Oncolytic adenovirus Ad657 for systemic virotherapy against prostate cancer

Directory of Open Access Journals (Sweden)

Nguyen TV

2018-05-01

Full Text Available Tien V Nguyen,1,* Catherine M Crosby,2,* Gregory J Heller,3 Zachary I Mendel,3 Mary E Barry,1 Michael A Barry1,4,5 1Department of Internal Medicine, Division of Infectious Diseases, 2Virology and Gene Therapy Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, 3Postbaccalaureate Research Education Program, Mayo Clinic Graduate School of Biomedical Sciences, 4Department of Immunology, 5Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA *These authors contributed equally to this work Background: Human species C adenovirus serotype 5 (Ad5 is the archetype oncolytic adenovirus and has been used in the vast majority of preclinical and clinical tests. While Ad5 can be robust, species C Ad6 has lower seroprevalence, side effects, and appears to be more potent as a systemic therapy against a number of tumors than Ad5. Historically, there have only been four species C human adenoviruses: serotypes 1, 2, 5, and 6. More recently a new species C adenovirus, Ad57, was identified. Ad57 is most similar to Ad6 with virtually all variation in their capsid proteins occurring in the hypervariable regions (HVRs of their hexon proteins. Most adenovirus neutralizing antibodies target the HVRs on adenoviruses. This led us to replace the hexon HVRs in Ad6 with those from Ad57 to create a new virus called Ad657 and explore this novel species C platform’s utility as an oncolytic virus. Methods: The HVR region from Ad57 was synthesized and used to replace the Ad6 HVR region by homologous recombination in bacteria generating a new viral platform that we call Ad657. Replication-competent Ad5, Ad6, and Ad657 were compared in vitro and in vivo for liver damage and oncolytic efficacy against prostate cancers after single intravenous treatment in mice. Results: Ad5, Ad6, and Ad657 had similar in vitro oncolytic activity against human prostate cancer cells. Ad5 provoked the highest level of liver toxicity after intravenous injection and Ad657

Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.

Science.gov (United States)

Zhi, Yan; Figueredo, Joanita; Kobinger, Gary P; Hagan, Heather; Calcedo, Roberto; Miller, James R; Gao, Guangping; Wilson, James M

2006-05-01

Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.

Replication-competent human adenovirus 11p vectors can propagate in Vero cells

International Nuclear Information System (INIS)

Gokumakulapalle, Madhuri; Mei, Ya-Fang

2016-01-01

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

Replication-competent human adenovirus 11p vectors can propagate in Vero cells

Energy Technology Data Exchange (ETDEWEB)

Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

2016-08-15

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

The complete nucleotide sequence, genome organization, and origin of human adenovirus type 11

International Nuclear Information System (INIS)

Stone, Daniel; Furthmann, Anne; Sandig, Volker; Lieber, Andre

2003-01-01

The complete DNA sequence and transcription map of human adenovirus type 11 are reported here. This is the first published sequence for a subgenera B human adenovirus and demonstrates a genome organization highly similar to those of other human adenoviruses. All of the genes from the early, intermediate, and late regions are present in the expected locations of the genome for a human adenovirus. The genome size is 34,794 bp in length and has a GC content of 48.9%. Sequence alignment with genomes of groups A (Ad12), C (Ad5), D (Ad17), E (Simian adenovirus 25), and F (Ad40) revealed homologies of 64, 54, 68, 75, and 52%, respectively. Detailed genomic analysis demonstrated that Ads 11 and 35 are highly conserved in all areas except the hexon hypervariable regions and fiber. Similarly, comparison of Ad11 with subgroup E SAV25 revealed poor homology between fibers but high homology in proteins encoded by all other areas of the genome. We propose an evolutionary model in which functional viruses can be reconstituted following fiber substitution from one serotype to another. According to this model either the Ad11 genome is a derivative of Ad35, from which the fiber was substituted with Ad7, or the Ad35 genome is the product of a fiber substitution from Ad21 into the Ad11 genome. This model also provides a possible explanation for the origin of group E Ads, which are evolutionarily derived from a group C fiber substitution into a group B genome

Enhanced reactivation and mutagenesis of UV-irradiated adenovirus in normal human fibroblasts

International Nuclear Information System (INIS)

Bennett, C.B.; Rainbow, A.J.

1988-01-01

UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) for two adenovirus temperature-sensitive mutants were examined following the infection of normal human fibroblasts. UV-irradiation of the virus alone resulted in dose-dependent increase in the UV-induced reversion frequency (RF) of viral progeny and a dose-dependent exponential decrease in progeny survival, when infecting non-irradiated cells. Analysis of the slopes of the UV-induced reversion curves suggested that 2.5 ± 0.3 and 2.4 ± 0.5 'hits' were required to produce a targeted reversion event among the viral progeny of Ad5ts36 and Ad5ts125 respectively. UV-irradiation of cells 24 h prior to infection resulted in a significant increase in progeny survival for UV-irradiated virus (UVER factor = 3.4 ± 0.8) concomitant with a significant increase in RF for UV-irradiated virus (targeted increase = 1.9 ± 0.3). The UV-induced RF per lethal hit to the virus was also significantly greater in UV-irradiated compared with non-irradiated cells. These results are consistent with the existence of a UV-inducible error-prone DNA repair mechanism in normal human cells. (author)

Protection of non-human primates against rabies with an adenovirus recombinant vaccine

International Nuclear Information System (INIS)

Xiang, Z.Q.; Greenberg, L.; Ertl, H.C.; Rupprecht, C.E.

2014-01-01

Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus

Protection of non-human primates against rabies with an adenovirus recombinant vaccine

Energy Technology Data Exchange (ETDEWEB)

Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

2014-02-15

Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

Science.gov (United States)

Freimuth, P; Anderson, C W

1993-03-01

The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

36 CFR 1002.36 - Gambling.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Gambling. 1002.36 Section 1002.36 Parks, Forests, and Public Property PRESIDIO TRUST RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 1002.36 Gambling. (a) Gambling in any form, or the operation of gambling devices, is prohibited...

Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells

International Nuclear Information System (INIS)

Rainbow, A.J.

1989-01-01

The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D 0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus. (author)

36 CFR 2.36 - Gambling.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Gambling. 2.36 Section 2.36 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.36 Gambling. (a) Gambling in any form, or the operation of gambling...

A mosaic adenovirus possessing serotype Ad5 and serotype Ad3 knobs exhibits expanded tropism

International Nuclear Information System (INIS)

Takayama, Koichi; Reynolds, Paul N.; Short, Joshua J.; Kawakami, Yosuke; Adachi, Yasuo; Glasgow, Joel N.; Rots, Marianne G.; Krasnykh, Victor; Douglas, Joanne T.; Curiel, David T.

2003-01-01

The efficiency of cancer gene therapy with recombinant adenoviruses based on serotype 5 (Ad5) has been limited partly because of variable, and often low, expression by human primary cancer cells of the primary cellular-receptor which recognizes the knob domain of the fiber protein, the coxsackie and adenovirus receptor (CAR). As a means of circumventing CAR deficiency, Ad vectors have been retargeted by utilizing chimeric fibers possessing knob domains of alternate Ad serotypes. We have reported that ovarian cancer cells possess a primary receptor for Ad3 to which the Ad3 knob binds independently of the CAR-Ad5 knob interaction. Furthermore, an Ad5-based chimeric vector, designated Ad5/3, containing a chimeric fiber proteins possessing the Ad3 knob, demonstrates CAR-independent tropism by virtue of targeting the Ad3 receptor. Based on these findings, we hypothesized that a mosaic virus possessing both the Ad5 knob and the Ad3 knob on the same virion could utilize either primary receptor, resulting in expanded tropism. In this study, we generated a dual-knob mosaic virus by coinfection of 293 cells with Ad5-based and Ad5/3-based vectors. Characterization of the resultant virions confirmed the incorporation of both Ad5 and Ad3 knobs in the same particle. Furthermore, this mosaic virus was able to utilize either receptor, CAR and the Ad3 receptor, for virus attachment to cells. Enhanced Ad infectivity with the mosaic virus was shown in a panel of cell lines, with receptor profiles ranging from CAR-dominant to Ad3 receptor-dominant. Thus, this mosaic virus strategy may offer the potential to improve Ad-based gene therapy approaches by infectivity enhancement and tropism expansion

Soluble CD36- a marker of the (pathophysiological) role of CD36 in the metabolic syndrome?

DEFF Research Database (Denmark)

Koonen, Debby P Y; Jensen, Majken K; Handberg, Aase

2011-01-01

associated with obesity and lipid components of the metabolic syndrome, with risk of heart disease and type 2 diabetes. Recently, non-cell bound CD36 was identified in human plasma and was termed soluble CD36 (sCD36). In this review we will describe the functions of CD36 in tissues and address the role of s......CD36 in the context of the metabolic syndrome. We will also highlight recent findings from human genetic studies looking at the CD36 locus in relation to metabolic profile in the general population. Finally, we present a model in which insulin resistance, oxLDL, low-grade inflammation and liver...

36 CFR 1207.36 - Procurement.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Procurement. 1207.36 Section 1207.36 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL RULES... resonableness can be established on the basis of a catalog or market price of a commercial product sold in...

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines

Directory of Open Access Journals (Sweden)

Conor M. Henry

2016-02-01

Full Text Available Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ∼500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis.

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

Directory of Open Access Journals (Sweden)

Xingui Tian

2015-10-01

Full Text Available Human adenovirus type 55 (HAdV55 is a newly identified re-emergent acute respiratory disease (ARD pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152, A55R2 (residues 179 to 187, A55R4 (residues 247 to 259 and A55R7 (residues 429 to 443, were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA and neutralization tests (NT. Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3 and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis.

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

Science.gov (United States)

Tian, Xingui; Ma, Qiang; Jiang, Zaixue; Huang, Junfeng; Liu, Qian; Lu, Xiaomei; Luo, Qingming; Zhou, Rong

2015-01-01

Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152), A55R2 (residues 179 to 187), A55R4 (residues 247 to 259) and A55R7 (residues 429 to 443), were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3) and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis. PMID:26516903

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines.

Science.gov (United States)

Henry, Conor M; Sullivan, Graeme P; Clancy, Danielle M; Afonina, Inna S; Kulms, Dagmar; Martin, Seamus J

2016-02-02

Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ~500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Development of replication-deficient adenovirus malaria vaccines.

Science.gov (United States)

Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

2017-03-01

Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

Comparison of detector systems for the separation of 36Cl and 36S with a 3-MV tandem

International Nuclear Information System (INIS)

Orlowski, Tobias; Forstner, Oliver; Golser, Robin; Kutschera, Walter; Merchel, Silke; Martschini, Martin; Priller, Alfred; Steier, Peter; Vockenhuber, Christof; Wallner, Anton

2010-01-01

The possibility of detecting 36 Cl for geological exposure dating has been explored for several years at VERA (the Vienna Environmental Research Accelerator). First results on real samples were obtained with an ionization chamber (developed at the ETH/PSI, Zuerich, Switzerland) with two anodes. To improve the suppression of 36 S, we equipped the ionization chamber with an exit window and added a Time-of-Flight (TOF) system with a double-sided silicon strip detector (50 x 50 mm 2 ) as stop detector. We optimized the TOF setup by using silicon nitride foils to reduce scattering tails in the energy spectra. At 3 MV terminal voltage, corresponding to a particle energy of 24 MeV of 36 Cl 7+ , we achieved a 36 S 7+ -suppression of 21,500 (50% 36 Cl-detector-efficiency).

Effect of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on the growth and radiotherapeutic sensitivity of human lymphoma cell lines

International Nuclear Information System (INIS)

Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wang Yongqing; Wu Jinchang

2008-01-01

Objective: To explore the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Methods: Human lymphoma cell lines Raji and Daudi were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTT. The p53 protein expression was detected by Western blotting, and p53 mRNA was detected by BT-PCB. Results: The MTT results showed that the inhibitory effect and radiosensitivity enhancement of rAd-p53 on human lymphoma cell lines were not obvious [Raji: (27.5±4.1)%; Daudi: (28.1±1.6)%]. The results of Western blotting and BT-PCB showed that extrinsic p53 protein and p53 mRNA were expressed to some degree, but not at high-level. In addition, the results didn't demonstrate obvious radiosensitivity enhancement. Conclusions: The role of inhibition and radiosensitivity enhancement of rAd-p53 was not significant on human lymphoma cell lines. (authors)

The complete genome sequence of human adenovirus 84, a highly recombinant new Human mastadenovirus D type with a unique fiber gene.

Science.gov (United States)

Kaján, Győző L; Kajon, Adriana E; Pinto, Alexis Castillo; Bartha, Dániel; Arnberg, Niklas

2017-10-15

A novel human adenovirus was isolated from a pediatric case of acute respiratory disease in Panama City, Panama in 2011. The clinical isolate was initially identified as an intertypic recombinant based on hexon and fiber gene sequencing. Based on the analysis of its complete genome sequence, the novel complex recombinant Human mastadenovirus D (HAdV-D) strain was classified into a new HAdV type: HAdV-84, and it was designated Adenovirus D human/PAN/P309886/2011/84[P43H17F84]. HAdV-D types possess usually an ocular or gastrointestinal tropism, and respiratory association is scarcely reported. The virus has a novel fiber type, most closely related to, but still clearly distant from that of HAdV-36. The predicted fiber is hypothesised to bind sialic acid with lower affinity compared to HAdV-37. Bioinformatic analysis of the complete genomic sequence of HAdV-84 revealed multiple homologous recombination events and provided deeper insight into HAdV evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

Science.gov (United States)

Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

2014-01-01

Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. PMID:24503087

“Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity

NARCIS (Netherlands)

Ginneken, van V.J.T.; Sitnyakowsky, L.; Jeffery, J.E.

2009-01-01

In recent years viral infections have been recognized as possible cause of obesity, alongside the traditionally recognized causes (genetic inheritance, and behaviour/environmental causes such as diet exercise, cultural practices and stress). Although four viruses have been reported to induce obesity

Serotonin 2A receptor agonist binding in the human brain with [C]Cimbi-36

DEFF Research Database (Denmark)

Ettrup, A.; da Cunha-Bang, S.; McMahon, Barry P.

2014-01-01

[C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely ....... Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68....... than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input...

36 CFR 223.36 - Volume determination.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Volume determination. 223.36... Volume determination. (a) Timber sale contracts may provide for volume determination by scaling... the contract or permit provides for the determination of volume by tree measurement and the timber has...

A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity.

Science.gov (United States)

Smaill, Fiona; Jeyanathan, Mangalakumari; Smieja, Marek; Medina, Maria Fe; Thanthrige-Don, Niroshan; Zganiacz, Anna; Yin, Cindy; Heriazon, Armando; Damjanovic, Daniela; Puri, Laura; Hamid, Jemila; Xie, Feng; Foley, Ronan; Bramson, Jonathan; Gauldie, Jack; Xing, Zhou

2013-10-02

There is an urgent need to develop new tuberculosis (TB) vaccines to safely and effectively boost Bacille Calmette-Guérin (BCG)-triggered T cell immunity in humans. AdHu5Ag85A is a recombinant human type 5 adenovirus (AdHu5)-based TB vaccine with demonstrated efficacy in a number of animal species, yet it remains to be translated to human applications. In this phase 1 study, we evaluated the safety and immunogenicity of AdHu5Ag85A in both BCG-naïve and previously BCG-immunized healthy adults. Intramuscular immunization of AdHu5Ag85A was safe and well tolerated in both trial volunteer groups. Moreover, although AdHu5Ag85A was immunogenic in both trial volunteer groups, it much more potently boosted polyfunctional CD4(+) and CD8(+) T cell immunity in previously BCG-vaccinated volunteers. Furthermore, despite prevalent preexisting anti-AdHu5 humoral immunity in most of the trial volunteers, we found little evidence that such preexisting anti-AdHu5 immunity significantly dampened the potency of AdHu5Ag85A vaccine. This study supports further clinical investigations of the AdHu5Ag85A vaccine for human applications. It also suggests that the widely perceived negative effect of preexisting anti-AdHu5 immunity may not be universally applied to all AdHu5-based vaccines against different types of human pathogens.

The structural basis for the integrity of adenovirus Ad3 dodecahedron.

Directory of Open Access Journals (Sweden)

Ewa Szolajska

Full Text Available During the viral life cycle adenoviruses produce excess capsid proteins. Human adenovirus serotype 3 (Ad3 synthesizes predominantly an excess of free pentons, the complexes of pentameric penton base and trimeric fiber proteins, which are responsible for virus penetration. In infected cells Ad3 pentons spontaneously assemble into dodecahedral virus-like nano-particles containing twelve pentons. They also form in insect cells during expression in the baculovirus system. Similarly, in the absence of fiber protein dodecahedric particles built of 12 penton base pentamers can be produced. Both kinds of dodecahedra show remarkable efficiency of intracellular penetration and can be engineered to deliver several millions of foreign cargo molecules to a single target cell. For this reason, they are of great interest as a delivery vector. In order to successfully manipulate this potential vector for drug and/or gene delivery, an understanding of the molecular basis of vector assembly and integrity is critical. Crystallographic data in conjunction with site-directed mutagenesis and biochemical analysis provide a model for the molecular determinants of dodecamer particle assembly and the requirements for stability. The 3.8 Å crystal structure of Ad3 penton base dodecamer (Dd shows that the dodecahedric structure is stabilized by strand-swapping between neighboring penton base molecules. Such N-terminal strand-swapping does not occur for Dd of Ad2, a serotype which does not form Dd under physiological conditions. This unique stabilization of the Ad3 dodecamer is controlled by residues 59-61 located at the site of strand switching, the residues involved in putative salt bridges between pentamers and by the disordered N-terminus (residues 1-47, as confirmed by site directed mutagenesis and biochemical analysis of mutant and wild type protein. We also provide evidence that the distal N-terminal residues are externally exposed and available for attaching cargo.

Comparison of detector systems for the separation of {sup 36}Cl and {sup 36}S with a 3-MV tandem

Energy Technology Data Exchange (ETDEWEB)

Orlowski, Tobias, E-mail: a0447924@unet.univie.ac.a [VERA Laboratory, Fakultaet fuer Physik, Universitaet Wien, Waehringer Str. 17, Wien 1090 (Austria); Forstner, Oliver; Golser, Robin; Kutschera, Walter [VERA Laboratory, Fakultaet fuer Physik, Universitaet Wien, Waehringer Str. 17, Wien 1090 (Austria); Merchel, Silke [CEREGE, CNRS-IRD-Universite Aix-Marseille, Europole Mediterraneen de L' Arbois, BP 80, Aix-en-Provence 13545 (France); Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); Martschini, Martin; Priller, Alfred; Steier, Peter [VERA Laboratory, Fakultaet fuer Physik, Universitaet Wien, Waehringer Str. 17, Wien 1090 (Austria); Vockenhuber, Christof [HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Wallner, Anton [VERA Laboratory, Fakultaet fuer Physik, Universitaet Wien, Waehringer Str. 17, Wien 1090 (Austria)

2010-04-15

The possibility of detecting {sup 36}Cl for geological exposure dating has been explored for several years at VERA (the Vienna Environmental Research Accelerator). First results on real samples were obtained with an ionization chamber (developed at the ETH/PSI, Zuerich, Switzerland) with two anodes. To improve the suppression of {sup 36}S, we equipped the ionization chamber with an exit window and added a Time-of-Flight (TOF) system with a double-sided silicon strip detector (50 x 50 mm{sup 2}) as stop detector. We optimized the TOF setup by using silicon nitride foils to reduce scattering tails in the energy spectra. At 3 MV terminal voltage, corresponding to a particle energy of 24 MeV of {sup 36}Cl{sup 7+}, we achieved a {sup 36}S{sup 7+}-suppression of 21,500 (50% {sup 36}Cl-detector-efficiency).

British and German manufacturing productivity compared : A new benchmark for 1935/36 based on double deflated value added

NARCIS (Netherlands)

Fremdling, Rainer; de Jong, Herman; Timmer, Marcel P.

We present a new estimate of Anglo-German manufacturing productivity levels for 1935/36. It is based on archival data on German manufacturing and published British census data. We calculate comparative levels of value added, correcting for differences in prices for outputs and inputs. This so-called

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3.

Science.gov (United States)

Sirena, Dominique; Ruzsics, Zsolt; Schaffner, Walter; Greber, Urs F; Hemmi, Silvio

2005-12-20

Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.

Characteristics of 36ClO3 and 36Cl- uptake into pisum sativum L. seedlings: Limitations and uses of 36CPO3- as an analogue for NO3

International Nuclear Information System (INIS)

Deane-Drummond, C.E.

1985-01-01

The characteristics of 36 Cl 3 - influx and 36 ClO 3 - influx into pisum sativum L.cv. Feltham First seedlings have been investigated. The kinetics of these fluxes at different external substrate concentrations were generated by computer fits to the data, and for 36 Cl - influx apparent Vsub(maxCl - ) and Ksub(m.Cl - ) were 1.62 u mol g - 1 fresh wt. h - l and 0.135 mol m -3 , respectively, (r 2 = 0.90); for 36 ClO 3 - influx apparent Vsub(max ClO 3 - ) and Ksub(m ClO 3 - ) were 15.29 u mol g -1 fresh wt. h - l and 0.69 mol m -3 respectively (r 2 =0.95). When a range of nitrate concentrations were added to 36 ClO 3 - there was no significant difference between NO 3 - or ClO 3 - at low concentrations (0.25 mol m -3 ), but some divergence at higher concentrations. Initial 36 ClO 3 - /NO 3 - influx into P. sativum seedlings was higher than that following extended incubation, which approached that of steady state net nitrate uptake. The difference between 36 ClO 3 - accumulation (J) was used to measure nitrate efflux (E). There was no detectable 36 Cl - efflux when a similar procedure was adopted using 36 Cl - efflux when a similar procedure for J was set by 1, and was stimulated in conditions of N starvation or innoculation with Rhizobium. The rate of substrate cycling (E/1) and the parameter (1 + E/J) were increased in the former case and when a mixed source of N was used in the culture medium, 36 Cl - influx was inhibited by NH 4 + regimes in these experiments. The purported anion blocker diisothiocyanostilbene-2-2' disulphonate (DIDS) inhibited 36 Cl - influx, but in the latter case only that 'induced' by N-starvation. The results are discussed in terms of current models for nitrate uptake. (author)

75 FR 34347 - Airworthiness Directives; Honeywell International Inc. Auxiliary Power Unit Models GTCP36-150(R...

Science.gov (United States)

2010-06-17

... Airworthiness Directives; Honeywell International Inc. Auxiliary Power Unit Models GTCP36-150(R) and GTCP36-150...) models GTCP36- 150(R) and GTCP36-150(RR). This AD requires inspecting the fuel control unit (FCU...-150(R) and GTCP36-150(RR). We published the proposed AD in the Federal Register on December 23, 2009...

Doxycycline-Regulated 3T3-L1 Preadipocyte Cell Line with Inducible, Stable Expression of Adenoviral E4orf1 Gene: A Cell Model to Study Insulin-Independent Glucose Disposal

OpenAIRE

Krishnapuram, Rashmi; Dhurandhar, Emily J.; Dubuisson, Olga; Hegde, Vijay; Dhurandhar, Nikhil V.

2013-01-01

Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we establis...

Taxonomy proposal for Old World monkey adenoviruses: characterisation of several non-human, non-ape primate adenovirus lineages.

Science.gov (United States)

Pantó, Laura; Podgorski, Iva I; Jánoska, Máté; Márkó, Orsolya; Harrach, Balázs

2015-12-01

A species classification regarding Old World monkey adenoviruses is proposed. We determined the nucleotide sequences of PCR-amplified fragments from the genes of the IVa2, DNA-dependent DNA polymerase, penton base, and hexon proteins from every simian adenovirus (SAdV) serotype that originated from Old World monkeys for which the full genome sequence had not yet been published. We confirmed that the majority of Old Word monkey SAdVs belong to two previously established species. Interestingly, one is the most recently established human AdV species, Human mastadenovirus G, which includes a single human virus, HAdV-52, as well as SAdV-1, -2, -7, -11, -12, and -15. The other approved species, Simian mastadenovirus A includes SAdV-3, -4, -6, -9, -10, -14, and -48. Several SAdVs (SAdV-5, -8, -49, -50) together with baboon AdV-1 and rhesus monkey AdV strains A1139, A1163, A1173, A1258, A1285, A1296, A1312, A1327 and A1335 have been proposed to be classified into an additional species, Simian mastadenovirus B. Another proposed species, Simian mastadenovirus C has been described for SAdV-19, baboon AdV-2/4 and -3. Our study revealed the existence of four additional AdV lineages. The corresponding new candidate species are Simian mastadenovirus D (for SAdV-13), Simian mastadenovirus E (for SAdV-16), Simian mastadenovirus F (for SAdV-17 and -18), and Simian mastadenovirus G (for SAdV-20). Several biological and genomic properties, such as the host origin, haemagglutination profile, number of fibre genes, and G+C content of the genome, strongly support this classification. Three SAdV strains originating from the American Type Culture Collection turned out to be mixtures of at least two virus types, either of the same species (SAdV-12 and -15 types from Human mastadenovirus G) or of two different species (SAdV-5 types from Simian mastadenovirus B and Human mastadenovirus G).

Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage.

Science.gov (United States)

Xu, Kun; Song, Yufeng; Dai, Lianpan; Zhang, Yongli; Lu, Xuancheng; Xie, Yijia; Zhang, Hangjie; Cheng, Tao; Wang, Qihui; Huang, Qingrui; Bi, Yuhai; Liu, William J; Liu, Wenjun; Li, Xiangdong; Qin, Chuan; Shi, Yi; Yan, Jinghua; Zhou, Dongming; Gao, George F

2018-03-15

The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control. IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M

Serum lipase activity and concentration during intravenous infusions of GLP-1 and PYY3-36 and after ad libitum meal ingestion in overweight men

DEFF Research Database (Denmark)

Schmidt, Julie Berg; Sjödin, Anders Mikael; Stevner, Lene Susanne

2016-01-01

To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double-blinded, pl......To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double...... the infusion and after intake of an ad libitum meal for measurement of serum lipase. Serum lipase levels measured by enzyme-linked immunosorbent assay (ELISA) following mono-infusions of GLP-1 and PYY3-36 were comparable to serum lipase levels following placebo (P = 0.054 and P = 0.873, respectively......). Following the co-infusion of GLP-1 and PYY3-36, serum lipase levels measured by ELISA decreased over time compared to placebo (P = 0.012). However, the between-group difference was not consistent when each time point was analyzed separately. On the placebo day, serum lipase levels measured by ELISA after...

42 CFR 423.36 - Disenrollment process.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Disenrollment process. 423.36 Section 423.36 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Disenrollment process. (a) General rule. An individual may disenroll from a PDP during the periods specified in...

Historieportal 3.-6. - historie3-6.gyldendal.dk

DEFF Research Database (Denmark)

Poulsen, Jens Aage

Portal, der indeholder tekster, video, billeder, interaktive opgaver m.m. til undervisningen i historie i 3.-6. klasse......Portal, der indeholder tekster, video, billeder, interaktive opgaver m.m. til undervisningen i historie i 3.-6. klasse...

MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver.

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Erkko Ylösmäki

Full Text Available MicroRNAs (miRNAs are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer virotherapy in normal tissues. In order to avoid liver damage associated with systemic or intrahepatic delivery of oncolytic adenoviruses we have introduced the concept of suppressing adenovirus replication in hepatic cells by inserting target elements for the liver-specific miR122 into the viral genome. Here we show using ex vivo cultured tissue specimens that six perfectly complementary miR122 target sites in the 3' untranslated region of the viral E1A gene are sufficient in the absence of any other genetic modifications to prevent productive replication of serotype 5 adenovirus (Ad5 in normal human liver. This modification did not compromise the replicative capacity of the modified virus in cancer tissue derived from a colon carcinoma liver metastasis or its oncolytic potency in a human lung cancer xenograft mouse model. Unlike wild-type Ad5, the modified virus did not result in increased serum levels of liver enzymes in infected mice. These results provide a strong preclinical proof of concept for the use of miR122 target sites for reducing the risk of liver damage caused by oncolytic adenoviruses, and suggest that ectopic miR122 target elements should be considered as an additional safety measure included in any therapeutic virus or viral vector posing potential hazard to the liver.

[Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities].

Science.gov (United States)

Grinenko, N F; Savitskaia, N V; Pashvykina, G V; Al'tshteĭn, A D

2003-06-01

A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

Decay of 36K

International Nuclear Information System (INIS)

Fritts, M.J.

1976-01-01

36 K was produced via the 36 Ar(p, n) 36 K reaction. Measurement of 27 β + delayed γ rays associated with the decay of 36 K implied 10 new β + branches to energy levels in 36 Ar. Branching ratios and logft values are calculated for the β + branches. Restrictions on spin and parity assignments for the 36 Ar levels are given, as well as branching ratios for γ transitions from these levels. The half-life of 36 K is determined to be 344 +- 3 msec

Killing Effect of Ad5/F35-APE1 siRNA Recombinant Adenovirus in Combination with Hematoporphrphyrin Derivative-Mediated Photodynamic Therapy on Human Nonsmall Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Lei Xia

2013-01-01

Full Text Available The main goal of this work is to investigate the killing effects and molecular mechanism of photodynamic therapy (PDT mediated by the Ad5/F35-APE1 siRNA recombinant adenovirus in combination with a hematoporphrphyrin derivative (HpD in the A549 human lung adenocarcinoma cell line in vitro to provide a theoretical reference for treating lung cancer by HpD-PDT. By using the technologies of MTT, flow cytometry, ELISA, and western blot, we observed that the proliferation inhibition and apoptosis of the A549 cells were significantly higher than the control group ( after HpD-PDT was performed. The inhibitory efficiency is dependent on the HpD concentration and laser intensity dose. The inhibitory effect on the proliferation of A549 cells of Ad5/F35-APE1 siRNA is more significant after combining with PDT, as indicated by a significant elevation of the intracellular ROS level and the expression of inflammatory factors (. The HpD-PDT-induced expression of the APE1 protein reached the peak after 24 h in A549 cells. The inhibition of APE1 expression in A549 cells was most significant after 48 hours of infection by Ad5/F35-APE1 siRNA recombinant adenovirus (10 MOI. In conclusion, the Ad5/F35-APE1 siRNA recombinant adenovirus could efficiently inhibit the HpD-PDT-induced APE1 expression hence could significantly enhance the killing effect of HpD-PDT in lung cancer cells.

