanisms seem to be responsible for preventing uncontrolled IgG (autoAb-induced inflammation in mice and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc glycosylation patterns might explain different outcomes of IgG-mediated immune responses and provide new therapeutic options through the induction, enrichment, or application of antigen-specific sialylated human IgG4 to prevent complement and FcγR activation as well.

An interpenetrating HA/G/CS biomimic hydrogel via Diels-Alder click chemistry for cartilage tissue engineering.

Science.gov (United States)

Yu, Feng; Cao, Xiaodong; Zeng, Lei; Zhang, Qing; Chen, Xiaofeng

2013-08-14

In order to mimic the natural cartilage extracellular matrix, a novel biological degradable interpenetrating network hydrogel was synthesized from the gelatin (G), hyaluronic acid (HA) and chondroitin sulfate (CS) by Diels-Alder "click" chemistry. HA was modified with furylamine and G was modified with furancarboxylic acid respectively. (1)H NMR spectra and elemental analysis showed that the substitution degrees of HA-furan and G-furan were 71.5% and 44.5%. Then the hydrogels were finally synthesized by cross-linking furan-modified HA and G derivatives with dimaleimide poly(ethylene glycol) (MAL-PEG-MAL). The mechanical and degradation properties of the hydrogels could be tuned simply through varying the molar ratio between furan and maleimide. Rheological, mechanical and degradation studies demonstrated that the Diels-Alder "click" chemistry is an efficient method for preparing high performance biological interpenetrating hydrogels. This biomimic hydrogel with improved mechanical properties could have great potential applications in cartilage tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rasputin, more promiscuous than ever: a review of G3BP.

Science.gov (United States)

Irvine, Katharine; Stirling, Renee; Hume, David; Kennedy, Derek

2004-12-01

In this review, we highlight what G3BP's domain structure initially suggested; that G3BPs are "scaffolding" proteins linking signal transduction to RNA metabolism. Whilst it is most attractive to hypothesise about G3BP's role in signalling to mRNA metabolism, it is not known whether all G3BP functions impinge on their RNA-binding activities, so any theories are naturally subject to this qualification. It is hypothesised that, in coordination with an array of other proteins, G3BP, in a phosphorylation-dependent manner, is involved in the post-transcriptional regulation of a subset of mRNAs, at least some of which are in common with those regulated by Hu proteins. These transcripts, partially controlled at the post-transcriptional level by G3BPs, code for proteins important in transcription (e.g. c-Myc) and cytoskeletal arrangement (e.g. Tau), amongst other as yet undetermined pathways. The subtle differences between G3BP family members could dictate binding to a variety of signalling proteins, so each of the G3BPs may participate in different, though possibly related mRNPs, which are assembled in response to different stimuli. The combinatorial nature of the mRNP complex offers a powerful means of regulating gene expression, beyond that provided by a simple mRNA sequence. The ways in which mRNP flexibility and specificity may be harnessed to coordinate gene expression of functionally or structurally related mRNAs are not yet fully appreciated. Characterising mRNP composition and the function/s of mRNP components, such as the G3BPs, will aid in the understanding of how post-transcriptional mechanisms contribute to the global regulation of gene expression.

The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE).

Science.gov (United States)

Basu, Amitava; Dasari, Vasanthi; Mishra, Rakesh K; Khosla, Sanjeev

2014-01-01

DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.

The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE.

Directory of Open Access Journals (Sweden)

Amitava Basu

Full Text Available DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.

Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

Science.gov (United States)

Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

2014-04-11

Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

Structure of human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7)

International Nuclear Information System (INIS)

Arai, Ryoichi; Yoshikawa, Seiko; Murayama, Kazutaka; Imai, Yuzuru; Takahashi, Ryosuke; Shirouzu, Mikako; Yokoyama, Shigeyuki

2006-01-01

The crystal structure of human UBE2G2/UBC7 was solved at 2.56 Å resolution. The superimposition of UBE2G2 on UbcH7 in a c-Cbl–UbcH7–ZAP70 ternary complex suggested that the two loop regions of UBE2G2 interact with the RING domain in a similar way as UbcH7. The human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7) is involved in protein degradation, including a process known as endoplasmic reticulum-associated degradation (ERAD). The crystal structure of human UBE2G2/UBC7 was solved at 2.56 Å resolution. The UBE2G2 structure comprises a single domain consisting of an antiparallel β-sheet with four strands, five α-helices and two 3 10 -helices. Structural comparison of human UBE2G2 with yeast Ubc7 indicated that the overall structures are similar except for the long loop region and the C-terminal helix. Superimposition of UBE2G2 on UbcH7 in a c-Cbl–UbcH7–ZAP70 ternary complex suggested that the two loop regions of UBE2G2 interact with the RING domain in a similar way to UbcH7. In addition, the extra loop region of UBE2G2 may interact with the RING domain or its neighbouring region and may be involved in the binding specificity and stability

Application of Blue Ocean Strategy to Chinese 3G Mobile Telecom Industry

OpenAIRE

Wang, Zang; Yang, Jin Wei

2010-01-01

The purpose of this study was to apply “Blue Ocean” strategy to Chinese 3G mobile telecom industry. Chinese 3G mobile telecom industry is a rapidly growing multiple industry which served a lot of services to customers. The thesis tries to find whether all services are important to Chinese 3G operators’ competiveness and how to create a blue ocean for Chinese 3G operators, help Chinese 3G operators to find their core service from the customers’ opinion and create a new blue ocean industry of m...

A Comparison between the Swedish 3G Beauty Contest and the UK 3G Auction

OpenAIRE

Welin, Erik

2006-01-01

This thesis compares the two different version of public franchise bidding for awarding 3G licenses used in Sweden and the UK, respectively a beauty contest and an auction. The fact is that the Swedish beauty contest has failed to tackle many of the problems discussed in connection with public franchise bidding in an effective way. Sweden has first of all had problems with enforcing the ambitious coverage criteria. The UK has on the other hand succeeded in tackling the problems and raised gov...

Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells▿

Science.gov (United States)

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

2007-01-01

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

G3//BMK and Its Application to Calculation of Bond Dissociation Enthalpies.

Science.gov (United States)

Zheng, Wen-Rui; Fu, Yao; Guo, Qing-Xiang

2008-08-01

On the basis of systematic examinations it was found that the BMK functional significantly outperformed the other popular density functional theory methods including B3LYP, B3P86, KMLYP, MPW1P86, O3LYP, and X3LYP for the calculation of bond dissociation enthalpies (BDEs). However, it was also found that even the BMK functional might dramatically fail in predicting the BDEs of some chemical bonds. To solve this problem, a new composite ab initio method named G3//BMK was developed by combining the strengths of both the G3 theory and BMK. G3//BMK was found to outperform the G3 and G3//B3LYP methods. It could accurately predict the BDEs of diverse types of chemical bonds in various organic molecules within a precision of ca. 1.2 kcal/mol.

Associations between an IgG3 polymorphism in the binding domain for FcRn, transplacental transfer of malaria-specific IgG3, and protection against Plasmodium falciparum malaria during infancy: A birth cohort study in Benin.

Directory of Open Access Journals (Sweden)

Celia Dechavanne

2017-10-01

Full Text Available Transplacental transfer of maternal immunoglobulin G (IgG to the fetus helps to protect against malaria and other infections in infancy. Recent studies have emphasized the important role of malaria-specific IgG3 in malaria immunity, and its transfer may reduce the risk of malaria in infancy. Human IgGs are actively transferred across the placenta by binding the neonatal Fc receptor (FcRn expressed within the endosomes of the syncytiotrophoblastic membrane. Histidine at position 435 (H435 provides for optimal Fc-IgG binding. In contrast to other IgG subclasses, IgG3 is highly polymorphic and usually contains an arginine at position 435, which reduces its binding affinity to FcRn in vitro. The reduced binding to FcRn is associated with reduced transplacental transfer and reduced half-life of IgG3 in vivo. Some haplotypes of IgG3 have histidine at position 435. This study examines the hypotheses that the IgG3-H435 variant promotes increased transplacental transfer of malaria-specific antibodies and a prolonged IgG3 half-life in infants and that its presence correlates with protection against clinical malaria during infancy.In Benin, 497 mother-infant pairs were included in a longitudinal birth cohort. Both maternal and cord serum samples were assayed for levels of IgG1 and IgG3 specific for MSP119, MSP2 (both allelic families, 3D7 and FC27, MSP3, GLURP (both regions, R0 and R2, and AMA1 antigens of Plasmodium falciparum. Cord:maternal ratios were calculated. The maternal IgG3 gene was sequenced to identify the IgG3-H435 polymorphism. A multivariate logistic regression was used to examine the association between maternal IgG3-H435 polymorphism and transplacental transfer of IgG3, adjusting for hypergammaglobulinemia, maternal malaria, and infant malaria exposure. Twenty-four percent of Beninese women living in an area highly endemic for malaria had the IgG3-H435 allele (377 women homozygous for the IgG3-R435 allele, 117 women heterozygous for the IgG

Single Day Construction of Multigene Circuits with 3G Assembly.

Science.gov (United States)

Halleran, Andrew D; Swaminathan, Anandh; Murray, Richard M

2018-05-18

The ability to rapidly design, build, and test prototypes is of key importance to every engineering discipline. DNA assembly often serves as a rate limiting step of the prototyping cycle for synthetic biology. Recently developed DNA assembly methods such as isothermal assembly and type IIS restriction enzyme systems take different approaches to accelerate DNA construction. We introduce a hybrid method, Golden Gate-Gibson (3G), that takes advantage of modular part libraries introduced by type IIS restriction enzyme systems and isothermal assembly's ability to build large DNA constructs in single pot reactions. Our method is highly efficient and rapid, facilitating construction of entire multigene circuits in a single day. Additionally, 3G allows generation of variant libraries enabling efficient screening of different possible circuit constructions. We characterize the efficiency and accuracy of 3G assembly for various construct sizes, and demonstrate 3G by characterizing variants of an inducible cell-lysis circuit.

