Karikaturist Aivar Juhanson näitab KuKu klubis oma töid

Index Scriptorium Estoniae

2009-01-01

Loit Jõekalda kureeritud joonistustriennaali raames eksponeerivad oma töid Ave Avalo, Kärt Hammer, Eero Ijavoinen, Kristjan Kittus, Mari-Liis Laanemaa, Triinu Lille, Valli Lember-Bogatkina jpt. kunstnikud. Ajalehe "Eesti Ekspress" karikaturisti Aivar Juhansoni tööde näitus Tallinnas KuKu klubis

Osteopontin is a tumor autoantigen in prostate cancer patients

Science.gov (United States)

TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

2011-01-01

Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

Epigenetics of Autoantigens: New Opportunities for Therapy of Autoimmune Diseases

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Marko Radic

2013-01-01

Full Text Available The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.

Er KU et mobbeuniversitet?

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Olden-Jørgensen, Sebastian

2009-01-01

Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende.......Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende....

Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

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Yannic C. Bartsch

2018-06-01

Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

A novel small molecule inhibitor of the DNA repair protein Ku70/80.

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Weterings, Eric; Gallegos, Alfred C; Dominick, Lauren N; Cooke, Laurence S; Bartels, Trace N; Vagner, Josef; Matsunaga, Terry O; Mahadevan, Daruka

2016-07-01

Non-Homologous End-Joining (NHEJ) is the predominant pathway for the repair of DNA double strand breaks (DSBs) in human cells. The NHEJ pathway is frequently upregulated in several solid cancers as a compensatory mechanism for a separate DSB repair defect or for innate genomic instability, making this pathway a powerful target for synthetic lethality approaches. In addition, NHEJ reduces the efficacy of cancer treatment modalities which rely on the introduction of DSBs, like radiation therapy or genotoxic chemotherapy. Consequently, inhibition of the NHEJ pathway can modulate a radiation- or chemo-refractory disease presentation. The Ku70/80 heterodimer protein plays a pivotal role in the NHEJ process. It possesses a ring-shaped structure with high affinity for DSBs and serves as the first responder and central scaffold around which the rest of the repair complex is assembled. Because of this central position, the Ku70/80 dimer is a logical target for the disruption of the entire NHEJ pathway. Surprisingly, specific inhibitors of the Ku70/80 heterodimer are currently not available. We here describe an in silico, pocket-based drug discovery methodology utilizing the crystal structure of the Ku70/80 heterodimer. We identified a novel putative small molecule binding pocket and selected several potential inhibitors by computational screening. Subsequent biological screening resulted in the first identification of a compound with confirmed Ku-inhibitory activity in the low micro-molar range, capable of disrupting the binding of Ku70/80 to DNA substrates and impairing Ku-dependent activation of another NHEJ factor, the DNA-PKCS kinase. Importantly, this compound synergistically sensitized human cell lines to radiation treatment, indicating a clear potential to diminish DSB repair. The chemical scaffold we here describe can be utilized as a lead-generating platform for the design and development of a novel class of anti-cancer agents. Copyright © 2016 Elsevier B.V. All

25-hydroxyvitamin D, autoantigenic and total antibody concentrations

DEFF Research Database (Denmark)

Thorsen, Steffen Ullitz; Pipper, Christian B; Johannesen, Jesper

2018-01-01

conducted within this field. OBJECTIVE: Our objective was to investigate if higher 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A). Further, we also wanted to examine......BACKGROUND: B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been...... the relationship between 25(OH)D and total antibody concentrations. METHODS: We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH)D, antibody and genetic analysis from the population-based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC) in the mean...

Mycobacterium smegmatis Ku binds DNA without free ends.

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Kushwaha, Ambuj K; Grove, Anne

2013-12-01

Ku is central to the non-homologous end-joining pathway of double-strand-break repair in all three major domains of life, with eukaryotic homologues being associated with more diversified roles compared with prokaryotic and archaeal homologues. Ku has a conserved central 'ring-shaped' core domain. While prokaryotic homologues lack the N- and C-terminal domains that impart functional diversity to eukaryotic Ku, analyses of Ku from certain prokaryotes such as Pseudomonas aeruginosa and Mycobacterium smegmatis have revealed the presence of distinct C-terminal extensions that modulate DNA-binding properties. We report in the present paper that the lysine-rich C-terminal extension of M. smegmatis Ku contacts the core protein domain as evidenced by an increase in DNA-binding affinity and a decrease in thermal stability and intrinsic tryptophan fluorescence upon its deletion. Ku deleted for this C-terminus requires free DNA ends for binding, but translocates to internal DNA sites. In contrast, full-length Ku can directly bind DNA without free ends, suggesting that this property is conferred by its C-terminus. Such binding to internal DNA sites may facilitate recruitment to sites of DNA damage. The results of the present study also suggest that extensions beyond the shared core domain may have independently evolved to expand Ku function.

Ku80-deleted cells are defective at base excision repair

International Nuclear Information System (INIS)

Li, Han; Marple, Teresa; Hasty, Paul

2013-01-01

Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H 2 O 2 and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs

Ku80-deleted cells are defective at base excision repair

Energy Technology Data Exchange (ETDEWEB)

Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

2013-05-15

Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

Dysregulated homeostasis of target tissues or autoantigens - A novel principle in autoimmunity.

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Petersen, Frank; Yue, Xiaoyang; Riemekasten, Gabriela; Yu, Xinhua

2017-06-01

Monogenic autoimmune disorders provide a powerful tool for our understanding of the principles of autoimmunity due to the obvious impact of a single gene on the disease. So far, approximately 100 single gene defects causing murine monogenic autoimmune disorders have been reported and the functional characterization of these genes will provide significant progress in understanding the nature of autoimmunity. According to their function, genes leading to monogenic autoimmune disorders can be categorized into two groups. An expectable first group contains genes involved in the homeostasis of the immune system, including homeostasis of immune organs and immune cells. Intriguingly, the second group consists of genes functionally involved in the homeostasis of target tissues or autoantigens. According to our novel hypothesis, we propose that autoimmunity represents a consequence of a dysregulated homeostasis of the immune system and/or its targets including autoantigens and target tissues. In this review we refer to both aspects of homeostasis in autoimmunity with a highlight on the role of the homeostasis of target tissues and autoantigens. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutrophil Extracellular DNA Traps Induce Autoantigen Production by Airway Epithelial Cells

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Youngwoo Choi

2017-01-01

Full Text Available The hypothesis of autoimmune involvement in asthma has received much recent interest. Autoantibodies, such as anti-cytokeratin (CK 18, anti-CK19, and anti-α-enolase antibodies, react with self-antigens and are found at high levels in the sera of patients with severe asthma (SA. However, the mechanisms underlying autoantibody production in SA have not been fully determined. The present study was conducted to demonstrate that neutrophil extracellular DNA traps (NETs, cytotoxic molecules released from neutrophils, are a key player in the stimulation of airway epithelial cells (AECs to produce autoantigens. This study showed that NETs significantly increased the intracellular expression of tissue transglutaminase (tTG but did not affect that of CK18 in AECs. NETs induced the extracellular release of both tTG and CK18 in a concentration-dependent manner. Moreover, NETs directly degraded intracellular α-enolase into small fragments. However, antibodies against neutrophil elastase (NE or myeloperoxidase (MPO attenuated the effects of NETs on AECs. Furthermore, each NET isolated from healthy controls (HC, nonsevere asthma (NSA, and SA had different characteristics. Taken together, these findings suggest that AECs exposed to NETs may exhibit higher autoantigen production, especially in SA. Therefore, targeting of NETs may represent a new therapy for neutrophilic asthma with a high level of autoantigens.

A moonlighting function of Mycobacterium smegmatis Ku in zinc homeostasis?