UL36 Rescues Apoptosis Inhibition and In vivo Replication of a Chimeric MCMV Lacking the M36 Gene

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M. Zeeshan Chaudhry

2017-07-01

Full Text Available Apoptosis is an important defense mechanism mounted by the immune system to control virus replication. Hence, cytomegaloviruses (CMV evolved and acquired numerous anti-apoptotic genes. The product of the human CMV (HCMV UL36 gene, pUL36 (also known as vICA, binds to pro-caspase-8, thus inhibiting death-receptor apoptosis and enabling viral replication in differentiated THP-1 cells. In vivo studies of the function of HCMV genes are severely limited due to the strict host specificity of cytomegaloviruses, but CMV orthologues that co-evolved with other species allow the experimental study of CMV biology in vivo. The mouse CMV (MCMV homolog of the UL36 gene is called M36, and its protein product (pM36 is a functional homolog of vICA that binds to murine caspase-8 and inhibits its activation. M36-deficient MCMV is severely growth impaired in macrophages and in vivo. Here we show that pUL36 binds to the murine pro-caspase-8, and that UL36 expression inhibits death-receptor apoptosis in murine cells and can replace M36 to allow MCMV growth in vitro and in vivo. We generated a chimeric MCMV expressing the UL36 ORF sequence instead of the M36 one. The newly generated MCMVUL36 inhibited apoptosis in macrophage lines RAW 264.7, J774A.1, and IC-21 and its growth was rescued to wild type levels. Similarly, growth was rescued in vivo in the liver and spleen, but only partially in the salivary glands of BALB/c and C57BL/6 mice. In conclusion, we determined that an immune-evasive HCMV gene is conserved enough to functionally replace its MCMV counterpart and thus allow its study in an in vivo setting. As UL36 and M36 proteins engage the same molecular host target, our newly developed model can facilitate studies of anti-viral compounds targeting pUL36 in vivo.

[Rapid expression and preparation of the recombinant fusion protein sTNFRII-gAD by adenovirus vector system].

Science.gov (United States)

Lu, Yue; Liu, Dan; Zhang, Xiaoren; Liu, Xuerong; Shen, Wei; Zheng, Gang; Liu, Yunfan; Dong, Xiaoyan; Wu, Xiaobing; Gao, Jimin

2011-08-01

We expressed and prepared the recombinant fusion protein sTNFRII-gAD consisted of soluble TNF receptor II and the globular domain of adiponectin by Adenovirus Vector System in mammalian BHK21c022 cells. First we used the adenovirus vector containing EGFP gene (rAd5-EGFP) to infect BHK21c022 cells at different MOI (from 0 to 1 000), and then evaluated their transduction efficiency and cytotoxicity. Similarly, we constructed the replication-deficient adenovirus type 5-sTNFRII-gAD (rAd5-sTNFRII-gAD). We collected the supernatants for Western blotting to determine the optimal MOI by comparing the expression levels of sTNFRII-gAD fusion protein, 48 h after the BHK21c022 cells were infected by rAd5-sTNFRII-gAD at different MOIs (from 0 to 1 000). Then, we chose rAd5-sTNFRII-gAD at MOI 100 to infect five bottles of BHK21c022 cells in 100 mL of serum-free chemically defined media 100 mL, harvested the supernatant every 48 h for 6 times, and condense and purify sTNFRII-gAD fusion protein by ammonium sulfate salt-out and size-exclusion chromatography, respectively. Finally, we analyzed anti-TNFalpha activity of sTNFRII-gAD fusion protein on L929 cells in vitro. The results showed that the number of BHK21c022 cells expressing EGFP protein was increased significantly with the increase of MOI. However, some cells died at MOI of 1 000 while there was no significant cytotoxicity at MOI from 0 to 100. Western blotting analysis showed that the more adenoviruses, the higher expression of sTNFRII-gAD fusion protein in the supernatant with the highest expression at MOI 1 000. We successfully obtained about 11 mg bioactive and purified sTNFRII-gAD fusion protein at last. The in vitro assay demonstrated that the sTNFRII-gAD fusion protein was potent to antagonize TNFalpha's cytotoxicity to L929 cells. Put together, we established a recombinant adenovirus vector/BHK21 cell expression system, characteristic of the efficient serum-free culture and easy scaling-up.

Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

Directory of Open Access Journals (Sweden)

Grace E Cooper

Full Text Available Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031 and CD36 gene expression (p = 0.031 by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.

Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.

Science.gov (United States)

Guzman, Efrain; Taylor, Geraldine; Hope, Jayne; Herbert, Rebecca; Cubillos-Zapata, Carolina; Charleston, Bryan

2016-10-01

Dendritic cells (DC) are central to the initiation of immune responses, and various approaches have been used to target vaccines to DC in order to improve immunogenicity. Cannulation of lymphatic vessels allows for the collection of DC that migrate from the skin. These migrating DC are involved in antigen uptake and presentation following vaccination. Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B-Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B-Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed.

[Adenovirus-mediated canine interferon-gamma expression and its antiviral activity against canine parvovirus].

Science.gov (United States)

Zhang, Kao; Jin, Huijun; Zhong, Fei; Li, Xiujin; Neng, Changai; Chen, Huihui; Li, Wenyan; Wen, Jiexia

2012-11-04

To construct recombinant adenovirus containing canine interferon-gamma (cIFN-gamma) gene and to investigate its antiviral activity against canine parvovirus in Madin-Darby canine kidney cells (MDCK). [Methods] The cIFN-gamma gene was inserted into adenovirus shuttle plasmid to construct pShuttle3-cIFN-gamma expression vector, from which the cIFN-gamma expression cassette was transferred into the adenovirus genomic plasmid pAdeno-X by specific restriction sites to generate recombinant adenovirus genomic plasmid pAd-cIFN-gamma. The pAd-cIFN-gamma plasmid was linearized by digestion and transfected into human embryonic kidney (HEK) 293T cells to generate the replication-defective cIFN-gamma recombinant adenovirus (Ad-cIFN-gamma). To analyze its anti-canine parvovirus activity, the MDCK cells were pre-infected by Ad-cIFN-gamma recombinant adenovirus, and then infected by canine parvovirus. The antiviral activity of the Ad-cIFN-gamma recombinant adenovirus against parvovirus was analyzed. The recombinant adenovirus containing cIFN-gamma gene was constructed by the ligation method. The recombinant adenovirus could mediates recombinant cIFN-gamma secretory expression in MDCK cells. The Ad-cIFN-gamma recombinant adenovirus could significantly inhibit canine parvovirus replication in MDCK cells pre-infected with the recombinant adenovirus. These results indicate that the Ad-cIFN-gamma recombinant adenovirus has the potent antiviral activity against canine parvovirus. The Ad-cIFN-gamma recombinant adenovirus was successfully constructed by the ligation method and possessed a powerful antiviral activity against canine parvovirus.

Radiation enhanced reactivation of irradiated human adenovirus type 2 in human cells

International Nuclear Information System (INIS)

Jeeves, W.P.

1981-04-01

Radiation-enhanced reactivation (ER) of a radiation-damaged mammalian virus is the term given to the observation that the survival of irradiated virus can be enhanced by irradiation of an appropriate host cell prior to infection. In this work, both UV-enhanced reactivation (UVER) and gamma-ray-enhanced reactivation (γRER) of irradiated human adenovirus type 2 (AD 2) were studied in a variety of normal and DNA repair-deficient human fibroblast host cell strains. In order to examine the lesion specificity of ER in human cells, experiments were performed using UV-irradiated and γ-irradiated virus. The investigation was carried out using a sensitive technique of indirect immunofluorescence, according to which irradiated and unirradiated cell cultures were infected with irradiated or unirradiated AD 2 and were subsequently examined for the presence of viral structural antigens ('V' Ag) at a fixed time after infection

Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects

DEFF Research Database (Denmark)

Sloth, Birgitte; Holst, Jens Juul; Flint, Anne

2006-01-01

Peptide YY (PYY)(3-36) has been shown to produce dramatic reductions in energy intake (EI), but no human data exist regarding energy expenditure (EE), glucose and fat metabolism. Nothing is known regarding PYY1-36. To compare effects of PYY(1-36) and PYY(3-36) on appetite, EI, EE, insulin, glucose...... and eight obese participants completed 0.2 pmol x kg(-1) x min(-1) PYY(3-36) and 1.6 pmol x kg(-1) x min(-1) PYY(1-36) infusions. PYY(3-36) [corrected] produced [corrected] lower ratings of well-being and [corrected] increases in heart rate, [corrected] FFA, and [corrected] postprandial [corrected] insulin...

Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity

NARCIS (Netherlands)

Thorner, Anna R.; Lemckert, Angelique A. C.; Goudsmit, Jaap; Lynch, Diana M.; Ewald, Bonnie A.; Denholtz, Matthew; Havenga, Menzo J. E.; Barouch, Dan H.

2006-01-01

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have

42 CFR 86.36 - Duration and continuation.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Duration and continuation. 86.36 Section 86.36 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeship...

42 CFR 60.36 - Consequence of using an agent.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Consequence of using an agent. 60.36 Section 60.36 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS HEALTH EDUCATION ASSISTANCE LOAN PROGRAM The Lender and Holder § 60.36 Consequence of using an agent. The delegation of...

Serotonin 2A receptor agonist binding in the human brain with [¹¹C]Cimbi-36

DEFF Research Database (Denmark)

Ettrup, Anders; Svarer, Claus; McMahon, Brenda

2016-01-01

INTRODUCTION: [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C...... test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures...... and with voxel-based analysis. RESULTS: Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently correlation between regional...

Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

Science.gov (United States)

Zhou, Li; Todorovic, Viktor; Kakavas, Steve; Sielaff, Bernhard; Medina, Limary; Wang, Leyu; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L; DiGiammarino, Enrico; Sun, Chaohong; Scott, Victoria

2018-01-12

IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 μm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Screening for adenoviruses in haematological neoplasia: High prevalence in mantle cell lymphoma.

Science.gov (United States)

Kosulin, Karin; Rauch, Margit; Ambros, Peter F; Pötschger, Ulrike; Chott, Andreas; Jäger, Ulrich; Drach, Johannes; Nader, Alexander; Lion, Thomas

2014-02-01

Human adenoviruses possess oncogenic capacity which is well documented in mammalian animal models, but their possible implication in human malignancy has remained enigmatic. Following primary infection, adenoviruses can persist in a latent state in lymphocytes where the virus is apparently able to evade immune surveillance. In the present study, we have employed a broad-spectrum adenovirus polymerase chain reaction (PCR) assay to systematically screen more than 200 diagnostic specimens of different lymphoid malignancies including acute lymphocytic leukaemia (n=50), chronic lymphocytic leukaemia (n=50), various types of malignant lymphoma (n=100) and multiple myeloma (n=11) for the presence of adenoviral sequences. While most entities analysed revealed negative findings in virtually all specimens tested, adenoviral DNA was detected in 15/36 (42%) mantle cell lymphomas investigated. The most prevalent adenoviral species detected was C, and less commonly B. Adenovirus-positive findings in patients with mantle cell lymphoma were made at different sites including bone marrow (n=7), intestine (n=5), lymph nodes (n=2) and tonsillar tissue (n=1). The presence of adenoviral sequences identified by PCR was confirmed in individual cells by fluorescence in-situ hybridisation (FISH). The frequent observation of adenoviruses in mantle cell lymphoma is intriguings, and raises questions about their possible involvement in the pathogenesis of this lymphoid malignancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chlorine-36 in seawater

International Nuclear Information System (INIS)

Argento, David C.; Stone, John O.; Keith Fifield, L.; Tims, Stephen G.

2010-01-01

Natural cosmogenic 36 Cl found in seawater originates from spallation of atmospheric 40 Ar, capture of secondary cosmic-ray neutrons by dissolved 35 Cl, and river runoff which contains 36 Cl produced in situ over the surface of the continents. The long residence time of chloride in the ocean and long half-life of 36 Cl compared to the oceanic mixing time should result in a homogenous 36 Cl/Cl ratio throughout the ocean. Production by neutron capture in the course of nuclear weapons testing should be insignificant averaged over the oceans as a whole, but may have led to regions of elevated 36 Cl concentration. Previous attempts to measure the 36 Cl/Cl ratio of seawater have been hindered by interferences, contamination, or insufficient analytic sensitivity. Here we report preliminary measurements on seawater samples, which demonstrate that the 36 Cl/Cl ratio is 0.5 ± 0.3 x 10 -15 , in reasonable agreement with calculated contributions from the sources listed above.

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development.

Science.gov (United States)

Hegde, Vijay; Na, Ha-Na; Dubuisson, Olga; Burke, Susan J; Collier, J Jason; Burk, David; Mendoza, Tamra; Dhurandhar, Nikhil V

2016-02-01

Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. 8-9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the

50 CFR 36.36 - Sled dogs and household pets.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Sled dogs and household pets. 36.36... Sled dogs and household pets. The general trespass provisions of 50 CFR 26.21 shall not apply to household pets and sled, work, or pack dogs under the direct control of their owners or handlers, but such...

Intratracheal injection of adenovirus containing the human MNSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis

International Nuclear Information System (INIS)

Epperly, Michael W.; Bray, Jenifer A.; Krager, Stephen; Berry, Luann M.; Gooding, William; Engelhardt, John F.; Zwacka, Ralf; Travis, Elizabeth L.; Greenberger, Joel S.

1999-01-01

for LacZ protein in adenovirus LacZ (Ad-LacZ)-injected mice demonstrated expression of LacZ in both the upper and lower airway. Nested RT-PCR showed lung expression of MnSOD and Cu/ZnSOD for at least 11 days following infection with each respective adenovirus construct. Nested RT-PCR using primers specific for human MnSOD demonstrated increased expression of the human MnSOD transgene in the trachea and alveolar type II cells 4 days after virus injection on the day of irradiation. At this time point, increased biochemical activity of MnSOD and Cu/ZnSOD respectively, was detected in lungs from these two adenovirus groups, compared to each other or to control or adenovirus LacZ mice. Slot blot analysis of RNA from lungs of mice in each group following 850 cGy irradiation demonstrated decreased expression of mRNA for interleukin-I (IL-1), TNF-α, and transforming growth factor-beta (TGF-β) in the MnSOD adenovirus-injected mice, compared to irradiated control, LacZ, or Cu/ZnSOD adenovirus-injected, irradiated mice. Mice receiving adenovirus MnSOD showed decreased organizing alveolitis at 132 days in all three dose groups, compared to irradiated control or Ad-LacZ, or Ad-Cu/ZnSOD mice. Conclusions: Overexpression of MnSOD in the lungs of mice prior to irradiation prevents irradiation-induced acute and chronic damage quantitated as decreased levels of mRNA for IL-1, TNF-α, and TGF-β in the days immediately following irradiation, and decrease in the percent of lung demonstrating fibrosis or organizing alveolitis at 132 days. These data provide a rational basis for development of gene therapy as a method of protection of the normal lung from acute and chronic sequellae of ionizing irradiation

29 CFR 36.310 - Recruitment.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Recruitment. 36.310 Section 36.310 Labor Office of the... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 36.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 36.300 through 36.310...

Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man

DEFF Research Database (Denmark)

Witte, A-B; Grybäck, P; Holst, Jens Juul

2009-01-01

Peptide tyrosine-tyrosine (PYY) is a prandially controlled hormone in endocrine ileal and colonic mucosa cells. In plasma, PYY appears as full-length PYY1-36 and truncated PYY3-36. Both have different pharmacological profile, and PYY3-36 seems to inhibit food intake. We aimed at investigating...... the effect of intravenously administered PYY1-36 and PYY3-36 on gastric emptying and short-term metabolic control. Eight healthy adults were studied in single-blinded, randomized design. At separate occasions, intravenous infusion of saline, PYY1-36 or PYY3-36 (0.8 pmol kg(-1) min(-1)) and a radio......-labelled omelette were given. Gastric emptying (scintigraphy), appetite ratings (VAS), and plasma concentrations of insulin, glucose, GLP-1 and PYY were measured. PYY3-36 and PYY1-36 both inhibited gastric emptying, PYY3-36 most effectively. Half-emptying time was prolonged from 63.1+/-5.2 (saline) to 87...

Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human airway epithelial cells.

Science.gov (United States)

Bae, Chang Hoon; Choi, Yoon Seok; Na, Hyung Gyun; Song, Si-Youn; Kim, Yong-Dae

2018-03-01

Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated. The objective of this study was to determine whether IL-36 gamma might play a role in the regulation of mucin secretion in airway epithelial cells. We investigated the effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells. Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (PCR), and real-time PCR were performed in mucin-producing human airway epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA). IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression. These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells.

The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

International Nuclear Information System (INIS)

Francis, W.R.; Owens, S.E.; Wilde, C.; Pallister, I.; Kanamarlapudi, V.; Zou, W.; Xia, Z.

2014-01-01

Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments

Effect of recombinant adenovirus encoding human p53 tumor suppressor gene combined with radiation therapy on human lymphoma cells lines

International Nuclear Information System (INIS)

Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wan Jianmei; Wang Yongqing; Wu Jinchang

2008-01-01

This paper analyzes the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Human lymphoma cell lines were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTF. The cell cycle and apoptosis were detected by flow cytometry, and the p53 protein expression was detected by Western blotting. The results showed that extrinsic p53 gene have expressed to some degree, but not at high level. The role of inhibition and radiation sensitivity of rAd-p53 was not significant to human lymphoma cell lines. (authors)

[Role of infection in the pathogenesis of obesity].

Science.gov (United States)

Hainer, Vojtěch; Hainerová, Irena Aldhoon; Zamrazilová, Hana

2012-01-01

Current global epidemic of obesity is mainly related to increased consumption of high energy density foods and sedentary lifestyle that leads to a positive energy balance with subsequent accumulation of fat stores, primarily in genetically predisposed individuals. However, additional pathogenetic factors should be considered, including an infection. Several viruses causing obesity have been described in mice, chicken, rats, hamsters and monkeys. In humans, a significant positive association between being overweight and IgG antibodies was found for Helicobacter pylori and Chlamydia pneumoniae. This association of bacterial infections with increased BMI might not represent a causal relationship but could be a marker for greater susceptibility of obese individuals to infection. Crucial role in the development of "infectious obesity" in humans may be played by adenovirus infection, particularly AD-36 type that is also capable of inducing obesity in experimental animals as chicken, mice and monkeys. AD-36-induced obesity is paradoxically associated with lower levels of serum cholesterol and triglycerides both in humans and in experimental animals. Moreover, AD-36 enhances insulin sensitivity and improves hepatic steatosis. AD-36 effects in target organs as adipose tissue, liver and skeletal muscle are mediated through the viral protein E4orf1. This way AD-36 improves metabolic profile, as indicated by a greater glucose uptake by adipose tissue and skeletal muscle, reduced glucose output by hepatocytes, increased adiponectin levels and increased expression of adipogenic genes as peroxisome proliferator-activated receptor gamma. If E4orf1 improves glycemic control without reducing dietary fat intake and body fat stores, this viral protein would be highly valuable to develop novel anti-diabetic agents that mimic its effects.Key words: obesity, infection, adenovirus AD-36, diabetes mellitus, lipid profile, insulin sensitivity.

33 CFR 83.36 - Signals to attract attention (Rule 36).

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Signals to attract attention... SECURITY INLAND NAVIGATION RULES RULES Sound and Light Signals § 83.36 Signals to attract attention (Rule 36). If necessary to attract the attention of another vessel, any vessel may make light or sound...

E4orf1: A Novel Ligand That Improves Glucose Disposal in Cell Culture

OpenAIRE

Dhurandhar, Emily J.; Dubuisson, Olga; Mashtalir, Nazar; Krishnapuram, Rashmi; Hegde, Vijay; Dhurandhar, Nikhil V.

2011-01-01

Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest...

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

International Nuclear Information System (INIS)

Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan; Kim, Hyung Sik; Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung; Oh, Seon-Hee; Jun, Dae Won; Lee, Byung-Hoon

2017-01-01

Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

Energy Technology Data Exchange (ETDEWEB)

Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyung Sik [School of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Oh, Seon-Hee [The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Jun, Dae Won [Internal Medicine, Hanyang University School of Medicine, Seoul 133-791 (Korea, Republic of); Lee, Byung-Hoon, E-mail: lee@snu.ac.kr [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of)

2017-02-01

Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

36 CFR 219.36 - Definitions.

Science.gov (United States)

2010-07-01

... Forest System Land and Resource Management Planning Definitions § 219.36 Definitions. Definitions of the... vision for a specific area of land or type of land within the plan area. Statements of desired conditions... species of plants or animals which are not indigenous to an area but valued for their contribution to...

Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36

Directory of Open Access Journals (Sweden)

Roger S. Holmes

2012-09-01

Full Text Available Platelet glycoprotein 4 (CD36 (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3] is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA contributing to a high gene expression level (6.6 times average. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate

The Quest for the 1p36 Tumor Suppressor

Science.gov (United States)

Bagchi, Anindya; Mills, Alea A.

2010-01-01

Genomic analyses of late-stage human cancers have uncovered deletions encompassing 1p36, thereby providing an extensive body of literature supporting the idea that a potent tumor suppressor resides in this interval. Although a number of genes have been proposed as 1p36 candidate tumor suppressors, convincing evidence that their encoded products protect from cancer has been scanty. A recent functional study identified CHD5 as a novel tumor suppressor mapping to 1p36. Here we discuss evidence supporting CHD5’s tumor suppressive role. Together, these findings suggest that strategies designed to enhance CHD5 activity could provide novel approaches for treating a broad range of human malignancies. PMID:18413720

Study of sample preparation in the measurement of 36Ar(n, p)36Cl reaction cross section

International Nuclear Information System (INIS)

Jiang Songsheng; Hemick, T.K.

1992-01-01

The preparation of enriched 36 Ar gas samples and 36 Cl samples for the use in the AMS measurement of 36 Ar(n, p) 36 Cl reaction cross section was described. The 36 Ar samples prepared had the volumes of about 0.4 ml and the weights of about 0.5 mg. The uncertainty in atomic numbers of 36 Ar was (0.3∼0.4)%. The reaction product, 36 Cl, in the 36 Ar was collected and the AgCl samples were prepared

Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

Science.gov (United States)

Gharib, Mohamed; Tao, Huan; Fungwe, Thomas V; Hajri, Tahar

2016-01-01

Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

EQ3/6: status and applications

Energy Technology Data Exchange (ETDEWEB)

Wolery, T.J.; Isherwood, D.J.; Jackson, K.J.; Delany, J.M.; Puigdomenech, I.

1984-12-01

EQ3/6 is a set of related computer codes and data files for use in geochemical modeling of aqueous systems. The EQ3/6 package centers around two large computer codes, EQ3NR and EQ6, which are supported by a common thermodynamic data base. EQ3NR is a speciation-solubility code, whose function is to compute a model of the state of an aqueous solution. This code is very flexible in terms of the input that it will accept. EQ6 is a reaction-path code, which calculates models of changes in aqueous systems as they proceed toward a state of overall chemical equilibrium. EQ3/6 prior to FY83 had no capability for modeling brines, because the approximations for calculating the thermodynamic activity of water and the activity coefficients of the solute species were restricted to low ionic strengths ({le} 1.0 molal). An option has been added to use Pitzer`s equations for such calculations. At present, EQ3/6 contains two alternate Pitzer coefficient data bases. Several improvements have been made to the EQ6 code. Prior to FY83, the code could run models of mineral dissolution kinetics, but could not calculate models of precipitation kinetics. This problem has been overcome by additional code development. The speed of non-kinetic EQ6 calculations has recently been enhanced by the creation of two new calculational modes, economy mode and super economy mode. A calculational mode to simulate systems open to large gas reservoirs has also been developed. 34 references.

Genetic reconstitution of the human Adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape

Directory of Open Access Journals (Sweden)

Gastaldelli Michele

2009-10-01

Full Text Available Abstract Human Adenoviruses infect the upper and lower respiratory tracts, the urinary and digestive tracts, lymphoid systems and heart, and give rise to epidemic conjunctivitis. More than 51 human serotypes have been identified to-date, and classified into 6 species A-F. The species C Adenoviruses Ad2 and Ad5 (Ad2/5 cause upper and lower respiratory disease, but how viral structure relates to the selection of particular infectious uptake pathways is not known. An adenovirus mutant, Ad2-ts1 had been isolated upon chemical mutagenesis in the past, and shown to have unprocessed capsid proteins. Ad2-ts1 fails to package the viral protease L3/p23, and Ad2-ts1 virions do not efficiently escape from endosomes. It had been suggested that the C22187T point mutation leading to the substitution of the conserved proline 137 to leucine (P137L in the L3/p23 protease was at least in part responsible for this phenotype. To clarify if the C22187T mutation is necessary and sufficient for the Ad2-ts1 phenotype, we sequenced the genes encoding the structural proteins of Ad2-ts1, and confirmed that the Ad2-ts1 DNA carries the point mutation C22187T. Introduction of C22187T to the wild-type Ad2 genome in a bacterial artificial chromosome (Ad2-BAC gave Ad2-BAC46 virions with the full Ad2-ts1 phenotype. Reversion of Ad2-BAC46 gave wild-type Ad2 particles indicating that P137L is necessary and sufficient for the Ad2-ts1 phenotype. The kinetics of Ad2-ts1 uptake into cells were comparable to Ad2 suggesting similar endocytic uptake mechanisms. Surprisingly, infectious Ad2 or Ad5 but not Ad2-ts1 uptake required CALM (clathrin assembly lymphoid myeloid protein, which controls clathrin-mediated endocytosis and membrane transport between endosomes and the trans-Golgi-network. The data show that no other mutations than P137L in the viral protease are necessary to give rise to particles that are defective in capsid processing and endosomal escape. This provides a basis for

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists.

Science.gov (United States)

Moody, Terry W; Tashakkori, Nicole; Mantey, Samuel A; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T

2017-01-01

While peptide antagonists for the gastrin-releasing peptide receptor (BB 2 R), neuromedin B receptor (BB 1 R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB 1 R, BB 2 R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB 1 R, BB 2 R, and BRS-3 with similar affinity ( K i = 1.4-10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca 2+ in human lung cancer cells transfected with BB 1 R, BB 2 R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

Transition probabilities of 36Cl and 36Ar excited states in heavy ion reactions

International Nuclear Information System (INIS)

Costa, G.J.; Alexander, T.K.; Forster, J.S.; McDonald, A.B.; Towner, I.S.

The reactions 2 H( 35 Cl,pγ) and 2 H( 35 Cl,nγ) have been used to determine by the recoil-distance method, the lifetimes of levels in 36 Cl and 36 Ar respectively. Large discrepancies exist in the literature for some lifetimes of 36 Cl levels. Transition rates found for decay of the negative parity states in 36 Ar (4178 (3 - ), 4974 (2 - ) and 5171 (5 - ) keV), are compared whith the Maripuu-Hokken model and RPA and TDA predictions [fr

Where does Chlorine-36 go?

International Nuclear Information System (INIS)

Anon.

2000-01-01

Chlorine-36 and Iodine-129 are the unique long-life radionuclides in the halogen family and halogens are known to be very mobile in the environment. Chlorine-36 is present in slight quantities in radioactive wastes containing carbon or issued from spent fuel reprocessing. The migration of Chlorine-36 in the environment has been very little studied, so a collaboration between the French institute of protection and nuclear safety (IPSN) and the Ukrainian institute for agricultural radioecology (UIAR) has been launched. IPSN will study the migration of Chlorine-36 in soils and UIAR will be in charge of studying the transfer of Chlorine-36 from soil to plants. (A.C.)

47 CFR 36.301 - Section arrangement.

Science.gov (United States)

2010-10-01

.... Category 1—Local Bus. Office Expense 36.377. Category 2—Customer Services (Revenue Accounting) 36.378... Billing and Collecting Expense 36.381. Category 3—All other Customer Service Expense 36.382. Corporate...

A potential role for neuronal connexin 36 in the pathogenesis of amyotrophic lateral sclerosis.

Science.gov (United States)

Belousov, Andrei B; Nishimune, Hiroshi; Denisova, Janna V; Fontes, Joseph D

2018-02-14

Neuronal gap junctional protein connexin 36 (Cx36) contributes to neuronal death following a range of acute brain insults such as ischemia, traumatic brain injury and epilepsy. Whether Cx36 contributes to neuronal death and pathological outcomes in chronic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), is not known. We show here that the expression of Cx36 is significantly decreased in lumbar segments of the spinal cord of both human ALS subjects and SOD1 G93A mice as compared to healthy human and wild-type mouse controls, respectively. In purified neuronal cultures prepared from the spinal cord of wild-type mice, knockdown of Cx36 reduces neuronal death caused by overexpression of the mutant human SOD1-G93A protein. Taken together, these data suggest a possible contribution of Cx36 to ALS pathogenesis. A perspective for the use of blockers of Cx36 gap junction channels for ALS therapy is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Time-dependent biodistribution and transgene expression of a recombinant human adenovirus serotype 5-luciferase vector as a surrogate agent for rAd5-FMDV vaccines in cattle

Science.gov (United States)

Replication-defective recombinant adenovirus 5 (rAd5) vectors carrying foot-and-mouth disease virus (FMDV) transgenes elicit a robust immune response to FMDV challenge in cattle; however vaccine function mechanisms are incompletely understood. Recent efforts addressing critical interactions of rAd5 ...

The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases.