99mTcO(MAG2-3G3-dimer): a new integrin αvβ3-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics

International Nuclear Information System (INIS)

Shi, Jiyun; Wang, Lijun; Kim, Young-Seung; Zhai, Shizhen; Liu, Shuang; Jia, Bing; Wang, Fan

2009-01-01

This report presents the synthesis of a cyclic RGD dimer conjugate, MAG 2 -G 3 -E[G 3 -c(RGDfK)] 2 (MAG 2 -3G 3 -dimer, G 3 = Gly-Gly-Gly, MAG 2 = S-benzoyl mercaptoacetylglycylglycyl), and evaluation of its 99m Tc complex, 99m TcO(MAG 2 -3G 3 -dimer), as a new radiotracer for imaging the tumor integrin α v β 3 expression. An in vitro displacement assay was used to determine the integrin α v β 3 binding affinity of MAG 2 -3G 3 -dimer against 125 I-c(RGDyK) bound to U87MG human glioma cells. The athymic nude mice bearing U87MG glioma xenografts were used for biodistribution and planar imaging studies. We found that (1) MAG 2 is such a highly effective bifunctional chelator that 99m TcO(MAG 2 -3G 3 -dimer) can be prepared in high yield (radiochemical purity >95%) and with high specific activity (∝5 Ci/μmol) using a kit formulation; (2) 99m TcO(MAG 2 -3G 3 -dimer) has very high solution stability in the kit matrix; and (3) 99m TcO(MAG 2 -3G 3 -dimer) has very fast clearance kinetics from the intestine, liver, and kidneys. Among the 99m Tc-labeled cyclic RGD peptides evaluated in the xenografted U87MG glioma models, 99m TcO(MAG 2 -3G 3 -dimer) has the best pharmacokinetics and tumor to background ratios (tumor/liver = 4.29 ± 1.00 at 30 min postinjection and 8.29 ± 1.50 at 120 min postinjection; tumor/kidney = 1.16 ± 0.19 at 30 min postinjection and 2.49 ± 0.25 at 120 min postinjection). Planar imaging studies showed that tumors in the glioma-bearing mice administered with 99m TcO(MAG 2 -3G 3 -dimer) can be visualized with excellent contrast as early as 15 min postinjection. 99m TcO(MAG 2 -3G 3 -dimer) was able to maintain its chemical integrity in kidneys (>80% intact) and liver (>95% intact) over the 2-h period. However, there was significant metabolism (>50% of the injected radioactivity) detected in both urine and feces samples. 99m TcO(MAG 2 -3G 3 -dimer) is a very attractive radiotracer for early detection of integrin α v β 3 -positive tumors and has

RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism

International Nuclear Information System (INIS)

Yamaki, Nao; Negishi, Manabu; Katoh, Hironori

2007-01-01

In normal epithelial cells, cell-matrix interaction is required for cell survival and proliferation, whereas disruption of this interaction causes epithelial cells to undergo apoptosis called anoikis. Here we show that the small GTPase RhoG plays an important role in the regulation of anoikis. HeLa cells are capable of anchorage-independent cell growth and acquire resistance to anoikis. We found that RNA interference-mediated knockdown of RhoG promoted anoikis in HeLa cells. Previous studies have shown that RhoG activates Rac1 and induces several cellular functions including promotion of cell migration through its effector ELMO and the ELMO-binding protein Dock180 that function as a Rac-specific guanine nucleotide exchange factor. However, RhoG-induced suppression of anoikis was independent of the ELMO- and Dock180-mediated activation of Rac1. On the other hand, the regulation of anoikis by RhoG required phosphatidylinositol 3-kinase (PI3K) activity, and constitutively active RhoG bound to the PI3K regulatory subunit p85α and induced the PI3K-dependent phosphorylation of Akt. Taken together, these results suggest that RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1

16 CFR Appendix G3 to Part 305 - Furnaces-Oil

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Furnaces-Oil G3 Appendix G3 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE CONCERNING... Part 305—Furnaces—Oil Manufacturer's rated heating capacities (Btu's/hr.) Range of annual fuel...

The 3'-untranslated region of the HLA-G gene in relation to pre-eclampsia: revisited

DEFF Research Database (Denmark)

Larsen, M H; Hylenius, S; Andersen, Anne-Marie Nybo

2010-01-01

Abnormal human leukocyte antigen G (HLA-G) expression may be involved in pre-eclampsia. A 14 bp insertion/deletion polymorphism exists in exon 8 of the HLA-G gene. Fetal +14/+14 bp HLA-G genotype may predispose to pre-eclampsia in the mother. Other polymorphisms, besides the 14 bp polymorphism (rs......66554220), in the 3'-untranslated region (3'-UTR) (exon 8) of the HLA-G gene might be associated with severe pre-eclampsia, especially in primiparas. By haplotype-specific polymerase chain reaction amplification and DNA sequence analysis in the offspring from 50 pre-eclamptic cases and 85 controls (35.......008, P(C) = 0.04) were significantly associated with severe pre-eclampsia in primiparas. In conclusion, this study indicates that the +14 bp HLA-G allele defines a nearly unique exon 8 haplotype, and fetuses homozygous for this haplotype [SNP 2995(C)/SNP 3127(G)/SNP 3172(A)/SNP 3181(G)/+14 bp...

Delivering service adaptation with 3G technology

NARCIS (Netherlands)

Liotta, A.; Yew, A.; Bohoris, C.; Pavlou, G.; Feridun, M.; Kropf, P.G.; Babin, G.

2002-01-01

Now that 3G technologies have reached their maturity, newly advanced services can be delivered to the mobile user. These include context- aware services, adaptable services and Virtual Home Environment (VHE)-like services. Important research issues relate, however, to managing such services through

Coexistence of Terrestrial and HAP 3G Networks during Disaster Scenarios

Directory of Open Access Journals (Sweden)

P. Pechac

2008-12-01

Full Text Available The aim of this paper is to show the possible coexistence of an HAP and a terrestrial component of 3G networks at a single carrier frequency. The main goal is to compare the basic parameters of terrestrial and HAP com-ponent 3G networks modeled in suburban (macrocell and urban (macro/microcell areas and to demonstrate the way they impact on each other. This study should present what we assume are the better capabilities of HAP 3G networks compared to their terrestrial counterparts. The parameters of the HAP and terrestrial component of 3G networks, were the terrestrial cells to be disabled during disasters, are also presented.

G3-C12 Peptide Reverses Galectin-3 from Foe to Friend for Active Targeting Cancer Treatment.

Science.gov (United States)

Sun, Wei; Li, Lian; Yang, Qingqing; Shan, Wei; Zhang, Zhirong; Huang, Yuan

2015-11-02

Galectin-3 is overexpressed by numerous carcinomas and is a potential target for active tumor treatments. On the other hand, galectin-3 also plays a key role in cancer progression and prevents cells from undergoing apoptosis, thereby offsetting the benefits of active targeting drugs. However, the relative contribution of the protective antiapoptotic effects of galectin-3 and the proapoptotic effects of galectin-3-targeted therapies has remained yet unrevealed. Here, we show that a galectin-3-binding peptide G3-C12 could reverse galectin-3 from foe to friend for active targeting delivery system. Results showed G3-C12 modified N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin conjugates (G3-C12-HPMA-Dox) could internalize into galectin-3 overexpressed PC-3 cells via a highly specific ligand-receptor pathway (2.2 times higher cellular internalization than HPMA-Dox). The internalized Dox stimulated the translocation of galectin-3 to the mitochondria to prevent from apoptosis. In turn, this caused G3-C12-HPMA-Dox to concentrate into the mitochondria after binding to galectin-3 intracellularly. Initially, mitochondrial galectin-3 weakened Dox-induced mitochondrial damage; however, as time progressed, G3-C12 active-mediation allowed increasing amounts of Dox to be delivered to the mitochondria, which eventually induced higher level of apoptosis than nontargeted copolymers. In addition, G3-C12 downregulates galectin-3 expression, 0.43 times lower than control cells, which could possibly be responsible for the suppressed cell migration. Thus, G3-C12 peptide exerts sequential targeting to both cell membrane and mitochondria via regulating galectin-3, and eventually reverses and overcomes the protective effects of galectin-3; therefore, it could be a promising agent for the treatment of galectin-3-overexpressing cancers.

Effects of the radiolysis products of sennoside A on HepG2 and PC-3 cell

International Nuclear Information System (INIS)

Kim, Dong Ho; Jo, Min Ho

2016-01-01

Radiolysis of sennoside A was carried out by gamma irradiation and the anti-cancer activities of the radiolysis product were evaluated. An aqueous solution of sennoside A was exposed to 0.5-3 kGy of gamma irradiation and the radiolysis products were analyzed by HPLC. A fraction of radiolysis product (RLF) of sennoside A was isolated and the RLF was presumed as a rhein-8-β-D-glucoside. The anticancer effect of the RLF was compared with the sennoside and rhein using a in vitro assay system of human prostate cancer cells (PC-3) and human hepatoma HepG2 cells. The cell viability of PC-3 and HepG2 cell was significantly decreased to 12.4±1.2% and 32.4±2.1%, respectively, by the treatment of 0.6 μM of RLF. The sennoside A (range from 0 to 25 μM) had no cytotoxic effect on PC-3 and HepG2 cells, while the rhein had the effect on HepG2 cells with a LD_5_0 at 80 μM

Effects of the radiolysis products of sennoside A on HepG2 and PC-3 cell

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Ho; Jo, Min Ho [Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

2016-11-15

Radiolysis of sennoside A was carried out by gamma irradiation and the anti-cancer activities of the radiolysis product were evaluated. An aqueous solution of sennoside A was exposed to 0.5-3 kGy of gamma irradiation and the radiolysis products were analyzed by HPLC. A fraction of radiolysis product (RLF) of sennoside A was isolated and the RLF was presumed as a rhein-8-β-D-glucoside. The anticancer effect of the RLF was compared with the sennoside and rhein using a in vitro assay system of human prostate cancer cells (PC-3) and human hepatoma HepG2 cells. The cell viability of PC-3 and HepG2 cell was significantly decreased to 12.4±1.2% and 32.4±2.1%, respectively, by the treatment of 0.6 μM of RLF. The sennoside A (range from 0 to 25 μM) had no cytotoxic effect on PC-3 and HepG2 cells, while the rhein had the effect on HepG2 cells with a LD{sub 50} at 80 μM.

Preparation of WO{sub 3}/g-C{sub 3}N{sub 4} composites and their application in oxidative desulfurization

Energy Technology Data Exchange (ETDEWEB)

Zhao, Rongxiang, E-mail: zylhzrx@126.com; Li, Xiuping, E-mail: lilili_171717@126.com; Su, Jianxun; Gao, Xiaohan

2017-01-15

Highlights: • The WO{sub 3}/g-C{sub 3}N{sub 4} was successfully synthesized through simple calcination. • The process is simple and the cost raw materials is cheap. • The WO{sub 3}/g-C{sub 3}N{sub 4} firstly applied to ODS. • The desulpurization rate of WO{sub 3}/g-C{sub 3}N{sub 4} may attach to 91.2%. • Five recycles of WO{sub 3}/g-C{sub 3}N{sub 4} still attach to 89.5% due to heterogeneous catalysis. - Abstract: WO{sub 3}/graphitic carbon nitride (g-C{sub 3}N{sub 4}) composites were successfully synthesized through direct calcining of a mixture of WO{sub 3} and g-C{sub 3}N{sub 4} at 400 °C for 2 h. The WO{sub 3} was prepared by calcination of phosphotungstic acid at 550 °C for 4 h, and the g-C{sub 3}N{sub 4} was obtained by calcination of melamine at 520 °C for 4 h. The WO{sub 3}/g-C{sub 3}N{sub 4} composites were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and Brunner−Emmett−Teller analysis (BET). The WO{sub 3}/g-C{sub 3}N{sub 4} composites exhibited stronger XRD peaks of WO{sub 3} and g-C{sub 3}N{sub 4} than the WO{sub 3} and pure g-C{sub 3}N{sub 4}. In addition, two WO{sub 3} peaks at 25.7° and 26.6° emerged for the 36% −WO{sub 3}/g-C{sub 3}N{sub 4} composite. This finding indicated that WO{sub 3} was highly dispersed on the surface of the g-C{sub 3}N{sub 4} nanosheets and interacted with the nanosheets, which resulted in the appearance of (012) and (022) planes of WO{sub 3}. The WO{sub 3}/g-C{sub 3}N{sub 4} composite also exhibited a larger specific surface area and higher degree of crystallization than WO{sub 3} or pure g-C{sub 3}N{sub 4}, which resulted in high catalytic activity of the catalyst. Desulfurization experiments demonstrated that the desulfurization rate of dibenzothiophene (DBT) in model oil reached 91.2% under optimal conditions. Moreover, the activity of the catalyst was not significantly decreased after five recycles.

Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density

DEFF Research Database (Denmark)

Barres, Romain; Osler, Megan E; Yan, Jie

2009-01-01

-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non......-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter....

Eesti tarbijate huvi 3G teenuste vastu on loid / Toivo Tänavsuu

Index Scriptorium Estoniae

Tänavsuu, Toivo

2005-01-01

Pärast EMT esimese 3G mobiilsidevõrgu avamist Tallinnas on selle teenuse kasutajate hulk kasvanud ligikaudu saja inimese võrra, 3G telefonide müük on hästi edenenud Lisa: EMT rajab 3G võrgu ka Tartusse

Genetic characterization of human hydatid cysts shows coinfection by Echinococcus canadensis G7 and Echinococcus granulosus sensu stricto G1 in Argentina.

Science.gov (United States)

Debiaggi, María Florencia; Soriano, Silvia Viviana; Pierangeli, Nora Beatriz; Lazzarini, Lorena Evelina; Pianciola, Luis Alfredo; Mazzeo, Melina Leonor; Moguillansky, Sergio; Farjat, Juan Angel Basualdo

2017-09-01

Human cystic echinococcosis caused by the larval stage of Echinococcus granulosus sensu lato (s.l.) is a highly endemic disease in the province of Neuquén, Patagonia, Argentina. Human infections with E. granulosus sensu stricto (s.s.) G1 and Echinococcus canadensis G6 were reported in Neuquén in previous studies, whereas four genotypes were identified in livestock: G1, G3, G6, and G7. The aim of this study was to identify the genotypes of E. granulosus s.l. isolates from humans of Neuquén province, Patagonia, Argentina, through the 2005-2014 period. Twenty six hydatid cysts were obtained from 21 patients. The most frequent locations were the liver and lungs. Single cysts were observed in 81.0% of patients, and combined infection of liver and lungs was detected in 9.5% of cases. Partial sequencing of mitochondrial cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes identified the presence of E. granulosus s.s. G1 (n = 11; 42.3%) including three different partial sequences; E. canadensis G6 (n = 14; 53.8%) and E. canadensis G7 (n = 1; 3.9%). Coinfection with G1 and G7 genotypes was detected in one patient who harbored three liver cysts. Most of the liver cysts corresponded to G1 and G6 genotypes. This study presents the first report in the Americas of a human infection with E. canadensis G7 and the second worldwide report of a coinfection with two different species and genotypes of E. granulosus s.l in humans. The molecular diversity of this parasite should be considered to redesign or improve the control program strategies in endemic regions.

ABT-263 induces G1/G0-phase arrest, apoptosis and autophagy in human esophageal cancer cells in vitro.

Science.gov (United States)

Lin, Qing-Huan; Que, Fu-Chang; Gu, Chun-Ping; Zhong, De-Sheng; Zhou, Dan; Kong, Yi; Yu, Le; Liu, Shu-Wen

2017-12-01

Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC 50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 μmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 μmol/L) dose-dependently induced G 1 /G 0 -phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21 Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G 1 /G 0 -phase arrest. Knockdown of p21 Waf1/Cip1 attenuated ABT-263-induced G 1 /G 0 -phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.

Cytotoxic effects of the synthetic oestrogens and androgens on Balb/c 3T3 and HepG2 cells

Directory of Open Access Journals (Sweden)

Minta Maria

2014-12-01

Full Text Available The aim of the study was to test and compare the cytotoxic potential of two synthetic oestrogens: diethylstilboestrol (DES and ethinyloestradiol (EE2 and two androgens: testosterone propionate (TP and trenbolone (TREN on two cell lines. The fibroblast cell line Balb/c 3T3 and the hepatoma cell line HepG2 were selected. To get more insight into the mode of toxic action, four methods were used, which evaluated different biochemical endpoints: mitochondrial activity (3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide reduction assay, lysosomal activity (neutral red uptake assay, total protein content, and lactate dehydrogenase release. Cytotoxicity was assessed after 24, 48, and 72 h exposure to eight concentrations ranging from 0.78 to 100 μg/mL. Concentration- and time- dependent effects were observed. Depending on the line and assay used, half maximal effective concentration after 72 h (EC50-72h values ranged as follows: DES 1-13.7 μg/mL (Balb/c 3T3 and 3.7-5.2 μg/mL (HepG2; EE2 2.1-14.3 μg/mL (Balb/c 3T3 and 1.8-7.8 μg/mL (HepG2; TP-14.9-17.5 μg/mL (Balb/c 3T3, and 63.9- 100 μg/mL (HepG2; and TREN 11.3-31.4 μg/mL (Balb/c 3T3 and 12.5-59.4 μg/mL (HepG2. The results revealed that oestrogens were more toxic than androgens and the most affected endpoint was mitochondrial activity. In contrast to oestrogens, for which EC50-72h values were similar in both lines and by all assays used, Balb/c 3T3 cells were more sensitive than HepG2 cells to TP.

The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates

International Nuclear Information System (INIS)

Zereshkian, Arman; Leyton, Jeffrey V.; Cai, Zhongli; Bergstrom, Dane; Weinfeld, Michael; Reilly, Raymond M.

2014-01-01

Introduction: Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, 111 In-NLS-7G3, which recognizes the CD123 + /CD131 - phenotype uniquely displayed by LSCs. Methods: The surviving fraction (SF) of CD123 + /CD131 - AML-5 cells exposed to 111 In-NLS-7G3 (33–266 nmols/L; 0.74 MBq/μg) or to γ-radiation (0.25-5 Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with 111 In-NLS-7G3 (16–66 nmols/L) or with γ-radiation (0.25–2 Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of 111 In-NLS-7G3 measured by cell fractionation. Results: Binding of 111 In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1 μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123 + /CD131 - epitope. 111 In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25 Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with 111 In-NLS-7G3 (16–66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25–0.5 Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to

Research on Image Transmission System Based on 3G Communication Platform

Directory of Open Access Journals (Sweden)

Jingfeng Zang

2014-07-01

Full Text Available A wireless image real-time transmission system is designed by using 3G wireless communication platform and ARM + DSP embedded system. In the environment of 3G networks, the embedded equipment has realized the functions of coding, acquisition, network transmission, decoding and playing. It is realized for real-time video of intelligent control and video compression, storage and playback in the 3G embedded image transmission system. It is especially suitable for remote location or irregular cable network transmission conditions applications. It is shown that in the 3G network video files are transferred quickly. The real-time transmission of H.264 video is broadcasted smoothly, and color distortion is less. The server can control client by remote intelligent units.

Detection of radioactive gases in the CO{sub 2} cooling the reactors G 2 - G 3; Detection des gaz radioactifs dans le CO{sub 2} de refroidissement des piles G2 - G3

Energy Technology Data Exchange (ETDEWEB)

Pouthier, J; Rossi, J [Commissariat a l' Energie Atomique, Chusclan (France). Centre de Production de Plutonium de Marcoule

1968-07-01

The carbon dioxide cooling the reactors G2 - G3 contains activation gases and fission gases. It is of interest to know their concentration, for example to be able to deduce rapidly the norms which would have to be applied in the case of an incident in the circuit. Gas-phase chromatography is applied daily for carrying out analyses. The chromatogram has separate peaks due to tritium, argon 41, krypton 85 and the 133 and 135 isotopes of xenon. By integrating each peak it is possible to calculate the specific activity of each product. The construction of an apparatus for carrying out continuous measurements is under consideration. (authors) [French] Le gaz carbonique, refroidissant les reacteurs G2 - G3, contient des gaz d'activation et des gaz de fission. Il est interessant de connaitre leur teneur par exemple pour etre en mesure de deduire rapidement les normes qu'il y aurait lieu d'appliquer en cas d'incidents sur le circuit. La methode de chromatographie en phase gazeuse est employee quotidiennement pour faire des analyses. Le chromatogramme se presente sous forme de pics distincts dus au tritium, a l'argon 41, au krypton 85 et aux isotopes 133 et 135 du xenon. L'integration de chaque pic permet de calculer l'activite specifique de chaque compose. Il est envisage de construire un appareil pour des mesures en continu. (auteurs)

Genomic sequence of Heliothis virescens ascovirus 3g isolated from Spodoptera exigua.

Science.gov (United States)

Huang, Guo-Hua; Wang, Yun-Sheng; Wang, Xing; Garretson, Tyler A; Dai, Liang-Ying; Zhang, Chuan-Xi; Cheng, Xiao-Wen

2012-11-01

Heliothis virescens ascovirus 3a (HvAV-3a), a member of the family Ascoviridae, has the highest diversity among ascovirus species that have been reported in Australia, Indonesia, China, and the United States. To understand the diversity and origin of this important ascovirus, the complete genome of the HvAV Indonesia strain (HvAV-3g), isolated from Spodoptera exigua, was determined to be 199,721 bp, with a G+C content of 45.9%. Therefore, HvAV-3g has the largest genome among the reported ascovirus genomes to date. There are 194 predicted open reading frames (ORFs) encoding proteins of 50 or more amino acid residues. In comparison to HvAV-3e reported from Australia, HvAV-3g has all the ORFs in HvAV-3e with 6 additional ORFs unique to HvAV-3g, including 1 peptidase C26 gene with the highest identity to Drosophila spp. and 2 gas vesicle protein U (GvpU) genes with identities to Bacillus megaterium. The five unique homologous regions (hrs) and 25 baculovirus repeat ORFs (bro) of HvAV-3g are highly variable.

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

Science.gov (United States)

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

2014-10-01

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

Network planning study of the metro-optical-network-oriented 3G application

Science.gov (United States)

Gong, Qian; Xu, Rong; Lin, Jin Tong

2005-02-01

To compare with the 2G mobile communication, 3G technologies can supply the perfect service scope and performance. 3G is the trend of the mobile communication. So now to build the transmission network, it is needed to consider how the transmission network to support the 3G applications. For the 3G network architecture, it include the 2 part: Utran access network and core network. So the metro optical network should consider how to build the network to adapt the 3G applications. Include the metro core and access layer. In the metro core, we should consider the network should evolved towards the Mesh architecture with ASON function to realize the fast protection and restoration, quick end-to-end service provision, and high capacity cross-connect matrix etc. In the access layer, the network should have the ability to access the 3G services such as ATM interface with IMA function. In addition, the traffic grooming should be provided to improve the bandwidth utility. In this paper, first we present the MCC network situation, the network planning model will be introduced. Then we present the topology architecture, node capacity and traffic forecast. At last, based on our analysis, we will give a total solution to MCC to build their metro optical network toward to the mesh network with the consideration of 3G services.

A three-layer immunoradiometric assay for determination of IgG subclass antibodies in Human Sera (''IgG subclass RAST'')

International Nuclear Information System (INIS)

Djurup, R.; Soendergaard, I.; Weeke, B.; University of Copenhagen, Denmark); Magnusson, C.G.M.