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Kushwaha, Ambuj K; Deochand, Dinesh K; Grove, Anne

2015-02-01

Ku protein participates in DNA double-strand break repair via the nonhomologous end-joining pathway. The three-dimensional structure of eukaryotic Ku reveals a central core consisting of a β-barrel domain and pillar and bridge regions that combine to form a ring-like structure that encircles DNA. Homologs of Ku are encoded by a subset of bacterial species, and they are predicted to conserve this core domain. In addition, the bridge region of Ku from some bacteria is predicted from homology modeling and sequence analyses to contain a conventional HxxC and CxxC (where x is any residue) zinc-binding motif. These potential zinc-binding sites have either deteriorated or been entirely lost in Ku from other organisms. Using an in vitro metal binding assay, we show that Mycobacterium smegmatis Ku binds two zinc ions. Zinc binding modestly stabilizes the Ku protein (by ∼3°C) and prevents cysteine oxidation, but it has little effect on DNA binding. In vivo, zinc induces significant upregulation of the gene encoding Ku (∼sixfold) as well as a divergently oriented gene encoding a predicted zinc-dependent MarR family transcription factor. Notably, overexpression of Ku confers zinc tolerance on Escherichia coli. We speculate that zinc-binding sites in Ku proteins from M. smegmatis and other mycobacterial species have been evolutionarily retained to provide protection against zinc toxicity without compromising the function of Ku in DNA double-strand break repair. © 2014 The Protein Society.

Identification of new celiac disease autoantigens using proteomic analysis

Czech Academy of Sciences Publication Activity Database

Stulík, J.; Hernychová, L.; Porkertová, S.; Pozler, O.; Tučková, Ludmila; Sánchez, Daniel; Bureš, J.

2003-01-01

Roč. 3, - (2003), s. 951-956 ISSN 1615-9853 R&D Projects: GA ČR GA310/00/1373; GA AV ČR IBS5020203 Institutional research plan: CEZ:AV0Z5020903 Keywords : autoantigens * cells disease Subject RIV: EE - Microbiology, Virology Impact factor: 5.766, year: 2003

Radiometallating antibodies and autoantigenic peptides

International Nuclear Information System (INIS)

Mercer-Smith, J.A.; Lewis, D.; Cole, D.A.; Newmyer, S.L.; Schulte, L.D.; Mixon, P.L.; Schreyer, S.A.; Burns, T.P.; Roberts, J.C.; Figard, S.D.; McCormick, D.J.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

1991-01-01

We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N- benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have one functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies and have developed methods to label smaller biologically active molecules, such as autoantigenic peptides (fragments of the acetylcholine receptor), which are pertinent to myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules, the radiometallation chemistry, and biological characterization of the radiolabeled compounds will be discussed

Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

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Lu YF

2014-10-01

Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

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Wesley H. Brooks

2013-04-01

Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

Regulation of homologous recombination repair protein Rad51 by Ku70

International Nuclear Information System (INIS)

Du Liqing; Liu Qiang; Wang Yan; Xu Chang; Cao Jia; Fu Yue; Chen Fenghua; Fan Feiyue

2013-01-01

Objective: To explore the regulative effect of non-homologous end joining (NHEJ)protein Ku70 on homologous recombination repair protein Rad51, and to investigate the synergistic mechanism of homologous recombination repair in combination with NHEJ. Methods: Observed Rad51 protein expression after transfect Ku70 small interfering RNA or Ku70 plasmid DNA into tumor cells using Western blot. Results: Expression of Rad51 was obviously reduced after pretreated with Ku70 small interfering RNA. And with the increasing expression of Ku70 protein after transfection of Ku70 plasmid DNA PGCsi3.0-hKu70 into tumor cell lines, the Rad51 protein expression was increased. Conclusion: Ku70 protein has regulating effect on gene expression of Rad51, and it might participate in the collaboration between homologous recombination repair and NHEJ. (authors)

Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

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Rajwahrdhan Yadav

2010-08-01

Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

Gode råd til KU om bæredygtig omstilling

DEFF Research Database (Denmark)

Lund, Jens Friis

2016-01-01

I gennemsnit flyver alle KU-ansatte retur til Cairo årligt. KU's stigende internationalisering skader klimaet, og det kræver bæredygtig omstilling.......I gennemsnit flyver alle KU-ansatte retur til Cairo årligt. KU's stigende internationalisering skader klimaet, og det kræver bæredygtig omstilling....

Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis.

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Huafei Zou

Full Text Available Caveolin-1, the structural protein component of caveolae, acts as a scaffolding protein that functionally regulates signaling molecules. We show that knockdown of caveolin-1 protein expression enhances chemotherapeutic drug-induced apoptosis and inhibits long-term survival of colon cancer cells. In vitro studies demonstrate that caveolin-1 is a novel Ku70-binding protein, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101 to the caveolin-binding domain (CBD of Ku70 (amino acids 471-478. Cell culture data show that caveolin-1 binds Ku70 after treatment with chemotherapeutic drugs. Mechanistically, we found that binding of caveolin-1 to Ku70 inhibits the chemotherapeutic drug-induced release of Bax from Ku70, activation of Bax, translocation of Bax to mitochondria and apoptosis. Potentiation of apoptosis by knockdown of caveolin-1 protein expression is greatly reduced in the absence of Bax expression. Finally, we found that overexpression of wild type Ku70, but not a mutant form of Ku70 that cannot bind to caveolin-1 (Ku70 Φ→A, limits the chemotherapeutic drug-induced Ku70/Bax dissociation and apoptosis. Thus, caveolin-1 acts as an anti-apoptotic protein in colon cancer cells by binding to Ku70 and inhibiting Bax-dependent cell death.

Ku-pa-ro en las tablillas de Cnoso

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José L. Melena

1974-12-01

Full Text Available This paper is intended to be a comprehensive analysis of the evidence of ku-pa-ro in the Knossos Linear B tablets. Its main purpose is to set up the importance of such aromatic plant in the Mycenaean economy at Knossos and to identify what kind of sedge was concealed under the name ku-pa-ro and what part of the plant was used and for what purposes. What it is stressed is the usage of the Cyperus rotundus L. (i. e. the ku-pa-ro in the industry of perfumes and as a food additive as well. What is inferred from the discussion on the evidence of ku-pa-ro issues a series of valuable data concerning the localization of certain place-names in the map of Crete, and concerning the explanation of ideogram *171. The high qualities of ku-pa-ro preserved in the tablets lead the author to assume that such a plant was cultivated in Crete and was one of the main aromatic plants used by the Mycenaeans in the making of perfumes.

Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells.

Science.gov (United States)

Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D; Herzog, Roland; Daniell, Henry

2013-06-15

Among 12billion injections administered annually, unsafe delivery leads to >20million infections and >100million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1 diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. Copyright © 2012 Elsevier B.V. All rights reserved.

Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

International Nuclear Information System (INIS)

Pucci, Sabina; Polidoro, Chiara; Joubert, Alessandro; Mastrangeli, Francesca; Tolu, Barbara; Benassi, Michaela; Fiaschetti, Valeria; Greco, Laura; Miceli, Roberto; Floris, Roberto; Novelli, Giuseppe; Orlandi, Augusto; Santoni, Riccardo

2017-01-01

Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively

Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Pucci, Sabina, E-mail: sabina.pucci@uniroma2.it; Polidoro, Chiara; Joubert, Alessandro; Mastrangeli, Francesca; Tolu, Barbara; Benassi, Michaela; Fiaschetti, Valeria; Greco, Laura; Miceli, Roberto; Floris, Roberto; Novelli, Giuseppe; Orlandi, Augusto; Santoni, Riccardo

2017-02-01

Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively

Discovery and characterization of Ku acetylation in Mycobacterium smegmatis.