Science.gov (United States)

Walsh, Patrick T; Fallon, Padraic G

2018-04-01

The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets. In humans, inactivating mutations in the gene encoding the IL-36R antagonist, which lead to unregulated IL-36R signaling, lead to an autoinflammatory condition termed deficiency of the IL-36R antagonist, which primarily manifests as a severe form of pustular psoriasis. While such discoveries have prompted deeper mechanistic studies highlighting the important role of IL-36 cytokines in psoriatic skin inflammation, it is now evident that IL-36 cytokines can also play important roles in inflammatory disorders in other organs, such as the gastrointestinal tract and the lungs. Given these emerging roles, strategies to specifically target the expression and activity of the IL-36 family have the potential to uncover novel therapeutic approaches aimed at treating inflammatory diseases in humans. © 2016 New York Academy of Sciences.

40 CFR 36.655 - Individual.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Individual. 36.655 Section 36.655 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.655 Individual. Individual means a...

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

Directory of Open Access Journals (Sweden)

Terry W. Moody

2017-07-01

Full Text Available While peptide antagonists for the gastrin-releasing peptide receptor (BB2R, neuromedin B receptor (BB1R, and bombesin (BB receptor subtype-3 (BRS-3 exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM. AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

Science.gov (United States)

Moody, Terry W.; Tashakkori, Nicole; Mantey, Samuel A.; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T.

2017-01-01

While peptide antagonists for the gastrin-releasing peptide receptor (BB2R), neuromedin B receptor (BB1R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists. PMID:28785244

28 CFR 36.102 - Application.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Application. 36.102 Section 36.102... ACCOMMODATIONS AND IN COMMERCIAL FACILITIES General § 36.102 Application. (a) General. This part applies to any... courses related to applications, licensing, certification, or credentialing for secondary or postsecondary...

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

Science.gov (United States)

Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

2013-12-05

Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

Vibration test and endurance test for HANARO 36-element fuel assembly

International Nuclear Information System (INIS)

Ryu, Jeong Soo; Kim, Heon ll; Chung, Heung June

1998-06-01

Vibration test and endurance test for HANARO DU (depleted uranium) 36-element fuel assembly which was fabricated by KAERI were carried out based on the HANARO operation conditions. The endurance test of 22 days was added to the previous 18 days test. The vibration test was performed at various flow rates. Vibration frequency for the 36-element fuel assembly is between 11 to 14.5 Hz. And the maximum vibration displacement is less than 100 μm. From the endurance test result, it can be concluded that the appreciable fretting wear for the 36-element fuel assembly and the hexagonal flow tube was not observed. (author). 4 refs., 5 tabs., 29 figs

18 CFR 35.36 - Generally.

Science.gov (United States)

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Generally. 35.36 Section 35.36 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... Sales of Electric Energy, Capacity and Ancillary Services at Market-Based Rates § 35.36 Generally. (a...

Presence of adenovirus species C in infiltrating lymphocytes of human sarcoma.

Directory of Open Access Journals (Sweden)

Karin Kosulin

Full Text Available Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation.

40 CFR 36.640 - Employee.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Employee. 36.640 Section 36.640... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.640 Employee. (a) Employee means the employee of a recipient directly engaged in the performance of work under the award, including— (1...

10 CFR 36.83 - Reports.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Reports. 36.83 Section 36.83 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Records § 36.83 Reports. (a) In addition to the reporting requirements in other parts of NRC regulations, the licensee shall report the...

29 CFR 36.540 - Advertising.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Advertising. 36.540 Section 36.540 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING... Activities Prohibited § 36.540 Advertising. A recipient shall not in any advertising related to employment...

40 CFR 73.36 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Banking. 73.36 Section 73.36... ALLOWANCE SYSTEM Allowance Tracking System § 73.36 Banking. (a) Compliance accounts. Any allowance in a compliance account not deducted pursuant to § 73.35 will remain in the compliance account. (b) General...

Development of the penis during the human fetal period (13 to 36 weeks after conception).

Science.gov (United States)

Gallo, Carla B M; Costa, Waldemar S; Furriel, Angelica; Bastos, Ana L; Sampaio, Francisco J B

2013-11-01

We analyzed the development of the area of the penis and erectile structures (corpora cavernosa and corpus spongiosum) and the thickness of the tunica albuginea during the fetal period (13 to 36 weeks after conception) in humans to establish normative patterns of growth. We studied 56 male human fetuses at 13 to 36 weeks after conception. We used histochemical and morphometric techniques to analyze the parameters of total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea in the dorsal and ventral regions using ImageJ software (National Institutes of Health, Bethesda, Maryland). Between 13 and 36 weeks after conception the area of the penis varies from 0.95 to 24.25 mm2. The area of the corpora cavernosa varies from 0.28 to 9.12 mm2, and the area of the corpus spongiosum varies from 0.14 to 3.99 mm2. The thickness of the tunica albuginea varies from 0.029 to 0.296 mm in the dorsal region and from 0.014 to 0.113 mm in the ventral region of the corpora cavernosa. We found a strong correlation between the total penile area, corpora cavernosa and corpus spongiosum with fetal age (weeks following conception). The growth rate was more intense during the second trimester (13 to 24 weeks of gestation) compared to the third trimester (25 to 36 weeks). Tunica albuginea thickness also was strongly correlated with fetal age and this structure was thicker in the dorsal vs ventral region. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

29 CFR 36.510 - Recruitment.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Recruitment. 36.510 Section 36.510 Labor Office of the... Activities Prohibited § 36.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has...

28 CFR 36.210 - Smoking.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Smoking. 36.210 Section 36.210 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES General Requirements § 36.210 Smoking. This part does not preclude the prohibition of, or the imposition of...

40 CFR 36.665 - State.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false State. 36.665 Section 36.665 Protection... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.665 State. State means any of the States of the United States, the District of Columbia, the Commonwealth of Puerto Rico, or any territory...

Inhibitory effect of recombinant adenovirus carrying immunocaspase-3 on hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaohua [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Fan, Rui [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Zou, Xue [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Gao, Lin [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Jin, Haifeng [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Du, Rui [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Xia, Lin [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China); Fan, Daiming [State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi' an 710032 (China)

2007-06-29

Previously, Srinivasula devised a contiguous molecule (C-cp-3 or immunocaspase-3) containing the small and large subunits similar to that in the active form of caspas-3 and found C-cp-3 had similar cleavage activity to the active form of caspase-3. To search for a new clinical application of C-cp-3 to treat hepatocellular carcinoma, recombinant adenoviruses carrying the C-cp-3 and a-fetoprotein (AFP) promoter (Ad-rAFP-C-cp-3) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-C-cp-3 on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-C-cp-3 and the antitumor effect of Ad-rAFP-C-cp-3 on transplanted tumor in nude mice were detected in vivo. The results suggested that Ad-rAFP-C-cp-3 can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo and adenovirus-mediated C-cp-3 transfer could be used as a new method to treat human hepatocarcinoma.

Inhibitory effect of recombinant adenovirus carrying immunocaspase-3 on hepatocellular carcinoma

International Nuclear Information System (INIS)

Li, Xiaohua; Fan, Rui; Zou, Xue; Gao, Lin; Jin, Haifeng; Du, Rui; Xia, Lin; Fan, Daiming

2007-01-01

Previously, Srinivasula devised a contiguous molecule (C-cp-3 or immunocaspase-3) containing the small and large subunits similar to that in the active form of caspas-3 and found C-cp-3 had similar cleavage activity to the active form of caspase-3. To search for a new clinical application of C-cp-3 to treat hepatocellular carcinoma, recombinant adenoviruses carrying the C-cp-3 and a-fetoprotein (AFP) promoter (Ad-rAFP-C-cp-3) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-C-cp-3 on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-C-cp-3 and the antitumor effect of Ad-rAFP-C-cp-3 on transplanted tumor in nude mice were detected in vivo. The results suggested that Ad-rAFP-C-cp-3 can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo and adenovirus-mediated C-cp-3 transfer could be used as a new method to treat human hepatocarcinoma

Non-Replicating Adenovirus-Vectored Anthrax Vaccine

International Nuclear Information System (INIS)

Van Kampen, K. R.; Zhang, J.; Jex, E.; Tang, D. C.

2007-01-01

As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

International Nuclear Information System (INIS)

Shashkova, Elena V.; May, Shannon M.; Barry, Michael A.

2009-01-01

Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.

Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-Ad-IU-1

National Research Council Canada - National Science Library

Gardner, Thomas A

2005-01-01

.... The goal of this research is to develop a novel therapeutic agent, Ad-IU-1, using PSES to control the replication of adenovirus and the expression of a therapeutic gene, herpes simplex thymidine kinase (TK...

36 CFR 1254.36 - What care must I take when handling documents?

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false What care must I take when... Room Rules Rules Relating to Using Original Documents § 1254.36 What care must I take when handling... must not use paper clips, rubber bands, self-stick notes or similar devices to identify documents. (e...

Cytotoxic Activity of 3,6-Dihydroxyflavone in Human Cervical Cancer Cells and Its Therapeutic Effect on c-Jun N-Terminal Kinase Inhibition

Directory of Open Access Journals (Sweden)

Eunjung Lee

2014-08-01

Full Text Available Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 μM and 9.8 μM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR 4/CD14, p38 mitogen-activated protein kinase (MAPK, Jun-N terminal kinase (JNK, extracellular-signaling regulated kinase (ERK, and cyclooxygenase (COX-2 pathways in lipopolysaccharide (LPS-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M−1 and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects.

Circumvention of Immunity to the Adenovirus Major Coat Protein Hexon

Science.gov (United States)

Roy, Soumitra; Shirley, Pamela S.; McClelland, Alan; Kaleko, Michael

1998-01-01

Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5. PMID:9658137

Integrative genomic analysis of interleukin-36RN and its prognostic value in cancer.

Science.gov (United States)

Lv, Zhilei; Fan, Jinshuo; Zhang, Xiuxiu; Huang, Qi; Han, Jieli; Wu, Feng; Hu, Guorong; Guo, Mengfei; Jin, Yang

2016-02-01

Interleukin (IL)-36RN, previously known as IL1-F5 and IL-1δ, shares a 360-kb region of chromosome 2q13 with members of IL-1 systems. IL-36RN encodes an anti-inflammatory cytokine, IL-36 receptor antagonist (IL-36Ra). In spite of IL-36Ra showing the highest homology to IL-1 receptor (IL-1R) antagonist, it differs from the latter in aspects including its binding to IL-lRrp2 but not to IL-1R1. IL-36RN is mainly expressed in epithelial cells and has important roles in inflammatory diseases. In the present study, IL-36RN was identified in the genomes of 27 species, including human, chimpanzee, mouse, horse and dolphin. Human IL-36RN was mainly expressed in the eye, head and neck, fetal heart, lung, testis, cervix and placenta; furthermore, it was highly expressed in bladder and parathyroid tumors. Furthermore, a total of 30 single nucleotide polymorphisms causing missense mutations were determined, which are considered to be the causes of various diseases, such as generalized pustular psoriasis. In addition, the link between IL-36RN and the prognosis of certain cancer types was revealed through meta-analysis. Tumor-associated transcriptional factors c-Fos, activator protein-1, c-Jun and nuclear factor κB were found to bind to the upstream region in the IL-36RN gene. This may indicate that IL-36RN is involved in tumorigenesis and tumor progression through the regulation of tumor-associated transcriptional factors. The present study identified IL-36RN in various species and investigated the associations between IL-36RN and cancer prognosis, which would determine whether IL-36RN drove the evolution of the various species with regard to tumorigenesis.

Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands

DEFF Research Database (Denmark)

Šteiner, Petr; Andreasen, Simon; Grossmann, Petr

2018-01-01

Adenoid cystic carcinoma (AdCC) of the salivary glands is characterized by MYB-NFIB or MYBL1-NFIB fusion, prolonged but relentlessly progressive clinical course with frequent recurrences, and development of distant metastasis resulting in high long-term mortality. Currently, no effective therapy...... is available for patients with advanced non-resectable and/or metastatic disease. Complicating the clinical management of this patient group is the lack of prognostic markers. The purpose of this study is to investigate the prognostic value of 1p36 loss in patients with AdCC. The presence of 1p36 deletion...... and gene fusions involving the MYB, NFIB, and MYBL1 genes in a cohort of 93 salivary gland AdCCs was studied using fluorescence in situ hybridization. These results were statistically correlated with clinical data and outcome. Deletion of 1p36 in AdCC was identified in 13 of 85 analyzable cases (15...

The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

DEFF Research Database (Denmark)

Meier, Juris J; Gethmann, Arnica; Nauck, Michael A

2006-01-01

Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7-36) amide is degraded to the metabolite GLP-1-(9-36) amide. The effects of GLP-1-(9-36) amide in humans are less well characterized. Fourteen...... healthy volunteers were studied with intravenous infusion of GLP-1-(7-36) amide, GLP-1-(9-36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements....... Administration of GLP-1-(7-36) amide and GLP-1-(9-36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 +/- 5 pmol/l during the infusion of GLP-1-(7-36) amide but remained unchanged during GLP-1-(9-36) amide infusion [5 +/- 3 pmol/l; P

Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

Directory of Open Access Journals (Sweden)

Sadhak Sengupta

2011-03-01

Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-AD-IU-1

National Research Council Canada - National Science Library

Gardner, Thomas

2004-01-01

... independent prostate cancers. The goal of this research is to develop a novel therapeutic agent, Ad-lu-1, using PSES to control the replication of adenovirus and the expression of a therapeutic gene, herpes simplex thymidine kinase...

Chlorine-36 dating of continental evaporites

International Nuclear Information System (INIS)

Huang Qi

1990-01-01

Teh chloring-36 production, principle and experimental method of 36 Cl dating are briefly described. The ages calculated from the 36 Cl/Cl ratios are generally concordant with those obtained by using 14 C, 230 Th and magnetostratigraphic techniques. It confirms the constancy of the chlorine input ratio over the last million years and implys that 36 Cl can provide accurate dates on continental saline sediments

Suppressing IL-36-driven inflammation using peptide pseudosubstrates for neutrophil proteases.

Science.gov (United States)

Sullivan, Graeme P; Henry, Conor M; Clancy, Danielle M; Mametnabiev, Tazhir; Belotcerkovskaya, Ekaterina; Davidovich, Pavel; Sura-Trueba, Sylvia; Garabadzhiu, Alexander V; Martin, Seamus J

2018-03-07

Sterile inflammation is initiated by molecules released from necrotic cells, called damage-associated molecular patterns (DAMPs). Members of the extended IL-1 cytokine family are important DAMPs, are typically only released through necrosis, and require limited proteolytic processing for activation. The IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, are expressed as inactive precursors and have been implicated as key initiators of psoriatic-type skin inflammation. We have recently found that IL-36 family cytokines are proteolytically processed and activated by the neutrophil granule-derived proteases, elastase, and cathepsin G. Inhibitors of IL-36 processing may therefore have utility as anti-inflammatory agents through suppressing activation of the latter cytokines. We have identified peptide-based pseudosubstrates for cathepsin G and elastase, based on optimal substrate cleavage motifs, which can antagonize activation of all three IL-36 family cytokines by the latter proteases. Human psoriatic skin plaques displayed elevated IL-36β processing activity that could be antagonized by peptide pseudosubstrates specific for cathepsin G. Thus, antagonists of neutrophil-derived proteases may have therapeutic potential for blocking activation of IL-36 family cytokines in inflammatory conditions such as psoriasis.

Investigation of the impact of the $^{39}$Ar(n , $\\alpha)^{36}$S reaction on the nucleosynthesis of the rare isotope $^{36}$S

CERN Multimedia

Geltenbort, P

2002-01-01

The origin of the rare, neutron rich isotope $^{36}$S remains a debated question. One of the key reactions in the s-process nucleosynthesis network leading to $^{36}$S is $^{39}$Ar(n , $\\alpha) ^{36}\\!$S. This reaction has never been studied so far, which is due to the fact that $^{39}$Ar is a radioactive (T$_{1/2}$ = 269 y) gas, which is not commercially available. During a three days experimental campaign, an optimized $^{39}$Ar sample was prepared at ISOLDE. A dedicated titaniumoxide target (8 g/cm$^{2}$) was bombarded with 1 GeV protons from the PS Booster. In order to obtain a pure argon beam, a water-cooled transfer line was used to freeze-out less volatile isobars before they can reach the ion source. Adding stable argon with a calibrated leak to the ion source enabled to determine the ionization efficiency (3.5%). For the isotope separation, the low-mass side (GLM) of the General Purpose Separator was used. After magnetic separation, $^{39}$Ar ions (1+) were implanted at 60 keV in a 12 mm thick alumin...

Normative data and discriminative properties of short form 36 (SF-36 in Turkish urban population

Directory of Open Access Journals (Sweden)

Akvardar Yildiz

2006-10-01

Full Text Available Abstract Background SF-36 has been both translated into different languages and adapted to different cultures to obtain comparable data on health status internationally. However there have been only a limited number of studies focused on the discriminative ability of SF-36 regarding social and disease status in developing countries. The aim of this study was to obtain population norms of the short form 36 (SF-36 health survey and the association of SF-36 domains with demographic and socioeconomic variables in an urban population in Turkey. Methods A cross-sectional study. Face to face interviews were carried out with a sample of households. The sample was systematically selected from two urban Health Districts in Izmir, Turkey. The study group consisted of 1,279 people selected from a study population of 46,290 people aged 18 and over. Results Internal consistencies of the scales were high, with the exception of mental health and vitality. Physical health scales were associated with both age and gender. On the other hand, mental health scales were less strongly associated with age and gender. Women reported poorer health compared to men in general. Social risk factors (employment status, lower education and economic strain were associated with worse health profiles. The SF-36 was found to be capable of discriminating disease status. Conclusion Our findings, cautiously generalisable to urban population, suggest that the SF-36 can be a valuable tool for studies on health outcomes in Turkish population. SF-36 may also be a promising measure for research on health inequalities in Turkey and other developing countries.

Role of cellular heparan sulfate proteoglycans in infection of human adenovirus serotype 3 and 35.

Directory of Open Access Journals (Sweden)

Sebastian Tuve

2008-10-01

Full Text Available Species B human adenoviruses (Ads are increasingly associated with outbreaks of acute respiratory disease in U.S. military personnel and civil population. The initial interaction of Ads with cellular attachment receptors on host cells is via Ad fiber knob protein. Our previous studies showed that one species B Ad receptor is the complement receptor CD46 that is used by serotypes 11, 16, 21, 35, and 50 but not by serotypes 3, 7, and 14. In this study, we attempted to identify yet-unknown species B cellular receptors. For this purpose we used recombinant Ad3 and Ad35 fiber knobs in high-throughput receptor screening methods including mass spectrometry analysis and glycan arrays. Surprisingly, we found that the main interacting surface molecules of Ad3 fiber knob are cellular heparan sulfate proteoglycans (HSPGs. We subsequently found that HSPGs acted as low-affinity co-receptors for Ad3 but did not represent the main receptor of this serotype. Our study also revealed a new CD46-independent infection pathway of Ad35. This Ad35 infection mechanism is mediated by cellular HSPGs. The interaction of Ad35 with HSPGs is not via fiber knob, whereas Ad3 interacts with HSPGs via fiber knob. Both Ad3 and Ad35 interacted specifically with the sulfated regions within HSPGs that have also been implicated in binding physiologic ligands. In conclusion, our findings show that Ad3 and Ad35 directly utilize HSPGs as co-receptors for infection. Our data suggest that adenoviruses evolved to simulate the presence of physiologic HSPG ligands in order to increase infection.

Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-AD-IU-1

National Research Council Canada - National Science Library

Gardner, Thomas A

2006-01-01

... independent prostate cancers. The goal of this research is to develop a novel therapeutic agent, Ad-IU-1, using PSES to control the replication of adenovirus and the expression of a therapeutic gene, herpes simplex thymidine kinase (TK...

Regulation and function of interleukin-36 cytokines.

Science.gov (United States)

Bassoy, Esen Yonca; Towne, Jennifer E; Gabay, Cem

2018-01-01

The interleukin (IL)-36 cytokines include 3 agonists, IL-36α, IL-36β, and IL-36γ that bind to a common receptor composed of IL-36R and IL-1RAcP to stimulate inflammatory responses. IL-36Ra is a natural antagonist that binds to IL-36R, but does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. The IL-36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An infection of human adenovirus 31 affects the differentiation of preadipocytes into fat cells, its metabolic profile and fat accumulation.

Science.gov (United States)

Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Sawicki, Grzegorz; Woźniak, Mieczysław

2016-03-01

The primary issue undertaken in this study was to test the hypothesis that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to HAdV31 infection. To prove that, the metabolic and molecular mechanisms responsible for HAdV31-induced adipogenesis were examined. 3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a surrogate model to analyze an increased proliferation, differentiation, and maturation of preadipocytes infected with human adenovirus. An expression of E4orf1, C/EBP-β, PPAR-γ, GAPDH, aP2, LEP, and fatty acid synthase genes, intracellular lipid accumulation as well as cytokine release from the fat cells were assessed. Data showed that HAdV31 increased an expression of C/EBP-β and PPAR-γ genes leading to an enhanced differentiation of preadipocytes into fat cells. Besides, overexpression of GAPDH and fatty acid synthase, and decreased expression of leptin caused an increased accumulation of intracellular lipids. Secretion of TNF-α and IL-6 from HAdV31-infected cells was strongly decreased, leading to unlimited virus replication. The results obtained from this study provided the evidences that HAdV31, likewise previously documented HAdV36, is a subsequent human adenovirus affecting the differentiation and lipid accumulation of 3T3L1 cells. © 2015 Wiley Periodicals, Inc.

Coercivity enhancement of Dy-free Nd–Fe–B sintered magnets by intergranular adding Ho{sub 63.4}Fe{sub 36.6} alloy

Energy Technology Data Exchange (ETDEWEB)

Liang, Liping; Ma, Tianyu, E-mail: maty@zju.edu.cn; Wu, Chen; Zhang, Pei; Liu, Xiaolian; Yan, Mi, E-mail: mse_yanmi@zju.edu.cn

2016-01-01

High coercivity Nd–Fe–B sintered magnets serving in high-temperature environments always consume expensive and scarce heavy rare-earth Dy, which has simulated considerable interest to reduce Dy usage. In this work, coercivity of Dy-free magnets was investigated through intergranular adding eutectic Ho{sub 63.4}Fe{sub 36.6} powders. The coercivity increases gradually up to 4 wt% Ho{sub 63.4}Fe{sub 36.6} addition, however the remanence starts to deteriorate drastically as the addition is over 2.5 wt%. Coercivity above 18.0 kOe is obtained at the expense of a slight reduction in remanence through optimizing the addition amount and sintering conditions. The coercivity enhancement is explained through microstructural observations and elemental distribution analysis. (i) (Nd, Ho){sub 2}Fe{sub 14}B shell forms in the outer region of 2:14:1 phase grains, strengthening the local magnetic anisotropy filed, (ii) RE-rich grain boundary phase with low Fe content is thickened, weakening the magnetic coupling between adjacent 2:14:1 phase grains, and (iii) 2:14:1 phase grains are refined upon lowering sintering temperature, reducing the microstructural defects and the stray fields aroused from neighboring grains. - Highlights: • Eutectic Ho{sub 63.4}Fe{sub 36.6} powders were intergranular added to NdFeB sintered magnets. • The doped Dy-free magnet possessed coercivity of 18.0 kOe, remanence of 13.15 kGs. • (Nd, Ho){sub 2}Fe{sub 14}B shell formed in the surface of the matrix grains, increasing the H{sub A}. • Thick grain boundaries with low Fe content formed, decoupling the matrix grains. • By sintered at lower temperature, the matrix phase grains were refined.

Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36

Directory of Open Access Journals (Sweden)

Joubert-Caron Raymonde

2001-12-01

Full Text Available Abstract Background 5-AzaCytidine (AzaC is a DNA demethylating drugs that has been shown to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced expression of the galectin1 (Gal1 protein, a galactoside-binding protein distributed widely in immune cells, has been described in cultured hepatoma-derived cells treated with AzaC and this event may have a role in the effect of the drug. According to this hypothesis, we investigated the effect of AzaC and Gal1 on human lymphoid B cells phenotype. Methods The effect of AzaC and Gal1 on cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36. An immunocytochemical analysis for detection of Gal1 protein expression was performed in AzaC-treated cells. To investigate the direct effects of Gal1, recombinant Gal1 was added to cells. Results Treatment of lymphoid B cells with AzaC results in: i a decrease in cell growth with an arrest of the cell cycle at G0/G1 phase, ii phenotypic changes consistent with a differentiated phenotype, and iii the expression of p16, a tumor-suppressor gene whose expression was dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the plasma membrane follows its cytosolic expression. To determine which of the effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was added to BL36 cells. Treated cells displayed growth inhibition and phenotypic changes consistent with a commitment toward differentiation. Conclusions Altered cell growth and expression of the cell surface plasma cell antigen, CD138 are detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC-induced Gal1 expression and consequent binding of Gal1 on its cell membrane receptor may be, in part, involved in AzaC-induced plasmacytic differentiation.

ERα36, a variant of estrogen receptor α, is predominantly localized in mitochondria of human uterine smooth muscle and leiomyoma cells.

Directory of Open Access Journals (Sweden)

Yitang Yan

Full Text Available ERα36 is a naturally occurring, membrane-associated, isoform of estrogen receptor α. The expression of ERα36 is due to alternative splicing and different promoter usage. ERα36 is a dominant-negative effector of ERα66-mediated transactivational activities and has the potential to trigger membrane-initiated mitogenic, nongenomic, estrogen signaling; however, the subcellular localization of ERα36 remains controversial. To determine the cellular localization of ERα36 in estrogen-responsive human uterine smooth muscle (ht-UtSMC and leiomyoma (fibroid; ht-UtLM cells, we conducted systematic confocal microscopy and subcellular fractionation analysis using ERα36 antibodies. With Image J colocalizaton analysis plugin, confocal images were analyzed to obtain a Pearson's Correlation Coefficient (PCC to quantify signal colocalization of ERα36 with mitochondrial, endoplasmic reticulum, and cytoskeletal components in both cell lines. When cells were double-stained with an ERα36 antibody and a mitochondrial-specific dye, MitoTracker, the PCC for the two channel signals were both greater than 0.75, indicating strong correlation between ERα36 and mitochondrial signals in the two cell lines. A blocking peptide competition assay confirmed that the mitochondria-associated ERα36 signal detected by confocal analysis was specific for ERα36. In contrast, confocal images double-stained with an ERα36 antibody and endoplasmic reticulum or cytoskeletal markers, had PCCs that were all less than 0.4, indicating no or very weak signal correlation. Fractionation studies showed that ERα36 existed predominantly in membrane fractions, with minimal or undetected amounts in the cytosol, nuclear, chromatin, and cytoskeletal fractions. With isolated mitochondrial preparations, we confirmed that a known mitochondrial protein, prohibitin, was present in mitochondria, and by co-immunoprecipitation analysis that ERα36 was associated with prohibitin in ht-UtLM cells. The

14 CFR 36.801 - Noise measurement.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Noise measurement. 36.801 Section 36.801 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT NOISE STANDARDS: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Helicopters § 36.801 Noise measurement. For primary, normal...

Cholesteryl ester hydroperoxides increase macrophage CD36 gene expression via PPARα

International Nuclear Information System (INIS)

Jedidi, Iness; Couturier, Martine; Therond, Patrice; Gardes-Albert, Monique; Legrand, Alain; Barouki, Robert; Bonnefont-Rousselot, Dominique; Aggerbeck, Martine

2006-01-01

The uptake of oxidized LDL by macrophages is a key event in the development of atherosclerosis. The scavenger receptor CD36 is one major receptor that internalizes oxidized LDL. In differentiated human macrophages, we compared the regulation of CD36 expression by copper-oxidized LDL or their products. Only oxidized derivatives of cholesteryl ester (CEOOH) increased the amount of CD36 mRNA (2.5-fold). Both oxidized LDL and CEOOH treatment increased two to fourfold the transcription of promoters containing peroxisome-proliferator-activated-receptor responsive elements (PPRE) in the presence of PPARα or γ. Electrophoretic-mobility-shift-assays with nuclear extracts prepared from macrophages treated by either oxidized LDL or CEOOH showed increased binding of PPARα to the CD36 gene promoter PPRE. In conclusion, CEOOH present in oxidized LDL increase CD36 gene expression in a pathway involving PPARα

Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses.

Science.gov (United States)

Yu, Xiaodi; Veesler, David; Campbell, Melody G; Barry, Mary E; Asturias, Francisco J; Barry, Michael A; Reddy, Vijay S

2017-05-01

Human adenoviruses (HAdVs) cause acute respiratory, ocular, and gastroenteric diseases and are also frequently used as gene and vaccine delivery vectors. Unlike the archetype human adenovirus C5 (HAdV-C5), human adenovirus D26 (HAdV-D26) belongs to species-D HAdVs, which target different cellular receptors, and is differentially recognized by immune surveillance mechanisms. HAdV-D26 is being championed as a lower seroprevalent vaccine and oncolytic vector in preclinical and human clinical studies. To understand the molecular basis for their distinct biological properties and independently validate the structures of minor proteins, we determined the first structure of species-D HAdV at 3.7 Å resolution by cryo-electron microscopy. All the hexon hypervariable regions (HVRs), including HVR1, have been identified and exhibit a distinct organization compared to those of HAdV-C5. Despite the differences in the arrangement of helices in the coiled-coil structures, protein IX molecules form a continuous hexagonal network on the capsid exterior. In addition to the structurally conserved region (3 to 300) of IIIa, we identified an extra helical domain comprising residues 314 to 390 that further stabilizes the vertex region. Multiple (two to three) copies of the cleaved amino-terminal fragment of protein VI (pVIn) are observed in each hexon cavity, suggesting that there could be ≥480 copies of VI present in HAdV-D26. In addition, a localized asymmetric reconstruction of the vertex region provides new details of the three-pronged "claw hold" of the trimeric fiber and its interactions with the penton base. These observations resolve the previous conflicting assignments of the minor proteins and suggest the likely conservation of their organization across different HAdVs.

10 CFR 36.55 - Personnel monitoring.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Personnel monitoring. 36.55 Section 36.55 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Operation of Irradiators § 36.55 Personnel monitoring. (a) Irradiator operators shall wear a personnel dosimeter that is...