1984-01-01

We report the development of a three-layer immunoradiometric assay (TIRA) for measurement of IgG antibodies of all four subclasses in human sera. The first layer consists of diluted human serum, the second layer is monoclonal mouse antibodies to human IgG subclasses, and the third layer is 125 I-labelled rabbit anti-mouse IgG. Monoclonal anti-IgGI, anti-IgG3 and anti-IgG4 reacted only with their complementary IgG subclass, whereas the anti-IgG2 showed slight cross-reactivity to immunoglobins of other subclasses and classes and to light chain proteins. The observed cross-reactivity was found to be without importance, when the TIRA was applied to measurement of IgG subclass antibodies. Equipotency was established by use of appropriate dilutions of the monoclonal antibodies, and the assay was calibrated by use of human reference serum. The TIRA therefore permits reliable inter-individual and intra-individual comparisons of the IgG antibody response in all four subclasses. Non-specific binding obtained with pooled normal human serum was below 0.33%. Inter-assay coefficient of variation was between 18 and 27%. The TIRA was applied to measurement of IgG subclass antibodies to timothy grass pollen in sera from grass pollen allergies undergoing immunotherapy. (author)

Providing QoS guarantee in 3G wireless networks

Science.gov (United States)

Chuah, MooiChoo; Huang, Min; Kumar, Suresh

2001-07-01

The third generation networks and services present opportunities to offer multimedia applications and services that meet end-to-end quality of service requirements. In this article, we present UMTS QoS architecture and its requirements. This includes the definition of QoS parameters, traffic classes, the end-to-end data delivery model, and the mapping of end-to-end services to the services provided by the network elements of the UMTS. End-to-end QoS of a user flow is achieved by the combination of the QoS control over UMTS Domain and the IP core Network. In the Third Generation Wireless network, UMTS bearer service manager is responsible to manage radio and transport resources to QoS-enabled applications. The UMTS bearer service consists of the Radio Access Bearer Service between Mobile Terminal and SGSN and Core Network bearer service between SGSN and GGSN. The Radio Access Bearer Service is further realized by the Radio Bearer Service (mostly air interface) and Iu bearer service. For the 3G air interface, one can provide differentiated QoS via intelligent burst allocation scheme, adaptive spreading factor control and weighted fair queueing scheduling algorithms. Next, we discuss the requirements for the transport technologies in the radio access network to provide differentiated QoS to multiple classes of traffic. We discuss both ATM based and IP based transport solutions. Last but not least, we discuss how QoS mechanism is provided in the core network to ensure e2e quality of service requirements. We discuss how mobile terminals that use RSVP as QoS signaling mechanisms can be are supported in the 3G network which may implement only IETF diffserv mechanism. . We discuss how one can map UMTS QoS classes with IETF diffserv code points. We also discuss 2G/3G handover scenarios and how the 2G/3G QoS parameters can be mapped.

Effect of fuel assembly when changing from AFA 2G to AFA 3G on seismic loads of reactor internal

International Nuclear Information System (INIS)

Liu Wenjin; Zeng Zhongxiu; Ye Xianhui; Wu Wanjun

2013-01-01

Nonlinear seismic model for reactor with fuel assemblies of AFA 2G and AFA 3G is established. Using ANSYS software, seismic nonlinear time -history analysis is completed and the effects on seismic loads of reactor system are obtained. The result shows that when the fuel assembly changing from AFA 2G to AFA 3G, it is necessary to reevaluate the fuel assembly itself, but not the reactor internal. (authors)

3G nõrk pulss ärikliendile

Index Scriptorium Estoniae

2005-01-01

Mobi turundusjuht Rain Rannu, Elisa tegevjuht Sami Seppänen, EMT arendus- ja tehnoloogiadirektor Tõnu Grünberg ning andmeside ja sisuteenuste juht Ando Meentalo vaagivad nn kolmanda mobiilipõlvkonna 3G plusse ja miinuseid ning võimalusi Eesti turul läbi lüüa. Lisa: Mobiilivõrgud

Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

Science.gov (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

2008-01-01

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

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.

Impact of DNA3'pp5'G capping on repair reactions at DNA 3' ends.

Science.gov (United States)

Das, Ushati; Chauleau, Mathieu; Ordonez, Heather; Shuman, Stewart

2014-08-05

Many biological scenarios generate "dirty" DNA 3'-PO4 ends that cannot be sealed by classic DNA ligases or extended by DNA polymerases. The noncanonical ligase RtcB can "cap" these ends via a unique chemical mechanism entailing transfer of GMP from a covalent RtcB-GMP intermediate to a DNA 3'-PO4 to form DNA3'pp5'G. Here, we show that capping protects DNA 3' ends from resection by Escherichia coli exonucleases I and III and from end-healing by T4 polynucleotide 3' phosphatase. By contrast, the cap is an effective primer for DNA synthesis. E. coli DNA polymerase I and Mycobacterium DinB1 extend the DNAppG primer to form an alkali-labile DNApp(rG)pDNA product. The addition of dNTP depends on pairing of the cap guanine with an opposing cytosine in the template strand. Aprataxin, an enzyme implicated in repair of A5'pp5'DNA ends formed during abortive ligation by classic ligases, is highly effective as a DNA 3' decapping enzyme, converting DNAppG to DNA3'p and GMP. We conclude that the biochemical impact of DNA capping is to prevent resection and healing of a 3'-PO4 end, while permitting DNA synthesis, at the price of embedding a ribonucleotide and a pyrophosphate linkage in the repaired strand. Aprataxin affords a means to counter the impact of DNA capping.

Fabrication of Detector Arrays for the SPT-3G Receiver

Science.gov (United States)

Posada, C. M.; Ade, P. A. R.; Ahmed, Z.; Anderson, A. J.; Austermann, J. E.; Avva, J. S.; Thakur, R. Basu; Bender, A. N.; Benson, B. A.; Carlstrom, J. E.; Carter, F. W.; Cecil, T.; Chang, C. L.; Cliche, J. F.; Cukierman, A.; Denison, E. V.; de Haan, T.; Ding, J.; Divan, R.; Dobbs, M. A.; Dutcher, D.; Everett, W.; Foster, A.; Gannon, R. N.; Gilbert, A.; Groh, J. C.; Halverson, N. W.; Harke-Hosemann, A. H.; Harrington, N. L.; Henning, J. W.; Hilton, G. C.; Holzapfel, W. L.; Huang, N.; Irwin, K. D.; Jeong, O. B.; Jonas, M.; Khaire, T.; Kofman, A. M.; Korman, M.; Kubik, D.; Kuhlmann, S.; Kuo, C. L.; Lee, A. T.; Lowitz, A. E.; Meyer, S. S.; Michalik, D.; Miller, C. S.; Montgomery, J.; Nadolski, A.; Natoli, T.; Nguyen, H.; Noble, G. I.; Novosad, V.; Padin, S.; Pan, Z.; Pearson, J.; Rahlin, A.; Ruhl, J. E.; Saunders, L. J.; Sayre, J. T.; Shirley, I.; Shirokoff, E.; Smecher, G.; Sobrin, J. A.; Stan, L.; Stark, A. A.; Story, K. T.; Suzuki, A.; Tang, Q. Y.; Thompson, K. L.; Tucker, C.; Vale, L. R.; Vanderlinde, K.; Vieira, J. D.; Wang, G.; Whitehorn, N.; Yefremenko, V.; Yoon, K. W.; Young, M. R.

2018-05-01

The South Pole Telescope third-generation (SPT-3G) receiver was installed during the austral summer of 2016-2017. It is designed to measure the cosmic microwave background across three frequency bands centered at 95, 150, and 220 GHz. The SPT-3G receiver has ten focal plane modules, each with 269 pixels. Each pixel features a broadband sinuous antenna coupled to a niobium microstrip transmission line. In-line filters define the desired band-passes before the signal is coupled to six bolometers with Ti/Au/Ti/Au transition edge sensors (three bands × two polarizations). In total, the SPT-3G receiver is composed of 16,000 detectors, which are read out using a 68× frequency-domain multiplexing scheme. In this paper, we present the process employed in fabricating the detector arrays.

A review on g-C{sub 3}N{sub 4}-based photocatalysts

Energy Technology Data Exchange (ETDEWEB)

Wen, Jiuqing; Xie, Jun [College of Materials and Energy, Key Laboratory of Energy Plants Resource and Utilization, Ministry of Agriculture, Key Laboratory of Biomass Energy of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou, 510642 (China); Chen, Xiaobo, E-mail: chenxiaobo@umkc.edu [Department of Chemistry, University of Missouri – Kansas City, Kansas City, MO, 64110 (United States); Li, Xin, E-mail: Xinliscau@yahoo.com [College of Materials and Energy, Key Laboratory of Energy Plants Resource and Utilization, Ministry of Agriculture, Key Laboratory of Biomass Energy of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou, 510642 (China)

2017-01-01

Graphical abstract: The photocatalytic fundamentals, versatile properties, design strategies and potential applications of g-C{sub 3}N{sub 4}-based photocatalysts were systematically summarized and addressed. - Highlights: • The photocatalytic fundamentals of g-C{sub 3}N{sub 4} were systematically summarized. • The versatile properties of g-C{sub 3}N{sub 4} photocatalysts were highlighted. • The different design strategies of g-C{sub 3}N{sub 4} photocatalysts were reviewed. • The important photocatalytic applications of g-C{sub 3}N{sub 4} were also addressed. - Abstract: As one of the most appealing and attractive technologies, heterogeneous photocatalysis has been utilized to directly harvest, convert and store renewable solar energy for producing sustainable and green solar fuels and a broad range of environmental applications. Due to their unique physicochemical, optical and electrical properties, a wide variety of g-C{sub 3}N{sub 4}-based photocatalysts have been designed to drive various reduction and oxidation reactions under light irradiation with suitable wavelengths. In this review, we have systematically summarized the photocatalytic fundamentals of g-C{sub 3}N{sub 4}-based photocatalysts, including fundamental mechanism of heterogeneous photocatalysis, advantages, challenges and the design considerations of g-C{sub 3}N{sub 4}-based photocatalysts. The versatile properties of g-C{sub 3}N{sub 4}-based photocatalysts are highlighted, including their crystal structural, surface phisicochemical, stability, optical, adsorption, electrochemical, photoelectrochemical and electronic properties. Various design strategies are also thoroughly reviewed, including band-gap engineering, defect control, dimensionality tuning, pore texture tailoring, surface sensitization, heterojunction construction, co-catalyst and nanocarbon loading. Many important applications are also addressed, such as photocatalytic water splitting (H{sub 2} evolution and overall water

Reactor Dosimetry Applications Using RAPTOR-M3G:. a New Parallel 3-D Radiation Transport Code

Science.gov (United States)

Longoni, Gianluca; Anderson, Stanwood L.