Science.gov (United States)

Zhou, Ying; Chen, Tao; Zhou, Lin; Fleming, Joy; Deng, Jiaoyu; Wang, Xude; Wang, Liwei; Wang, Yingying; Zhang, Xiaoli; Wei, Wenjing; Bi, Lijun

2015-03-01

Lysine acetylation is an important post-translational modification and is known to regulate many eukaryotic cellular processes. Little, however, is known about acetylated proteins in prokaryotes. Here, using immunoblotting, mass spectrometry and mutagenesis studies, we investigate the acetylation dynamics of the DNA repair protein Ku and its relationship with the deacetylase protein Sir2 and the non-homologous end joining (NHEJ) pathway in Mycobacterium smegmatis. We report that acetylation of Ku increases with growth, while NHEJ activity decreases, providing support for the hypothesis that acetylation of Ku may be involved in the DNA damage response in bacteria. Ku has multiple lysine sites. Our results indicate that K29 is an important acetylation site and that deficiency of Sir2 or mutation of K29 affects the quantity of Ku and its acetylation dynamics. Our findings expand knowledge of acetylation targets in prokaryotes and indicate a new direction for further research on bacterial DNA repair mechanisms. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antibodies against linear epitopes on Goodpasture autoantigen in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Science.gov (United States)

Jia, Xiao-Yu; Yu, Jun-Tao; Hu, Shui-Yi; Li, Jian-Nan; Wang, Miao; Wang, Chen; Chen, Min; Cui, Zhao; Zhao, Ming-Hui

2017-09-01

In a substantial number of patients with crescentic glomerulonephritis, both anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) are detected simultaneously. ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the antibodies against linear epitopes on Goodpasture autoantigen in sera from patients with ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of autoantibodies. Thirty-one patients with ANCA-associated vasculitis were enrolled in this study. Twenty-four overlapping linear peptides were synthesized across the whole sequence of Goodpasture autoantigen. Serum antibodies against linear peptides were detected by ELISA and their associations with clinical features were further analyzed. Twenty-five out of the thirty-one (80.6%) sera from patients with ANCA-associated vasculitis possessed antibodies against linear peptides on Goodpasture autoantigen. These antibodies could be detected in 50% of patients with normal renal function (Scr ≤ 133 μmol/L), 70% of patients with moderate renal dysfunction (133 μmol/L  600 μmol/L) (P = 0.032). The highest recognition frequencies were found for peptides P4 (51.6%), P14 (54.8%), and P24 (54.8%), which contained the sequences that constitute the conformational epitopes of E A (P4) and E B (P14) recognized by anti-GBM antibodies. The level of anti-P4 antibodies was positively correlated with the percentage of crescents in glomeruli (r = 0.764, P = 0.027). Patients with anti-P24 antibodies had a significantly higher prevalence of renal dysfunction on diagnosis (88.2 vs. 42.9%, P = 0.018). Antibodies against linear epitopes on Goodpasture autoantigen could be detected in sera of patients with ANCA-associated vasculitis, which might mediate the production of antibodies towards the conformational epitopes on Goodpasture autoantigen, namely, the anti-GBM antibodies.

Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation

International Nuclear Information System (INIS)

Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami

2010-01-01

Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.

Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Keiji, E-mail: kzsuzuki@nagasaki-u.ac.jp [Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Kodama, Seiji [Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-machi, Sakai 599-8570 (Japan); Watanabe, Masami [Kyoto University Research Reactor Institute, Kumatori-cho Sennan-gun, Osaka 590-0494 (Japan)

2010-01-05

Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.

The radiosensitizing effect of Ku70/80 knockdown in MCF10A cells irradiated with X-rays and p(66)+Be(40) neutrons.

Science.gov (United States)

Vandersickel, Veerle; Mancini, Monica; Slabbert, Jacobus; Marras, Emanuela; Thierens, Hubert; Perletti, Gianpaolo; Vral, Anne

2010-04-27

A better understanding of the underlying mechanisms of DNA repair after low- and high-LET radiations represents a research priority aimed at improving the outcome of clinical radiotherapy. To date however, our knowledge regarding the importance of DNA DSB repair proteins and mechanisms in the response of human cells to high-LET radiation, is far from being complete. We investigated the radiosensitizing effect after interfering with the DNA repair capacity in a human mammary epithelial cell line (MCF10A) by lentiviral-mediated RNA interference (RNAi) of the Ku70 protein, a key-element of the nonhomologous end-joining (NHEJ) pathway. Following irradiation of control and Ku-deficient cell lines with either 6 MV X-rays or p(66)+Be(40) neutrons, cellular radiosensitivity testing was performed using a crystal violet cell proliferation assay. Chromosomal radiosensitivity was evaluated using the micronucleus (MN) assay. RNAi of Ku70 caused downregulation of both the Ku70 and the Ku80 proteins. This downregulation sensitized cells to both X-rays and neutrons. Comparable dose modifying factors (DMFs) for X-rays and neutrons of 1.62 and 1.52 respectively were obtained with the cell proliferation assay, which points to the similar involvement of the Ku heterodimer in the cellular response to both types of radiation beams. After using the MN assay to evaluate chromosomal radiosensitivity, the obtained DMFs for X-ray doses of 2 and 4 Gy were 2.95 and 2.66 respectively. After neutron irradiation, the DMFs for doses of 1 and 2 Gy were 3.36 and 2.82 respectively. The fact that DMFs are in the same range for X-rays and neutrons confirms a similar importance of the NHEJ pathway and the Ku heterodimer for repairing DNA damage induced by both X-rays and p(66)+Be(40) neutrons. Interfering with the NHEJ pathway enhanced the radiosensitivity of human MCF10A cells to low-LET X-rays and high-LET neutrons, pointing to the importance of the Ku heterodimer for repairing damage induced by both

Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Tomonaga, Takeshi [Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki (Japan); Yoshitomi, Hideyuki [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Imazeki, Fumio [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Takizawa, Hirotaka [Kashiwado Clinic in Port-Square of the Kashiwado Memorial Foundation, Chiba (Japan); Mogushi, Kaoru [Information Center for Medical Sciences, Tokyo Dental and Medical University, Tokyo (Japan); Miyazaki, Masaru [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. Black-Right-Pointing-Pointer Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. Black-Right-Pointing-Pointer Anti-Ku86 may be more sensitive than the conventional markers for early detection. Black-Right-Pointing-Pointer Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. Black-Right-Pointing-Pointer Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 {+-} 0.28 vs. 0.18 {+-} 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of

Expression of Ku correlates with radiation sensitivities in the head and neck cancer cell lines

International Nuclear Information System (INIS)

Lee, Sang Wook; Yu, Eun Sil; Yi, So Lyoung; Son, Se Hee; Kim, Jong Hoon; Ahn, Seung Do; Shin, Seong Soo; Choi, Eun Kyung

2004-01-01

DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa (Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Ku80 increased expression by radiation, wheras Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku80 expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer

Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble

DEFF Research Database (Denmark)

Christgau, S; Schierbeck, H; Aanstoot, H J

1991-01-01

The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic...... acid decarboxylase. We have identified two autoantigenic forms of this protein in rat pancreatic beta-cells, a Mr 65,000 (GAD65) hydrophilic and soluble form of pI 6.9-7.1 and a Mr 64,000 (GAD64) component of pI 6.7. GAD64 is more abundant than GAD65 and has three distinct forms with regard to cellular...

Ku must load directly onto the chromosome end in order to mediate its telomeric functions.

Directory of Open Access Journals (Sweden)

Christopher R Lopez

2011-08-01

Full Text Available The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding-defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance.

Ku must load directly onto the chromosome end in order to mediate its telomeric functions.

Science.gov (United States)

Lopez, Christopher R; Ribes-Zamora, Albert; Indiviglio, Sandra M; Williams, Christopher L; Haricharan, Svasti; Bertuch, Alison A

2011-08-01

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding-defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance.

Application of indirect immunofluorescent test with an improved HEp-2 substrate tranfected with human Ro60/SSA autoantigens

International Nuclear Information System (INIS)

Lv Liangjing; Chen Shunle; Gu Yueying; Shen Nan; Bao Chunde; Wang Yuan; Xue Feng; Ye Peng; Yu Chongzhao

2006-01-01

To develop an improved substrate for indirect immunofluorescent test (IIF) to detect anti-Ro/SSA autoantibodies, the human 60-kDa Ro/SSA autoantigens (Ro60) cDNAs were obtained from placental cDNA library using PCR and were cloned into the mammalian expression vectorpEGFP-C1. Then the recombinant plasmids were transfected into HEp-2 cells. We con- firmed the overexpression, localization and antigenicity of fusion proteins in transfected cells by means of fluorescence microscopy, immunoblotting and IIF. HEp-2 and HEp-Ro60 was analyzed by IIF using a panel of 10 precipitinpositive anti-Ro human sera simultaneously. Stable expression of Ro60-GFP (green fluorescent protein) fusion proteins maintained ten more generations. And Ro60-GFP kept the antigenicity of Ro and had its own characteristic immunofluorescent pattern in HEp-Ro60 cells. The transfectants dramatically increased the sensitivity of IIF testing (a mean increase of 6.7-fold in endpoint titer, P<0.01). Eight (8/10) positive an- ti-Ro sera showed characteristic immunofluorescent pattern on HEp-Ro60, including two sera which were antinuclear antibodies (ANA) negative on untransfected HEp-2. IIF-ANA in all healthy sera were negative on HEp-Ro60. As a kind of new substrate of IIF, the Ro60 transfectants can be used to detect anti-Ro antibodies. In addition, transfected HEp-2 cells kept the immunofluorescent property of HEp-2 cells in IIF-ANA tests and could be employed as substrate for the routine IIF-ANA detection. The method improved the sensitivity of IIF-ANA. (authors)

Somatic mutation frequency in the stamen hairs of Tradescantia KU 7 and KU 9 clones exposed to low-level gamma rays

International Nuclear Information System (INIS)

Ichikawa, S.; Nagashima, C.; Takahashi, C.S.