22 CFR 92.36 - Authentication defined.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36... Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness of... recognized in another jurisdiction. Documents which may require authentication include legal instruments...

7 CFR 29.36 - Auction market.

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Auction market. 29.36 Section 29.36 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.36 Auction market. A place to which tobacco is delivered by the...

10 CFR 905.36 - Marketing criteria.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Marketing criteria. 905.36 Section 905.36 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.36 Marketing criteria. Western shall retain applicable provisions of existing marketing criteria for projects where...

30 CFR 36.41 - Testing methods.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Testing methods. 36.41 Section 36.41 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF... Requirements § 36.41 Testing methods. Mobile diesel-powered transportation equipment submitted for...

28 CFR 36.204 - Administrative methods.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Administrative methods. 36.204 Section 36... PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES General Requirements § 36.204 Administrative methods... standards or criteria or methods of administration that have the effect of discriminating on the basis of...

IL-36 cytokines in autoimmunity and inflammatory disease.

Science.gov (United States)

Ding, Liping; Wang, Xiaohui; Hong, Xiaoping; Lu, Liwei; Liu, Dongzhou

2018-01-05

The inteleukin-36 (IL-36) cytokines include IL-36α, IL-36β, IL-36γ and IL-36Ra, which belong to the IL-1 family and exert pro-inflammatory effects on various target cells such as keratinocytes, synoviocytes, dendritic cells and T cells. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory diseases. Here, we provide a brief review on the activation of IL-36 family cytokines and their involvement in autoimmunity and inflammatory diseases, which will provide further insights in understanding the functions of IL-36 family cytokines in the pathophysiology of autoimmunity and inflammatory diseases.

Adenovirus-dependent changes in cell membrane permeability: role of Na/sup +/, K/sup +/-ATPase

Energy Technology Data Exchange (ETDEWEB)

Seth, P.; Pastan, I.; Willingham, M.C.

1987-03-01

Adenovirus-dependent release of choline phosphate from KB cells at pH 6.0 was partially blocked by ouabain. In K/sup +/-containing medium, maximum inhibition of release was obtained by 10/sup -5/ M ouabain and half-maximal inhibition was achieved by about 0.5 x 10/sup -6/ M ouabain. Ouabain did not block either the binding or the uptake of adenovirus by KB cells. Without K/sup +/, about 25% of cell-associated choline phosphate was released by adenovirus, whereas with 1 mM K/sup +/ about 50% was released. This activation by K/sup +/ was blocked by 0.1 mM ouabain. HeLa cells behaved like KB cells, but a mutant of HeLa cells resistant to ouabain (D98-OR) released much lower amounts of choline phosphate in response to human adenovirus type 2 (Ad2). Wild-type D98-OR cells bound nearly the same amount of adenovirus as did normal HeLa cells. Ad2 also increased the activity of Na/sup +/, K/sup +/-ATPase in KB cells, with maximum activation at 50..mu..g of Ad2 per ml. In D98-OR cells, Ad2 failed to activate Na/sup +/, K/sup +/, ATPase activity. Ad2-dependent lysis of endocytic vesicles (receptosomes) was assayed by measuring Ad2-dependent enhancement of epidermal growth factor-Pseudomonas exotoxin toxicity. This action of adenovirus was increased when K/sup +/ was present in the medium. Under the conditions used, K/sup +/ had no effect on the amount of Ad2 or epidermal growth factor taken up by the cells. On the basis of these results, it is suggested that Ad2-dependent cellular efflux of choline phosphate and adenovirus-dependent lysis of receptosomes may require Na/sup +/, K/sup +/-ATPase activity.

Hawaii 36 arc-second DEM

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The 36-second Hawaii Elevation Grid provides bathymetric data in ASCII raster format of 36-second resolution in geographic coordinates. This grid is strictly for...

42 CFR 424.36 - Signature requirements.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Signature requirements. 424.36 Section 424.36... (CONTINUED) MEDICARE PROGRAM CONDITIONS FOR MEDICARE PAYMENT Claims for Payment § 424.36 Signature requirements. (a) General rule. The beneficiary's own signature is required on the claim unless the beneficiary...

34 CFR 300.36 - Secondary school.

Science.gov (United States)

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Secondary school. 300.36 Section 300.36 Education... DISABILITIES General Definitions Used in This Part § 300.36 Secondary school. Secondary school means a nonprofit institutional day or residential school, including a public secondary charter school that provides...

10 CFR 36.27 - Fire protection.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Fire protection. 36.27 Section 36.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Design and Performance Requirements for Irradiators § 36.27 Fire protection. (a) The radiation room at a panoramic irradiator must...

Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

Science.gov (United States)

Janovitz, Tyler; Wong, Susan; Young, Neal S; Oliveira, Thiago; Falck-Pedersen, Erik

2017-11-01

The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of natural in situ production of 36Ar via 36Cl: geochemical and geochronological implications

International Nuclear Information System (INIS)

Fontes, J.C.; Napier Andrews, J.; Walgenwitz, F.

1991-01-01

Argon-36 ingrowth through the decay of chlorine-36 generated by natural neutron activation of chlorine-35, may reach significant amounts for rock samples from high altitudes and for minerals rich in chloride (fluid inclusions, feldspathoids). The extent of sample contamination by atmospheric argon-40 may be over estimated if based on the 40 Ar/ 36 Ar at atmospheric ratio (295.5) [fr

CD36- and GPR120-mediated Ca²⁺ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice.

Science.gov (United States)

Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A; Khan, Naim Akhtar

2014-04-01

It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca(2+) signaling in fungiform taste bud cells (TBC). We measured Ca(2+) signaling in human TBC, transfected with small interfering RNAs against messenger RNAs encoding CD36 and GPR120 (or control small interfering RNAs). We also studied Ca(2+) signaling in TBC from CD36(-/-) mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and glucagon-like peptide-1 from human and mice TBC in response to CD36 and GPR120 activation. High concentrations of linoleic acid induced Ca(2+) signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca(2+) signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid down-regulated CD36 and up-regulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca(2+) and serotonin responses, but increased release of glucagon-like peptide-1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

29 CFR 1919.36 - Heat treatment.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Heat treatment. 1919.36 Section 1919.36 Labor Regulations...) GEAR CERTIFICATION Certification of Vessels: Tests and Proof Loads; Heat Treatment; Competent Persons § 1919.36 Heat treatment. (a) The annealing of wrought iron gear required by this part shall be...

27 CFR 4.36 - Alcoholic content.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36...

29 CFR 36.500 - Employment.

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2010-07-01

...) Application. The provisions of §§ 36.500 through 36.550 apply to: (1) Recruitment, advertising, and the..., leave for persons of either sex to care for children or dependents, or any other leave; (7) Fringe...

43 CFR 36.5 - Application review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application review. 36.5 Section 36.5... ACROSS, AND ACCESS INTO, CONSERVATION SYSTEM UNITS IN ALASKA § 36.5 Application review. (a) When there is... the purpose of coordinating appropriate Federal agency actions in the review and processing of the SF...

10 CFR 1003.36 - OHA evaluation.

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2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false OHA evaluation. 1003.36 Section 1003.36 Energy DEPARTMENT....36 OHA evaluation. (a)(1) The OHA may initiate an investigation of any statement in an appeal and utilize in its evaluation any relevant facts obtained by such investigation. The OHA may solicit and...

29 CFR 36.525 - Fringe benefits.

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2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Fringe benefits. 36.525 Section 36.525 Labor Office of the... Activities Prohibited § 36.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit...

29 CFR 1602.36 - Schools exemption.

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2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Schools exemption. 1602.36 Section 1602.36 Labor... REQUIREMENTS UNDER TITLE VII, THE ADA AND GINA State and Local Government Information Report § 1602.36 Schools... to State or local educational institutions or to school districts or school systems or any other...

30 CFR 36.24 - Engine joints.

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2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Engine joints. 36.24 Section 36.24 Mineral... Construction and Design Requirements § 36.24 Engine joints. (a) Cylinder head. The joint between the cylinder head and block of the engine shall be fitted with a metal or metal-clad gasket satisfactory to MSHA...

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

OpenAIRE

Suk, Fat-Moon; Chang, Chi-Ching; Lin, Ren-Jye; Lin, Shyr-Yi; Liu, Shih-Chen; Jau, Chia-Feng; Liang, Yu-Chih

2018-01-01

ZFP36 family members include ZFP36, ZFP36L1, and ZFP36L2, which belong to CCCH-type zinc finger proteins with two tandem zinc finger (TZF) regions. Whether ZFP36L1 and ZFP36L2 have antiproliferative activities similar to that of ZFP36 is unclear. In this study, when ZFP36L1 or ZFP36L2 was overexpressed in T-REx-293 cells, cell proliferation was dramatically inhibited and the cell cycle was arrested at the G1 phase. The levels of cell-cycle-related proteins, including cyclin B, cyclin D, cycli...

Anatomical relationships between testis and epididymis during the fetal period in humans (10-36 weeks postconception)

NARCIS (Netherlands)

Favorito, LA; Sampaio, FJB

1998-01-01

Objective: To determine the anatomy of the epididymis and its relationship with the testis during the fetal period in normal individuals. Methods: We studied bilaterally 146 testes and epididymides taken from 73 normal fresh human fetuses ranging in age from 10 to 36 weeks postconception. The

Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

DEFF Research Database (Denmark)

Hempel, Casper; Wang, Christian William; Kurtzhals, Jorgen Anders Lindholm

2017-01-01

FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1-4 days after seeding was quantified by using a static binding assay. Results: The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic...... labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody......-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2-4 days. Conclusion: The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has...

Activation of the human beta interferon gene by the adenovirus type 12 E1B gene

International Nuclear Information System (INIS)

Shiroki, K.; Toth, M.

1988-01-01

The transcription of endogenous beta interferon mRNA was activated in human embryo kidney (HEK) cells infected with adenovirus 12 (Ad12) but was activated only inefficiently or not at all in HEK cells infected with Ad5 and rc-1 (Ad5 dl312 containing the Ad12 E1A region). The analysis with Ad12 mutants showed that Ad12 E1B products, especially the 19K protein, were important for the expression of the endogenous beta interferon gene and Ad12 E1A products were not involved in the expression. The expression of exogeneously transfected pIFN-CAT (a hybrid plasmid having the human beta interferon promoter fused with the CAT gene) was activated in HEK and chicken embryo fibroblast (CEF) cells infected with either Ad12 or Ad5. The analysis of cotransfection of CEF cells with pIFN-CAT and plasmids containing fragments of Ad12 or Ad5 DNA showed that Ad12 or Ad5 E1B (possibly the 19K protein) was and E1A was not involved in the expression of the exogenous pIFN-CAT

Alternative promoter usage of the membrane glycoprotein CD36

Directory of Open Access Journals (Sweden)

Whatling Carl

2006-03-01

Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

Production of Recombinant Adenovirus Containing Human Interlukin-4 Gene

OpenAIRE

Mojarrad, Majid; Abdolazimi, Yassan; Hajati, Jamshid; Modarressi, Mohammad Hossein

2011-01-01

Objective(s) Recombinant adenoviruses are currently used for a variety of purposes, including in vitro gene transfer, in vivo vaccination, and gene therapy. Ability to infect many cell types, high efficiency in gene transfer, entering both dividing and non dividing cells, and growing to high titers make this virus a good choice for using in various experiments. In the present experiment, a recombinant adenovirus containing human IL-4 coding sequence was made. IL-4 has several characteristics ...

Radiological assessment of 36Cl in the disposal of used CANDU fuel

International Nuclear Information System (INIS)

Johnson, L.H.; Goodwin, B.W.; Sheppard, S.C.; Tait, J.C.; Wuschke, D.M.; Davison, C.C.

1995-06-01

An assessment of the potential radiological impact of 36 Cl in the disposal of used CANDU fuel has been performed. The assessment was based on new data on chlorine impurity levels in used fuel. Data bases for the vault, geosphere, and biosphere models used in the EIS postclosure assessment case study (Goodwin et al. 1994) were modified to include the necessary 36 Cl data. The resulting safety analysis shows that estimated radiological risks from 36 Cl are forty times lower than from 129 I at 10 4 a; this, incorporation of 36 Cl into the models does not change the overall conclusions of the study of Goodwin et al. (1994a). For human intrusion scenarios, an analysis using the methodology of Wuschke (1992) showed that the maximum risk is unaffected by the inclusion of 36 Cl. (author). 51 refs., 5 tabs., 15 figs

A novel adenovirus of Western lowland gorillas (Gorilla gorilla gorilla

Directory of Open Access Journals (Sweden)

Ludwig Carsten

2010-11-01

Full Text Available Abstract Adenoviruses (AdV broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL, preterminal protein (pTP and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2 - 10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B. Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses.

Interferon induction by adenoviruses

Energy Technology Data Exchange (ETDEWEB)

Beladi, I; Bakay, M; Pusztai, R; Mucsi, I; Tarodi, B [University Medical School, Szeged (Hungary). Inst. of Microbiology

1979-02-01

All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and there-fore the adenovirus-specific T antigen was resitant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.

Detection of adenoviruses in shellfish by means of conventional-PCR, nested-PCR, and integrated cell culture PCR (ICC/PCR).

Science.gov (United States)

Rigotto, C; Sincero, T C M; Simões, C M O; Barardi, C R M

2005-01-01

We tested three PCR based methodologies to detect adenoviruses associated with cultivated oysters. Conventional-PCR, nested-PCR, and integrated cell culture-PCR (ICC/PCR) were first optimized using oysters seeded with know amounts of Adenovirus serotype 5 (Ad5). The maximum sensitivity for Ad5 detection was determined for each method, and then used to detect natural adenovirus contamination in oysters from three aquiculture farms in Florianopolis, Santa Catarina State, Brazil, over a period of 6 months. The results showed that the nested-PCR was more sensitive (limit of detection: 1.2 PFU/g of tissue) than conventional-PCR and ICC-PCR (limit of detection for both: 1.2 x 10(2)PFU/g of tissue) for detection of Ad5 in oyster extracts. Nested-PCR was able to detect 90% of Ad5 contamination in harvested oyster samples, while conventional-PCR was unable to detect Ad5 in any of the samples. The present work suggests that detection of human adenoviruses can be used as a tool to monitor the presence of human viruses in marine environments where shellfish grow, and that nested-PCR is the method of choice.

21 CFR 1403.36 - Procurement.

Science.gov (United States)

2010-04-01

... be a selection criteria provided its application leaves an appropriate number of qualified firms... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Procurement. 1403.36 Section 1403.36 Food and.... No employee, officer or agent of the grantee or subgrantee shall participate in selection, or in the...

28 CFR 36.504 - Relief.

Science.gov (United States)

2010-07-01

... COMMERCIAL FACILITIES Enforcement § 36.504 Relief. (a) Authority of court. In a civil action under § 36.503, the court— (1) May grant any equitable relief that such court considers to be appropriate, including... disabilities; (2) May award other relief as the court considers to be appropriate, including monetary damages...

Genetic analysis of a novel human adenovirus with a serologically unique hexon and a recombinant fiber gene.

Directory of Open Access Journals (Sweden)

Elizabeth B Liu

Full Text Available In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487 was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was sequenced to elucidate its origin. Bioinformatic and phylogenetic analyses of this genome demonstrate that this virus, heretofore referred to as HAdV-D58, contains a novel hexon gene as well as a recombinant fiber gene. In addition, serological analysis demonstrated that HAdV-D58 has a different neutralization profile than all previously characterized HAdVs. Bootscan analysis of the HAdV-D58 fiber gene strongly suggests one recombination event.

Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

DEFF Research Database (Denmark)

Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

2011-01-01

of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

DEFF Research Database (Denmark)

Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

2011-01-01

of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

Chlorine-36 and the initial value problem

Science.gov (United States)

Davis, Stanley N.; Cecil, DeWayne; Zreda, Marek; Sharma, Pankaj

Chlorine-36 is a radionuclide with a half-life of 3.01×105a. Most 36Cl in the hydrosphere originates from cosmic radiation interacting with atmospheric gases. Large amounts were also produced by testing thermonuclear devices during 1952-58. Because the monovalent anion, chloride, is the most common form of chlorine found in the hydrosphere and because it is extremely mobile in aqueous systems, analyses of both total Cl- as well as 36Cl have been important in numerous hydrologic studies. In almost all applications of 36Cl, a knowledge of the initial, or pre-anthropogenic, levels of 36Cl is useful, as well as essential in some cases. Standard approaches to the determination of initial values have been to: (a) calculate the theoretical cosmogenic production and fallout, which varies according to latitude; (b) measure 36Cl in present-day precipitation and assume that anthropogenic components can be neglected; (c) assume that shallow groundwater retains a record of the initial concentration; (d) extract 36Cl from vertical depth profiles in desert soils; (e) recover 36Cl from cores of glacial ice; and (f) calculate subsurface production of 36Cl for water that has been isolated from the atmosphere for more than one million years. The initial value from soil profiles and ice cores is taken as the value that occurs directly below the depth of the easily defined bomb peak. All six methods have serious weaknesses. Complicating factors include 36Cl concentrations not related to cosmogenic sources, changes in cosmogenic production with time, mixed sources of chloride in groundwater, melting and refreezing of water in glaciers, and seasonal groundwater recharge that does not contain average year-long concentrations of 36Cl. Résumé Le chlore-36 est un radionucléide de période 3.01×105a. Pour l'essentiel, le 36Cl dans l'hydrosphère provient des effets du rayonnement cosmique sur les gaz atmosphériques. De grandes quantités de 36Cl ont aussi été produites au cours des

43 CFR 423.36 - Swimming.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Swimming. 423.36 Section 423.36 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR... Swimming. (a) You may swim, wade, snorkel, scuba dive, raft, or tube at your own risk in Reclamation waters...

29 CFR 36.405 - Housing.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Housing. 36.405 Section 36.405 Labor Office of the Secretary....405 Housing. (a) Generally. A recipient shall not, on the basis of sex, apply different rules or regulations, impose different fees or requirements, or offer different services or benefits related to housing...

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

Science.gov (United States)

Richardson, Jason S; Yao, Michel K; Tran, Kaylie N; Croyle, Maria A; Strong, James E; Feldmann, Heinz; Kobinger, Gary P

2009-01-01

The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

Directory of Open Access Journals (Sweden)

Jason S Richardson

Full Text Available BACKGROUND: The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP. The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. METHODOLOGY/PRINCIPAL FINDINGS: Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP. Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. CONCLUSIONS/SIGNIFICANCE: We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the

The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3.

Science.gov (United States)

Sirena, Dominique; Lilienfeld, Benjamin; Eisenhut, Markus; Kälin, Stefan; Boucke, Karin; Beerli, Roger R; Vogt, Lorenz; Ruedl, Christiane; Bachmann, Martin F; Greber, Urs F; Hemmi, Silvio

2004-05-01

Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery.

Spinocerebellar ataxia 36 (SCA36): «Costa da Morte ataxia».

Science.gov (United States)

Arias, M; García-Murias, M; Sobrido, M J

To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

38 CFR 36.4221 - Delegation of authority.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Delegation of authority. 36.4221 Section 36.4221 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Site Preparation General Provisions § 36.4221 Delegation of authority. (a) Except as hereinafter...

ENTERIC ADENOVIRUS INFECTION IN INFANTS AND YOUNG CHILDREN WITH ACUTE GASTROENTERITIS IN TEHRAN

Directory of Open Access Journals (Sweden)

F. Jam-Afzon S. Modarres

2006-09-01

Full Text Available Adenoviruses are one of the most important etiological agents of serious gastroenteritis among infants and young children. Fecal specimens from patients with an acute gastroenteritis were evaluated for the presence of adenovirus (Ad40, 41 from April 2002 to February 2004. During the study, 1052 samples were collected from children under the age of 5 years in six educational and therapeutic pediatric centers. The specimens were tested for adenovirus (Ad40, 41 by EIA technique in the Virology Department of Pasteur Institute of Iran. Adenoviruses (Ad40, 41 were detected from 27(2.6% samples, but were not detected in 150 samples of healthy control group. In this study the highest rate of adenovirus was found in children aged 6 to 12 months (40.7%, but the male to female ratio inpatients was approximately equal. Adenovirus (Ad40, 41 infections peaked in the winter as 48.1% was detected from December to March. There were a statistically significant difference between age and infection (P < 0.001, also between season with adenovirus (Ad40, 41 infection (P = 0.005. Breast-feeding had a protective action against adenovirus (Ad40, 41 infection. This study revealed that enteric adenovirus (Ad40, 41 is an etiological agent of acute gastroenteritis among children in Tehran.

Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma

NARCIS (Netherlands)

Kuhlmann, K.F.D.; Geer, M.A. van; Bakker, C.T.; Dekker, J.E.M.; Havenga, M.J.E.; Oude Elferink, R.P.J.; Gouma, D.J.; Bosma, P.J.; Wesseling, J.G.

2009-01-01

Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved

Expression of estrogen receptor α 36 (ESR36) in the hamster ovary throughout the estrous cycle: effects of gonadotropins.

Science.gov (United States)

Chakraborty, Prabuddha; Roy, Shyamal K

2013-01-01

Estradiol-17β (E) plays an important role in ovarian follicular development. Evidence indicates that some of the effect of E is mediated by the transmembrane estrogen receptor. In this study, we examined the spatio-temporal expression of recently discovered ERα36 (ESR36), a splice variant of Esr1 and a receptor for non-genomic E signaling, in the hamster ovary during the estrous cycle and the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36 expression was high on estrus (D1:0900 h) and declined precipitously by proestrus (D4:0900 h) and remained low up to D4:1600 h. Immunofluorescence findings corroborated immunoblot findings and revealed that ESR36 was expressed only in the cell membrane of both follicular and non-follicular cells, except the oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx) resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or combined, markedly upregulated ESR36 protein in Hx hamsters to the levels observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36 expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH replacement on D4 afternoon. This is the first report to show that ESR36, which is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian follicular and non-follicular cells, binds to E and its expression is regulated directly by the gonadotropins. In light of our previous findings, the results suggest that ovarian cells contain at least two distinct membrane estrogen receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action of E regulating ovarian follicular functions.

Expression of estrogen receptor α 36 (ESR36 in the hamster ovary throughout the estrous cycle: effects of gonadotropins.

Directory of Open Access Journals (Sweden)

Prabuddha Chakraborty

Full Text Available Estradiol-17β (E plays an important role in ovarian follicular development. Evidence indicates that some of the effect of E is mediated by the transmembrane estrogen receptor. In this study, we examined the spatio-temporal expression of recently discovered ERα36 (ESR36, a splice variant of Esr1 and a receptor for non-genomic E signaling, in the hamster ovary during the estrous cycle and the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36 expression was high on estrus (D1:0900 h and declined precipitously by proestrus (D4:0900 h and remained low up to D4:1600 h. Immunofluorescence findings corroborated immunoblot findings and revealed that ESR36 was expressed only in the cell membrane of both follicular and non-follicular cells, except the oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or combined, markedly upregulated ESR36 protein in Hx hamsters to the levels observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36 expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH replacement on D4 afternoon. This is the first report to show that ESR36, which is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian follicular and non-follicular cells, binds to E and its expression is regulated directly by the gonadotropins. In light of our previous findings, the results suggest that ovarian cells contain at least two distinct membrane estrogen receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action of E regulating ovarian follicular functions.

Radiochemical analysis of chlorine-36

International Nuclear Information System (INIS)

Rodriguez, M.; Pina, G.; Lara, E.

2006-01-01

The radioactive chlorine isotope, 36 Cl, decays with a half-life of 3x10 5 years by emitting a beta particle (98 %) and by electron capture. The aim of this paper is to propose a radiochemical separation method of 36 Cl from the other beta-gamma emitters present in low and medium radioactive wastes such as spent ion exchange resins and evaporator concentrates, that arise from Nuclear Power Plants and particularly in the wastes that come from decommissioning activities of graphite reactors, in order to provide data for 36 Cl inventory calculations. The separation method proposed is based on an oxidation technique where chlorine is trapped by NaOH. 36 Cl beta emissions are measured by liquid scintillation counting by the dual label technique in order to avoid the contamination produced by 14 C which is also trapped by NaOH and which is the main contaminant present in graphite samples. The sensitivity of this method is sufficient to achieve the needed thresholds for the radiological characterization of the radioactive materials to which this method can be applied. (author)

38 CFR 36.4520 - Delegation of authority.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Delegation of authority. 36.4520 Section 36.4520 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) LOAN GUARANTY Direct Loans § 36.4520 Delegation of authority. (a) Except as hereinafter provided...

47 CFR 36.182 - Cash working capital.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cash working capital. 36.182 Section 36.182... PROCEDURES; STANDARD PROCEDURES FOR SEPARATING TELECOMMUNICATIONS PROPERTY COSTS, REVENUES, EXPENSES, TAXES... Cash Working Capital § 36.182 Cash working capital. (a) The amount for cash working capital, if not...

24 CFR 200.36 - Financial reporting requirements.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Financial reporting requirements. 200.36 Section 200.36 Housing and Urban Development Regulations Relating to Housing and Urban... Regulations § 200.36 Financial reporting requirements. The mortgagor must comply with the financial reporting...

Cooperation of Ad-hING4 and 125I seed in tumor-suppression on human pancreatic cancer xenograft in nude mice

International Nuclear Information System (INIS)

Zhai Hongyan; Fa Yihua; Su Chenghai; Yang Jicheng; Sheng Weihua; Xie Yufeng

2009-01-01

This work is to investigate the combined tumor-suppression effect of Adenovirus-mediated human ING4 (Ad-hING4) and 125 I seed on human pancreatic cancer xenograft and the possible mechanisms. Ad-hING4 recombinant adenovirus vector was transected into QBI-293A cells and high titre adenovirus was obtained. Subcutaneous tumor models were established with 25 nude mice with human pancreatic cancer cell line PANC-1. They were randomly divided into 5 groups: PBS control group, Ad carrier group, 125 I seed brachytherapy group, Ad-hING4 gene treatment group, combined 125 I seed and Ad-hING4 group. The tumor volumes were measured every 5 days after treatment, and were sacrificed on the 20th day. The tumors were measured and weighed to determine the ratio of tumor-suppression and Jin-Shi q value. Morphological changes of tumor cells,the tissue injury and apoptotic index AI were examined on pathological sections. MVD, Survivin and Caspase3 were tested in immunohistochemistry. The results show that the tumor-suppressive ratio of the 125 I seed group, Ad-hING4 group, combined treatment group were,respectively, 34.19%(P 0.05). It can be concluded that 125 I seed and Ad-hING4 inhibit the growth of PANC-1 pancreatic cancer on nude mice significantly. These indicate a synergy of the combined treatments in tumor-suppression and Ad-hING4 is a promising novel radiosensitizer. The mechanisms of tumor-suppressive may be multi-pathways such as down-regulation the expression of Survivin and up-regulation the expression of Caspase3 to induce apoptosis and inhibit angiogenesis. (authors)

USC-087 protects Syrian hamsters against lethal challenge with human species C adenoviruses.

Science.gov (United States)

Toth, Karoly; Spencer, Jacqueline F; Ying, Baoling; Tollefson, Ann E; Hartline, Caroll B; Richard, Eric T; Fan, Jiajun; Lyu, Jinglei; Kashemirov, Boris A; Harteg, Cheryl; Reyna, Dawn; Lipka, Elke; Prichard, Mark N; McKenna, Charles E; Wold, William S M

2018-05-01

Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, AdV can cause serious infection in severely immunosuppressed individuals, especially pediatric patients undergoing allogeneic hematopoietic stem cell transplantation, where mortality rates are up to 80% with disseminated disease. Despite the seriousness of AdV disease, there are no drugs approved specifically to treat AdV infections. We report here that USC-087, an N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analog of cidofovir, is highly effective against multiple AdV types in cell culture. USC-087 is also effective against AdV-C6 in our immunosuppressed permissive Syrian hamster model. In this model, hamsters are immunosuppressed by treatment with high dose cyclophosphamide. Injection of AdV-C6 (or AdV-C5) intravenously leads to a disseminated infection that resembles the disease seen in humans, including death. We have tested the efficacy of orally-administered USC-087 against the median lethal dose of intravenously administered AdV-C6. USC-087 completely prevented or significantly decreased mortality when administered up to 4 days post challenge. USC-087 also prevented or significantly decreased liver damage caused by AdV-C6 infection, and suppressed virus replication even when administered 4 days post challenge. These results imply that USC-087 is a promising candidate for drug development against HAdV infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Studies on methods of measurement of radioactivities of 36Cl and 3H in dual labelled samples

International Nuclear Information System (INIS)

Hirano, Shusuke; Asou, Hiroaki; Oishi, Katsuhiko; Hirano, Kiyoshi; Sato, Isamu

1985-01-01

In order to clarify how chloride molecules are transported into nervous tissue cells, we simultaneously used [ 36 Cl] -NaCl and [ 3 H] -inulin, and added AgNO 3 to the extract from the nervous tissue, obtaining 36 Cl-samples from the AgCl-precipitate and 3 H-samples from the supernatant. As for radioactivity of 36 Cl or 3 H in the dual-labelled samples, the recovery rates by our separation method were about 100%. Using cultured astrocytoma cells, 36 Cl-uptake into the cells, which was calculated by inulin assumption, was investigated. Intracellular 36 Cl-radioactivity changed vis-a-vis with that in the extracellular space. The volume of intracellular water, which was calculated by 3 H-inulin assumption, remained unchanged, even though a few variations in 36 Cl-radioactivity in cells were determined by both our separation method and spill-over method. (author)

Northern California 36 arc-second DEM

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The 36-second Northern California Elevation Grid provides bathymetric data in ASCII raster format of 36-second resolution in geographic coordinates. This grid is...

IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis.

Science.gov (United States)

Ahsan, Fadhil; Maertzdorf, Jeroen; Guhlich-Bornhof, Ute; Kaufmann, Stefan H E; Moura-Alves, Pedro

2018-01-24

Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. We report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL-36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb.