2009-08-01

The numerical solution of the Linearized Boltzmann Equation (LBE) via the Discrete Ordinates method (SN) requires extensive computational resources for large 3-D neutron and gamma transport applications due to the concurrent discretization of the angular, spatial, and energy domains. This paper will discuss the development RAPTOR-M3G (RApid Parallel Transport Of Radiation - Multiple 3D Geometries), a new 3-D parallel radiation transport code, and its application to the calculation of ex-vessel neutron dosimetry responses in the cavity of a commercial 2-loop Pressurized Water Reactor (PWR). RAPTOR-M3G is based domain decomposition algorithms, where the spatial and angular domains are allocated and processed on multi-processor computer architectures. As compared to traditional single-processor applications, this approach reduces the computational load as well as the memory requirement per processor, yielding an efficient solution methodology for large 3-D problems. Measured neutron dosimetry responses in the reactor cavity air gap will be compared to the RAPTOR-M3G predictions. This paper is organized as follows: Section 1 discusses the RAPTOR-M3G methodology; Section 2 describes the 2-loop PWR model and the numerical results obtained. Section 3 addresses the parallel performance of the code, and Section 4 concludes this paper with final remarks and future work.

H.264/AVC error resilience tools suitable for 3G mobile video services

Institute of Scientific and Technical Information of China (English)

LIU Lin; YE Xiu-zi; ZHANG San-yuan; ZHANG Yin

2005-01-01

The emergence of third generation mobile system (3G) makes video transmission in wireless environment possible,and the latest 3GPP/3GPP2 standards require 3G terminals support H.264/AVC. Due to high packet loss rate in wireless environment, error resilience for 3G terminals is necessary. Moreover, because of the hardware restrictions, 3G mobile terminals support only part of H.264/AVC error resilience tool. This paper analyzes various error resilience tools and their functions, and presents 2 error resilience strategies for 3G mobile streaming video services and mobile conversational services. Performances of the proposed error resilience strategies were tested using off-line common test conditions. Experiments showed that the proposed error resilience strategies can yield reasonably satisfactory results.

Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans.

Science.gov (United States)

Pietsch, Corinna; Liebert, Uwe G

2018-05-31

Species A rotaviruses are highly diverse and impose a substantial burden to human and animal health. Interspecies transmission between livestock, domestic animals and humans is commonly observed, but spread of animal-like rotaviruses within the human population is limited. During the continued monitoring of rotavirus strains in Germany, an unusual G6P[9] rotavirus strain was detected in feces of a child. The complete rotavirus coding sequences revealed a unique G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E2-H3 genotype constellation. The virus was phylogenetically related to feline G3P[9] strains and other human G6P[9] rotaviruses of presumable zoonotic origin. Analysis of primer binding sites of G6 specific genotyping revealed further evidence of a G6P[9] feline reservoir. Moreover, substantial deficits of conventional semi-nested PCR genotyping approaches in detecting contemporary G6P[9] were revealed. Rotavirus strain GER29-14 most likely resulted from a direct or recent interspecies transmission from a cat to human. Further studies could assess nucleic acid sequences and genotype constellations of feline rotavirus to confirm the likely feline origin of sporadic human G6P[9] strains. Copyright © 2018 Elsevier B.V. All rights reserved.

Up-regulation of the G3PDH 'housekeeping' gene by estrogen.

Science.gov (United States)

Galal, Nadia; El-Beialy, Waleed; Deyama, Yoshiaki; Yoshimura, Yoshitaka; Tei, Kanchu; Suzuki, Kuniaki; Totsuka, Yasunori

2010-01-01

Proteomic and genomic studies commonly involve the assessment of mRNA levels using reverse transcription-polymerase chain reaction (PCR) and real-time quantitative PCR. An internal standard RNA is fundamentally analyzed along with the investigated mRNA to document the specificity of the effect(s) on mRNA and to correct for inter-sample variations. In our studies implementing estrogen treatments on different cell lines, we initially used glyceraldehyde-3-phosphate dehydrogenase (G3PDH) as an internal standard. However, the results of PCR amplification demonstrated that 17β-estradiol enhanced the expression of the G3PDH gene, rendering it impossible to use G3PDH as an unbiased comparative control.

Mutations in the G6PC3 gene cause Dursun syndrome.

Science.gov (United States)

Banka, Siddharth; Newman, William G; Ozgül, R Koksal; Dursun, Ali

2010-10-01

Dursun syndrome is a triad of familial primary pulmonary hypertension, leucopenia, and atrial septal defect. Here we demonstrate that mutations in G6PC3 cause Dursun syndrome. Mutations in G6PC3 are known to also cause severe congenital neutropenia type 4. Identification of the genetic basis of Dursun syndrome expands the pre-existing knowledge about the phenotypic effects of mutations in G6PC3. We propose that Dursun syndrome should now be considered as a subset of severe congenital neutropenia type 4 with pulmonary hypertension as an important clinical feature. Copyright © 2010 Wiley-Liss, Inc.

Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients.

Science.gov (United States)

Jekic, Biljana; Lukovic, Ljiljana; Bunjevacki, Vera; Milic, Vera; Novakovic, Ivana; Damnjanovic, Tatjana; Milasin, Jelena; Popovic, Branka; Maksimovic, Nela; Damjanov, Nemanja; Radunovic, Goran; Kovacevic, Ljiljana; Krajinovic, Maja

2013-03-01

Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G > T and 452 C > T), CCND1 (870 A > G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as non-responders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p = 0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p = 0.003). No other significant association were observed. The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T > G polymorphism may have high predictive value for myelosuppression in RA patients.

A Differentially Driven Dual-Polarized Dual-Wideband Complementary Antenna for 2G/3G/LTE Applications

Directory of Open Access Journals (Sweden)

Botao Feng

2014-01-01

Full Text Available A novel differentially driven dual-polarized dual-wideband complementary patch antenna with high isolation is proposed for 2G/3G/LTE applications. In order to generate dual-polarization and dual-wideband properties, a pair of biorthogonal dual-layer η-shaped tapered line feeding structures is utilized to feed two pairs of dual-layer U-shaped patches, respectively. The upper-layer U-shaped patches mainly serve the upper frequency band, while the lower-layer ones chiefly work for the lower frequency band. Besides, a horned reflector is introduced to improve radiation patterns and provide stable gain. The prototype antenna can achieve a bandwidth of 25.7% (0.78 GHz–1.01 GHz with a stable gain of 7.8±0.7 dBi for the lower band, and a bandwidth of 45.7% (1.69 GHz–2.69 GHz with a gain of 9.5±1.1 dBi for the upper band. Input isolation exceeding 30 dB has been obtained in the wide bandwidth. Thus, it can be potentially used as a base station antenna for 2G/3G/LTE networks.

C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

Science.gov (United States)

Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

2016-11-01

It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

Effects of electromagnetic interference on the functional usage of medical equipment by 2G/3G/4G cellular phones: A revie

Directory of Open Access Journals (Sweden)

Periyasamy M. Mariappan

2016-09-01

Full Text Available There has been an increase in the potential use of wireless devices in healthcare domain for a variety of reasons. The most commonly used device is the cellular phone, which emits strong electromagnetic energy affecting thereby the functionality of the vital medical equipment such as ventilators, ECG monitors, cardiac monitors, and defibrillators. This prompted the healthcare concerns to restrict the use of these phones in the proximity of critical and non-critical care medical equipment. Due to the developments made in the design of medical equipment to comply with the EMC standards, the restriction had been slowly laid off. Still, the researchers are concerned about the electromagnetic interference with medical devices by cellular phones in the healthcare domain and recommend for conducting continuous research to study their interaction with medical equipment. This paper overviews the certain investigations carried out in the recent years to study the electromagnetic interference between medical devices and 2G/3G/4G LTE cellular phones. During the initial development of cellular phones, the 2G cellular phones had caused more interference that affects the function and operation of some medical devices. The possibility of interference from 3G cellular phones with medical devices was considerably lower than the 2G phones, but still exists. Furthermore, almost all of the 4G phones have little to no interference with the medical devices. Currently, with the development of the medical devices industry, the current medical devices are designed to operate safely under any conditions of usage. Finally, a careful analysis would require statistics on the frequency of adverse events across the healthcare system, which apparently do not exist.

Enhanced opsonisation of Rhesus D-positive human red blood cells by recombinant polymeric immunoglobulin G anti-G antibodies.

Science.gov (United States)

Díaz-Solano, Dylana; Fuenmayor, Jaheli; Montaño, Ramon F

2018-02-01

Anti-RhD antibodies (anti-D) are important in the prophylaxis of haemolytic disease of the foetus and newborn (HDFN) due to RhD incompatibility. Current preparations of anti-D are sourced from hyperimmune human plasma, so its production carries a risk of disease and is dependent on donor availability. Despite the efforts to develop a monoclonal preparation with similar prophylactic properties to the plasma-derived anti-D, no such antibody is yet available. Here we studied the agglutinating, opsonic and haemolytic activities of two recombinant polymeric immunoglobulins (Ig) against the G antigen of the Rh complex. Recombinant polymeric anti-G IgG1 (IgG1μtp) and IgG3 (IgG3μtp) were produced in vitro, purified by protein G-affinity chromatography, and analysed by gel electrophoresis. Their agglutinating, opsonic and haemolytic activities were evaluated using haemagglutination, erythrophagocytosis, and complement activation assays. The recombinant IgG1μtp and IgG3μtp anti-G antibodies ranged from 150,000 to 1,000,000 Da in molecular weight, indicating the formation of polymeric IgG. No complement activation or haemolytic activity was detected upon incubation of RhD-positive red-blood cells with the polymeric anti-G IgG. Both polymers were better opsonins than a prophylactic preparation of plasma-derived anti-D. The enhanced opsonic properties of the polymeric anti-G IgG1μtp and IgG3μtp could allow them to mediate the clearance of RhD-positive red blood cells from circulation more efficiently than natural or other synthetic prophylactic anti-D options. Their inability to induce complement-mediated haemolysis would be prophylactically convenient and is comparable in vitro to that of the available plasma-derived polyclonal anti-D preparations. The described properties suggest that polymeric antibodies like these (but with anti-D specificity) may be testable candidates for prophylaxis of HDFN caused by anti-D.