1981-01-01

Two triploid clones (KU 7 and KU 9) of Tradescantia heterozygous for flower color were exposed to 1 to 42.3R of gamma rays or the scattering radiation in the gamma field of the Institute of Radiation . Breeding. Occurrence of somatic pink mutations in the stamen hairs was investigated 10 to 16 (or 14) days after irradiation. The mutation frequency was found to increase linearly with increasing gamma-ray exposure in the both clones, and the frequencies of 0.437 and 0.468 pink mutant events per 10 3 hairs per R were determined for KU 7 and KU 9, respectively. When the data collected in the present study were analyzed together with those obtained in earlier experiments in the gamma field, linear relationships of the somatic mutation frequency with gamma-ray (2.1 to 201.6R) and scattering radiation (0.72 to 57.6R) exposures were confirmed. Scattering radiation was found to have a genetical efficiency more than two times higher than that of gamma rays. Variation of spontaneous mutation frequency observed in the present study and in earlier studies was inversely correlated to temperature variation

The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends

DEFF Research Database (Denmark)

Weterings, Eric; Verkaik, Nicole S; Keijzers, Guido

2008-01-01

Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA-PK(CS)) an......Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA......-PK(CS)) and the XRCC4/ligase IV complex. Activation of the DNA-PK(CS) serine/threonine kinase requires an interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In contrast to previous models, we found that the carboxy terminus of Ku80 is not absolutely required for the recruitment and activation...... was phosphorylated to normal levels. This resulted in severely reduced levels of Artemis nuclease activity in vivo and in vitro. We therefore conclude that the Ku80 carboxy terminus is important to support DNA-PK(CS) autophosphorylation at specific sites, which facilitates DNA end processing by the Artemis...

Expression of Ku70 predicts results of radiotherapy in prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Hasegawa, Tomokazu; Someya, Masanori; Hori, Masakazu; Nakata, Kensei; Kitagawa, Mio; Tsuchiya, Takaaki; Sakata, Koh-ichi [Sapporo Medical University School of medicine, Department of Radiology, Chuo-ku, Sapporo, Hokkaido (Japan); Matsumoto, Yoshihisa [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Meguro-ku, Tokyo (Japan); Nojima, Masanori [The University of Tokyo, The Institute of Medical Science Hospital, Minatoku, Tokyo (Japan); Masumori, Naoya [Sapporo Medical University School of medicine, Department of Urology, Chuo-ku, Sapporo, Hokkaido (Japan); Hasegawa, Tadashi [Sapporo Medical University School of medicine, Department of Surgical Pathology, Chuo-ku, Sapporo, Hokkaido (Japan)

2017-01-15

Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches. (orig.) [German] Die Behandlung beim Prostatakarzinom ist abhaengig von T-Stadium, Gleason-Score und prostataspezifischem Antigen (PSA). Diese klinischen Faktoren sind jedoch zu ungenau, um das individuelle Lokalrezidivrisiko beim Prostatakarzinom nach

Expression of recombinant proteinase 3, the autoantigen in Wegener's granulomatosis, in insect cells

NARCIS (Netherlands)

Van der Geld, YM; Smook, MLF; Huitema, MG; Harmsen, MC; Limburg, PC; Kallenberg, CGM

2002-01-01

Proteinase 3 (PR3) is the major autoantigen for anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis. Little is known about the major antigenic sites on PR3. To facilitate epitope mapping, PR3 was cloned in insect cells using a baculovirus expression system. Four

Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Rafael Herrera-Esparza

2006-01-01

Full Text Available In subacute cutaneous lupus eryhematosus (SCLE the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2 equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.

DNA requirements for interaction of the C-terminal region of Ku80 with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs).

Science.gov (United States)

Radhakrishnan, Sarvan Kumar; Lees-Miller, Susan P

2017-09-01

Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks (DSBs) in human cells. Critical to NHEJ is the DNA-dependent interaction of the Ku70/80 heterodimer with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the DNA-PK holoenzyme. However, precisely how Ku recruits DNA-PKcs to DSBs ends to enhance its kinase activity has remained enigmatic, with contradictory findings reported in the literature. Here we address the role of the Ku80 C-terminal region (CTR) in the DNA-dependent interaction of Ku70/80 with DNA-PKcs using purified components and defined DNA structures. Our results show that the Ku80 CTR is required for interaction with DNA-PKcs on short segments of blunt ended 25bp dsDNA or 25bp dsDNA with a 15-base poly dA single stranded (ss) DNA extension, but this requirement is less stringent on longer dsDNA molecules (35bp blunt ended dsDNA) or 25bp duplex DNA with either a 15-base poly dT or poly dC ssDNA extension. Moreover, the DNA-PKcs-Ku complex preferentially forms on 25 bp DNA with a poly-pyrimidine ssDNA extension.Our work clarifies the role of the Ku80 CTR and dsDNA ends on the interaction of DNA-PKcs with Ku and provides key information to guide assembly and biology of NHEJ complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

Directory of Open Access Journals (Sweden)

Eun Young Yu

2015-10-01

Full Text Available A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR. These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs. The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

Aberrant accumulation of the diabetes autoantigen GAD65 in Golgi membranes in conditions of ER stress and autoimmunity

DEFF Research Database (Denmark)

Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P

2016-01-01

Pancreatic islet beta cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in beta cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes GABA......, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary beta cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes...... release from stressed and/or damaged beta cells, triggering autoimmunity....

Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair.

Directory of Open Access Journals (Sweden)

Yong Jun Choi

Full Text Available Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS to repair DNA double strand breaks (DSBs through the nonhomologous end joining (NHEJ pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70(-/- cells and ku80(-/- cells also appeared to have a defect in base excision repair (BER. BER corrects base lesions, apurinic/apyrimidinic (AP sites and single stand breaks (SSBs utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1 and DNA Polymerase β (Pol β. In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80 and/or free Ku80 (not bound to Ku70 possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80(-/- mice had a shorter life span than dna-pkcs(-/- mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT, an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER.

Ku recruits XLF to DNA double-strand breaks.

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Yano, Ken-ichi; Morotomi-Yano, Keiko; Wang, Shih-Ya; Uematsu, Naoya; Lee, Kyung-Jong; Asaithamby, Aroumougame; Weterings, Eric; Chen, David J

2008-01-01

XRCC4-like factor (XLF)--also known as Cernunnos--has recently been shown to be involved in non-homologous end-joining (NHEJ), which is the main pathway for the repair of DNA double-strand breaks (DSBs) in mammalian cells. XLF is likely to enhance NHEJ by stimulating XRCC4-ligase IV-mediated joining of DSBs. Here, we report mechanistic details of XLF recruitment to DSBs. Live cell imaging combined with laser micro-irradiation showed that XLF is an early responder to DSBs and that Ku is essential for XLF recruitment to DSBs. Biochemical analysis showed that Ku-XLF interaction occurs on DNA and that Ku stimulates XLF binding to DNA. Unexpectedly, XRCC4 is dispensable for XLF recruitment to DSBs, although photobleaching analysis showed that XRCC4 stabilizes the binding of XLF to DSBs. Our observations showed the direct involvement of XLF in the dynamic assembly of the NHEJ machinery and provide mechanistic insights into DSB recognition.