40 CFR 36.635 - Drug-free workplace.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Drug-free workplace. 36.635 Section 36... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific...

32 CFR 310.36 - OMB training guidelines.

Science.gov (United States)

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false OMB training guidelines. 310.36 Section 310.36... PROGRAM DOD PRIVACY PROGRAM Training Requirements § 310.36 OMB training guidelines. The OMB guidelines (OMB Privacy Guidelines, 40 FR 28948 (July 9, 1975) require all agencies additionally to: (a) Instruct...

12 CFR 560.36 - De minimis investments.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false De minimis investments. 560.36 Section 560.36 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY LENDING AND INVESTMENT Lending and Investment Powers for Federal Savings Associations § 560.36 De minimis investments. A Federal...

Cryo-EM structures of two bovine adenovirus type 3 intermediates

International Nuclear Information System (INIS)

Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin; Xiong, Wei; Sun, Wei; Yang, Chongwen; Zhang, Kai; Wang, Ying; Liu, Hongrong; Huang, Xiaojun; Ji, Gang; Sun, Fei; Zheng, Congyi; Zhu, Ping

2014-01-01

Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process

Cryo-EM structures of two bovine adenovirus type 3 intermediates

Energy Technology Data Exchange (ETDEWEB)

Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Xiong, Wei [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Sun, Wei; Yang, Chongwen; Zhang, Kai; Wang, Ying [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Hongrong [College of Physics and Information Science, Hunan Normal University, Changsha, Hunan 410081 (China); Huang, Xiaojun; Ji, Gang; Sun, Fei [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Zheng, Congyi, E-mail: cctcc202@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Zhu, Ping, E-mail: zhup@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

2014-02-15

Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process.

36Cl AMS measurement of JCO samples

International Nuclear Information System (INIS)

Arai, D.; Seki, R.; Nagashima, Y.; Takahashi, T.; Kume, H.; Mawatari, R.

2000-01-01

A critical nuclear accident occurred at the nuclear fuel processing facility, JCO, in Tokaimura, Ibaraki prefecture, Japan on 30 September 1999, and a lot of neutron particle were released in the environment. In order to estimate the total neutron flux, we measured the yield of 36 Cl radioisotopes in the samples being collected from the accident site. The neutron flux can be estimated from the ratio of 36 Cl to 35 Cl because the 36 Cl nuclei are created from 35 Cl through a thermal neutron capture process, 35 Cl(n,γ) 36 Cl. (author)

Longitudinal changes in awareness over 36 months in patients with mild Alzheimer's disease

DEFF Research Database (Denmark)

Vogel, Asmus; Waldorff, Frans Boch; Waldemar, Gunhild

2015-01-01

MMSE, Neuropsychiatric Inventory (NPI-Q), and Cornell scale for Depression in Dementia also were applied. Results: At 12 months, 26% had lower awareness rating as compared to baseline and at 36 months lower awareness ratings were found in 39%. At both visits, 16% had higher awareness rating as compared......Background: Longitudinal changes in awareness in dementia have been studied with short follow-up time and mostly in small patient groups (including patients with moderate dementia). We investigated awareness in patients with mild Alzheimer’s disease (AD) over 36 months and studied if a decline...

19 CFR 145.36 - Articles for institutions.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Articles for institutions. 145.36 Section 145.36... TREASURY (CONTINUED) MAIL IMPORTATIONS Special Classes of Merchandise § 145.36 Articles for institutions. Books and other articles classifiable under subheading 4903.00.00, 4904.00.00, 4905.91.00, 4905.99.00...

6 CFR 13.36 - Post-hearing briefs.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Post-hearing briefs. 13.36 Section 13.36 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.36 Post-hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event...

30 CFR 36.27 - Fuel-supply system.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fuel-supply system. 36.27 Section 36.27 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF... Construction and Design Requirements § 36.27 Fuel-supply system. (a) Fuel tank. (1) The fuel tank shall not...

12 CFR 5.36 - Other equity investments.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Other equity investments. 5.36 Section 5.36... PROCEDURES FOR CORPORATE ACTIVITIES Expansion of Activities § 5.36 Other equity investments. (a) Authority... types of equity investments pursuant to 12 U.S.C. 24(Seventh) and other statutes. These investments are...

IL-36 receptor deletion attenuates lung injury and decreases mortality in murine influenza pneumonia.

Science.gov (United States)

Aoyagi, T; Newstead, M W; Zeng, X; Kunkel, S L; Kaku, M; Standiford, T J

2017-07-01

Influenza virus causes a respiratory disease in humans that can progress to lung injury with fatal outcome. The interleukin (IL)-36 cytokines are newly described IL-1 family cytokines that promote inflammatory responses via binding to the IL-36 receptor (IL-36R). The mechanism of expression and the role of IL-36 cytokines are poorly understood. Here, we investigated the role of IL-36 cytokines in modulating the innate inflammatory response during influenza virus-induced pneumonia in mice. The intranasal administration of influenza virus upregulated IL-36α mRNA and protein production in the lungs. In vitro, influenza virus-mediated IL-36α but not IL-36γ is induced and secreted from alveolar epithelial cells (AECs) through both a caspase-1 and caspase-3/7 dependent pathway. IL-36α was detected in microparticles shed from AECs and promoted the production of pro-inflammatory cytokines and chemokines in respiratory cells. IL-36R-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced early accumulation of neutrophils and monocytes/macrophages, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines, and permeability of the alveolar-epithelial barrier in despite impaired viral clearance. Taken together, these data indicate that IL-36 ligands exacerbate lung injury during influenza virus infection.

10 CFR 36.63 - Pool water purity.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Pool water purity. 36.63 Section 36.63 Energy NUCLEAR... § 36.63 Pool water purity. (a) Pool water purification system must be run sufficiently to maintain the conductivity of the pool water below 20 microsiemens per centimeter under normal circumstances. If pool water...

50 CFR 12.36 - Donation or loan.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Donation or loan. 12.36 Section 12.36... SEIZURE AND FORFEITURE PROCEDURES Disposal of Forfeited or Abandoned Property § 12.36 Donation or loan. (a... and security for the item. (b) Any donation or loan may be made only after execution of a transfer...

25 CFR 36.41 - Standard XIV-Textbooks.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Standard XIV-Textbooks. 36.41 Section 36.41 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY SITUATIONS Instructional Support § 36.41 Standard XIV—Textbooks. (a) Each school shal...

10 CFR 36.35 - Source rack protection.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Source rack protection. 36.35 Section 36.35 Energy NUCLEAR... Requirements for Irradiators § 36.35 Source rack protection. If the product to be irradiated moves on a product conveyor system, the source rack and the mechanism that moves the rack must be protected by a barrier or...

Chlorine-36 investigations of salt lakes

International Nuclear Information System (INIS)

Chivas, A.R.; Kiss, E.

1987-01-01

The first chlorine-36 measurements are reported for surficial halite in lakes from a west-to-east traverse in Western Australia and from Lake Amadeus NT. Measurements of chlorine-36 were made using a 14 MV tandem accelerator. Isotopic chlorine ratios ranged from 8 to 53 x 10 exp-15, with no clear evidence for bomb-spike chlorine-36. The Western Australian samples have values close to secular equilibrium values for typical granite and groundwaters in this rock type. Studies are aimed at calculating the residence time of chloride in the surficial environment. 1 tab

Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus

Directory of Open Access Journals (Sweden)

Fuminori Sakurai

2016-01-01

Full Text Available Circulating tumor cells (CTCs are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP–expressing conditionally replicating adenovirus (Ad (rAd-GFP was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells.

Up-regulation of integrin β3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy

International Nuclear Information System (INIS)

Egami, Takuya; Ohuchida, Kenoki; Yasui, Takaharu; Onimaru, Manabu; Toma, Hiroki; Sato, Norihiro; Tanaka, Masao; Mizumoto, Kazuhiro; Matsumoto, Kunio

2009-01-01

Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P<0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (author)

48 CFR 36.604 - Performance evaluation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Performance evaluation. 36.604 Section 36.604 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL... Performance evaluation. See 42.1502(f) for the requirements for preparing past performance evaluations for...

9 CFR 381.36 - Facilities required.

Science.gov (United States)

2010-01-01

... laundry service for inspectors' outer work clothing, or disposable outer work garments designed for one... 381.36 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Holiday Service; Billing Establishments § 381.36 Facilities required. (a) Inspector's Office. Office space...

Radiological assessment of {sup 36}Cl in the disposal of used CANDU fuel

Energy Technology Data Exchange (ETDEWEB)

Johnson, L H; Goodwin, B W; Sheppard, S C; Tait, J C; Wuschke, D M; Davison, C C

1995-06-01

An assessment of the potential radiological impact of {sup 36}Cl in the disposal of used CANDU fuel has been performed. The assessment was based on new data on chlorine impurity levels in used fuel. Data bases for the vault, geosphere, and biosphere models used in the EIS postclosure assessment case study (Goodwin et al. 1994) were modified to include the necessary {sup 36}Cl data. The resulting safety analysis shows that estimated radiological risks from {sup 36}Cl are forty times lower than from {sup 129}I at 10{sup 4} a; this, incorporation of {sup 36}Cl into the models does not change the overall conclusions of the study of Goodwin et al. (1994a). For human intrusion scenarios, an analysis using the methodology of Wuschke (1992) showed that the maximum risk is unaffected by the inclusion of {sup 36}Cl. (author). 51 refs., 5 tabs., 15 figs.

A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

Science.gov (United States)

Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

2012-01-01

The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

40 CFR 273.36 - Employee training.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Employee training. 273.36 Section 273.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED... Employee training. A large quantity handler of universal waste must ensure that all employees are...

48 CFR 36.513 - Accident prevention.

Science.gov (United States)

2010-10-01

... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 36.513 Accident prevention. (a) The contracting officer shall insert the clause at 52.236-13, Accident Prevention, in... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Accident prevention. 36...

9 CFR 355.36 - Obsolete labels.

Science.gov (United States)

2010-01-01

... CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION, CERTIFICATION, AND... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Obsolete labels. 355.36 Section 355.36 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY...

Atmospheric production rate of 36Cl

International Nuclear Information System (INIS)

Parrat, Y.; Hajdas, W.; Baltensperger, U.; Synal, H.A.; Kubik, P.W.; Gaeggeler, H.W.; Suter, M.

1997-01-01

Using experimental cross sections, a new calculation of the atmospheric production rate of 36 Cl was carried out. A mean production rate of 20 atoms m -2 s -1 was obtained, which is lower than mean 36 Cl deposition rates. (author) 2 figs., 7 refs

36Cl-AMS measurements with 3-MV tandem accelerator

International Nuclear Information System (INIS)

Wang Huijuan; Guan Yongjing; Zhang Wei; Jiang Shan; Ming He

2013-01-01

36 C- is one of the most interesting nuclides in accelerator mass spectrometry (AMS) measurements. The application of 36 Cl has been widely applied in various fields. All most all of 36 Cl AMS measurements at natural isotopic concentrations have yet been performed at tandem accelerator with 5 MV or higher terminal voltage. The measure improvement of 36 Cl and other medium heavy isotopes performed at 3 MV in AMS facilities is one of the hottest topics in AMS measurements. In order to increase the suppression factor of 36 S, the energy loss straggling and angular straggling of 36 Cl and 36 S ions in various counter gases (P10, isobutane and propane) were investigated. Some groundwater samples were measured with energy of 32 MeV, and the results were in good agreement with the result obtained with ion energy of 72 MeV. The results indicate that the approximate detection limit of 36 Cl in 3 MV AMS facility is 36 Cl/Cl=1 × 10 -14 , and the uncertainty is 30% when the sample with isotopic ration 36 Cl/Cl≈10 -13 . (authors)

Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro.

Science.gov (United States)

Gallenberger, Martin; Meinel, Dominik M; Kroeber, Markus; Wegner, Michael; Milkereit, Philipp; Bösl, Michael R; Tamm, Ernst R

2011-02-01

Mutations in WD repeat domain 36 gene (WDR36) play a causative role in some forms of primary open-angle glaucoma, a leading cause of blindness worldwide. WDR36 is characterized by the presence of multiple WD40 repeats and shows homology to Utp21, an essential protein component of the yeast small subunit (SSU) processome required for maturation of 18S rRNA. To clarify the functional role of WDR36 in the mammalian organism, we generated and investigated mutant mice with a targeted deletion of Wdr36. In parallel experiments, we used RNA interference to deplete WDR36 mRNA in mouse embryos and cultured human trabecular meshwork (HTM-N) cells. Deletion of Wdr36 in the mouse caused preimplantation embryonic lethality, and essentially similar effects were observed when WDR36 mRNA was depleted in mouse embryos by RNA interference. Depletion of WDR36 mRNA in HTM-N cells caused apoptotic cell death and upregulation of mRNA for BAX, TP53 and CDKN1A. By immunocytochemistry, staining for WDR36 was observed in the nucleolus of cells, which co-localized with that of nucleolar proteins such as nucleophosmin and PWP2. In addition, recombinant and epitope-tagged WDR36 localized to the nucleolus of HTM-N cells. By northern blot analysis, a substantial decrease in 21S rRNA, the precursor of 18S rRNA, was observed following knockdown of WDR36. In addition, metabolic-labeling experiments consistently showed a delay of 18S rRNA maturation in WDR36-depleted cells. Our results provide evidence that WDR36 is an essential protein in mammalian cells which is involved in the nucleolar processing of SSU 18S rRNA.

The search for adenovirus 14 in children in Houston, Texas.

Science.gov (United States)

Laham, Federico R; Jewell, Alan M; Schoonover, Shauna L; Demmler, Gail J; Piedra, Pedro A

2008-07-01

Adenovirus (Ad)14 has recently emerged in the United States causing outbreaks of severe respiratory disease. To determine if Ad14 circulated in Houston, Texas, during the same time as an outbreak in military recruits in nearby San Antonio, 215 pediatric adenovirus isolates were serotyped using microneutralization. None were Ad14; Ad1, Ad2, and Ad3 were the most common identified serotypes.

Construction of a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen and mouse 4-1BBL genes and its effect on dendritic cells

Directory of Open Access Journals (Sweden)

Xiaodong Weng

2011-03-01

Full Text Available Our aim was to construct a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen (tPSMA and mouse 4-1BBL genes and to determine its effect on dendritic cells (DCs generated from bone marrow suspensions harvested from C57BL/6 mice for which the effect of 4-1BBL on DCs is not clear, especially during DCs processing tumor-associated antigen. Replication deficient adenovirus AdMaxTM Expression System was used to construct recombinant adenovirus Ad-tPSMA-internal ribosome entry site-mouse 4-1BBL (Ad-tPSMA-IRES-m4-1BBL and Ad-enhanced green fluorescent protein. Day 7 proliferating DC aggregates generated from C57BL/6 mice were collected as immature DCs and further mature DCs were obtained by lipopolysaccharide activated immature DCs. After DCs were exposed to the recombinant adenovirus with 250 multiplicity of infection, the expression of tPSMA and m4-1BBL proteins were detected by Western blot, and the apoptosis and phenotype of DCs were analyzed by flow cytometry. Cytokines (IL-6 and IL-12 in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA. Proliferation of T cells was detected by allogeneic mixed lymphocyte reactions. The tPSMA and m4-1BBL proteins were expressed correctly. The apoptosis rate of DCs transfected with Ad-tPSMA-IRES-m4-1BBL was 14.6%, lower than that of control DCs. The expression of co-stimulatory molecules [CD80 (81.6 ± 5.4% and CD86 (80.13 ± 2.81%] up-regulated in Ad-tPSMA-IRES-m4-1BBL-pulsed DCs, and the level of IL-6 (3960.2 ± 50.54 pg/mL and IL-12 (249.57 ± 12.51 pg/mL production in Ad-tPSMA-IRES-m4-1BBL-transduced DCs were significantly higher (P < 0.05 than those in control DCs. Ad-tPSMA-IRES-m4-1BBL induced higher T-cell proliferation (OD450 = 0.614 ± 0.018, indicating that this recombinant adenovirus can effectively enhance the activity of DCs.

Interleukin (IL)-8 and IL-36γ but not IL-36Ra are related to acrosyringia in pustule formation associated with palmoplantar pustulosis.

Science.gov (United States)

Xiaoling, Y; Chao, W; Wenming, W; Feng, L; Hongzhong, J

2018-06-12

Palmoplantar pustulosis (PPP) is a refractory, nonbacterial impetigo confined to the palms and soles. Its pathogenesis is still obscure, but it may be associated with the large eccrine sweat glands and pores of palmoplantar skin. PPP is considered to be a localized pustular psoriasis. Interleukin (IL)-8, IL-36γ and IL-36Ra play important roles in the pathogenesis of pustular psoriasis, but their role in PPP is unclear. To evaluate IL-8, IL-36γ and IL-36Ra expression in PPP, and their relationship with acrosyringia and pustule formation. mRNA expression was quantified in skin samples from patients with PPP (n = 7), patients with psoriasis vulgaris (PSV; n = 8) and healthy controls (HCs) (n = 6) by reverse-transcription-real-time PCR. Protein expression was characterized by immunohistochemistry (PPP, n = 17; PSV, n = 14; HCs, n = 12). Sweat ducts, including acrosyringia, were stained for epithelial membrane antigen (EMA). IL-8 mRNA and protein were markedly increased in PPP lesions compared with PSV lesions or HC skin. IL-36γ mRNA and protein were significantly more abundant in PPP lesions than in HC skin. IL-36Ra mRNA was significantly overexpressed in PPP lesions compared with HC skin, but there was no difference in IL-36Ra protein between PPP, PSV and HCs. IL-8 was abundantly expressed by neutrophils in PPP pustules, while IL36Ra was localized in the keratinocytes of PPP, PSV and HC skin. IL-36γ and EMA were colocalized in cells surrounding PPP pustules, and IL-36γ was also expressed in sweat duct cells in the dermis. IL-8, IL-36γ and IL-36Ra are overexpressed in PPP lesions. IL-8, IL-36γ and acrosyringia, rather than IL-36Ra, are associated with pustule formation in PPP. © 2018 British Association of Dermatologists.

Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis.

Science.gov (United States)

Furue, Kazuhisa; Yamamura, Kazuhiko; Tsuji, Gaku; Mitoma, Chikage; Uchi, Hiroshi; Nakahara, Takeshi; Kido-Nakahara, Makiko; Kadono, Takafumi; Furue, Masutaka

2018-01-12

Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-?)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis. Although the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R are fundamentally involved in plaque psoriasis and pustular psoriasis, respectively, the 2 pathways are closely related and mutually reinforced, resulting in full-blown clinical manifestations. This review summarizes current topics on how IL-36 agonists (IL-36?, IL-36?, IL-36?) signal IL-36R, the pathological expression of IL-36 agonists and IL-36Ra in plaque and pustular psoriatic lesions, and the cross-talk between the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R in the epidermal milieu.

28 CFR 2.36 - Rescission guidelines.

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2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Rescission guidelines. 2.36 Section 2.36... guidelines. (a) The following guidelines shall apply to the sanctioning of disciplinary infractions or new... such period of confinement has resulted from initial parole to a detainer). These guidelines specify...

48 CFR 36.504 - Physical data.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Physical data. 36.504... CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 36.504 Physical data. The contracting officer shall insert the clause at 52.236-4, Physical Data, in solicitations and contracts when a...

40 CFR 82.36 - Approved refrigerant handling equipment.

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2010-07-01

... equipment. 82.36 Section 82.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Servicing of Motor Vehicle Air Conditioners § 82.36...-12, Extraction and Recycle Equipment for Mobile Automotive Air-Conditioning Systems, and Standard of...

38 CFR 36.4227 - Advertising and Solicitation Requirements.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Advertising and Solicitation Requirements. 36.4227 Section 36.4227 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Lots, Including Site Preparation General Provisions § 36.4227 Advertising and Solicitation Requirements...

Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons

International Nuclear Information System (INIS)

Ticku, M.K.; Lowrimore, P.; Lehoullier, P.

1986-01-01

Ethanol has a pharmacological profile similar to other centrally acting drugs, which facilitate GABAergic transmission. GABA is known to produce its effects by increasing the conductance to Cl- ions. In this study, we have examined the effect of ethanol on GABA-induced 36Cl-influx in primary spinal cord cultured neurons. GABA produces a concentration-dependent, and saturable effect on 36Cl-influx in these neurons. Ethanol potentiates the effect of GABA on 36Cl-influx in these neurons. GABA (20 microM) increased the 36Cl-influx by 75% over the basal value, and in the presence of 50 mM ethanol, the observed increase was 142%. Eadie-Hoffstee analysis of the saturation curves indicated that ethanol decreases the Km value of GABA (10.6 microM to 4.2 microM), and also increases the Vmax. Besides potentiating the effect of GABA, ethanol also appears to have a direct effect in the absence of added GABA. These results suggest that ethanol enhances GABA-induced 36Cl-influx and indicate a role of GABAergic system in the actions of ethanol. These results also support the behavioral and electrophysiological studies, which have implicated GABA systems in the actions of ethanol. The potential mechanism(s) and the role of direct effect of ethanol is not clear at this time, but is currently being investigated

High 36Cl/Cl ratios in Chernobyl groundwater

International Nuclear Information System (INIS)

Roux, Céline; Le Gal La Salle, Corinne; Simonucci, Caroline; Van Meir, Nathalie; Fifield, L. Keith; Diez, Olivier; Bassot, Sylvain

2014-01-01

After the explosion of the Chernobyl Nuclear Power Plant in April 1986, contaminated material was buried in shallow trenches within the exclusion zone. A 90 Sr plume was evidenced downgradient of one of these trenches, trench T22. Due to its conservative properties, 36 Cl is investigated here as a potential tracer to determine the maximal extent of the contamination plume from the trench in groundwater. 36 Cl/Cl ratios measured in groundwater, trench soil water and leaf leachates are 1–5 orders of magnitude higher than the theoretical natural 36 Cl/Cl ratio. This contamination occurred after the Chernobyl explosion and currently persists. Trench T22 acts as an obvious modern point source of 36 Cl, however other sources have to be involved to explain such contamination. 36 Cl contamination of groundwater can be explained by dilution of trench soil water by uncontaminated water (rainwater or deep groundwater). With a plume extending further than that of 90 Sr, radionuclide which is impacted by retention and decay processes, 36 Cl can be considered as a suitable tracer of contamination from the trench in groundwater provided that modern release processes of 36 Cl from trench soil are better characterized. - Highlights: • High 36 Cl/Cl ratios measured in the Chernobyl Pilot Site groundwater. • Trench T22 acts as a modern source of groundwater contamination by 36 Cl but other sources are involved. • Contamination results from dilution of a contaminated “T22” soil water with rainwater. • Processes involved in the modern release need to be investigated

19 CFR 210.36 - General provisions for hearings.

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2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false General provisions for hearings. 210.36 Section 210.36 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Prehearing Conferences and Hearings § 210.36 General...

48 CFR 36.201 - Evaluation of contractor performance.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Evaluation of contractor performance. 36.201 Section 36.201 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Contracting for Construction 36.201 Evaluation of contractor performance. See 42.1502(e) for the requirements...

38 CFR 36.4370 - Advertising and solicitation requirements.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Advertising and solicitation requirements. 36.4370 Section 36.4370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Reporting § 36.4370 Advertising and solicitation requirements. Any advertisement or solicitation in any form...

36Cl AMS measurement with 3 MV tandem accelerator

International Nuclear Information System (INIS)

Wang Huijuan; Guan Yongjing; Zhang Wei; Jiang Shan; He Ming

2012-01-01

Developing the 36 Cl and other medium heavy isotopes measurement at 3 MV AMS facilities is one of the vital trends in AMS measurement. To further increase suppression factor of 36 S, the energy loss straggling and angular straggling of 36 C1 and 36 S ions in various counter gases (Pl0, isobutane and propane) were investigated. Some water samples were measured with the energy of 32 MeV, the results are in good agreement with the result by ion energy of 72 MeV. The results indicate that the detection limit of 36 C1 with 3 MV AMS facility is approximately 36 Cl/Cl ≈ l0 -14 , and the uncertainty is 30% for the sample with isotopic ration 36 Cl/Cl ≈ lO -13 . (authors)

36Cl in shallow, perched aquifers from central Indiana

Science.gov (United States)

Vogt, S.; Elmore, D.; Fritz, S. J.

1994-06-01

36Cl/Cl ratios and chloride concentrations were measured in several shallow, perched aquifers situated within glacial till in west-central Indiana (USA). Most of these aquifers show 36Cl/Cl ratios which have to be attributed to admixed 36Cl from nuclear weapons tests in the 1950s and 1960s. Two wells from Purdue's Horticultural Farm tap perched aquifers uninfluenced by anthropogenic sources of chloride, and their 36Cl/Cl ratios are comparable with ratios measured in modern, local precipitation. As such, the chloride contents of these wells (1 to 3 ppm) reflect evaporative concentration of the precipitation's chloride contents (averaging 0.17 ppm) in the vadose zone. Since one of these two wells (HA-2a) does not contain any detectable tritium, we conclude that recent pre-bomb 36Cl/Cl ratios and 36Cl deposition in precipitation are quite similar to those in modern precipitation. We attribute the slight 36Cl excess of about 20% in both of these wells largely to 36Cl deposition associated with dry fall-out. As much as 2 × 10 4 at. 36Cl/cm 2 might reach the surface via dry fall-out annually.

38 CFR 36.4324 - Guaranty claims; subsequent accounting.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Guaranty claims; subsequent accounting. 36.4324 Section 36.4324 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... § 36.4324 Guaranty claims; subsequent accounting. (a) Subject to the limitation that the total amounts...

38 CFR 36.4707 - Determination fees.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Determination fees. 36...) LOAN GUARANTY Sale of Loans, Guarantee of Payment, and Flood Insurance § 36.4707 Determination fees. (a... will be located in a special flood hazard area. A determination fee may also include, but is not...

43 CFR 36.7 - Decision process.

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2010-10-01

... so notify the applicant in writing. (2) Each appropriate Federal agency in making its decision shall... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Decision process. 36.7 Section 36.7 Public Lands: Interior Office of the Secretary of the Interior TRANSPORTATION AND UTILITY SYSTEMS IN AND ACROSS...

A new 36Cl hydrological model and 36Cl systematics in the Jordan River/Dead Sea system

International Nuclear Information System (INIS)

Paul, M.; Fink, D.; Meirav, O.; Kaim, R.

1986-01-01

Accelerator mass spectrometry results of 36 Cl for the Jordan River/Dead Sea system show that the amount of chloride leached from rocks ranges from approx. 70% in source springs to >90% in water bodies downstream. Furthermore, the amount of water left after evaporation decreases from approx. 50% in the source springs to 20% in the intermediate Lake Kinneret. In the terminal Dead Sea, 99% of the stable chloride originates from ancient rocks and evaporite formations while approx. 80% of its 36 Cl content is of meteoric origin. Using 36 Cl measurements, the accumulation time of the Dead Sea salt is estimated to be 19,000-25,000 yr. (author)

10 CFR 36.31 - Control of source movement.

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2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Control of source movement. 36.31 Section 36.31 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Design and Performance Requirements for Irradiators § 36.31 Control of source movement. (a) The mechanism that moves the...

25 CFR 36.42 - Standard XV-Counseling services.

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2010-04-01

... the students being served; (iii) Preventative and crisis counseling on both individual and group bases... 25 Indians 1 2010-04-01 2010-04-01 false Standard XV-Counseling services. 36.42 Section 36.42... § 36.42 Standard XV—Counseling services. Each school shall offer student counseling services concerned...

[Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency].

Science.gov (United States)

Watanabe, K; Miyajima, S; Kusano, Y; Tanabe, N; Hirokawa, Y

1997-07-01

A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

Directory of Open Access Journals (Sweden)

Charlie Bridgewood

2018-02-01

Full Text Available The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis.

Science.gov (United States)

Bridgewood, Charlie; Fearnley, Gareth W; Berekmeri, Anna; Laws, Philip; Macleod, Tom; Ponnambalam, Sreenivasan; Stacey, Martin; Graham, Anne; Wittmann, Miriam

2018-01-01

The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

28 CFR 36.209 - Illegal use of drugs.

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2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Illegal use of drugs. 36.209 Section 36... PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES General Requirements § 36.209 Illegal use of drugs. (a... discrimination against an individual based on that individual's current illegal use of drugs. (2) A public...

30 CFR 36.26 - Composition of exhaust gas.

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2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Composition of exhaust gas. 36.26 Section 36.26... EQUIPMENT Construction and Design Requirements § 36.26 Composition of exhaust gas. (a) Preliminary engine... methane) is a satisfactory substitute for pure methane in these tests. (c) Coupling or adapter. The...

High (36)Cl/Cl ratios in Chernobyl groundwater.

Science.gov (United States)

Roux, Céline; Le Gal La Salle, Corinne; Simonucci, Caroline; Van Meir, Nathalie; Fifield, L Keith; Diez, Olivier; Bassot, Sylvain; Simler, Roland; Bugai, Dmitri; Kashparov, Valery; Lancelot, Joël

2014-12-01

After the explosion of the Chernobyl Nuclear Power Plant in April 1986, contaminated material was buried in shallow trenches within the exclusion zone. A (90)Sr plume was evidenced downgradient of one of these trenches, trench T22. Due to its conservative properties, (36)Cl is investigated here as a potential tracer to determine the maximal extent of the contamination plume from the trench in groundwater. (36)Cl/Cl ratios measured in groundwater, trench soil water and leaf leachates are 1-5 orders of magnitude higher than the theoretical natural (36)Cl/Cl ratio. This contamination occurred after the Chernobyl explosion and currently persists. Trench T22 acts as an obvious modern point source of (36)Cl, however other sources have to be involved to explain such contamination. (36)Cl contamination of groundwater can be explained by dilution of trench soil water by uncontaminated water (rainwater or deep groundwater). With a plume extending further than that of (90)Sr, radionuclide which is impacted by retention and decay processes, (36)Cl can be considered as a suitable tracer of contamination from the trench in groundwater provided that modern release processes of (36)Cl from trench soil are better characterized. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.