Neutronic Analysis of the RSG-GAS Compact Core without CIP Silicide 3.55 g U/cc and 4.8 g U/cc

International Nuclear Information System (INIS)

Jati S; Lily S; Tukiran S

2004-01-01

Fuel conversion from U 3 O 8 -Al to U 3 Si 2 -Al 2.96 g U/cc density in the RSG-GAS core had done successfully step by step since 36 th core until 44 th core. So that, since the 45 th core until now (48 th core) had been using full of silicide 2.96 g U/cc. Even though utilization program of silicide fuel with high density (3.55 g U/cc and 4.8 g U/cc) and optimize operation of RSG-GAS core under research. Optimalitation of core with increasing operation cycle have been analyzing about compact core. The mean of compact core is the RSG-GAS core with decrease number of IP or CIP position irradiation. In this research, the neutronic calculation to cover RSG-GAS core and RSG-GAS core without CIP that are using U 3 Si 2 -Al 2.96 g U/cc, 3.55 g U/cc and 4.8 g U/cc had done. Two core calculation done at 15 MW power using SRAC-ASMBURN code. The calculation result show that fuel conversion from 2.96 g U/cc density to 3.55 g U/cc and 4.8 g U/cc will increasing cycle length for both RSG-GAS core and RSG-GAS compact core without CIP. However, increasing of excess reactivity exceeded from nominal value of first design that 9.2%. Change of power peaking factor is not show significant value and still less than 1.4. Core fuelled with U 3 Si 2 -Al 4.8 g U/cc density have maximum discharge burn-up which exceeded from licensing value (70%). RSG-GAS compact core without CIP fuelled U 3 Si 2 -Al 2.96 g U/cc have longer cycle operation then RSG-GAS core and fulfil limitation neutronic parameter at the first design value. (author)

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

Science.gov (United States)

Kamei, J; Onodera, K; Kawaguchi, M; Shibata, M; Kagawa, M; Wachi, M; Kojima, J

2002-10-01

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Detection of tritium in the CO{sub 2} of the reactors G2/G3 using gas chromatography; La detection du tritium par chromatographie gazeuse dans le CO{sub 2} des piles G2/G3

Energy Technology Data Exchange (ETDEWEB)

Guillermin, P; Rossi, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1965-07-01

This gas-phase chromatographic method, based on the principle of the decomposition of a gas mixture into its pure constituents, makes it possible to identify and rapidly measure the tritium present in the heat-carrying fluid of the reactors G2/G3. The sensitivity limit corresponds to 5 x 10{sup -6} {mu}Ci/cm{sup 3} of tritiated gas, whereas the threshold reading of the D.C.C.A. is 10{sup -3} {mu}Ci/cm{sup 3} in the presence of {sup 41}A. This apparatus has interesting applications in the conditions where certain {beta} emitters (products of fission or of activation) interfere with the measurement of the tritium. It can easily be adapted to the detection of tritiated steam on condition that a reducing chemical treatment is applied for the atmospheric humidity. In fact, although this method is not as sensitive for the measurement of tritiated vapour as p-spectrometry in a scintillating medium, it may be set up very easily for measuring the C.M.A of tritium in air and is not affected by the presence of radio-active gases. (authors) [French] Cette methode de chromatographie en phase gazeuse, basee sur le principe de decomposition d'un melange gazeux en ses constituants purs, permet l'identification et la mesure rapide du tritium present dans le fluide caloporteur des piles G2/G3. La limite de sensibilite correspond a 5.10{sup -6} {mu}Ci/cm{sup 3} de gaz tritie, alors que le seuil de lecture du D.C.C.A. s'eleve a 10{sup -3} {mu}Ci/cm{sup 3} en presence de {sup 41}A. Cet appareillage presente un champ d'application interessant dans les domaines ou certains emetteurs {beta} (produits de fission ou d'activation) genent la mesure du tritium. Il peut s'adapter sans difficulte a la detection de la vapeur tritiee moyennant un traitement chimique reducteur de l'humidite atmospherique. En definitive, bien que cette methode ne soit pas aussi sensible pour la determination de la vapeur tritiee que la spectrometrie {beta} en milieu scintillant, elle permet de mesurer la C.M.A de

Reactions of small negative ions with O2(a 1[Delta]g) and O2(X 3[Sigma]g-)

Science.gov (United States)

Midey, Anthony; Dotan, Itzhak; Seeley, J. V.; Viggiano, A. A.

2009-02-01

The rate constants and product ion branching ratios were measured for the reactions of various small negative ions with O2(X 3[Sigma]g-) and O2(a 1[Delta]g) in a selected ion flow tube (SIFT). Only NH2- and CH3O- were found to react with O2(X) and both reactions were slow. CH3O- reacted by hydride transfer, both with and without electron detachment. NH2- formed both OH-, as observed previously, and O2-, the latter via endothermic charge transfer. A temperature study revealed a negative temperature dependence for the former channel and Arrhenius behavior for the endothermic channel, resulting in an overall rate constant with a minimum at 500 K. SF6-, SF4-, SO3- and CO3- were found to react with O2(a 1[Delta]g) with rate constants less than 10-11 cm3 s-1. NH2- reacted rapidly with O2(a 1[Delta]g) by charge transfer. The reactions of HO2- and SO2- proceeded moderately with competition between Penning detachment and charge transfer. SO2- produced a SO4- cluster product in 2% of reactions and HO2- produced O3- in 13% of the reactions. CH3O- proceeded essentially at the collision rate by hydride transfer, again both with and without electron detachment. These results show that charge transfer to O2(a 1[Delta]g) occurs readily if the there are no restrictions on the ion beyond the reaction thermodynamics. The SO2- and HO2- reactions with O2(a) are the only known reactions involving Penning detachment besides the reaction with O2- studied previously [R.S. Berry, Phys. Chem. Chem. Phys., 7 (2005) 289-290].

A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

Directory of Open Access Journals (Sweden)

Leili Aghebati Maleki

2013-08-01

Full Text Available Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG. Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases.

A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

Science.gov (United States)

Aghebati Maleki, Leili; Baradaran, Behzad; Abdolalizadeh, Jalal; Ezzatifar, Fatemeh; Majidi, Jafar

2013-01-01

Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG). Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases. PMID:24312857

Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen

International Nuclear Information System (INIS)

Dienhart, D.G.; Schmelter, R.F.; Lear, J.L.; Miller, G.J.; Glenn, S.D.; Bloedow, D.C.; Kasliwal, R.; Moran, P.; Seligman, P.; Murphy, J.R.

1990-01-01

To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted

Improving g-C3N4 photocatalysis for NOx removal by Ag nanoparticles decoration

International Nuclear Information System (INIS)

Sun, Yanjuan; Xiong, Ting; Ni, Zilin; Liu, Jie; Dong, Fan; Zhang, Wei; Ho, Wing-Kei

2015-01-01

Graphical abstract: Ag/g-C 3 N 4 nanocomposites were prepared via a facile method for enhanced photocatalytic NO x removal due to surface plasmon resonance of Ag. - Highlights: • The Ag/g-C 3 N 4 nanocomposites were prepared using urea as the precursor. • The Ag/g-C 3 N 4 nanocomposites were applied in removal of NO x in air. • The Ag nanoparticles enhanced the photocatalytic activity of g-C 3 N 4 . • The surface plasmon resonance of Ag played a key role in photocatalysis. - Abstract: In order to overcome the intrinsic drawback of pristine g-C 3 N 4 , we prepared g-C 3 N 4 nanosheets with enhanced photocatalytic performance by Ag nanoparticles decoration using urea as the precursor. It was revealed that the monodispersed Ag nanoparticles were deposited on the surface of g-C 3 N 4 nanosheets. The Ag/g-C 3 N 4 nanocomposites were applied in removal of NO x in air under visible light irradiation. The results showed that the decoration of Ag nanoparticles not only enhanced the photocatalytic activity of g-C 3 N 4 nanosheets, but also benefited the oxidation of NO to final products. The increased visible light absorption arising from the surface plasmon resonance of Ag and improved separation and transfer of photoinduced carriers over Ag/g-C 3 N 4 composites were demonstrated by the UV–vis diffuse reflectance spectra and photoluminescence spectra, respectively. It was therefore proposed that the enhanced photocatalytic activity of Ag/g-C 3 N 4 composites could be attributed to the extended light response range and enhanced charge separation due to the introduction of Ag nanoparticles.

Evolution to 3G Mobile Communication - Second Generation ...

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 9. Evolution to 3G Mobile Communication - Second Generation Cellular Systems. R Ramachandran. General Article Volume 8 Issue 9 September 2003 pp 60-72 ... Keywords. Wireless communication; cellular networks; GSM; CdmaOne; TDMA ...

Graphene and g-C3N4 based photocatalysts for NOx removal: A review

Science.gov (United States)

Nikokavoura, Aspasia; Trapalis, Christos

2018-02-01

NOx liberated into atmosphere from automobile exhausts and fossil fuel combustion, comprise the major air pollutants. They are responsible for serious environmental problems such as acid rain, ozone accumulation, haze and photochemical smog. Besides they contribute to the deterioration of human health by causing decrease of the lung function and respiratory problems. The application of photocatalytic methods in order to mitigate the presence of NOx in the atmosphere is preferable as they are environmentally friendly, mild and low cost. Therefore, in this review, the photocatalytic activity of g-C3N4 and graphene based composites towards NOx removal was discussed. NOx oxidation to non volatile nitrates on the surface of graphene and g-C3N4 based photocatalysts has attracted much interest during the last years due to their structures with unique features such as large specific surface area, thermal and chemical stability and enhanced visible light utilization. The formation of 2D-2D intimate heterojunctions between graphene or g-C3N4 and other components ensures the enhanced charge transfer, lifetime of electron/hole pairs and thus photocatalytic activity. The increased visible light harvesting also contributes to their usefulness as effective photocatalytic materials. In the present work, the advantages of these novel photocatalysts and the differences/similarities between them were exhaustively highlighted. The role of graphene as catalyst promoter, electron reservoir, support and photosensitizer in its photocatalytic composites was emphasized. The effect of g-C3N4 doping and copolymerization with metals/semiconductors on its photocatalytic activity towards NOx oxidation was thoroughly discussed. Besides, the preparation methods, photocatalytic efficiencies, type of irradiation, utilization of appropriate cocatalysts, and reaction mechanisms during the photocatalytic NOx removal by graphene and g-C3N4 composies, were summarized. It was demonstrated that in the vast

What does a G-3 target zone mean for emerging-market economies?

OpenAIRE

Reinhart, Carmen; Reinhart, Vincent

2000-01-01

This paper examines the argument for a G-3 exchange rate target zone strictly from an emerging market perspective. A commitment to damping G-3 exchange rate fluctuations, however, requires a willingness on the part of G-3 authorities to use domestic monetary policy to that end. Under a system of target zones, then, relative prices for emerging market economies may become more stable, but debt-servicing costs may become less predictable. We use a simple trade model to show that the resulting c...

Oilfield automation with MRD-310 industrial 3G router

Energy Technology Data Exchange (ETDEWEB)

Anon.

2010-01-15

The SAM Well Manager is the most advanced technological solution for high precision monitoring and control of rod-pumping wells. It was developed by Lufkin-Automation to optimize pump performance and reliability. The company was formed by the merger of Delta X and Nabla Corporations, which are currently part of the oil field division, offering analysis, security and control solutions for rod pumping wells. The SAM Well Manager product is equipped with the Westermo MRD-310 3G router. It has been used in pilot projects in remote and harsh environments in Europe and Asia. The MRD-310 router has a very high level of connectivity and provides support for GSM, GPRS, 3G UMTS, HSDPA and HSUPA. It also supports IPSec encrypted VPN tunnels which is a requirement for safety critical applications that use unsecure public networks. In addition, the MRD-310 provides a serial interface and serial to IP conversion, which is required for connection to the controller. The router is used to analyze pump flow and calculate service and maintenance requirements before the event of mechanical failure. Energy consumption can also be optimized. This installation of the SAM Well Manager with MRD-310 industrial 3G router in several applications has demonstrated the potential for significant cost savings. 2 figs.

Identification of high-efficiency 3′GG gRNA motifs in indexed FASTA files with ngg2

Directory of Open Access Journals (Sweden)

Elisha D. Roberson

2015-11-01

Full Text Available CRISPR/Cas9 is emerging as one of the most-used methods of genome modification in organisms ranging from bacteria to human cells. However, the efficiency of editing varies tremendously site-to-site. A recent report identified a novel motif, called the 3′GG motif, which substantially increases the efficiency of editing at all sites tested in C. elegans. Furthermore, they highlighted that previously published gRNAs with high editing efficiency also had this motif. I designed a Python command-line tool, ngg2, to identify 3′GG gRNA sites from indexed FASTA files. As a proof-of-concept, I screened for these motifs in six model genomes: Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, and Homo sapiens. I also scanned the genomes of pig (Sus scrofa and African elephant (Loxodonta africana to demonstrate the utility in non-model organisms. I identified more than 60 million single match 3′GG motifs in these genomes. Greater than 61% of all protein coding genes in the reference genomes had at least one unique 3′GG gRNA site overlapping an exon. In particular, more than 96% of mouse and 93% of human protein coding genes have at least one unique, overlapping 3′GG gRNA. These identified sites can be used as a starting point in gRNA selection, and the ngg2 tool provides an important ability to identify 3′GG editing sites in any species with an available genome sequence.