Absence of hemolytic disease of fetus and newborn despite maternal high-titer IgG anti-Ku.

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Kakaiya, R M; Whaley, A; Howard-Menk, C; Rami, J; Papari, M; Campbell-Lee, S; Malecki, Z

2010-01-01

Anti-Ku seen in K(o) (Kell-null) individuals has previously been shown to cause severe hemolytic transfusion reactions. Maternal anti-Ku can cause none or moderate to severe hemolytic disease of the fetus and newborn (HDFN). In two of four previously described HDFN cases, intrauterine transfusions were required because of severe anemia. We report a case in which maternal anti-Ku did not cause HDFN. Standard serologic methods were used for RBC antibody screening and identification, adsorption and elution of RBC antibodies, and antigen typing. A gravida 3, para 3 (G3P3) woman was first evaluated in 2006 and was found to have an IgG RBC antibody that reacted against all panel RBCs in the anti-human globulin phase. A panel of RBCs treated with DTT did not react with the antibody. The antibody failed to react with one example of K(o) RBCs. The patient’s RBCs typed negative for the following Kell blood group antigens: KEL1, KEL2, KEL3, KEL4, KEL6, KEL7, KEL11, KEL13, and KEL18. These results established the presence of anti-Ku in maternal serum. The newborn was group A, D+ and required phototherapy for hyperbilirubinemia, but did not require transfusion. The woman was seen again in January 2010 during the third trimester (G4P3). At this time, anti-Ku titer was 256. She delivered a healthy group O, D+ baby boy at 37 weeks' gestation. Cord RBCs were 4+ for IgG by DAT. An eluate reacted with all RBCs tested, but did not react when tested against a panel of DTT-treated RBCs. K(o) phenotype is rare to begin with, and the maternal anti-Ku formation may require more than one pregnancy. Therefore, cases that can be evaluated for anti-Ku–related HDFN are rare. Our case contributes to serologic and clinical aspects of such rare cases.

RECQ HELICASE RECQL4 PARTICIPATES IN NON-HOMOLOGOUS END JOINING AND INTERACTS WITH THE KU COMPLEX

DEFF Research Database (Denmark)

Shamanna, Raghavendra A; Singh, Dharmendra Kumar; Lu, Huiming

2014-01-01

-irradiation and resulted in accumulation of 53BP1 foci after irradiation, indicating defects in the processing of DSB. We find that RECQL4 interacts with the Ku70/Ku80 heterodimer, part of the DNA-dependent protein kinase (DNA-PK) complex, via its N-terminal domain. Further, RECQL4 stimulates higher order DNA binding...... of Ku70/Ku80 to a blunt end DNA substrate. Taken together, these results implicate that RECQL4 participates in the NHEJ pathway of DSB repair via a functional interaction with the Ku70/Ku80 complex. This is the first study to provide both in vitro and in vivo evidence for a role of a RecQ helicase...

Review of autoantigens in Sjögren’s syndrome: an update

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Tong L

2017-08-01

Full Text Available Louis Tong,1–4 Vanessa Koh,3 Bernard Yu-Hor Thong5 1Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 2Corneal and External Eye Disease, Singapore National Eye Centre, 3Ocular Surface Research Group, Singapore Eye Research Institute, 4Eye Academic Clinical Program, Duke-NUS Medical School, 5Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore Abstract: Primary Sjögren’s syndrome (pSS is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren’s syndrome type A (Ro and Sjögren’s syndrome type B (La antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of

Construction of cell model of silenced Ku80 and the radiobiology change of HeLa cell

International Nuclear Information System (INIS)

Zhuang Liang; Yu Shiying; Huang Xiaoyuan; Xiong Huihua; Xiong Hua; Li Xiaolan; Leng Yan

2007-01-01

Objective: To construct the cell model of Ku80 with expression inhibited by siRNA and to explore the role of Ku80 in radiobiology. Methods: Ku80-siRNA expression plasmids were constructed and HeLa cells were transfected with these plasmids by lipofectamine. Western blotting was used to measure the expression of Ku80. After irradiation with 6 MV X ray, cells were collected and analyzed by flow cytometry for apoptosis and cell cycle at 24, 48 and 72 h; The radiobiology parameters of four cell lines were acquired by clone formation array. Results: Three stable transfected cell clones were obtained, and the inhibition rates of Ku80 protein expression of two positive clones were 89.3% and 96.4%; The apoptosis rates of HeLa cells Ku80 inhibited were higher than control cells at 48 and 72 after X ray irradiation (P 0.05). HeLa cells of silenced Ku80 had lower SF 2 and D 0 than control cells, and their SER (sensitization enhancement ratio) based on D 10 were 1.315 and 1.365, respectively. Conclusions: The HeLa cell models with Ku80 expression suppressed were successfully established; the inhibition of Ku80 by siRNA could enhance the radiosensitivity of HeLa cells. (authors)

The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends.

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Weterings, Eric; Verkaik, Nicole S; Keijzers, Guido; Florea, Bogdan I; Wang, Shih-Ya; Ortega, Laura G; Uematsu, Naoya; Chen, David J; van Gent, Dik C

2009-03-01

Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA-PK(CS)) and the XRCC4/ligase IV complex. Activation of the DNA-PK(CS) serine/threonine kinase requires an interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In contrast to previous models, we found that the carboxy terminus of Ku80 is not absolutely required for the recruitment and activation of DNA-PK(CS) at DSBs, although cells that harbored a carboxy-terminal deletion in the Ku80 gene were sensitive to ionizing radiation and showed reduced end-joining capacity. More detailed analysis of this repair defect showed that DNA-PK(CS) autophosphorylation at Thr2647 was diminished, while Ser2056 was phosphorylated to normal levels. This resulted in severely reduced levels of Artemis nuclease activity in vivo and in vitro. We therefore conclude that the Ku80 carboxy terminus is important to support DNA-PK(CS) autophosphorylation at specific sites, which facilitates DNA end processing by the Artemis endonuclease and the subsequent joining reaction.

The Ku80 Carboxy Terminus Stimulates Joining and Artemis-Mediated Processing of DNA Ends▿

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Weterings, Eric; Verkaik, Nicole S.; Keijzers, Guido; Florea, Bogdan I.; Wang, Shih-Ya; Ortega, Laura G.; Uematsu, Naoya; Chen, David J.; van Gent, Dik C.

2009-01-01

Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA-PKCS) and the XRCC4/ligase IV complex. Activation of the DNA-PKCS serine/threonine kinase requires an interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In contrast to previous models, we found that the carboxy terminus of Ku80 is not absolutely required for the recruitment and activation of DNA-PKCS at DSBs, although cells that harbored a carboxy-terminal deletion in the Ku80 gene were sensitive to ionizing radiation and showed reduced end-joining capacity. More detailed analysis of this repair defect showed that DNA-PKCS autophosphorylation at Thr2647 was diminished, while Ser2056 was phosphorylated to normal levels. This resulted in severely reduced levels of Artemis nuclease activity in vivo and in vitro. We therefore conclude that the Ku80 carboxy terminus is important to support DNA-PKCS autophosphorylation at specific sites, which facilitates DNA end processing by the Artemis endonuclease and the subsequent joining reaction. PMID:19103741

The Ku Heterodimer and the Metabolism of Single-Ended DNA Double-Strand Breaks

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Alessia Balestrini

2013-06-01

Full Text Available Single-ended double-strand breaks (DSBs are a common form of spontaneous DNA break, generated when the replisome encounters a discontinuity in the DNA template. Given their prevalence, understanding the mechanisms governing the fate(s of single-ended DSBs is important. We describe the influence of the Ku heterodimer and Mre11 nuclease activity on processing of single-ended DSBs. Separation-of-function alleles of yku70 were derived that phenocopy Ku deficiency with respect to single-ended DSBs but remain proficient for NHEJ. The Ku mutants fail to regulate Exo1 activity, and bypass the requirement for Mre11 nuclease activity in the repair of camptothecin-induced single-ended DSBs. Ku mutants exhibited reduced affinity for DNA ends, manifest as both reduced end engagement and enhanced probability of diffusing inward on linear DNA. This study reveals an interplay between Ku and Mre11 in the metabolism of single-ended DSBs that is distinct from repair pathway choice at double-ended DSBs.

Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

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Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

2017-02-13

Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression

International Nuclear Information System (INIS)

Ohno, Masae; Kunimoto, Masaaki; Nishizuka, Makoto; Osada, Shigehiro; Imagawa, Masayoshi

2009-01-01

The farnesoid X receptor (FXR; NR1H4) is a member of the nuclear receptor superfamily and regulates the expression of genes involved in enterohepatic circulation and the metabolism of bile acids. Based on functional analyses, nuclear receptors are divided into regions A-F. To explore the cofactors interacting with FXR, we performed a pull-down assay using GST-fused to the N-terminal A/B region and the C region, which are required for the ligand-independent transactivation and DNA-binding, respectively, of FXR, and nuclear extracts from HeLa cells. We identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku80, and Ku70 as FXR associated factors. These proteins are known to have an important role in DNA repair, recombination, and transcription. DNA-PKcs mainly interacted with the A/B region of FXR, whereas the Ku proteins interacted with the C region and with the D region (hinge region). Chromatin immunoprecipitation assays revealed that the Ku proteins associated with FXR on the bile salt export pump (BSEP) promoter. Furthermore, we demonstrated that ectopic expression of the Ku proteins decreased the promoter activity and expression of BSEP gene mediated by FXR. These results suggest that the Ku proteins function as corepressors for FXR.

Structural Basis for Recognition and Sequestration of UUUOH 3 ' Temini of Nascent RNA Polymerase III Transcripts by La, a Rheumatic Disease Autoantigen

Energy Technology Data Exchange (ETDEWEB)

Teplova,M.; Yuan, Y.; Phan, A.; Malinina, L.; Ilin, S.; Teplov, A.; Patel, D.

2006-01-01

The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUUOH 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 Angstroms crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9OH 3' end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the {beta} sheet edge, rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUUOH 3' ends of nascent RNA transcripts are protected during downstream processing and maturation events.

The Ku heterodimer and the metabolism of single-ended DNA double-strand breaks.

Science.gov (United States)

Balestrini, Alessia; Ristic, Dejan; Dionne, Isabelle; Liu, Xiao Z; Wyman, Claire; Wellinger, Raymund J; Petrini, John H J

2013-06-27

Single-ended double-strand breaks (DSBs) are a common form of spontaneous DNA break, generated when the replisome encounters a discontinuity in the DNA template. Given their prevalence, understanding the mechanisms governing the fate(s) of single-ended DSBs is important. We describe the influence of the Ku heterodimer and Mre11 nuclease activity on processing of single-ended DSBs. Separation-of-function alleles of yku70 were derived that phenocopy Ku deficiency with respect to single-ended DSBs but remain proficient for NHEJ. The Ku mutants fail to regulate Exo1 activity, and bypass the requirement for Mre11 nuclease activity in the repair of camptothecin-induced single-ended DSBs. Ku mutants exhibited reduced affinity for DNA ends, manifest as both reduced end engagement and enhanced probability of diffusing inward on linear DNA. This study reveals an interplay between Ku and Mre11 in the metabolism of single-ended DSBs that is distinct from repair pathway choice at double-ended DSBs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

International Nuclear Information System (INIS)

Cha, Seho; Lim, Chunghun; Lee, Jae Young; Song, Yoon-Jae; Park, Junsoo; Choe, Joonho; Seo, Taegun

2010-01-01

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

Airborn Ku-band polarimetric radar remote sensing of terrestrial snow cover

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Simon H. Yueh; Steve J. Dinardo; Ahmed Akgiray; Richard West; Donald W. Cline; Kelly Elder

2009-01-01

Characteristics of the Ku-band polarimetric scatterometer (POLSCAT) data acquired from five sets of aircraft flights in the winter months of 2006-2008 for the second Cold Land Processes Experiment (CLPX-II) in Colorado are described in this paper. The data showed the response of the Ku-band radar echoes to snowpack changes for various types of background vegetation in...

Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage.

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Chengwan Zhang

Full Text Available UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.

C-terminal low-complexity sequence repeats of Mycobacterium smegmatis Ku modulate DNA binding.

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Kushwaha, Ambuj K; Grove, Anne

2013-01-24

Ku protein is an integral component of the NHEJ (non-homologous end-joining) pathway of DSB (double-strand break) repair. Both eukaryotic and prokaryotic Ku homologues have been characterized and shown to bind DNA ends. A unique feature of Mycobacterium smegmatis Ku is its basic C-terminal tail that contains several lysine-rich low-complexity PAKKA repeats that are absent from homologues encoded by obligate parasitic mycobacteria. Such PAKKA repeats are also characteristic of mycobacterial Hlp (histone-like protein) for which they have been shown to confer the ability to appose DNA ends. Unexpectedly, removal of the lysine-rich extension enhances DNA-binding affinity, but an interaction between DNA and the PAKKA repeats is indicated by the observation that only full-length Ku forms multiple complexes with a short stem-loop-containing DNA previously designed to accommodate only one Ku dimer. The C-terminal extension promotes DNA end-joining by T4 DNA ligase, suggesting that the PAKKA repeats also contribute to efficient end-joining. We suggest that low-complexity lysine-rich sequences have evolved repeatedly to modulate the function of unrelated DNA-binding proteins.

Shuttle orbiter Ku-band radar/communications system design evaluation. Deliverable test equipment evaluation

Science.gov (United States)

Maronde, R. G.

1980-07-01

The Ku-band test equipment, known as the Deliverable System Test equipment (DSTE), is reviewed and evaluated. The DSTE is semiautomated and computer programs were generated for 14 communication mode tests and 17 radar mode tests. The 31 test modules provide a good cross section of tests with which to exercise the Ku-band system; however, it is very limited when being used to verify Ku-band system performance. More detailed test descriptions are needed, and a major area of concern is the DSTE sell-off procedure which is inadequate.

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

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Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

2015-11-01

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

Development of intense terahertz coherent synchrotron radiation at KU-FEL

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Sei, Norihiro, E-mail: sei.n@aist.go.jp [Research Institute for Measurement and Analytical Instrumentation, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Zen, Heishun; Ohgaki, Hideaki [Institute for Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

2016-10-01

We produced intense coherent synchrotron radiation (CSR) in the terahertz (THz) region using an S-band linac at the Kyoto University Free Electron Laser (KU-FEL), which is a mid-infrared free-electron laser facility. The CSR beam was emitted from short-pulse electron bunches compressed by a 180° arc, and was transferred to air at a large solid angle of 0.10 rad. The measured CSR energy was 55 μJ per 7 μs macropulse, and KU-FEL was one of the most powerful CSR sources in normal conducting linear accelerator facilities. The CSR spectra were measured using an uncooled pyroelectric detector and a Michelson-type interferometer designed specifically for the KU-FEL electron beam, and had a maximum at a frequency of 0.11 THz. We found that adjusting the energy slit enhanced the CSR energy and shortened the electron beam bunch length in the CSR spectra measurements. Our results demonstrated that the efficient use of the energy slit can help improve the characteristics of CSR. - Highlights: • We have developed intense coherent synchrotron radiation (CSR) at KU-FEL. • The elevation angle of the CSR was correctly measured by a new technique. • The CSR power extracted to the air was 55 μJ per 7 μs macropulse. • It was demonstrated that an energy slit was effective to improve the CSR properties.

Development of intense terahertz coherent synchrotron radiation at KU-FEL

International Nuclear Information System (INIS)

Sei, Norihiro; Zen, Heishun; Ohgaki, Hideaki

2016-01-01

We produced intense coherent synchrotron radiation (CSR) in the terahertz (THz) region using an S-band linac at the Kyoto University Free Electron Laser (KU-FEL), which is a mid-infrared free-electron laser facility. The CSR beam was emitted from short-pulse electron bunches compressed by a 180° arc, and was transferred to air at a large solid angle of 0.10 rad. The measured CSR energy was 55 μJ per 7 μs macropulse, and KU-FEL was one of the most powerful CSR sources in normal conducting linear accelerator facilities. The CSR spectra were measured using an uncooled pyroelectric detector and a Michelson-type interferometer designed specifically for the KU-FEL electron beam, and had a maximum at a frequency of 0.11 THz. We found that adjusting the energy slit enhanced the CSR energy and shortened the electron beam bunch length in the CSR spectra measurements. Our results demonstrated that the efficient use of the energy slit can help improve the characteristics of CSR. - Highlights: • We have developed intense coherent synchrotron radiation (CSR) at KU-FEL. • The elevation angle of the CSR was correctly measured by a new technique. • The CSR power extracted to the air was 55 μJ per 7 μs macropulse. • It was demonstrated that an energy slit was effective to improve the CSR properties.