Science.gov (United States)

Westerberg, Sonja; Hagbom, Marie; Rajan, Anandi; Loitto, Vesa; Persson, B David; Allard, Annika; Nordgren, Johan; Sharma, Sumit; Magnusson, Karl-Eric; Arnberg, Niklas; Svensson, Lennart

2018-04-01

Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

International Nuclear Information System (INIS)

Qi, Yanxin; Guo, Huanhuan; Hu, Ningning; He, Dongyun; Zhang, Shi; Chu, Yunjie; Huang, Yubin; Li, Xiao; Sun, LiLi; Jin, Ningyi

2014-01-01

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 10 8 , 2.5 × 10 9 , and 1.25 × 10 10 viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 × 10 8 , 2.5 × 10 9 , and 1.25 × 10 10 VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 10 10 VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 10 10 VP/kg) and beagles (2.5 × 10 9 VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 10 10 VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 10 8 VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad-hTERT-E1a-Apoptin

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

Energy Technology Data Exchange (ETDEWEB)

Qi, Yanxin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Guo, Huanhuan [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Changchun Brother Biotech Co., Ltd., Changchun, 130000 (China); Hu, Ningning; He, Dongyun [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Zhang, Shi [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); School of Clinical Medicine, Jilin University, Changchun 130001 (China); Chu, Yunjie [Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021 (China); Huang, Yubin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Li, Xiao, E-mail: lixiao06@mails.jlu.edu.cn [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Sun, LiLi, E-mail: linjiaxiaoya@163.com [Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun 130012 (China); Jin, Ningyi, E-mail: ningyij@126.com [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China)

2014-10-15

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 10{sup 10} VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 10{sup 10} VP/kg) and beagles (2.5 × 10{sup 9} VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 10{sup 10} VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 10{sup 8} VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad

Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes.

OpenAIRE

Weiss, R S; Lee, S S; Prasad, B V; Javier, R T

1997-01-01

An essential oncogenic determinant of subgroup D human adenovirus type 9 (Ad9), which uniquely elicits estrogen-dependent mammary tumors in rats, is encoded by early region 4 open reading frame 1 (E4 ORF1). Whereas Ad9 E4 ORF1 efficiently induces transformed foci on the established rat embryo fibroblast cell line CREF, the related subgroup A Ad12 and subgroup C Ad5 E4 ORF1s do not (R. T. Javier, J. Virol. 68:3917-3924, 1994). In this study, we found that the lack of transforming activity asso...

Glucagon-like peptide 1 (7-36) amide stimulates exocytosis in human pancreatic beta-cells by both proximal and distal regulatory steps in stimulus-secretion coupling

DEFF Research Database (Denmark)

Gromada, J; Bokvist, K; Ding, W G

1998-01-01

The effect of glucagon-like peptide 1(7-36) amide [GLP-1(7-36) amide] on membrane potential, whole-cell ATP-sensitive potassium channel (K[ATP]) and Ca2+ currents, cytoplasmic Ca2+ concentration, and exocytosis was explored in single human beta-cells. GLP-1(7-36) amide induced membrane...... depolarization that was associated with inhibition of whole-cell K(ATP) current. In addition, GLP-1(7-36) amide (and forskolin) produced greater than fourfold potentiation of Ca2+-dependent exocytosis. The latter effect resulted in part (40%) from acceleration of Ca2+ influx through voltage-dependent (L-type) Ca......2+ channels. More importantly, GLP-1(7-36) amide (via generation of cyclic AMP and activation of protein kinase A) potentiated exocytosis at a site distal to a rise in the cytoplasmic Ca2+ concentration. Photorelease of caged cAMP produced a two- to threefold potentiation of exocytosis when...

A tetravalent vaccine comprising hexon-chimeric adenoviruses elicits balanced protective immunity against human adenovirus types 3, 7, 14 and 55.

Science.gov (United States)

Tian, Xingui; Jiang, Zaixue; Fan, Ye; Qiu, Shuyan; Zhang, Ling; Li, Xiao; Zhou, Zhichao; Liu, Tiantian; Ma, Qiang; Lu, Xiaomei; Zhong, Baimao; Zhou, Rong

2018-04-04

Human adenovirus (Ad) species B contains several of the most important types associated with acute respiratory diseases, Ad3, -7, -14 and -55, which often lead to severe lower respiratory tract diseases and epidemic outbreaks. However, there is currently no Ad vaccine approved for general use. The major capsid protein, hexon, is the primary determinant recognized by neutralizing antibodies (NAbs). In this study, four recombinant Ads that have the same genome sequence as Ad3 with the exception of the hexon genes, rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55, were combined as a tetravalent Ad candidate vaccine against Ad3, -7, -14 and -55. The replication efficiencies of chimeric rAd3H14, rAd3H7 and rAd3H55 were similar to that of rAd3EGFP. Recombinant rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55 induced high titers of NAbs against Ad3, -7, -14 and -55, respectively, which were comparable to those induced by wild-type Ads. The mixture of the four recombinant Ads in equal proportions, rAdMix, or rAdMix inactivated by β-propiolactone, induced balanced NAb responses against Ad3, -7, -14 and -55 in mice without reciprocal immunological interference. In co-culture the four recombinant Ads replicated with a similar efficiency without reciprocal inhibition, and the progeny virions may be chimeric. Purified co-culture, rAdMix-C, also elicited balanced immune responses, suggesting a simple method for multivalent vaccine production. These results indicate the possible advantage of the four Ads as a live combined vaccine. Importantly, pre-immunization with rAdMix conferred protection against Ad3, -7, -14 or -55 challenge in mice in vivo. Thus, this research provides a novel tetravalent Ad vaccine candidate against Ad3, -7, -14 and -55. Copyright © 2018 Elsevier B.V. All rights reserved.

21 CFR 60.36 - Standard of due diligence.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Standard of due diligence. 60.36 Section 60.36... TERM RESTORATION Due Diligence Petitions § 60.36 Standard of due diligence. (a) In determining the due diligence of an applicant, FDA will examine the facts and circumstances of the applicant's actions during...

[Brodmann Areas 27, 28, 36 and 37: The Parahippocampal and the Fusiform Gyri].

Science.gov (United States)

Eifuku, Satoshi

2017-04-01

First, Brodmann areas 27, 28, 36 and 37, were anatomically defined in the beginning of this review. These areas exist in the parahippocampal or fusiform gyrus of the ventral temporal lobe in humans. Subsequently, the current understanding of their functions was summarized on the basis of recent findings mainly through human functional neuroimaging studies and animal studies. Rodent studies have shown the existence of neuronal activities for representing space, such as those involving head-direction cells or grid cells, in areas 27 (the parasubicular cortex) and 28 (the ventral entorhinal cortex). Recent human neuroimaging studies have provided support for the idea that grid cells may also exist in the human entorhinal cortex. Many previous animal studies have shown that area 36 (the lateral perirhinal cortex) is crucial for various types of associative learning. Earlier human neuroimaging studies have also indicated that faces, bodies and visual word forms are represented in different regions of area 37 in the posterior fusiform gyrus. Recent neuroimaging studies in humans have shown substantial functional differentiation between face-related regions in areas 37 and 36, which is similar to that seen in macaque monkeys, as shown through their face patches. This implies the crucial involvement of both areas in face processing.

Infiltration at Yucca Mountain, Nevada, traced by 36Cl

International Nuclear Information System (INIS)

Norris, A.E.; Wolfsberg, K.; Gifford, S.K.; Bentley, H.W.; Elmore, D.

1987-04-01

Measurements of chloride and 36 Cl in soils from two locations near Yucca Mountain, Nevada, have been used to trace the infiltration of precipitation in this arid region. The results show that the 36 Cl fallout from nuclear weapons testing formed a well-defined peak at one location, with a maximum 0.5m below the surface. The structure of the 36 Cl bomb pulse at the other location was much more complex, and quantity of 36 Cl in the bomb pulse was 12 atoms 36 Cl/m 2 in the bomb pulse at the first location. The data indicate hydrologic activity subsequent to the 36 Cl bomb pulse fallout at one location, but none at the other location. 11 refs

Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

Directory of Open Access Journals (Sweden)

Katalin Susztak

2005-02-01

Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis

Directory of Open Access Journals (Sweden)

Nipin Sp

2018-06-01

Full Text Available Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36 is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1, and then interacting with transforming growth factor beta 1 (TGFβ1. CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin’s anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3 rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB, suggesting that nobiletin also acts through the CD36/ (STAT3/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.

46 CFR 151.50-36 - Argon or nitrogen.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Argon or nitrogen. 151.50-36 Section 151.50-36 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-36 Argon or nitrogen. (a) A cargo tank that contains argon or nitrogen and that has a maximum allowable working pressure of 172 kPa (25...

29 CFR 36.455 - Textbooks and curricular material.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Textbooks and curricular material. 36.455 Section 36.455 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 36.455 Textbooks...

30 CFR 36.50 - Tests of fuel tank.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tests of fuel tank. 36.50 Section 36.50 Mineral... Requirements § 36.50 Tests of fuel tank. The fuel tank shall be inspected and tested to determine whether: (a) It is fuel-tight, (b) the vent maintains atmospheric pressure within the tank, and (c) the vent and...

Laser oriented 36K for time reversal symmetry measurements

International Nuclear Information System (INIS)

Young, A.R.; Anderson, W.S.; Calaprice, F.P.; Cates, G.D.; Jones, G.L.; Krieger, D.A.; Vogelaar, R.B.

1995-01-01

We have produced very large nuclear alignments in radioactive 36 K (half-life 0.34 sec) through laser optical pumping techniques. The 36 K was created through (p,n) reactions using a 50 nA, 22 MeV proton beam, and a 3.3 atmosphere 36 Ar target. Measurements were made with the target cell at room temperature, when direct optical pumping produces nuclear orientation in the 36 K, and at elevated temperatures 160 degree C and 180 degree C where the 36 K is oriented through a combination of direct optical pumping and spin exchange. The fraction of the maximal nuclear alignment for the 180 degree C data was determined to be 0.46±0.07 stat±0.05 syst through measurements of the γ-ray anisotropy following positron decay. Roughly 10 5 or more decays of oriented 36 K occurred each second. The application of the superallowed decay of 36 K to measurements of time-reversal symmetry in β decay is discussed

Core labeling of adenovirus with EGFP

International Nuclear Information System (INIS)

Le, Long P.; Le, Helen N.; Nelson, Amy R.; Matthews, David A.; Yamamoto, Masato; Curiel, David T.

2006-01-01

The study of adenovirus could greatly benefit from diverse methods of virus detection. Recently, it has been demonstrated that carboxy-terminal EGFP fusions of adenovirus core proteins Mu, V, and VII properly localize to the nucleus and display novel function in the cell. Based on these observations, we hypothesized that the core proteins may serve as targets for labeling the adenovirus core with fluorescent proteins. To this end, we constructed various chimeric expression vectors with fusion core genes (Mu-EGFP, V-EGFP, preVII-EGFP, and matVII-EGFP) while maintaining expression of the native proteins. Expression of the fusion core proteins was suboptimal using E1 expression vectors with both conventional CMV and modified (with adenovirus tripartite leader sequence) CMV5 promoters, resulting in non-labeled viral particles. However, robust expression equivalent to the native protein was observed when the fusion genes were placed in the deleted E3 region. The efficient Ad-wt-E3-V-EGFP and Ad-wt-E3-preVII-EGFP expression vectors were labeled allowing visualization of purified virus and tracking of the viral core during early infection. The vectors maintained their viral function, including viral DNA replication, viral DNA encapsidation, cytopathic effect, and thermostability. Core labeling offers a means to track the adenovirus core in vector targeting studies as well as basic adenovirus virology

Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells.

Science.gov (United States)

Elumalai, Suma; Karunakaran, Udayakumar; Lee, In Kyu; Moon, Jun Sung; Won, Kyu Chang

2017-04-01

We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chlorine-36 validation Study at Yucca Mountain, Nevada

International Nuclear Information System (INIS)

J. Paces

2006-01-01

The amount, spatial distribution, and velocity of water percolating through the unsaturated zone (UZ) at Yucca Mountain, Nevada, are important issues for assessing the performance of the proposed deep geologic repository for spent nuclear fuel and high-level radioactive waste. To help characterize the nature and history of UZ flow, isotopic studies were initiated in 1995, using rock samples collected from the Miocene ash-flow tuffs in the Exploratory Studies Facility (ESF), an 8-km-long tunnel constructed along the north-south extent of the repository block, and the Enhanced Characterization of the Repository Block (ECRB) Cross Drift, a 2.5-km-long tunnel constructed across the repository block (Figure 1-1, Sources: Modified from DOE 2002 [Figure 1-14] and USBR 1996). Scientists from Los Alamos National Laboratory (LANL) analyzed for chlorine-36 ( 36 Cl) in salts leached from whole-rock samples collected from tunnel walls and subsurface boreholes, and scientists from the U.S. Geological Survey (USGS) analyzed for isotopes of oxygen, carbon, uranium, lead, thorium, and strontium in secondary minerals collected from subsurface fractures and lithophysal cavities. Elevated values for ratios of 36 Cl to total chloride ( 36 Cl/CL) at the level of the proposed repository indicated that small amounts of water carrying bomb-pulse 36 Cl (i.e., 36 Cl/Cl ratios greater than 1250 x 10 -15 resulting from 36 Cl produced by atmospheric testing of nuclear devices during the 1950s and early 1960s) had percolated through welded and nonwelded tuffs to depths of 200 to 300 meters (m) beneath the land surface over the past 50 years. Because of the implications of short travel times to the performance of the proposed repository, the U.S. Department of Energy (DOE)/Office of Civilian Radioactive Waste Management (OCRWM), Office of Repository Development (ORD), decided to verify the 36 Cl/Cl data with an independent validation study. DOE asked the USGS to design and implement a validation

Chlorine-36 alidation Study at Yucca Mountain, Nevada

Energy Technology Data Exchange (ETDEWEB)

J. Paces

2006-08-28

The amount, spatial distribution, and velocity of water percolating through the unsaturated zone (UZ) at Yucca Mountain, Nevada, are important issues for assessing the performance of the proposed deep geologic repository for spent nuclear fuel and high-level radioactive waste. To help characterize the nature and history of UZ flow, isotopic studies were initiated in 1995, using rock samples collected from the Miocene ash-flow tuffs in the Exploratory Studies Facility (ESF), an 8-km-long tunnel constructed along the north-south extent of the repository block, and the Enhanced Characterization of the Repository Block (ECRB) Cross Drift, a 2.5-km-long tunnel constructed across the repository block (Figure 1-1, Sources: Modified from DOE 2002 [Figure 1-14] and USBR 1996). Scientists from Los Alamos National Laboratory (LANL) analyzed for chlorine-36 ({sup 36}Cl) in salts leached from whole-rock samples collected from tunnel walls and subsurface boreholes, and scientists from the U.S. Geological Survey (USGS) analyzed for isotopes of oxygen, carbon, uranium, lead, thorium, and strontium in secondary minerals collected from subsurface fractures and lithophysal cavities. Elevated values for ratios of {sup 36}Cl to total chloride ({sup 36}Cl/CL) at the level of the proposed repository indicated that small amounts of water carrying bomb-pulse {sup 36}Cl (i.e., {sup 36}Cl/Cl ratios greater than 1250 x 10{sup -15} resulting from {sup 36}Cl produced by atmospheric testing of nuclear devices during the 1950s and early 1960s) had percolated through welded and nonwelded tuffs to depths of 200 to 300 meters (m) beneath the land surface over the past 50 years. Because of the implications of short travel times to the performance of the proposed repository, the U.S. Department of Energy (DOE)/Office of Civilian Radioactive Waste Management (OCRWM), Office of Repository Development (ORD), decided to verify the {sup 36}Cl/Cl data with an independent validation study. DOE asked the USGS

CD36 is required for myoblast fusion during myogenic differentiation

International Nuclear Information System (INIS)

Park, Seung-Yoon; Yun, Youngeun; Kim, In-San

2012-01-01

Highlights: ► CD36 expression was induced during myogenic differentiation. ► CD36 expression was localized in multinucleated myotubes. ► The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. ► Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

CD36 is required for myoblast fusion during myogenic differentiation

Energy Technology Data Exchange (ETDEWEB)

Park, Seung-Yoon [Department of Biochemistry, College of Medicine, Dongguk University and Medical Institute of Dongguk University, Gyeongju 780-714 (Korea, Republic of); Yun, Youngeun [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, In-San, E-mail: iskim@knu.ac.kr [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Biomedical Research Institute, Korea Institute Science and Technology, Seoul (Korea, Republic of)

2012-11-02

Highlights: Black-Right-Pointing-Pointer CD36 expression was induced during myogenic differentiation. Black-Right-Pointing-Pointer CD36 expression was localized in multinucleated myotubes. Black-Right-Pointing-Pointer The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. Black-Right-Pointing-Pointer Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

The symbiotic star H1-36

International Nuclear Information System (INIS)

Allen, D.A.

1983-01-01

Optical and infrared spectrophotometry is presented of the high-excitation emission-line star H1-36. The presence of a variable M giant is established: H1-36 may therefore be classified as a symbiotic star. The observations are interpreted in terms of the usual binary model for symbiotic stars, namely that an unseen star is heated by accretion of gas from its companion M giant. (author)

Distribution of {sup 36}Cl/Cl in a river-recharged aquifer: Implications for the fallout rate of bomb-produced {sup 36}Cl

Energy Technology Data Exchange (ETDEWEB)

Tosaki, Yuki, E-mail: tosaki@tac.tsukuba.ac.j [Sustainable Environmental Studies, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572 (Japan); Massmann, Gudrun [Institute of Geological Sciences, Department of Earth Sciences, Freie Universitaet Berlin, Malteserstrasse 74-100, 12249 Berlin (Germany); Tase, Norio [Sustainable Environmental Studies, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572 (Japan); Sasa, Kimikazu; Takahashi, Tsutomu [Tandem Accelerator Complex, Research Facility Center for Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan); Matsushi, Yuki [Department of Nuclear Engineering and Management, School of Engineering, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Tamari, Michiko [Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571 (Japan); Nagashima, Yasuo [Tandem Accelerator Complex, Research Facility Center for Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan); Bessho, Kotaro; Matsumura, Hiroshi [Radiation Science Center, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan)

2010-04-15

Distribution of {sup 36}Cl/Cl ratios in a river-recharged aquifer was investigated in the Oderbruch area, northeastern Germany. The aquifer is confined up to 3.5-4 km inland, where it changes to an unconfined condition. The {sup 36}Cl/Cl ratios in the confined area were in the range between 4.6 x 10{sup -14} and 23.1 x 10{sup -14}, showing a peak at 2-3 km away from the river. A plot of {sup 36}Cl/Cl vs. reciprocal Cl{sup -} concentrations indicated possible effect of the Cl{sup -} concentration variation on the observed {sup 36}Cl/Cl ratios. After accounting for this effect, the estimated {sup 36}Cl fallout rates for the last 30 yrs show reasonable agreement with the Dye-3 data and the mid-latitude background value. The results suggest that a local {sup 36}Cl fallout curve can be constructed from groundwater when dispersive mixing is of minor importance.

/sup 36/Cl and /sup 10/Be profiles in Greenland ice: Dating and production rate variations

Energy Technology Data Exchange (ETDEWEB)

Elmore, D; Conard, N J; Kubik, P W; Gove, H E; Wahlen, M; Beer, J; Suter, M

1987-11-01

Concentrations of the cosmogenic radioistopes /sup 36/Cl and /sup 10/Be have been measured in the top portion of the 1966 Camp Century deep ice core using tandem accelerator mass spectrometry. The primary motivations were to look for correlations with solar activity and to test the possibility that the ratio of /sup 10/Be to /sup 36/Cl would provide a means for dating old ice. An increase in each radioisotope is seen during the Maunder sunspot minimum (1650 to 1715 A.D.), as expected, but there are fluctuations of a factor of 2 or more over short time periods and a possible correlation with solar activity is apparent only when the data is mathematically smoothed. Variations of the /sup 10/Be//sup 36/Cl ratio by about a factor of five are observed which means that dating of ice by single /sup 10/Be//sup 36/Cl measurements covering the precipitation of only a few years will not be possible.

28 CFR 32.36 - Payment and repayment.

Science.gov (United States)

2010-07-01

....36 Judicial Administration DEPARTMENT OF JUSTICE PUBLIC SAFETY OFFICERS' DEATH, DISABILITY, AND EDUCATIONAL ASSISTANCE BENEFIT CLAIMS Educational Assistance Benefit Claims § 32.36 Payment and repayment. (a... from the eligible educational institution as to the claimant's full-, three-quarter-, half-, or less...

CD36 Modulates Fasting and Preabsorptive Hormone and Bile Acid Levels.

Science.gov (United States)

Shibao, Cyndya A; Celedonio, Jorge E; Tamboli, Robyn; Sidani, Reem; Love-Gregory, Latisha; Pietka, Terri; Xiong, Yanhua; Wei, Yan; Abumrad, Naji N; Abumrad, Nada A; Flynn, Charles Robb

2018-05-01

Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM). Obese African American (AA) women carriers of the G allele of rs3211938 (G/T) and weight-matched noncarriers (T/T) were studied before and after a HFM. Two-center study. Obese AA women. HFM. Early preabsorptive responses (10 minutes) and extended excursions in plasma hormones [C-peptide, insulin, incretins, ghrelin fibroblast growth factor (FGF)19, FGF21], BAs, and serum lipoproteins (chylomicrons, very-low-density lipoprotein) were determined. At fasting, G-allele carriers had significantly reduced cholesterol and glycodeoxycholic acid and consistent but nonsignificant reductions of serum lipoproteins. Levels of GLP-1 and pancreatic polypeptide (PP) were reduced 60% to 70% and those of total BAs were 1.8-fold higher. After the meal, G-allele carriers displayed attenuated early (-10 to 10 minute) responses in insulin, C-peptide, GLP-1, gastric inhibitory peptide, and PP. BAs exhibited divergent trends in G allele carriers vs noncarriers concomitant with differential FGF19 responses. CD36 plays an important role in the preabsorptive hormone and BA responses that coordinate brain and gut regulation of energy metabolism.

Comparing 36.5°C with 37°C for human embryo culture: a prospective randomized controlled trial.

Science.gov (United States)

Fawzy, Mohamed; Emad, Mai; Gad, Mostafa A; Sabry, Mohamed; Kasem, Hesham; Mahmoud, Manar; Bedaiwy, Mohamed A

2018-03-27

This prospective, double-blind, randomized controlled trial was designed to evaluate the efficacy of a culture temperature of 36.5°C versus 37°C on human embryo development in vitro. A total of 412 women undergoing IVF were randomized to two groups: the oocytes and embryos of the intervention group were cultured at 36.5°C; those of the control group were cultured at 37°C. Although no significant effect of culture temperature was observed on pregnancy or implantation rates, differences were found in embryo development. Embryo culture at 36.5°C was associated with a significantly higher cleavage rate (OR 1.6, 95% CI 1.03 to 2.51), but a lower fertilization rate, fewer high-quality embryos on day 3, a lower blastocyst formation rate on day 5, and fewer high-quality and cryopreserved blastocysts (OR 0.87, 95% CI 0.78 to 0.98), (OR 0.60, 95% CI 0.53 to 0.69), (OR 0.85, 95% CI 0.75 to 0.97), (OR 0.5, 95% CI 0.44 to 0.56) and (OR 0.77, 95% CI 0.68 to 0.88), respectively, compared with 37°C. On the basis of these results, and in the absence of data on the optimal temperature for each stage of embryo development in vitro, we recommend continuation of the use of 37°C for human embryo culture. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

THE ORIGIN OF ASTEROID 101955 (1999 RQ36)

International Nuclear Information System (INIS)

Campins, Humberto; Morbidelli, Alessandro; Tsiganis, Kleomenis; De Leon, Julia; Licandro, Javier; Lauretta, Dante

2010-01-01

Near-Earth asteroid (NEA) 101955 (1999 RQ 36 ; henceforth RQ36) is especially accessible to spacecraft and is the primary target of NASA's OSIRIS-REx sample return mission; it is also a potentially hazardous asteroid. We combine dynamical and spectral information to identify the most likely main-belt origin of RQ36 and we conclude that it is the Polana family, located at a semimajor axis of about 2.42 AU. We also conclude that the Polana family may be the most important inner-belt source of low-albedo NEAs. These conclusions are based on the following results. (1) Dynamical evidence strongly favors an inner-belt, low-inclination (2.15 AU 0 ) origin, suggesting the ν 6 resonance as the preferred (95% probability) delivery route. (2) This region is dominated by the Nysa and Polana families. (3) The Polana family is characterized by low albedos and B-class spectra or colors, the same albedo and spectral class as RQ36. (4) The Sloan Digital Sky Survey colors show that the Polana family is the branch of the Nysa-Polana complex that extends toward the ν 6 resonance; furthermore, the Polana family has delivered objects of the size of RQ36 and larger into the ν 6 resonance. (5) A quantitative comparison of visible and near-infrared spectra does not yield a unique match for RQ36; however, it is consistent with a compositional link between RQ36 and the Polana family.

Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

Science.gov (United States)

Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

2015-02-01

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

Directory of Open Access Journals (Sweden)

Anton V Borovjagin

Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

Cl-36 in polar ice, rainwater and seawater

Science.gov (United States)

Finkel, R. C.; Nishiizumi, K.; Elmore, D.; Ferraro, R. D.; Gove, H. E.

1980-01-01

Concentrations of the cosmogenic radioisotope Cl-36 in Antarctic ice, rain, and an upper limit of the seawater value are determined using van de Graaff accelerator high energy mass spectrometry. Cl-36 concentrations in Antarctic ice range between 2.5 to 8.7 x 10 to the 6th atoms Cl-36/kg, while those concentrations in samples collected at the Alan Hills ice field locations where meteorites have been brought to the surface by glacial flow and ablation are found to vary by more than a factor of three. This variation is attributed either to the effects of atmospheric mixing and scavenging or to radioactive decay in old ice. The Cl-36 concentration found in a present sample of rainwater is much lower than that reported in samples collected in the early 1960's, suggesting the occurrence of a decrease in the concentration of atmospheric Cl-36 derived from nuclear weapons tests over this time period.

Beta-delayed proton and alpha emission from 36K

International Nuclear Information System (INIS)

Ewan, G.T.; Hagberg, E.; Hardy, J.C.; Jonson, B.; Mattsson, S.; Tidemand-Petersson, P.

1980-01-01

Protons and α-particles emitted from levels in 36 Ar following the β-decay of 36 K have been measured. Proton transitions were found from levels at 9217, 9493 and 9870 keV in 36 Ar and α-transitions from levels at 8860, 8890, 9680 and 10548 keV. Seven previously unreported β-transitions to highly excited states in 36 Ar have been identified. The assignments of spins and parities to the particle emitting levels are discussed. (orig.)

The Origin of Asteroid 101955 (1999 RQ36)

Science.gov (United States)

Campins, Humberto; Morbidelli, A.; de León, J.; Tsiganis, K.; Licandro, J.

2010-10-01

Near-Earth asteroid 101955 (1999 RQ36; henceforth RQ36) is particularly interesting. It's especially accessible to spacecraft and is the primary target of NASA's OSIRIS-REx sample return mission; it's also a potentially hazardous asteroid (Milani et al. 2009). We combine dynamical and spectral information to identify the most likely main-belt origin of RQ36 and conclude that it is the Polana family, located at a semi-major axis of about 2.42 AU (our approach is similar to that used by de León et al. (2010) to link 3200 Phaethon, parent body of the Geminids, to 2 Pallas). Our conclusion is based on the following results. a) Dynamical evidence favors strongly an inner-belt, low-inclination (2.15 AU families (families are favored over single objects because small fragments have already been produced). c) The Polana family is characterized by low albedos and B-class spectra or colors (Bus and Binzel 2002), which is the same spectral class, and albedo, as RQ36. d) The SDSS colors show that the Polana family is the branch of the Nysa-Polana complex that extends toward the ν6 resonance; furthermore, Polana has delivered objects the size of RQ36 and larger into the ν6 resonance. e) RQ36 is retrograde, consistent with the Yarkovsky effect having moved it inward from Polana into the ν6. f) A quantitative comparison of visible and near-infrared spectra does not yield a unique match for RQ36; however, it is consistent with a compositional link between RQ36 and the Polana family. Finally, the Polana Family is likely the most important inner-belt source of low albedo Near-Earth asteroids. This work was supported by NASA and NSF.

38 CFR 36.4408 - Delegation of authority.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Delegation of authority. 36.4408 Section 36.4408 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....4408 Delegation of authority. (a) Except as hereinafter provided, each employee of the Department of...

38 CFR 36.4345 - Delegation of authority.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Delegation of authority. 36.4345 Section 36.4345 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Delegation of authority. (a) Except as hereinafter provided, each employee of the Department of Veterans...

29 CFR 501.36 - Caption of proceeding.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Caption of proceeding. 501.36 Section 501.36 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF THE...

29 CFR 502.36 - Caption of proceeding.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Caption of proceeding. 502.36 Section 502.36 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF THE...

36Cl measurements of Hiroshima concrete samples

International Nuclear Information System (INIS)

Matsuhiro, T.; Nagashima, Y.; Seki, R.; Takahashi, T.

2002-01-01

The 36 Cl AMS studies are reported. A new steps of procedure of a sample preparation is developed and a tremendous reduction of sulphur background has been achieved. The 36 Cl contents of two atomic bombed concrete samples, old Hiroshima Bank one and Gokoku Shrine one, have been measured as a function of 36 Cl to Cl ratio by the Tsukuba AMS system. The 36 Cl to Cl ratio of the old Hiroshima Bank sample shows very nice agreement with the result of γ measurement of 152 Eu. Otherwise, the ratio is about 20% smaller than an estimation by the DS86 dosimetry system. A result of the Gokoku Shrine sample is also smaller than a depth profile estimation by the same DS86. It might be clear that the DS86 has a tendency of overestimation. It seems that a calculation method and/or the parameters used in the calculation are requested to be improved. (author)

Psychometric Properties of the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36) in the United States.