Magnetically Separable Fe2O3/g-C3N4 Nanocomposites with Cocoon-Like Shape: Magnetic Properties and Photocatalytic Activities

Science.gov (United States)

Yu, Xiaojia; Yang, Xiaoyu; Li, Guang

2018-01-01

We report magnetically separable Fe2O3/g-C3N4 nanocomposites as a photocatalyst under visible-light irradiation in this study. The Fe2O3/g-C3N4 nanocomposites were synthesized through a two-step hydrothermal method. The Fe2O3 with cocoon-like shape was obviously dispersed on the surface of g-C3N4 with porous and layered nanostructure as seen from micrographs of the particles. Furthermore, the magnetic conversion of the samples was studied via vibrating sample magnetometer technology. It was found that the saturated magnetization Ms of the Fe2O3/g-C3N4 nanoparticles obviously decreased in the presence of g-C3N4, and the photocatalytic activity of the samples investigated by degrading Rhodamine B suggested that the Fe2O3/g-C3N4 photocatalyst was prior to the pure Fe2O3 and g-C3N4 samples. In addition, the magnetically separable ability of Fe2O3/g-C3N4 nanocomposites was efficiently exhibited by an external magnet.

An ingenious strategy of preparing TiO2/g-C3N4 heterojunction photocatalyst: In situ growth of TiO2 nanocrystals on g-C3N4 nanosheets via impregnation-calcination method

Science.gov (United States)

Zhang, Guanghui; Zhang, Tianyong; Li, Bin; Jiang, Shuang; Zhang, Xia; Hai, Li; Chen, Xingwei; Wu, Wubin

2018-03-01

An ingenious method was employed to design and fabricate the TiO2/g-C3N4 heterojunction photocatalysts in this study. The thermal oxidation etching of g-C3N4 nanosheets and the in situ growth of TiO2 nanocrystal on the surface of g-C3N4 nanosheets were completed simultaneously by the calcination process. The g-C3N4 nanosheets played a crucial role in regulating and assembling the structures and morphologies of TiO2. Furthermore, the thickness and content of g-C3N4, and the crystallinity of TiO2 in TiO2/g-C3N4 composites could be regulated and controlled by the calcination temperature. Among the resultant TiO2/g-C3N4 samples, the TiO2/g-C3N4 sample with 41.6 wt% g-C3N4 exhibited the highest photocatalytic activity. It could degrade almost all MO molecules under visible light irradiation within 3 h. Moreover, it displayed higher visible light photocatalytic performance for degrading MO solution than pure g-C3N4 and D-TiO2. The synergistic effect between TiO2 and g-C3N4 makes significant contributions to the enhancement of the visible light photocatalytic activity. In addition, the favorable photocatalytic performance of TiO2/g-C3N4 nanocomposites is also attributed to the porous structures and uniform morphologies, and large surface area. Furthermore, the resultant TiO2/g-C3N4 exhibits excellent photocatalytic stability. Radical trapping experiments indicated that rad O2- and h+ were the main reactive species during the photodegradation process under visible light irradiation. Hopefully, the results can offer new design and strategy for preparing other g-C3N4-based nanocomposites for environmental and energy applications.

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

Science.gov (United States)

Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

2016-05-16

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

Potential energy and dipole moment surfaces of the triplet states of the O2(X3Σg-) - O2(X3Σg-,a1Δg,b1Σg+) complex.

Science.gov (United States)

Karman, Tijs; van der Avoird, Ad; Groenenboom, Gerrit C

2017-08-28

We compute four-dimensional diabatic potential energy surfaces and transition dipole moment surfaces of O 2 -O 2 , relevant for the theoretical description of collision-induced absorption in the forbidden X 3 Σ g -  → a 1 Δ g and X 3 Σ g -  → b 1 Σ g + bands at 7883 cm -1 and 13 122 cm -1 , respectively. We compute potentials at the multi-reference configuration interaction (MRCI) level and dipole surfaces at the MRCI and complete active space self-consistent field (CASSCF) levels of theory. Potentials and dipole surfaces are transformed to a diabatic basis using a recent multiple-property-based diabatization algorithm. We discuss the angular expansion of these surfaces, derive the symmetry constraints on the expansion coefficients, and present working equations for determining the expansion coefficients by numerical integration over the angles. We also present an interpolation scheme with exponential extrapolation to both short and large separations, which is used for representing the O 2 -O 2 distance dependence of the angular expansion coefficients. For the triplet ground state of the complex, the potential energy surface is in reasonable agreement with previous calculations, whereas global excited state potentials are reported here for the first time. The transition dipole moment surfaces are strongly dependent on the level of theory at which they are calculated, as is also shown here by benchmark calculations at high symmetry geometries. Therefore, ab initio calculations of the collision-induced absorption spectra cannot become quantitatively predictive unless more accurate transition dipole surfaces can be computed. This is left as an open question for method development in electronic structure theory. The calculated potential energy and transition dipole moment surfaces are employed in quantum dynamical calculations of collision-induced absorption spectra reported in Paper II [T. Karman et al., J. Chem. Phys. 147, 084307 (2017)].

The C-type lectin of the aggrecan G3 domain activates complement.

Directory of Open Access Journals (Sweden)

Camilla Melin Fürst

Full Text Available Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint.

Enhanced photocatalytic ozonation of organics by g-C3N4 under visible light irradiation

International Nuclear Information System (INIS)

Liao, Gaozu; Zhu, Dongyun; Li, Laisheng; Lan, Bingyan

2014-01-01

Highlights: • g-C 3 N 4 is employed as active catalyst in the photocatalytic ozonation system. • The more negative conduction band of g-C 3 N 4 benefits the transfer of electrons. • The synergistic effect between photocatalysis and ozonation is promoted by g-C 3 N 4 . • Enhanced degradation of oxalic acid and biphenol A is achieved via g-C 3 N 4 /Vis/O 3 . - Abstract: Graphitic carbon nitride (g-C 3 N 4 ) was employed as the active photocatalyst in the photocatalytic ozonation coupling system in the present study. g-C 3 N 4 was prepared by directly heating thiourea in air at 550 °C. XRD, FT-IR, UV–vis was used to characterize the structure and optical property. Oxalic acid and bisphenol A were selected as model substances for photocatalytic ozonation reactions to evaluate the catalytic ability of g-C 3 N 4 (g-C 3 N 4 /Vis/O 3 ). The results showed that the degradation ratio of oxalic acid with g-C 3 N 4 /Vis/O 3 was 65.2% higher than the sum of ratio when it was individually decomposed by g-C 3 N 4 /Vis and O 3 . The TOC removal of biphenol A with g-C 3 N 4 /Vis/O 3 was 2.17 times as great as the sum of the ratio when using g-C 3 N 4 /Vis and O 3 . This improvement was attributed to the enhanced synergistic effect between photocatalysis and ozonation by g-C 3 N 4 . Under visible light irradiation, the photo-generated electrons produced on g-C 3 N 4 facilitated the electrons transfer owing to the more negative conduction band potential (−1.3 V versus NHE). It meant that the photo-generated electrons could be trapped by ozone and reaction with it more easily. Subsequently, the yield of hydroxyl radicals was improved so as to enhance the organics degradation efficiency. This work indicated that metal-free g-C 3 N 4 could be an excellent catalyst for mineralization of organic compounds in waste control

The AFA 3G fuel assembly: a proven design for high burnups

International Nuclear Information System (INIS)

Forat, C.; Florentin, F.

1999-01-01

The AFA 3G fuel assembly design is based on the wide experience gained with the AFA 2G fuel assembly. More than 9500 AFA 2G fuel assemblies have been loaded in different reactors, worldwide, reaching discharged burnups in the range of 45 - 55 GWd/tU. This experience confirmed the features of the AFA 2G, such as the grids and the vanes arrangement for thermal hydraulic performance, the concept of the fuel rod support within the grid which avoids any rod fretting or vibration phenomenon, the efficiency of the anti-debris device. The AFA 3G also relies on and benefits from the results of the world's largest R and D program, in-pile and out-of(pile testing by Framatome with EDF and CEA, with a special focus on corrosion-resistant fuel rod cladding. The AFA 3G exhibits the following enhancements: a reinforced structure, which improves resistance to assembly bow as well as its consequences in terms of RCCA insertion fuel handling and core physics obtained from: MONOBLOC TM guide thimbles, characterized by a thickened and enlarged tube and reinforced dash-pot; a hold down spring system which has been optimized to accommodate fuel assembly hydraulic lift-off forces and to meet the fuel assembly bow resistance requirement; widened recrystallized Zircaloy-4 spacer grids; a high resistance to corrosion due to the M5 TM Zirconium-Niobium-Oxygen alloy for the fuel rod cladding, which contributes also to the bow resistance of the fuel assembly; an enhanced thermal-hydraulic behavior promoted by well proven mixing vane array of AFA 2G spacer grids, combined with three additional Mid Span Mixing Grids; a very effective debris protection with the use of the TRAPPER TM bottom nozzle. With these improvements, the AFA 3G fuel assembly is able to reach discharge burnup of 60 GWd/tU with margins on important characteristics like corrosion behavior, assembly bow and thermal-hydraulic performance. The AFA 3G design is so convincing that major utilities have decided to shift their fuel

Evaluation of past and future alterations in tuff at Yucca Mountain, Nevada, based on the clay mineralogy of drill cores USW G-1, G-2, and G-3

International Nuclear Information System (INIS)

Bish, D.L.

1989-03-01

The tuffs at Yucca Mountain in south-central Nevada are being studied by the Yucca Mountain Project (YMP) to determine their suitability for a high-level radioactive waste repository. For predictive purposes, it is important to understand the alteration history of Yucca Mountain and to know how the minerals in Yucca Mountain tuffs respond to changing conditions such as elevated temperatures. The clay mineralogy of these tuffs has been examined using x-ray powder diffraction, and approximation temperatures of alteration have been determined using available clay mineral data and fluid inclusion analyses. Also, several illites from drill holes USW G-1 and G-2 have been dated using K/Ar techniques, yielding ages of about 11 Myr. The clay mineral in Yucca Mountain tuffs are predominantly interstratified illite/smectites, with minor amounts of chloride, kaolinite, and interstratified chlorite/smectite at depth in USW G-1 and G-2. The reactions observed for these illite/smectites are similar to those observed in pelitic rocks. With depths, the illite/smectites transform from random interstratifications (R = 0) through ordered intermediates (R = 1) to illite in USW G-2 and to Kalkberg (R ≥ 3) interstratifications in USW G-1. The illite/smectites in USW G-3 have not significantly transformed. It appears that the illites in deeper rock results from hydrothermal and diagenetic reactions of earlier-formed smectites. These data demonstrate that the rocks at depth in the northern end of Yucca Mountain were significantly altered about 11 Myr ago. Both clay mineralogy and fluid inclusions suggest that the rocks at depth in USW G-2 have been subjected to postdepositional temperatures of at least 275/degree/C, those in USW G-1 have reached 200/degree/C, and USW G-3 rocks probably have not exceeded 100/degree/C. 64 refs., 9 figs., 3 tabs

The G3 Experience with Electronic Publishing: An Editor's Perspective

Science.gov (United States)

White, W. M.