Review of autoantigens in Sjögren's syndrome: an update.

Science.gov (United States)

Tong, Louis; Koh, Vanessa; Thong, Bernard Yu-Hor

2017-01-01

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren's syndrome type A (Ro) and Sjögren's syndrome type B (La) antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of autoimmunity, or even lead to potential biomarkers. In conclusion, the understanding of autoantigens has led to exciting major advances in the biology of pSS and may influence diagnosis and management of pSS in future.

Investigations of Caspr2, an autoantigen of encephalitis and neuromyotonia

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Lancaster, Eric; Huijbers, Maartje GM; Bar, Vered; Boronat, Anna; Wong, Andrew; Martinez-Hernandez, Eugenia; Wilson, Christina; Jacobs, Dina; Lai, Meizan; Walker, Russell W; Graus, Francesc; Bataller, Luis; Illa, Isabel; Markx, Sander; Strauss, Kevin A.; Peles, Elior; Scherer, Steven S; Dalmau, Josep

2010-01-01

Objective To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC). Methods Clinical analysis of patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity. Results Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients’ antibodies reacted with brain and peripheral nerve in a pattern that co-localized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients had also myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median 8 months, range 6–84). Interpretation Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important because it responds to immunotherapy. PMID:21387375

Double strand break rejoining by the Ku-dependent mechanism of non-homologous end-joining

International Nuclear Information System (INIS)

Jeggo, P.; Singleton, B.; Beamish, H.; Priestley, A.

1999-01-01

The DNA-dependent protein kinase functions in the repair of DNA double strand breaks (DSBs) and in V(D)J recombination. To gain insight into the function of DNA-PK in this process we have carried out a mutation analysis of Ku80 and DNA-PKcs. Mutations at multiple sites within the N-terminal two thirds of Ku80 result in loss of Ku70/80 interaction, loss of DNA end-binding activity and inability to complement Ku80 defective cell fines. In contrast, mutations in the carboxy terminal region of the protein do not impair DNA end-binding activity but decrease the ability of Ku to activate DNA-PK. To gain insight into important functional domains within DNA-PKcs, we have analysed defective mutants, including the mouse scid cell line, and the rodent mutants, ire-20 and V-3. Mutational changes in the carboxy terminal region have been identified in all cases. Our results strongly suggest that the C-terminus of DNA-PKcs is required for kinase activity. (author)

Vecāku un bērnu mantiskās attiecības

OpenAIRE

Krauja, Uldis

2009-01-01

Bakalaura darba "Vecāku un bērna mantiskās attiecības" mērķis ir izpētīt vecāku un bērna mantisko attiecību regulējumu Latvijas Republikas normatīvajos tiesību aktos, atklājot tajos iespējamās problēmas un nepilnības. Bakalaura darba pirmajā daļā apskatīts vecāku un bērna mantisko attiecību jēdziens un izpratne, pievērsta uzmanība uz vecāku un bērna mantisko attiecību pirmsākumiem caur vēstures prizmu, lai apzinātos ģimenes tiesību nozīmīgumu cilvēces attīstībā un tagadējā dzīvē. Bakalaura da...

Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

Science.gov (United States)

Lech, Maciej; Kulkarni, Onkar P.; Pfeiffer, Stephanie; Savarese, Emina; Krug, Anne; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2008-01-01

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. PMID:18644972

Immunogenicity of autoantigens

Directory of Open Access Journals (Sweden)

Keller Andreas

2011-07-01

Full Text Available Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i are evolutionary conserved

Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70

DEFF Research Database (Denmark)

Xing, Mengtan; Bjørås, Magnar; Daniel, Jeremy A

2017-01-01

DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF......, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3. Genetic inactivation of C-NHEJ factors, such as Ku70, Ku80, XLF, PAXX...... with severe apoptosis in the central nervous system. Here, we demonstrate that inactivation of the Ku70 gene rescues the synthetic lethality between XLF and DNA-PKcs, resulting in triple knockout mice that are indistinguishable from Ku70-deficient littermates by size or levels of genomic instability. Moreover...

Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

Directory of Open Access Journals (Sweden)

Antoine Marmignon

2014-08-01

Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium

Volba idolů ve školním věku (Pop-Pantheon)

OpenAIRE

Ryba, Zdeněk

2016-01-01

Title: Idolization In The School Age (Pop-Pantheon) Author: Zdeněk Ryba Department: Department of Psychology Supervizor: doc. PhDr. Miloš Kučera, CSc. The main theme of this thesis is basic-school-age children choice of idols. The work is a part of Miloš Kučera research at Faculty of Education UK and it follows up the Mikšíček (1999) and Kravcová (2008) conclusions in their diploma thesis and short Kučera's contribution. The goal of this thesis is to make a database of idols and to create mod...

Uloga kućnih ljubimaca u socioemocionalnom  razvoju djece školskog uzrasta

OpenAIRE

Smojver-Ažić, Sanja; Topalović, Zorica

2010-01-01

Rezultati istraživanja potvrđuju kako je odrastanje uz kućnoga ljubimca povezano sa socioemocionalnim razvojem djece. Cilj ovoga istraživanja bio je ispitati odnos u kojemu stoje privrženost majci, privrženost kućnomu ljubimcu i empatija, socijalna kompetencija i usamljenost. U istraživanju je sudjelovalo 480 učenika četvrtoga, šestoga i osmoga razreda osnovnih škola u Istri (226 djevojčica i 254 dječaka) te njihovi roditelji. U ispitanom uzorku 63 % djece ima jednoga ili više kućnih ljubi...

The Ku70/80 ring in Non-Homologous End-Joining

DEFF Research Database (Denmark)

Kragelund, Birthe Brandt; Weterings, Eric; Hartmann-Petersen, Rasmus

2016-01-01

/80 heterodimer is a key-player in the NHEJ pathway and binds to DNA termini with high affinity, where it helps to protect DNA ends from degradation and to recruit other NHEJ factors required for repair. The mechanism of Ku70/80 detachment from the DNA helix after completion of DNA repair is incompletely......Non-homologous end-joining (NHEJ) is an essential DNA double strand break repair pathway during all cell cycle stages. Deficiency in NHEJ factors can lead to accumulation of unrepaired DNA breaks or faulty DNA repair, which may ultimately result in cell death, senescence or carcinogenesis. The Ku70...... understood. Some data suggest that certain DNA repair factors are ubiquitylated and targeted for proteasomal degradation after repair. Recent studies suggest that Ku80 is conjugated to lysine48-linked ubiquitin chains by the Skp1-Cullin-F-box (SCF) complex and/or the RING finger protein 8 (RNF8) ubiquitin-protein...

Xrcc1-dependent and Ku-dependent DNA double-strand break repair kinetics in Arabidopsis plants.