Science.gov (United States)

Peipert, John D; Bentler, Peter M; Klicko, Kristi; Hays, Ron D

2018-04-01

The Centers for Medicare & Medicaid Services require that dialysis patients' health-related quality of life be assessed annually. The primary instrument used for this purpose is the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36), which includes the SF-12 as its generic core and 3 kidney disease-targeted scales: Burden of Kidney Disease, Symptoms and Problems of Kidney Disease, and Effects of Kidney Disease. Despite its broad use, there has been limited evaluation of KDQOL-36's psychometric properties. Secondary analyses of data collected by the Medical Education Institute to evaluate the reliability and factor structure of the KDQOL-36 scales. KDQOL-36 responses from 70,786 dialysis patients in 1,381 US dialysis facilities that permitted data analysis were collected from June 1, 2015, through May 31, 2016, as part of routine clinical assessment. We assessed the KDQOL-36 scales' internal consistency reliability and dialysis facility-level reliability using coefficient alpha and 1-way analysis of variance. We evaluated the KDQOL-36's factor structure using item-to-total scale correlations and confirmatory factor analysis. Construct validity was examined using correlations between SF-12 and KDQOL-36 scales and "known groups" analyses. Each of the KDQOL-36's kidney disease-targeted scales had acceptable internal consistency reliability (α=0.83-0.85) and facility-level reliability (r=0.75-0.83). Item-scale correlations and a confirmatory factor analysis model evidenced the KDQOL-36's original factor structure. Construct validity was supported by large correlations between the SF-12 Physical Component Summary and Mental Component Summary (r=0.40-0.52) and the KDQOL-36 scale scores, as well as significant differences on the scale scores between patients receiving different types of dialysis, diabetic and nondiabetic patients, and patients who were employed full-time versus not. Use of secondary data from a clinical registry. The study provides

36Cl accelerator mass spectrometry with a bespoke instrument

International Nuclear Information System (INIS)

Wilcken, K.M.; Freeman, S.P.H.T.; Schnabel, C.; Binnie, S.A.; Xu, S.; Phillips, R.J.

2013-01-01

Cosmogenic 36 Cl analysis by accelerator mass spectrometry (AMS) is a valuable environmental and geological sciences research tool. Overcoming the stable nuclide 36 S isobar interfering with measurement is challenging, however. Traditionally this has required large accelerators, but following recent technical advances it is now possible with ∼30 MeV ion energies. Consequently 5 MV or even smaller modern bespoke spectrometers are now 36 Cl-capable, increasing accessibility and promoting wider and more varied 36 Cl use. However, the technical ability to identify 36 Cl ions is quite distinct from demonstrated high-performance AMS. Such is the theme of this paper. We present a systematic analysis of the accurate measurement of sample radioisotope relative to the stable chlorine, the normalisation of the measured ratio and correction for remaining 36 S interference, all combined with the use of stable-isotope dilution to determine sample Cl concentration to begin with. We conclude by showing that repeated analyses support our claims for routine 3% 36 Cl-AMS data. Accordingly, the modest SUERC spectrometer well competes with the performance of larger longer-established instruments, and the results may be quite generic for modern bespoke instruments.

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

Science.gov (United States)

Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

2016-07-01

Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

34 CFR 668.36 - Social security number.

Science.gov (United States)

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Social security number. 668.36 Section 668.36 Education... Islands, and the Republic of Palau, the Secretary attempts to confirm the social security number a student... Security Administration. If the Social Security Administration confirms that number, the Secretary notifies...

48 CFR 31.205-36 - Rental costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rental costs. 31.205-36... CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-36 Rental costs. (a) This subsection is applicable to the cost of renting or leasing real or...

Atmospheric production rate of {sup 36}Cl

Energy Technology Data Exchange (ETDEWEB)

Parrat, Y.; Hajdas, W.; Baltensperger, U.; Synal, H.A.; Kubik, P.W.; Gaeggeler, H.W. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Suter, M. [Eidgenoessische Technische Hochschule, Zurich (Switzerland)

1997-09-01

Using experimental cross sections, a new calculation of the atmospheric production rate of {sup 36}Cl was carried out. A mean production rate of 20 atoms m{sup -2}s{sup -1} was obtained, which is lower than mean {sup 36}Cl deposition rates. (author) 2 figs., 7 refs.

12 CFR 3.6 - Minimum capital ratios.

Science.gov (United States)

2010-01-01

... should have well-diversified risks, including no undue interest rate risk exposure; excellent control... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Minimum capital ratios. 3.6 Section 3.6 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE...

14 CFR 1260.36 - Travel and transportation.

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2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Travel and transportation. 1260.36 Section... AGREEMENTS General Provisions § 1260.36 Travel and transportation. Travel and Transportation October 2000 (a... international air transportation of personnel and property to the extent that service by those carriers is...

40 CFR 60.36e - Inspection guidelines.

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2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Inspection guidelines. 60.36e Section...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Hospital/Medical/Infectious Waste Incinerators § 60.36e Inspection guidelines. (a) For approval, a State plan shall...

27 CFR 5.36 - Name and address.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Name and address. 5.36 Section 5.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for...

40 CFR 406.36 - Pretreatment standards for new sources.

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2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 406.36 Section 406.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Normal Wheat Flour Milling Subcategory § 406.36...

18 CFR 401.36 - Water supply projects-Conservation requirements.

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2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Water supply projects-Conservation requirements. 401.36 Section 401.36 Conservation of Power and Water Resources DELAWARE RIVER BASIN... Compact § 401.36 Water supply projects—Conservation requirements. Maximum feasible efficiency in the use...

X-36 arrival at Dryden

Science.gov (United States)

1996-01-01

NASA and McDonnell Douglas Corporation (MDC) personnel steady the X-36 Tailless Fighter Agility Research Aircraft following arrival at NASA Dryden Flight Research Center, Edwards, California, on July 2, 1996. The aircraft is being hoisted out of it's shipping crate. The NASA/Boeing X-36 Tailless Fighter Agility Research Aircraft program successfully demonstrated the tailless fighter design using advanced technologies to improve the maneuverability and survivability of possible future fighter aircraft. The program met or exceeded all project goals. For 31 flights during 1997 at the Dryden Flight Research Center, Edwards, California, the project team examined the aircraft's agility at low speed / high angles of attack and at high speed / low angles of attack. The aircraft's speed envelope reached up to 206 knots (234 mph). This aircraft was very stable and maneuverable. It handled very well. The X-36 vehicle was designed to fly without the traditional tail surfaces common on most aircraft. Instead, a canard forward of the wing was used as well as split ailerons and an advanced thrust-vectoring nozzle for directional control. The X-36 was unstable in both pitch and yaw axes, so an advanced, single-channel digital fly-by-wire control system (developed with some commercially available components) was put in place to stabilize the aircraft. Using a video camera mounted in the nose of the aircraft and an onboard microphone, the X-36 was remotely controlled by a pilot in a ground station virtual cockpit. A standard fighter-type head-up display (HUD) and a moving-map representation of the vehicle's position within the range in which it flew provided excellent situational awareness for the pilot. This pilot-in-the-loop approach eliminated the need for expensive and complex autonomous flight control systems and the risks associated with their inability to deal with unknown or unforeseen phenomena in flight. Fully fueled the X-36 prototype weighed approximately 1,250 pounds

48 CFR 36.517 - Layout of work.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Layout of work. 36.517... CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 36.517 Layout of work. The contracting officer shall insert the clause at 52.236-17, Layout of Work, in solicitations and contracts when...

26 CFR 36.3121(l)-0 - Introduction.

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2010-04-01

... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Introduction. 36.3121(l)-0 Section 36.3121(l)-0 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Introduction. (a) The regulations in this part deal with the circumstances under which a domestic corporation...

19 CFR 144.36 - Withdrawal for transportation.

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2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

34 CFR 200.36 - Communication with parents.

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2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Communication with parents. 200.36 Section 200.36... with parents. (a) Throughout the school improvement process, the State, LEA, or school must communicate with the parents of each child attending the school. (b) The State, LEA, or school must ensure that...

10 CFR 36.61 - Inspection and maintenance.

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2010-01-01

... emergency source return control required by § 36.31(c). (7) Leak-tightness of systems through which pool water circulates (visual inspection). (8) Operability of the heat and smoke detectors and extinguisher... for radioactive contamination in pool water required by § 36.59(b) using a radiation check source, if...

Isolation and sequence analysis of pCS36-4CPA, a small plasmid from Citrobacter sp. 36-4CPA.

Science.gov (United States)

Zharikova, Natalia V; Iasakov, Timur R; Bumazhkin, Boris K; Patutina, Ekaterina O; Zhurenko, Evgeniia I; Korobov, Vladislav V; Sagitova, Alina I; Kuznetsov, Boris B; Markusheva, Tatiana V

2018-05-01

A small plasmid designated pCS36-4CPA with a size of 5217 base pairs and G-C content of 50.74% was isolated from Citrobacter sp. 36-4CPA. The origin of replication ( ori ) of the plasmid was identified as a region of about 800 bp in length with an identity of 67.1% to the ColE1 plasmid at the nucleotide level. The replication region contained typical elements of ColE1-like plasmids: RNA I and RNA II with their corresponding -10 and -35 boxes, a single-strand initiation site ( ssi ), and a lagging-strand termination site ( terH ). As seen in other ColE1-like plasmids, pCS36-4CPA carried mobilisation machinery that include mobABCD genes but it did not possess the rom gene. Analysis of the multimer resolution site ( mrs ) was performed and XerC and XerD binding sites were identified. Also, the 70-nt transcript Rcd of pCS36-4CPA was predicted and similarity of the transcript's secondary structure with those of the ColE1-family was shown. The cargo module of pCS36-4CPA contained three open reading frames (ORFs). Two of them (ORF5 and ORF6) showed no significant homology to any known gene sequences but contained putative THAP DNA-binding (DBD) and type II restriction endonuclease Eco O109I domains. The seventh open reading frame (ORF7) encodes YhdJ-like DNA modification methylase. The region highly homologous to pCS36-4CPA was found in the Salmonella phage SE2 genome.

50 CFR 36.32 - Taking of fish and wildlife.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Taking of fish and wildlife. 36.32 Section 36.32 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM ALASKA NATIONAL WILDLIFE REFUGES Other Refuge Uses § 36.32...

41 CFR 50-204.36 - Radiation standards for mining.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Radiation standards for mining. 50-204.36 Section 50-204.36 Public Contracts and Property Management Other Provisions Relating to... CONTRACTS Radiation Standards § 50-204.36 Radiation standards for mining. (a) For the purpose of this...

Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

Science.gov (United States)

Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

2017-07-01

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

A hydrochemical investigation using 36Cl/Cl in groundwaters

International Nuclear Information System (INIS)

Metcalfe, Richard

2003-03-01

This report describes 36 Cl studies which were undertaken during the H14 financial year. The results of this study suggest that, if 36 Cl data can be obtained for groundwaters at spatial scales comparable with, or smaller than, the spatial scales of the variability in in-situ 36 Cl production in the host rock, the data could potentially be useful for interpreting groundwater origins and flow paths. Four groundwater samples and one onsen water sample from the Tono area were collected for 36 Cl analysis. The groundwater samples came from boreholes MSB-2 and MSB-4 in the MIU Construction Site, whereas the onsen water was taken from Oniiwa Onsen (Komatsuya). In addition, a single sample from borehole HDB-1 at Horonobe was also sent for analysis. Supporting rock chemical data and wireline geophysical data have also been evaluated, to provide a basis for interpreting the 36 Cl data. Rock analyses and spectral gamma wireline data were used to estimate theoretical limiting equilibrium 36 Cl/Cl ratios in the rock. These have been compared with the compositions measured for groundwater samples, enabling a judgement to be made as to: whether the waters have resided for long enough in the rock to approach equilibrium (> c. 1.5 Ma); the spatial scales of mixing of the dissolved Cl in the groundwater. The estimates of in-situ 36 Cl/Cl production made with the newly available rock chemical data and wireline geophysical data have enabled 36 Cl data obtained previously from MIU-4, KNA-6 and DH-12 during H12 and H13 to be interpreted more confidently. In particular it seems that 36 Cl/Cl ratios measured previously in groundwater samples from MIU-4 are not in equilibrium with in-situ production in the granite. Furthermore, they imply that the Cl is homogenised, at least on the scale of the upper half of borehole. In contrast, the data from DH-12 imply that the Cl could be in equilibrium with in-situ 36 Cl production in the granite, which would be consistent with a relatively long

38 CFR 36.4321 - Service of process.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Service of process. 36...) LOAN GUARANTY Guaranty or Insurance of Loans to Veterans With Electronic Reporting § 36.4321 Service of process. (a) In any legal or equitable proceeding to which the Secretary is a party (including probate and...

27 CFR 11.36 - Termination of franchise.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Termination of franchise. 11.36 Section 11.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... franchise. When an industry member has sold products for cash or credit to one of its wholesalers and the...

36-Item Short Form Survey (SF-36) Versus Gait Speed As Predictor of Preclinical Mobility Disability in Older Women: The Women's Health Initiative.

Science.gov (United States)

Laddu, Deepika R; Wertheim, Betsy C; Garcia, David O; Woods, Nancy F; LaMonte, Michael J; Chen, Bertha; Anton-Culver, Hoda; Zaslavsky, Oleg; Cauley, Jane A; Chlebowski, Rowan; Manson, JoAnn E; Thomson, Cynthia A; Stefanick, Marcia L

2018-04-01

To compare the value of clinically measured gait speed with that of the self-reported Medical Outcomes Study 36-item Short-Form Survey Physical Function Index (SF-36 PF) in predicting future preclinical mobility disability (PCMD) in older women. Prospective cohort study. Forty clinical centers in the United States. Women aged 65 to 79 enrolled in the Women's Health Initiative Clinical Trials with gait speed and SF-36 assessed at baseline (1993-1998) and follow-up Years 1, 3, and 6 (N = 3,587). Women were categorized as nondecliners or decliners based on changes (from baseline to Year 1) in gait speed and SF-36 PF scores. Logistic regression models were used to estimate incident PCMD (gait speed 36 PF with that of measured gait speed. Slower baseline gait speed and lower SF-36 PF scores were associated with higher adjusted odds of PCMD at Years 3 and 6 (all P 36, decliners were 1.42 times as likely to have developed PCMD by Year 3 and 1.49 times as likely by Year 6. Baseline gait speed (AUC = 0.713) was nonsignificantly better than SF-36 (AUC = 0.705) at predicting PCMD over 6 years (P = .21); including measures at a second time point significantly improved model discrimination for predicting PCMD (all P 36 PF did, although the results may be limited given that gait speed served as a predictor and to define the PCMD outcome. Nonetheless, monitoring trajectories of change in mobility are better predictors of future mobility disability than single measures. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

25 CFR 36.10 - Standard I-Philosophy and goals.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Standard I-Philosophy and goals. 36.10 Section 36.10... § 36.10 Standard I—Philosophy and goals. (a) Each school shall develop a written mission statement and philosophy of education that addresses the accumulation of knowledge and development of skills, interests...

7 CFR 900.36 - Words in the singular form.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Words in the singular form. 900.36 Section 900.36 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Marketing Orders § 900.36 Words in the singular form. Words in this subpart in the singular form shall be...

Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

Directory of Open Access Journals (Sweden)

Zhao Yarui

2011-01-01

Full Text Available Abstract Background Sphingomyelin synthase 2 (SMS2 contributes to de novo sphingomyelin (SM biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. Methods The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR and protein level examination (SMS activity assay. Result We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2 or GFP cDNA (AdV-GFP. On day six after intravenous infusion of 2 × 1011 particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p Conclusions Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.

Ad35 and ad26 vaccine vectors induce potent and cross-reactive antibody and T-cell responses to multiple filovirus species

NARCIS (Netherlands)

Zahn, Roland; Gillisen, Gert; Roos, Anna; Koning, Marina; van der Helm, Esmeralda; Spek, Dirk; Weijtens, Mo; Grazia Pau, Maria; Radošević, Katarina; Weverling, Gerrit Jan; Custers, Jerome; Vellinga, Jort; Schuitemaker, Hanneke; Goudsmit, Jaap; Rodríguez, Ariane

2012-01-01

Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was

Sensor-augmented pump therapy at 36 months

DEFF Research Database (Denmark)

Schmidt, Signe; Nørgaard, Kirsten

2012-01-01

This follow-up study investigates the metabolic and psychosocial effects of sensor-augmented pump (SAP) therapy in adults with type 1 diabetes 36 months after therapy start.......This follow-up study investigates the metabolic and psychosocial effects of sensor-augmented pump (SAP) therapy in adults with type 1 diabetes 36 months after therapy start....

7 CFR 868.36 - Loss of identity.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Loss of identity. 868.36 Section 868.36 Agriculture... identity. (a) Lots. The identity of a packaged lot, bulk lot, or sublot of a commodity shall be considered... or location after the time of original inspection, unless the identity is preserved; or (2) More...

Fiber mediated receptor masking in non-infected bystander cells restricts adenovirus cell killing effect but promotes adenovirus host co-existence.

Directory of Open Access Journals (Sweden)

Johan Rebetz

Full Text Available The basic concept of conditionally replicating adenoviruses (CRAD as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI, and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses.

Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential.

Science.gov (United States)

El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio

2012-10-01

In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

X-36 during First Flight

Science.gov (United States)

1997-01-01

The remotely-piloted X-36 Tailless Fighter Agility Research Aircraft climbs out from Rogers Dry Lake at the Dryden Flight Research Center on its first flight in May 1997. The aircraft flew for five minutes and reached an altitude of approximately 4,900 feet. The NASA/Boeing X-36 Tailless Fighter Agility Research Aircraft program successfully demonstrated the tailless fighter design using advanced technologies to improve the maneuverability and survivability of possible future fighter aircraft. The program met or exceeded all project goals. For 31 flights during 1997 at the Dryden Flight Research Center, Edwards, California, the project team examined the aircraft's agility at low speed / high angles of attack and at high speed / low angles of attack. The aircraft's speed envelope reached up to 206 knots (234 mph). This aircraft was very stable and maneuverable. It handled very well. The X-36 vehicle was designed to fly without the traditional tail surfaces common on most aircraft. Instead, a canard forward of the wing was used as well as split ailerons and an advanced thrust-vectoring nozzle for directional control. The X-36 was unstable in both pitch and yaw axes, so an advanced, single-channel digital fly-by-wire control system (developed with some commercially available components) was put in place to stabilize the aircraft. Using a video camera mounted in the nose of the aircraft and an onboard microphone, the X-36 was remotely controlled by a pilot in a ground station virtual cockpit. A standard fighter-type head-up display (HUD) and a moving-map representation of the vehicle's position within the range in which it flew provided excellent situational awareness for the pilot. This pilot-in-the-loop approach eliminated the need for expensive and complex autonomous flight control systems and the risks associated with their inability to deal with unknown or unforeseen phenomena in flight. Fully fueled the X-36 prototype weighed approximately 1,250 pounds. It was 19

Effect of alkali doping on the structural stability of solid C36

International Nuclear Information System (INIS)

Zettl, A.; Piskoti, C.; Grossman, Jeffery C.; Cohen, Marvin L.; Louie, Steven G.

1999-01-01

We demonstrate that alkali-doping C 36 solids causes the C 36 cage molecules to be bonded less strongly to each other in the solid. Laser irradiation mass spectroscopy experiments show that for pure C 36 solid, no isolated C 36 subunits are observed in the ablated material, while for potassium-doped C 36 , isolated C 36 molecules are readily produced by laser irradiation. Theoretical modelling shows that charge transfer from the alkali to the C 36 molecules greatly hinders C 36 dimer formation, consistent with these experiments. (c) 1999 American Institute of Physics

Immunization with a Novel Human type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models.

Science.gov (United States)

Guo, Qiang; Chan, Jasper Fuk-Woo; Poon, Vincent Kwok-Man; Wu, Shipo; Chan, Chris Chung-Sing; Hou, Lihua; Yip, Cyril Chik-Yan; Ren, Changpeng; Cai, Jian-Piao; Zhao, Mengsu; Zhang, Anna Jinxia; Song, Xiaohong; Chan, Kwok-Hung; Wang, Busen; Kok, Kin-Hang; Wen, Yanbo; Yuen, Kwok-Yung; Chen, Wei

2018-03-29

Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and non-vector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic as they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of two previously reported adenovirus-vectored ZIKV vaccines were performed using non-lethal animal models and/or non-epidemic ZIKV strain. We constructed and evaluated two human adenovirus-5-vectored vaccines containing the ZIKV premembrane-envelope(Ad5-Sig-prM-Env) and envelope(Ad5-Env) proteins, respectively, in multiple non-lethal and lethal animal models using epidemic ZIKV strains. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood/tissue viral loads than controls(Panimal models, Ad5-Sig-prM-Env-vaccinated mice had significantly(P<0.05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower(undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.

Charge-exchange reactions on 36 S

International Nuclear Information System (INIS)

Fifield, L.K.; Catford, W.N.; Orr, N.A.; Ophel, T.R.; Etchegoyen, A.; Etchegoyen, M.C.

1992-11-01

A series of charge-exchange reactions on 36 S targets have been investigated at beam energies ∼7 MeV/A. Pronounced selectivities to different final states in 36 P are observed which depend on the projectile employed. An interpretation of the data in terms of one- and two-step pictures of the reaction mechanism is presented. At least two, and probably all, of the reactions have a significant 1-step contribution to the reaction mechanism at these energies. 22 refs., 5 tabs., 5 figs

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

International Nuclear Information System (INIS)

Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

2016-01-01

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

Energy Technology Data Exchange (ETDEWEB)

Tomono, Takumi [Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Kajita, Masahiro [Laboratory of Molecular Pharmaceutics and Technology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Yano, Kentaro [Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Ogihara, Takuo, E-mail: togihara@takasaki-u.ac.jp [Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan)

2016-08-05

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.

Prevalence of spinocerebellar ataxia 36 in a US population.

Science.gov (United States)

Valera, Juliana M; Diaz, Tatyana; Petty, Lauren E; Quintáns, Beatriz; Yáñez, Zuleima; Boerwinkle, Eric; Muzny, Donna; Akhmedov, Dmitry; Berdeaux, Rebecca; Sobrido, Maria J; Gibbs, Richard; Lupski, James R; Geschwind, Daniel H; Perlman, Susan; Below, Jennifer E; Fogel, Brent L

2017-08-01

To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States. A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the NOP56 gene. Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of NOP56 in 4 index cases. These 4 SCA36-positive families comprised 2 distinct ethnic groups: white (European) (2) and Asian (Japanese [1] and Vietnamese [1]). Individuals affected by SCA36 exhibited typical clinical features with gait ataxia and age at onset ranging between 35 and 50 years. Patients also suffered from ataxic or spastic limbs, altered reflexes, abnormal ocular movement, and cognitive impairment. In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort.

Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2

OpenAIRE

Glaunsinger, Britt A.; Weiss, Robert S.; Lee, Siu Sylvia; Javier, Ronald

2001-01-01

Adenovirus type 9 (Ad9) is distinct among human adenoviruses because it elicits solely mammary tumors in animals and its primary oncogenic determinant is the E4 region-encoded ORF1 (E4-ORF1) protein. We report here that the PDZ domain-containing protein ZO-2, which is a candidate tumor suppressor protein, is a cellular target for tumorigenic Ad9 E4-ORF1 but not for non-tumorigenic wild-type E4-ORF1 proteins encoded by adenovirus types 5 and 12. Complex formation was mediated by the C-terminal...

Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

Science.gov (United States)

Zhang, Shuxiao; Wang, Wei; Li, Juan; Cheng, Ke; Zhou, Jingjing; Zhu, Dan; Yang, Deyu; Liang, Zihong; Fang, Liang; Liao, Li; Xie, Peng

2016-02-15

CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders. Copyright © 2015. Published by Elsevier B.V.

Cl36 and the age of the cosmic rays

International Nuclear Information System (INIS)

Casse, M.; Goret, P.; Regnier, S.

1975-01-01

The radioactive isotope 36 Cl (tau=γx3.10 5 y) is used as a time reference for the propagation of cosmic rays. New measurements of the production cross section of 36 Cl in Ti and Fe at 24GeV will be presented. A critical analysis of the cross sections leads to an estimate of the ratio 36 Cl/Cl=0.030+0.007 in the arriving cosmic rays. The comparison between the expected abundance of Cl in the arriving cosmic rays and the observations tend to support the decay of 36 Cl. The inferred cosmic ray confinement time is about 10 6 y [fr

E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

Directory of Open Access Journals (Sweden)

Yueting Zheng

2016-01-01

Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Science.gov (United States)

2010-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

A convenient preparation of 9 H -carbazole-3,6-dicarbonitrile and 9 H -carbazole-3,6-dicarboxylic acid

KAUST Repository

Weselinski, Lukasz Jan

2014-01-23

A catalytic, high yielding and scalable procedure for the synthesis of 9H-carbazole-3,6-dicarbonitrile has been developed. Subsequent hydrolysis of the dinitrile in the presence of a catalytic copper species (i.e., CuI) yields 9H-carbazole-3,6-dicarboxylic acid. Both compounds are versatile and fine-tunable organic building blocks and therefore offer potential in material science, medicinal and supramolecular chemistry. © Georg Thieme Verlag Stuttgart New York.

38 CFR 36.4709 - Notice of servicer's identity.

Science.gov (United States)

2010-07-01

... identity. 36.4709 Section 36.4709 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... servicer's identity. (a) Notice requirement. When the Secretary makes, increases, extends, renews, sells... the identity of the servicer of the loan. The Director of FEMA has designated the insurance provider...

48 CFR 36.506 - Superintendence by the contractor.

Science.gov (United States)

2010-10-01

... contractor. 36.506 Section 36.506 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Superintendence by the contractor. The contracting officer shall insert the clause at 52.236-6, Superintendence by the Contractor, in solicitations and contracts when a fixed-price construction contract or a fixed...

47 CFR 36.503 - Accumulated depreciation-Account 3100.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Accumulated depreciation-Account 3100. 36.503 Section 36.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Accumulated depreciation—Account 3100. (a) Amounts recorded in this account shall be separated on the basis of...

48 CFR 36.607 - Release of information on firm selection.

Science.gov (United States)

2010-10-01

... firm selection. 36.607 Section 36.607 Federal Acquisition Regulations System FEDERAL ACQUISITION... Services 36.607 Release of information on firm selection. (a) After final selection has taken place, the contracting officer may release information identifying only the architect-engineer firm with which a contract...

Chlorine-36 abundance in natural and synthetic perchlorate

Energy Technology Data Exchange (ETDEWEB)

Heikoop, Jeffrey M [Los Alamos National Laboratory; Dale, M [NON LANL; Sturchio, Neil C [UNIV OF ILLIONOIS; Caffee, M [PURDUE UNIV; Belosa, A D [UNIV OF ILLINOIS; Heraty, Jr., L J [UNIV OF ILLINOIS; Bohike, J K [RESTON, VA; Hatzinger, P B [SHAW ENIVIORNMENTAL C0.; Jackson, W A [TEXAS TECH; Gu, B [ORNL

2009-01-01

Perchlorate (ClO{sub 4}{sup -}) is ubiquitous in the environment. It occurs naturally as a product of atmospheric photochemical reactions, and is synthesized for military, aerospace, and industrial applications. Nitrate-enriched soils of the Atacama Desert (Chile) contain high concentrations of natural ClO{sub 4}{sup -}; nitrate produced from these soils has been exported worldwide since the mid-1800's for use in agriculture. The widespread introduction of synthetic and agricultural ClO{sub 4}{sup -} into the environment has complicated attempts to understand the geochemical cycle of ClO{sub 4}{sup -}. Natural ClO{sub 4}{sup -} samples from the southwestern United States have relatively high {sup 36}Cl abundances ({sup 36}Cl/Cl = 3,100 x 10{sup -15} to 28,800 x 10{sup -15}), compared with samples of synthetic ({sup 36}Cl/Cl = 0.0 x 10{sup -15} to 40 x 10{sup -15}) and Atacama Desert ({sup 36}Cl/Cl = 0.9 x 10{sup -15} to 590 x 10{sup -15}) ClO{sub 4}{sup -}. These data give a lower limit for the initial {sup 36}Cl abundance of natural ClO{sub 4}{sup -} and provide temporal and other constraints on its geochemical cycle.

A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

Science.gov (United States)

To, Kelvin K W; Tse, Herman; Chan, Wan-Mui; Choi, Garnet K Y; Zhang, Anna J X; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Chan, Andy S F; Woo, Patrick C Y; Lau, Susanna K P; Lo, Janice Y C; Chan, Kwok-Hung; Cheng, Vincent C C; Yuen, Kwok-Yung

2014-12-01

Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be

A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

Directory of Open Access Journals (Sweden)

Kelvin K W To

2014-12-01

Full Text Available Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1 was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention

16 CFR 1205.36 - Product certification and labeling by importers.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Product certification and labeling by importers. 1205.36 Section 1205.36 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR WALK-BEHIND POWER LAWN MOWERS Certification § 1205.36 Product...

Molecular epidemiology of human adenovirus infections in Denmark, 2011–2016

DEFF Research Database (Denmark)

Barnadas, Céline; Schmidt, Dennis Jelsbak; Fischer, Thea K.

2018-01-01

Background: Human adenoviruses (HAdVs) can cause respiratory tract infections, conjunctivitis, diarrhoea and outbreaks have been reported. However, little is known about the disease burden and the molecular epidemiology of HAdV. Objectives: To retrospectively perform a molecular characterization ...

Could viruses contribute to the worldwide epidemic of obesity?

Science.gov (United States)

Atkinson, Richard L

2008-01-01

The prevalence of obesity in children increased rapidly starting about 1980 in both developed and developing countries. Studies of changes in diet and physical activity, television watching, and food advertisements on television suggest that these are not sufficient to explain the epidemic. The pattern of rapid spread is suggestive of an infectious origin. The concept of virus-induced obesity is not new. Eight viruses have been shown to cause obesity in animals and there is evidence for virus-induced obesity in humans. Recent evidence on animal and human adenoviruses suggests that these adenoviruses may infect adipocytes to alter enzymes and transcription factors resulting in accumulation of triglycerides and differentiation of preadipocytes into mature adipocytes. The E4orf1 gene of Ad-36 has been shown to be responsible for the adipogenic effect. It appears that a portion of the worldwide epidemic of obesity since 1980 could be due to infections with human adenoviruses.