2003-12-01

G3 (Geochemistry, Geophysics, Geosystems) is an all-electronic journal published jointly by the AGU, the Geochemical Society, and the European Association of Geochemistry. G3 publishes original scientific contributions pertaining to understanding the Earth as a system, including relevant observational, experimental, and theoretical investigations of the solid Earth, hydrosphere, atmosphere, and biosphere. The journal was initiated as a result of a grass roots effort with the following goals in mind: a copyright policy designed to enhance, rather than inhibit, the dissemination of scientific information (for example, allowing authors to post electronic reprints on their web sites), provide a means of publishing, in immediately useable formats, large data sets, provide a means for ready dissemination of computer modeling and analysis tools, and provide a forum where authors could use novel ways of illustrating both data and models (e.g., formats such as movies, virtual reality images, sound, mathematical models, etc.), and finally to reduce costs and speed publication. In most respects, G3 has been enormously successful and has met most of its goals. G3 began publishing in December of 1999; in the subsequent 3 1/2 years 625 papers have been submitted to it and 325 have been published. It currently has over 600 institutional and personal subscribers. Papers are submitted through the web (a variety of formats are accepted, however, Microsoft Word is most common) and are converted to Adobe pdf format for peer review. Except that it is fully electronic using the web and e-mail, the peer review process is traditional, which insures the quality of the papers published. Accepted papers are copyedited and converted to SGML for archival purposes. HTML and Acrobat pdf versions are then generated from the SGML and published as they are ready on the G3 web site (www.g-cubed.org). Large data sets are routinely published in digital formats that can be readily downloaded by readers

Pythagorean hodograph spline spirals that match G3 Hermite data from circles

KAUST Repository

Li, Zhong; Ait-Haddou, Rachid; Biard, Luc

2015-01-01

A construction is given for a G3 piecewise rational Pythagorean hodograph convex spiral which interpolates two G3 Hermite data associated with two non-concentric circles, one being inside the other. The spiral solution is of degree 7 and is the involute of a G2 convex curve, referred to as the evolute solution, with prescribed length, and composed of two PH quartic curves. Conditions for G3 continuous contact with circles are then studied and it turns out that an ordinary cusp at each end of the evolute solution is required. Thus, geometric properties of a family of PH polynomial quartics, allowing to generate such an ordinary cusp at one end, are studied. Finally, a constructive algorithm is described with illustrative examples.

Pythagorean hodograph spline spirals that match G3 Hermite data from circles

KAUST Repository

Li, Zhong

2015-04-01

A construction is given for a G3 piecewise rational Pythagorean hodograph convex spiral which interpolates two G3 Hermite data associated with two non-concentric circles, one being inside the other. The spiral solution is of degree 7 and is the involute of a G2 convex curve, referred to as the evolute solution, with prescribed length, and composed of two PH quartic curves. Conditions for G3 continuous contact with circles are then studied and it turns out that an ordinary cusp at each end of the evolute solution is required. Thus, geometric properties of a family of PH polynomial quartics, allowing to generate such an ordinary cusp at one end, are studied. Finally, a constructive algorithm is described with illustrative examples.

Serum-induced G0/G1 transition in chemically transformed 3T3 cells

International Nuclear Information System (INIS)

Gray, H.E.; Buchou, T.; Mester, J.

1987-01-01

Quiescent, chemically transformed (benzo-a-pyrene) BALB/c 3T3 cells (BP A31) enter the cell division cycle when exposed to complete medium containing 10% fetal calf serum (FCS); the number of cells recruited is a function of the duration of serum exposure. The recruitment of cells by short (<4 h) serum pulses is not inhibited by simultaneous exposure to cycloheximide (CH), and therefore the initial commitment does not require protein synthesis. The cells enter S phase with a constant delay following the removal of CH, even if CH exposure has been continued for as long as 20 h after the end of the serum pulse. The cell recruitment by serum pulses was inhibited by 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of cytoplasmic mRNA accumulation. These data suggest that serum exposure produces a stable memory that is necessary and sufficient for the eventual progression through G1 to S phase that occurs when protein synthesis is resumed after the removal of CH; this memory probably consists of mRNA species that are induced by serum and that are stable in the absence of protein synthesis. Unexpectedly, pretreatment of quiescent BP A31 cells with CH (8-24 h) dramatically increased the fraction of the total cell population that is recruited by a serum pulse of fixed duration

Review: Hérodote: Revue de géographie et de géopolitique, 2011/3, no. 142: Géopolitique du Sahara, Paris: La Découverte Besprechung: Hérodote: Revue de géographie et de géopolitique, 2011/3, Nr. 142: Géopolitique du Sahara, Paris: La Découverte

Directory of Open Access Journals (Sweden)

Laurence Marfaing

2011-01-01

Full Text Available Review of the issue 2011/3, no. 142, of Hérodote: Revue de géographie et de géopolitique: Géopolitique du Sahara, Paris: La Découverte.Besprechung der Ausgabe 2011/3, Nr. 142, von Hérodote: Revue de géographie et de géopolitique: Géopolitique du Sahara, Paris: La Découverte.

3G 带宽叠加技术在河口管理中的应用%Application of Technology of 3G Bandwidth-Superposition on Estuary Management

Institute of Scientific and Technical Information of China (English)

何宗涛

2015-01-01

On the basis of the public network, the practical speed of 3G network among the Zhangwei river south bayou area is about 400kbit/s. However, the traditional monitoring system that based upon the public 3G network is not able to afford transmission of high-definition (D1 and higher resolutions) videos. For the need of normative law enforcement for the water administration and supervision, it is necessary to uses 3G bandwidth fusion technology, combining the classic 3G network video structural frame. It expounds the working principle and realizes image collection and transmission of high-definition images.%受公网覆盖的影响，在漳卫南河口管理区域的3G实际速率在400 kbit/s左右，传统的基于3G网络的监控系统无法传输高清晰度（D1及以上分辨率）的视频。为满足河口水政监察规范执法的需要，结合典型的3G网络视频架构，采用了3G带宽叠加技术，阐述其工作原理，实现高清晰度的图像采集和传输。

A Dual-Wideband Double-Layer Magnetoelectric Dipole Antenna with a Modified Horned Reflector for 2G/3G/LTE Applications

Directory of Open Access Journals (Sweden)

Botao Feng

2013-01-01

Full Text Available A novel dual-wideband double-layer magnetoelectric dipole unidirectional antenna with a modified horned reflector for 2G/3G/LTE applications is proposed. Firstly, a double-layer electric dipole structure is presented to provide a dualwideband, whose folded lower layer mainly serves the lower frequency band while the inclined upper layer works for the upper frequency band. In addition, to reduce the size of the antenna and improve impedance matching, a new feeding structure designed with inverted U-shaped and tapered line is introduced. Finally, a modified horn-shaped reflector, instead of a ground plane, is employed to achieve stable and high gains. The antenna prototype can achieve a bandwidth of 24.4% (790 MHz–1010 MHz with a stable gain of 7.2 ± 0.6 dBi for the lower band, and a bandwidth of 67.3% (1.38 GHz–2.78 GHz with a gain of 7.5 ± 0.8 dBi for the upper band covering all the frequency bands for 2G/3G/LTE systems. To the best of our knowledge, it is the first double-layer magnetoelectric dipole antenna proposed. Compared with the existing ME dipole antennas, the proposed antenna, which is completely made of copper, can be easily fabricated at low cost and thus is practicable for 2G/3G/LTE applications.

Construction of g-C_3N_4/Al_2O_3 hybrids via in-situ acidification and exfoliation with enhanced photocatalytic activity

International Nuclear Information System (INIS)

Wang, Xiao-jing; Liu, Chao; Li, Xu-li; Li, Fa-tang; Li, Yu-pei; Zhao, Jun; Liu, Rui-hong

2017-01-01

Highlights: • Ultrathin g-C_3N_4/Al_2O_3 hybrids are prepared via in-situ reaction. • The structure modification role of in-situ formed HNO_3 for g-C_3N_4 is found. • The ultrathin g-C_3N_4 nanosheets are formed by the acidified melamine and Al(OH)_3. • In-situ calcination of melamine and Al(OH)_3 benefits the contact of C_3N_4 and Al_2O_3. • The activity of g-C_3N_4/Al_2O_3 is 16.6 times that of pristine g-C_3N_4 in degrading RhB. - Abstract: Homogeneous ultrathin g-C_3N_4 nanosheets/Al_2O_3 heterojunctions are synthesized using melamine and Al(NO_3)_3 via in-situ reaction and the following thermal polymerization approach. The in-situ reaction between melamine and Al(NO_3)_3 results in the existence of HNO_3-acidified melamine and Al(OH)_3 aggregates via the hydrolysis of Al(NO_3)_3. After thermal polymerization, the aggregates are converted to g-C_3N_4/Al_2O_3 composites. The thermal polymerization of acidified melamine and the support effect of aluminum hydroxide for g-C_3N_4 during the calcination process lead to highly dispersed amrophous Al_2O_3 on ultrathin g-C_3N_4 nanosheets, which is beneficial for the separation of photogenerated electron-hole pairs in the heterojunction. The degradation rate for Rhodamine B (RhB) over the most activie sample is 16.6 times than that of pristine g-C_3N_4 under visible light irradiation, which can be attributed to the high specific surface area, highly dispersion of amorphous Al_2O_3 on ultrathin g-C_3N_4 nanosheet, and the effective electrons transfer from g-C_3N_4 to the amorphous Al_2O_3.

The southern molecular environment of SNR G18.8+0.3

OpenAIRE

Paron, S.; Peña, M. Celis; Ortega, M. E.; Petriela, A.; Dubner, G.; Giacina, E.; Rubio, M.

2015-01-01

In a previous paper we have investigated the molecular environment towardsthe eastern border of the SNR G18.8+0.3. Continuing with the study of thesurroundings of this SNR, in this work we focus on its southern border, whichin the radio continuum emission shows a very peculiar morphology with acorrugated corner and a very flattened southern flank. We observed two regionstowards the south of SNR G18.8+0.3 using the Atacama Submillimeter TelescopeExperiment (ASTE) in the 12CO J=3-2. One of thes...

Increased expression of G-protein-coupled receptor kinases 3 and 4 in hyperfunctioning thyroid nodules.

Science.gov (United States)

Voigt, Carsten; Holzapfel, Hans-Peter; Meyer, Silke; Paschke, Ralf

2004-07-01

G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha mutations. In conclusion, the increased expression of GRK 3 in HTNs and the ability of GRK 3 to desensitize the TSHR in vitro, suggest a potential role for GRK 3 as a negative feedback regulator for the constitutively activated cAMP pathway in HTNs.

INFRARED AND KINEMATIC PROPERTIES OF THE SUBSTELLAR OBJECT G 196-3 B