Application of 36Cl as a dating tool for modern groundwater

International Nuclear Information System (INIS)

Tosaki, Yuki; Tase, Norio; Massmann, Gudrun; Nagashima, Yasuo; Seki, Riki; Takahashi, Tsutomu; Sasa, Kimikazu; Sueki, Keisuke; Matsuhiro, Takeshi; Miura, Taichi; Bessho, Kotaro; Matsumura, Hiroshi; He, Ming

2007-01-01

The 36 Cl/Cl ratios of groundwater samples were measured by accelerator mass spectrometry (AMS) in order to investigate the potential use of 36 Cl as a dating tool for modern groundwater. Groundwater samples were obtained from several piezometers in the Oderbruch in northeastern Germany. The shallow confined aquifer of the area is mainly recharged by the infiltration from the River Oder. From the results of measurements, the pre-bomb and the recent background 36 Cl/Cl ratios in the basin of the Oder were estimated to be 7-9 x 10 -14 . The 36 Cl fallout values estimated from the 36 Cl/Cl ratios of the Oderbruch samples, which were dated by the 3 H/ 3 He method, show good agreement with Dye-3 ice core data. These results suggest that the distribution of 36 Cl in groundwaters reflects the influence of the 36 Cl bomb pulse. This, in turn, suggests that the distribution of 36 Cl/Cl in modern groundwaters could reveal groundwater ages and flow systems in a region

50 CFR 32.36 - Kentucky.

Science.gov (United States)

2010-10-01

... WILDLIFE REFUGE SYSTEM HUNTING AND FISHING Refuge-Specific Regulations for Hunting and Fishing § 32.36... bartering of permits. This permit is nontransferable. iv. You may place decoys out Saturday morning at the...

38 CFR 36.4304 - Deviations; changes of identity.

Science.gov (United States)

2010-07-01

... identity. 36.4304 Section 36.4304 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Deviations; changes of identity. A deviation of more than 5 percent between the estimates upon which a... change in the identity of the property upon which the original appraisal was based, will invalidate the...

47 CFR 36.126 - Circuit equipment-Category 4.

Science.gov (United States)

2010-10-01

... separating property associated with special services, circuit equipment included in Categories 4.12 (other... Equipment Excluding Wideband—Category 4.13—The cost of Circuit Equipment associated with exchange line plant... 47 Telecommunication 2 2010-10-01 2010-10-01 false Circuit equipment-Category 4. 36.126 Section 36...

Replicating Rather than Nonreplicating Adenovirus-Human Immunodeficiency Virus Recombinant Vaccines Are Better at Eliciting Potent Cellular Immunity and Priming High-Titer Antibodies

OpenAIRE

Peng, Bo; Wang, Liqun Rejean; Gómez-Román, Victor Raúl; Davis-Warren, Alberta; Montefiori, David C.; Kalyanaraman, V. S.; Venzon, David; Zhao, Jun; Kan, Elaine; Rowell, Thomas J.; Murthy, Krishna K.; Srivastava, Indresh; Barnett, Susan W.; Robert-Guroff, Marjorie

2005-01-01

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1MNenv/rev recombinants and boosting wit...

{sup 36}Cl exposure dating with a 3-MV tandem

Energy Technology Data Exchange (ETDEWEB)

Steier, Peter, E-mail: peter.steier@univie.ac.a [VERA Laboratory, Fakultaet fuer Physik - Isotopenforschung, Universitaet Wien, Waehringer Strasse 17, A-1090 Wien (Austria); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Forstner, Oliver; Golser, Robin; Kutschera, Walter; Martschini, Martin [VERA Laboratory, Fakultaet fuer Physik - Isotopenforschung, Universitaet Wien, Waehringer Strasse 17, A-1090 Wien (Austria); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Merchel, Silke [CEREGE, CNRS-IRD-Universite Aix-Marseille, Europole Mediterraneen de L' Arbois, 13545 Aix-en-Provence (France); Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Orlowski, Tobias; Priller, Alfred [VERA Laboratory, Fakultaet fuer Physik - Isotopenforschung, Universitaet Wien, Waehringer Strasse 17, A-1090 Wien (Austria); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Vockenhuber, Christof [Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland); Wallner, Anton [VERA Laboratory, Fakultaet fuer Physik - Isotopenforschung, Universitaet Wien, Waehringer Strasse 17, A-1090 Wien (Austria); HPK H 31, Institut fuer Teilchenphysik, ETH Zuerich, Schafmattstr. 20 CH-8093 Zuerich (Switzerland)

2010-04-15

{sup 36}Cl AMS measurements at natural isotopic concentrations have yet been performed only at tandem accelerators with 5 MV terminal voltage or beyond. We have developed a method to detect {sup 36}Cl at natural terrestrial isotopic concentrations with a 3-MV system, operated above specifications at 3.5 MV. An effective separation was obtained with an optimized split-anode ionization chamber design (adopted from the ETH/PSI Zurich AMS group), providing a suppression factor of up to 30,000 for the interfering isobar {sup 36}S. Despite the good separation, a relatively high sulfur output from the ion source ({sup 36}S{sup -}/{sup 35}Cl{sup -} approx 4 x 10{sup -10} for samples prepared from chemically pure reagents), and a possibly cross contamination resulted in a background corresponding to {sup 36}Cl/Cl approx 3 x 10{sup -14}. The method was applied to samples containing between 10{sup 5} and 10{sup 6} atoms {sup 36}Cl/g rock from sites in Italy and Iran, which were already investigated by other laboratories for surface exposure dating. The {sup 36}Cl/Cl ratios in the range from 2 x 10{sup -13} to 5 x 10{sup -12} show a generally good agreement with the previous results. These first measurements demonstrate that also 3-MV tandems, constituting the majority of dedicated AMS facilities, are capable of {sup 36}Cl exposure dating, which is presently the domain of larger facilities.

Chlorine cycling and fates of 36Cl in terrestrial environments

OpenAIRE

Bastviken, David; Svensson, Teresia; Sandén, Per; Kylin, Henrik

2013-01-01

Chlorine-36 (36Cl), a radioisotope of chlorine (Cl) with a half-life of 301,000 years, is present in some types of nuclear waste and is disposed in repositories for radioactive waste. As the release of 36Cl from such repositories to the near surface environment has to be taken into account it is of interest to predict possible fates of 36Cl under various conditions as a part of the safety assessments of repositories for radioactive waste. This report aims to summarize the state of the art kno...

49 CFR 230.36 - Hydrostatic testing of boilers.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hydrostatic testing of boilers. 230.36 Section 230... Appurtenances Pressure Testing of Boilers § 230.36 Hydrostatic testing of boilers. (a) Time of test. The... to any hydrostatic pressure. Hydrostatic testing required by these rules shall be conducted at 25...

29 CFR 36.440 - Health and insurance benefits and services.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Health and insurance benefits and services. 36.440 Section... Education Programs or Activities Prohibited § 36.440 Health and insurance benefits and services. Subject to § 36.235(d), in providing a medical, hospital, accident, or life insurance benefit, service, policy, or...

Covalent decoration of adenovirus vector capsids with the carbohydrate epitope αGal does not improve vector immunogenicity, but allows to study the in vivo fate of adenovirus immunocomplexes.

Science.gov (United States)

Kratzer, Ramona F; Espenlaub, Sigrid; Hoffmeister, Andrea; Kron, Matthias W; Kreppel, Florian

2017-01-01

Adenovirus-based vectors are promising tools for genetic vaccination. However, several obstacles have to be overcome prior to a routine clinical application of adenovirus-based vectors as efficacious vectored vaccines. The linear trisaccharide epitope αGal (alpha-Gal) with the carbohydrate sequence galactose-α-1,3-galactosyl-β-1,4-N-acetylglucosamine has been described as a potent adjuvant for recombinant or attenuated vaccines. Humans and α-1,3-galactosyltransferase knockout mice do not express this epitope. Upon exposure of α-1,3-galactosyltransferase-deficient organisms to αGal in the environment, large amounts of circulating anti-Gal antibodies are produced consistently. Immunocomplexes formed between recombinant αGal-decorated vaccines and anti-Gal antibodies exhibit superior immunogenicity. We studied the effects of the trisaccharide epitope on CD8 T cell responses that are directed specifically to vector-encoded transgenic antigens. For that, covalently αGal-decorated adenovirus vectors were delivered to anti-Gal α-1,3-galactosyltransferase knockout mice. We generated replication-defective, E1-deleted adenovirus type 5 vectors that were decorated with αGal at the hexon hypervariable regions 1 or 5, at fiber knob, or at penton base. Surprisingly, none of the adenovirus immunocomplexes being formed from αGal-decorated adenovirus vectors and anti-Gal immunoglobulins improved the frequencies of CD8 T cell responses against the transgenic antigen ovalbumin. Humoral immunity directed to the adenovirus vector was neither increased. However, our data indicated that decoration of Ad vectors with the αGal epitope is a powerful tool to analyze the fate of adenovirus immunocomplexes in vivo.

Development of an immunotherapeutic adenovirus targeting hormone-independent prostate cancer

Directory of Open Access Journals (Sweden)

Kim JS

2013-11-01

Full Text Available Jae Sik Kim,1 Sang Don Lee,2 Sang Jin Lee,3 Moon Kee Chung21Department of Urology, The Catholic University of Korea Incheon St Mary's Hospital, Incheon, 2Pusan National University Yangsan Hospital and Research Institute for Convergence of Biomedical Science and Technology, Yangsan, 3Genitourinary Cancer Branch, National Cancer Center, Goyang, KoreaBackground: To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating oncolytic adenovirus (Ad equipped with mRFP(monomeric red fluorescence protein/ttk (modified herpes simplex virus thymidine kinase This construct was then further modified to express both mRFP/ttk and a soluble form of cytokine FLT3L (fms-related tyrosine kinase 3 ligand simultaneously.Methods: To construct the recombinant oncolytic adenovirus, E1a and E4 genes, which are necessary for adenovirus replication, were controlled by the prostate-specific enhancer sequence (PSES targeting prostate cancer cells expressing prostate-specific antigen (PSA and prostate-specific membrane antigen (PSMA. Simultaneously, it expressed the mRFP/ttk fusion protein in order to be able to elicit the cytotoxic effect.Results: The Ad5/35PSES.mRFP/ttk chimeric recombinant adenovirus was generated successfully. When replication of Ad5/35PSES.mRFP/ttk was evaluated in prostate cancer cell lines under fluorescence microscopy, red fluorescence intensity increased more in LNCaP cells, suggesting that the mRFP/ttk fusion protein was folded functionally. In addition, the replication assay including wild-type adenovirus as a positive control showed that PSES-positive cells (LNCaP and CWR22rv permitted virus replication but not PSES-negative cells (DU145 and PC3. Next, we evaluated the killing activity of this recombinant adenovirus. The Ad5/35PSES.mRFP/ttk killed LNCaP and CWR22rv more effectively. Unlike PSES-positive cells, DU145 and PC3 were resistant to killing by this recombinant

Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

Directory of Open Access Journals (Sweden)

Chuan Wang

Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1

Science.gov (United States)

Musselman, Catherine A.; Avvakumov, Nikita; Watanabe, Reiko; Abraham, Christopher G.; Lalonde, Marie-Eve; Hong, Zehui; Allen, Christopher; Roy, Siddhartha; Nuñez, James K.; Nickoloff, Jac; Kulesza, Caroline A.; Yasui, Akira; Côté, Jacques; Kutateladze, Tatiana G.

2013-01-01

The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome maintenance. Here, we demonstrate that the Tudor domain of human PHF1 binds to histone H3 trimethylated at Lys36 (H3K36me3). We report a 1.9 Å resolution crystal structure of the Tudor domain in complex with H3K36me3 and describe the molecular mechanism of H3K36me3 recognition using NMR analysis. Binding of PHF1 to H3K36me3 inhibits the ability of the Polycomb PRC2 complex to methylate H3K27 in vitro and in vivo. Laser micro-irradiation data reveal that PHF1 is transiently recruited to DNA double-strand breaks (DSBs), and PHF1 mutants impaired in the H3K36me3 interaction exhibit reduced retention at DSB sites. Together, our findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark and acts as an early DNA damage response cofactor. PMID:23142980

36 CFR 1212.655 - Individual.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Individual. 1212.655 Section... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.655 Individual. Individual means a natural person. ...

7 CFR 201.36c - Hermetically-sealed containers.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Hermetically-sealed containers. 201.36c Section 201... ACT FEDERAL SEED ACT REGULATIONS Advertising § 201.36c Hermetically-sealed containers. The 5-month... been met: (a) The seed was packaged within 9 months after harvest; (b) The container used does not...

7 CFR 2.36 - Director, Office of Communications.

Science.gov (United States)

2010-01-01

... are made by the Secretary of Agriculture to Director, Office of Communications: (1) Related to public...) Organize and direct the activities of a public affairs office to include press relations of the secretary... 7 Agriculture 1 2010-01-01 2010-01-01 false Director, Office of Communications. 2.36 Section 2.36...

9 CFR 98.36 - Animal semen from Canada.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Animal semen from Canada. 98.36... CERTAIN ANIMAL EMBRYOS AND ANIMAL SEMEN Certain Animal Semen § 98.36 Animal semen from Canada. (a) General importation requirements for animal semen from Canada. If the product is . . . Then . . . (1) Equine semen...

Preparation and calibration by liquid scintillation of a sample of Cl 36. Preparacion y calibracion por centelleo liquido de una muestra de Cl 36

Energy Technology Data Exchange (ETDEWEB)

Grau Malonda, A; Los Arcos, J M; Rodriguez Barquero, L; Suarez, C [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, Madrid (Spain)

1989-01-01

A procedure to prepare a sample of Clorine 36, as Li{sup 36}Cl, able to be measured by liquid scintillation counting, is described. The sample is chemically stable, with no variation of the quenching parameter up to 4 mg of LiCl per 15 ml of scintillator, keeps constant the counting efficiency for concentration higher than 40 {mu}g of Li{sup 36}Cl in that volume, and shows no deterioration over a 3 weed period. The Li{sup 36}Cl solution has been standarized using the free parameter method with different volumes of toluene, PCS and Instagel, to an uncertainty of 0,3% (Author).

Strait of Juan de Fuca 36 arc-second DEM

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The 36-second Strait of Juan de Fuca Washington Elevation Grid provides bathymetric data in ASCII raster format of 36-second resolution in geographic coordinates....

25 CFR 12.36 - Does other law enforcement training count?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Does other law enforcement training count? 12.36 Section 12.36 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY LAW ENFORCEMENT Qualifications and Training Requirements § 12.36 Does other law enforcement training count? All requests for evaluation of equivalent...

29 CFR 785.36 - Home to work in emergency situations.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Home to work in emergency situations. 785.36 Section 785.36... Principles Traveltime § 785.36 Home to work in emergency situations. There may be instances when travel from home to work is overtime. For example, if an employee who has gone home after completing his day's work...

SF-36 total score as a single measure of health-related quality of life: Scoping review.

Science.gov (United States)

Lins, Liliane; Carvalho, Fernando Martins

2016-01-01

According to the 36-Item Short Form Health Survey questionnaire developers, a global measure of health-related quality of life such as the "SF-36 Total/Global/Overall Score" cannot be generated from the questionnaire. However, studies keep on reporting such measure. This study aimed to evaluate the frequency and to describe some characteristics of articles reporting the SF-36 Total/Global/Overall Score in the scientific literature. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was adapted to a scoping review. We performed searches in PubMed, Web of Science, SCOPUS, BVS, and Cochrane Library databases for articles using such scores. We found 172 articles published between 1997 and 2015; 110 (64.0%) of them were published from 2010 onwards; 30.0% appeared in journals with Impact Factor 3.00 or greater. Overall, 129 (75.0%) out of the 172 studies did not specify the method for calculating the "SF-36 Total Score"; 13 studies did not specify their methods but referred to the SF-36 developers' studies or others; and 30 articles used different strategies for calculating such score, the most frequent being arithmetic averaging of the eight SF-36 domains scores. We concluded that the "SF-36 Total/Global/Overall Score" has been increasingly reported in the scientific literature. Researchers should be aware of this procedure and of its possible impacts upon human health.

The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment.

Directory of Open Access Journals (Sweden)

Yuuri Hashimoto

Full Text Available Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin, in which the human telomerase reverse transcriptase (hTERT promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5. In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen or a hypoxic (1% oxygen condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.

48 CFR 36.602 - Selection of firms for architect-engineer contracts.

Science.gov (United States)

2010-10-01

... architect-engineer contracts. 36.602 Section 36.602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Architect-Engineer Services 36.602 Selection of firms for architect-engineer contracts. ...

Genomic structure in Europeans dating back at least 36,200 years

DEFF Research Database (Denmark)

Seguin-Orlando, Andaine; Korneliussen, Thorfinn Sand; Sikora, Martin

2014-01-01

The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000...

Future prospects for the development of cost-effective Adenovirus vaccines

DEFF Research Database (Denmark)

Fougeroux, Cyrielle; Holst, Peter J

2017-01-01

-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient...... as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes...

The Human SLC25A33 and SLC25A36 Genes of Solute Carrier Family 25 Encode Two Mitochondrial Pyrimidine Nucleotide Transporters*

Science.gov (United States)

Di Noia, Maria Antonietta; Todisco, Simona; Cirigliano, Angela; Rinaldi, Teresa; Agrimi, Gennaro; Iacobazzi, Vito; Palmieri, Ferdinando

2014-01-01

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport inorganic anions, amino acids, carboxylates, nucleotides, and coenzymes across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. Here two members of this family, SLC25A33 and SLC25A36, have been thoroughly characterized biochemically. These proteins were overexpressed in bacteria and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that SLC25A33 transports uracil, thymine, and cytosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism and SLC25A36 cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Both carriers also transported guanine but not adenine (deoxy)nucleotides. Transport catalyzed by both carriers was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. In confirmation of their identity (i) SLC25A33 and SLC25A36 were found to be targeted to mitochondria and (ii) the phenotypes of Saccharomyces cerevisiae cells lacking RIM2, the gene encoding the well characterized yeast mitochondrial pyrimidine nucleotide carrier, were overcome by expressing SLC25A33 or SLC25A36 in these cells. The main physiological role of SLC25A33 and SLC25A36 is to import/export pyrimidine nucleotides into and from mitochondria, i.e. to accomplish transport steps essential for mitochondrial DNA and RNA synthesis and breakdown. PMID:25320081

77 FR 42707 - 36(b)(1) Arms Sales Notification

Science.gov (United States)

2012-07-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-35] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Force (DAY) [[Page 42709

36 CFR 1275.22 - Security.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Security. 1275.22 Section... THE NIXON ADMINISTRATION Preservation and Protection § 1275.22 Security. The Archivist is responsible for providing adequate security for the Presidential historical materials. ...

48 CFR 36.609-3 - Work oversight in architect-engineer contracts.

Science.gov (United States)

2010-10-01

... architect-engineer contracts. 36.609-3 Section 36.609-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Architect-Engineer Services 36.609-3 Work oversight in architect-engineer contracts. The contracting officer...

Be-10 and Cl-36 interlaboratory comparisons

Energy Technology Data Exchange (ETDEWEB)

Merchel, Silke [CEREGE, Aix-en-Provence (France); FZD, Dresden (Germany); Bremser, Wolfram [BAM, Berlin (Germany); Alfimov, Vasily; Christl, Marcus; Kubik, Peter W. [PSI/ETH Zurich (Switzerland); Arnold, Maurice; Aumaitre, Georges; Benedetti, Lucilla; Bourles, Didier L.; Braucher, Regis [CEREGE, Aix-en-Provence (France); Caffee, Marc [PRIME Lab, Purdue, IN (United States); Fifield, L. Keith; Tims, Stephen G. [ANU, Canberra (Australia); Finkel, Robert C. [CEREGE, Aix-en-Provence (France); LLNL, Livermore, CA (United States); Freeman, Stewart P.H.T.; Wilcken, Klaus M.; Xu, Sheng [SUERC, East Kilbride (United Kingdom); Ruiz-Gomez, Aaron [CNA, Sevilla (Spain); Rood, Dylan H. [LLNL, Livermore, CA (United States); Sasa, Kimikazu [University of Tsukuba (Japan); Steier, Peter; Wallner, Anton [VERA, Wien (Austria)

2009-07-01

Driven by the progress in AMS and its spreading application within geosciences, measurements of increasing numbers of samples with low isotopic ratios will be required in the future. Therefore, we have examined the linearity of {sup 10}Be/{sup 9}Be as a function of isotope ratio by distributing 3 secondary standards (dilutions of NIST4325: 10{sup -12}-10{sup -14}) to 9 AMS labs. The problem of low ratio samples is even more crucial for {sup 36}Cl mainly due to the high volatility of chlorine. Thus, we have prepared large quantities of 3 {sup 36}Cl/Cl solutions from a certified {sup 36}Cl activity (NIST4943) by dilution with NaCl. AgCl precipitated from these solutions (10{sup -11}-10{sup -13}) has been distributed to 9 AMS labs. Some measurements are still ongoing. First results from 6 labs for each nuclide show that these interlaboratory exercises are very valuable.

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

Science.gov (United States)

Galloway, Alison; Saveliev, Alexander; Łukasiak, Sebastian; Hodson, Daniel J; Bolland, Daniel; Balmanno, Kathryn; Ahlfors, Helena; Monzón-Casanova, Elisa; Mannurita, Sara Ciullini; Bell, Lewis S; Andrews, Simon; Díaz-Muñoz, Manuel D; Cook, Simon J; Corcoran, Anne; Turner, Martin

2016-04-22

Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint. Copyright © 2016, American Association for the Advancement of Science.

Adenovirus serotype 5 vectors with Tat-PTD modified hexon and serotype 35 fiber show greatly enhanced transduction capacity of primary cell cultures.

Directory of Open Access Journals (Sweden)

Di Yu

Full Text Available Recombinant adenovirus serotype 5 (Ad5 vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus-receptor (CAR on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.

Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

Science.gov (United States)

Park, S; Park, H-L; Lee, S-Y; Nam, J-H

2016-03-01

Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

Energy Technology Data Exchange (ETDEWEB)

Weaver, Eric A. [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Camacho, Zenaido T. [Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States); Hillestad, Matthew L. [Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States); Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J. [Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States); Mercier, George T. [Department of Physics, University of Houston, Houston, TX 77004 (United States); Barry, Michael A., E-mail: mab@mayo.edu [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902 (United States)

2015-08-15

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

International Nuclear Information System (INIS)

Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.; Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J.; Mercier, George T.; Barry, Michael A.

2015-01-01

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5

nvj 36 2 new.cdr

African Journals Online (AJOL)

GRAPHICS DEPT

Vol 36 (2) 1065-1169. 1. 2. Department of Veterinary Obstetrics and Reproductive Diseases, University of Nigeria, Nsukka, Department of Veterinary. Pathology and Microbiology, University of Nigeria, Nsukka.*Corresponding Author: E-mail: Phone: davinson.anyogu@unn.edu.ng. 234-(0)7036841871. INTRODUCTION.

7 CFR 987.36 - Notice.

Science.gov (United States)

2010-01-01

... of communication to producers and handlers of the contents of each marketing policy report submitted... of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Marketing Policy § 987.36 Notice. The Committee shall...

Determination of the transforming activities of adenovirus oncogenes.

Science.gov (United States)

Speiseder, Thomas; Nevels, Michael; Dobner, Thomas

2014-01-01

The last 50 years of molecular biological investigations into human adenoviruses (Ads) have contributed enormously to our understanding of the basic principles of normal and malignant cell growth. Much of this knowledge stems from analyses of the Ad productive infection cycle in permissive host cells. Also, initial observations concerning the transforming potential of human Ads subsequently revealed decisive insights into the molecular mechanisms of the origins of cancer and established Ads as a model system for explaining virus-mediated transformation processes. Today it is well established that cell transformation by human Ads is a multistep process involving several gene products encoded in early transcription units 1A (E1A) and 1B (E1B). Moreover, a large body of evidence now indicates that alternative or additional mechanisms are engaged in Ad-mediated oncogenic transformation involving gene products encoded in early region 4 (E4) as well as epigenetic changes resulting from viral DNA integration. In particular, studies on the transforming potential of several E4 gene products have now revealed new pathways that point to novel general mechanisms of virus-mediated oncogenesis. In this chapter we describe in vitro and in vivo assays to determine the transforming and oncogenic activities of the E1A, E1B, and E4 oncoproteins in primary baby rat kidney cells, human amniotic fluid cells and athymic nude mice.

40 CFR 427.36 - Pretreatment standards for new sources.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for new sources. 427.36 Section 427.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Starch Binder...

A triplex quantitative real-time PCR assay for differential detection of human adenovirus serotypes 2, 3 and 7.

Science.gov (United States)

Qiu, Fang-Zhou; Shen, Xin-Xin; Zhao, Meng-Chuan; Zhao, Li; Duan, Su-Xia; Chen, Chen; Qi, Ju-Ju; Li, Gui-Xia; Wang, Le; Feng, Zhi-Shan; Ma, Xue-Jun

2018-05-02

Human adenovirus (HAdV) serotypes 2, 3 and 7 are more prevalent than other serotypes and have been associated with severe pneumonia in pediatric children. Molecular typing of HAdV is not routinely performed in clinical diagnostic laboratories as it is time-consuming and labor-intensive. In the present study, we developed a triplex quantitative real-time PCR assay (tq-PCR) in a single closed tube for differential detection and quantitative analysis of HAdV serotypes 2, 3 and 7. The sensitivity, specificity, reproducibility and clinical performance of tq-PCR were evaluated. The analytical sensitivity of the tq-PCR was 100 copies/reaction for each of HAdV serotypes 2, 3 and 7, and no cross-reaction with other common respiratory viruses or HAdV serotypes 1,4,5,6,31,55 and 57 was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.6% to 3.6%. Of 138 previously-defined HAdV-positive nasopharyngeal aspirates samples tested, the detection agreement between tq-PCR and nested PCR was 96.38% (133/138). The proposed tq-PCR assay is a sensitive, specific and reproducible method and has the potential for clinical use in the rapid and differential detection and quantitation of HAdV serotypes 2, 3 and 7.

Adenovirus Infection in Children with Diarrhea Disease in ...

African Journals Online (AJOL)

Ad40) and type 41(Ad41), can cause acute and severe diarrhea in young children worldwide. This study was conducted to delineate the epidemiological features of adenoviruses identified in children with gastroenteritis in Northwestern Nigeria.

Production and purification of non replicative canine adenovirus type 2 derived vectors.

Science.gov (United States)

Szelechowski, Marion; Bergeron, Corinne; Gonzalez-Dunia, Daniel; Klonjkowski, Bernard

2013-12-03

Adenovirus (Ad) derived vectors have been widely used for short or long-term gene transfer, both for gene therapy and vaccine applications. Because of the frequent pre-existing immunity against the classically used human adenovirus type 5, canine adenovirus type 2 (CAV2) has been proposed as an alternative vector for human gene transfer. The well-characterized biology of CAV2, together with its ease of genetic manipulation, offer major advantages, notably for gene transfer into the central nervous system, or for inducing a wide range of protective immune responses, from humoral to cellular immunity. Nowadays, CAV2 represents one of the most appealing nonhuman adenovirus for use as a vaccine vector. This protocol describes a simple method to construct, produce and titer recombinant CAV2 vectors. After cloning the expression cassette of the gene of interest into a shuttle plasmid, the recombinant genomic plasmid is obtained by homologous recombination in the E. coli BJ5183 bacterial strain. The resulting genomic plasmid is then transfected into canine kidney cells expressing the complementing CAV2-E1 genes (DK-E1). A viral amplification enables the production of a large viral stock, which is purified by ultracentrifugation through cesium chloride gradients and desalted by dialysis. The resulting viral suspension routinely has a titer of over 10(10) infectious particles per ml and can be directly administrated in vivo.

36 CFR 292.11 - Introduction.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Introduction. 292.11 Section 292.11 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL RECREATION AREAS Whiskeytown-Shasta-Trinity National Recreation Area § 292.11 Introduction. (a...

High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes.

Science.gov (United States)

Ukkola, Olavi H; Puurunen, Veli-Pekka; Piira, Olli-Pekka; Niva, Jarkko T; Lepojärvi, E Samuli; Tulppo, Mikko P; Huikuri, Heikki V

2011-10-10

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (pfasting glucose, impaired glucose tolerance and normal glucose tolerance (pfasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness. Copyright © 2011 Elsevier B.V. All rights reserved.

The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling.

Directory of Open Access Journals (Sweden)

Sabine Bavamian

Full Text Available Connexin36 (Cx36 plays an important role in insulin secretion by controlling the intercellular synchronization of Ca(2+ transients induced during stimulation. The lack of drugs acting on Cx36 channels is a major limitation in further unraveling the molecular mechanism underlying this effect. To screen for such drugs, we have developed an assay allowing for a semi-automatic, fluorimetric quantification of Ca(2+ transients in large populations of MIN6 cells. Here, we show that (1 compared to control cells, MIN6 cells with reduced Cx36 expression or function showed decreased synchrony of glucose-induced Ca(2+ oscillations; (2 glibenclamide, a sulphonylurea which promotes Cx36 junctions and coupling, increased the number of synchronous MIN6 cells, whereas quinine, an antimalarial drug which inhibits Cx36-dependent coupling, decreased this proportion; (3 several drugs were identified that altered the intercellular Ca(2+ synchronization, cell coupling and distribution of Cx36; (4 some of them also affected insulin content. The data indicate that the intercellular synchronization of Ca(2+ oscillations provides a reliable and non-invasive measurement of Cx36-dependent coupling, which is useful to identify novel drugs affecting the function of β-cells, neurons, and neuron-related cells that express Cx36.