Science.gov (United States)

Charbonnel, Cyril; Gallego, Maria E; White, Charles I

2010-10-01

Double-strand breakage (DSB) of DNA involves loss of information on the two strands of the DNA fibre and thus cannot be repaired by simple copying of the complementary strand which is possible with single-strand DNA damage. Homologous recombination (HR) can precisely repair DSB using another copy of the genome as template and non-homologous recombination (NHR) permits repair of DSB with little or no dependence on DNA sequence homology. In addition to the well-characterised Ku-dependent non-homologous end-joining (NHEJ) pathway, much recent attention has been focused on Ku-independent NHR. The complex interrelationships and regulation of NHR pathways remain poorly understood, even more so in the case of plants, and we present here an analysis of Ku-dependent and Ku-independent repair of DSB in Arabidopsis thaliana. We have characterised an Arabidopsis xrcc1 mutant and developed quantitative analysis of the kinetics of appearance and loss of γ-H2AX foci as a tool to measure DSB repair in dividing root tip cells of γ-irradiated plants in vivo. This approach has permitted determination of DSB repair kinetics in planta following a short pulse of γ-irradiation, establishing the existence of a Ku-independent, Xrcc1-dependent DSB repair pathway. Furthermore, our data show a role for Ku80 during the first minutes post-irradiation and that Xrcc1 also plays such a role, but only in the absence of Ku. The importance of Xrcc1 is, however, clearly visible at later times in the presence of Ku, showing that alternative end-joining plays an important role in DSB repair even in the presence of active NHEJ. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Molecular characterization of resistant chronic lymphocytic leukemia (CLL): function of a new phosphorylated form of Ku70

International Nuclear Information System (INIS)

Saad, Lina

2013-01-01

We have identified a new form of phospho-S27-S33-Ku70 constitutively over expressed in a subset of chronic lymphocytic leukemia (CLL) B cells resistant to apoptosis induced by DNA double strand breaks (DSB). Ku70 is one of the essential proteins involved in the maintenance of genomic stability through its role in DNA double strand break repair (non-homologous end-joining, NHEJ) and in telomeric protection. Laboratory previously established that resistant CLL cells disclose an up-regulated NHEJ DNA repair and an impaired structure of telomeres. The goal of this thesis was to characterize the biological function(s) of this new form of Ku70. For this purpose we have constructed specific EBV-based vectors (siRNA / cDNA) enabling a simultaneous inhibition of endogenous Ku70 and an expression of different forms (mutated, wild, phospho-mimetic at ser27-33) of Ku70 resistant to siRNA. Thus, we showed: i) a strict co-localisation of phospho-Ku70 with γ-H2AX foci; ii) that DSB induces the phosphorylation of Ku70 within minutes after genotoxic stress in heterodimer complex Ku70/Ku80. This phosphorylation necessitates both the physical interaction and the activity of pS2056-DNA-PKcs and/or ATM, linking phospho-Ku70 to NHEJ-mediated DNA DSB repair; iii) cells expressing mutated A27-A33-Ku70 exhibit a delayed G2/M cell cycle arrest, slower kinetic of DNA repair, lower level of genotoxic stress-induced chromosomal aberrations, and a higher cellular impedance correlated with translocation of transcriptional factor β-catenin from cytoplasmic membrane to the nucleus. Together, these data unveil an involvement of phospho-Ku70 in fast and inaccurate DNA repair; new paradigm for NHEJ regulation and to the control of resistance and maintenance of malignant cells.In parallel, we have initiated experimental approaches to explore other potential roles of phospho-Ku70. Especially, we were interested to determine whether it could play a role in an initiation of cell senescence induced by

A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65

Directory of Open Access Journals (Sweden)

Maxwell Denis

2008-11-01

Full Text Available Abstract Background Human glutamic acid decarboxylase 65 (hGAD65 is a key autoantigen in type 1 diabetes, having much potential as an important marker for the prediction and diagnosis of type 1 diabetes, and for the development of novel antigen-specific therapies for the treatment of type 1 diabetes. However, recombinant production of hGAD65 using conventional bacterial or mammalian cell culture-based expression systems or nuclear transformed plants is limited by low yield and low efficiency. Chloroplast transformation of the unicellular eukaryotic alga Chlamydomonas reinhardtii may offer a potential solution. Results A DNA cassette encoding full-length hGAD65, under the control of the C. reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs, was constructed and introduced into the chloroplast genome of C. reinhardtii by particle bombardment. Integration of hGAD65 DNA into the algal chloroplast genome was confirmed by PCR. Transcriptional expression of hGAD65 was demonstrated by RT-PCR. Immunoblotting verified the expression and accumulation of the recombinant protein. The antigenicity of algal-derived hGAD65 was demonstrated with its immunoreactivity to diabetic sera by ELISA and by its ability to induce proliferation of spleen cells from NOD mice. Recombinant hGAD65 accumulated in transgenic algae, accounts for approximately 0.25–0.3% of its total soluble protein. Conclusion Our results demonstrate the potential value of C. reinhardtii chloroplasts as a novel platform for rapid mass production of immunologically active hGAD65. This demonstration opens the future possibility for using algal chloroplasts as novel bioreactors for the production of many other biologically active mammalian therapeutic proteins.

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

Energy Technology Data Exchange (ETDEWEB)

Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

2010-04-16

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

A La autoantigen homologue is required for the internal ribosome entry site mediated translation of giardiavirus.

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Srinivas Garlapati

2011-03-01

Full Text Available Translation of Giardiavirus (GLV mRNA is initiated at an internal ribosome entry site (IRES in the viral transcript. The IRES localizes to a downstream portion of 5' untranslated region (UTR and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA, known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200-348aa of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus.

Functional Interplay of the Mre11 Nuclease and Ku in the Response to Replication-Associated DNA Damage ▿

Science.gov (United States)

Foster, Steven S.; Balestrini, Alessia; Petrini, John H. J.

2011-01-01

The Mre11 complex is a central component of the DNA damage response, with roles in damage sensing, molecular bridging, and end resection. We have previously shown that in Saccharomyces cerevisiae, Ku70 (yKu70) deficiency reduces the ionizing radiation sensitivity of mre11Δ mutants. In this study, we show that yKu70 deficiency suppressed the camptothecin (CPT) and methyl methanesulfonate (MMS) sensitivity of nuclease-deficient mre11-3 and sae2Δ mutants in an Exo1-dependent manner. CPT-induced G2/M arrest, γ-H2AX persistence, and chromosome breaks were elevated in mre11-3 mutants. These outcomes were reduced by yKu70 deficiency. Given that the genotoxic effects of CPT are manifest during DNA replication, these data suggest that Ku limits Exo1-dependent double-strand break (DSB) resection during DNA replication, inhibiting the initial processing steps required for homology-directed repair. We propose that Mre11 nuclease- and Sae2-dependent DNA end processing, which initiates DSB resection prevents Ku from engaging DSBs, thus promoting Exo1-dependent resection. In agreement with this idea, we show that Ku affinity for binding to short single-stranded overhangs is much lower than for blunt DNA ends. Collectively, the data define a nonhomologous end joining (NHEJ)-independent, S-phase-specific function of the Ku heterodimer. PMID:21876003

Interplay between Ku and Replication Protein A in the Restriction of Exo1-mediated DNA Break End Resection*

Science.gov (United States)

Krasner, Danielle S.; Daley, James M.; Sung, Patrick; Niu, Hengyao

2015-01-01

DNA double-strand breaks can be eliminated via non-homologous end joining or homologous recombination. Non-homologous end joining is initiated by the association of Ku with DNA ends. In contrast, homologous recombination entails nucleolytic resection of the 5′-strands, forming 3′-ssDNA tails that become coated with replication protein A (RPA). Ku restricts end access by the resection nuclease Exo1. It is unclear how partial resection might affect Ku engagement and Exo1 restriction. Here, we addressed these questions in a reconstituted system with yeast proteins. With blunt-ended DNA, Ku protected against Exo1 in a manner that required its DNA end-binding activity. Despite binding poorly to ssDNA, Ku could nonetheless engage a 5′-recessed DNA end with a 40-nucleotide (nt) ssDNA overhang, where it localized to the ssDNA-dsDNA junction and efficiently blocked resection by Exo1. Interestingly, RPA could exclude Ku from a partially resected structure with a 22-nt ssDNA tail and thus restored processing by Exo1. However, at a 40-nt tail, Ku remained stably associated at the ssDNA-dsDNA junction, and RPA simultaneously engaged the ssDNA region. We discuss a model in which the dynamic equilibrium between Ku and RPA binding to a partially resected DNA end influences the timing and efficiency of the resection process. PMID:26067273

Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

International Nuclear Information System (INIS)

Iwai, Hiroyuki; Matsuno, Etsuko; Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta

1994-01-01

In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair

NARCIS (Netherlands)

Y.J. Choi (Yong Jun); H. Li (Han); M.Y. Son (Mi Young); X.-H. Wang (Xiao-Hong); J.L. Fornsaglio (Jamie L.); R.W. Sobol (Robert W.); M. Lee (Moonsook); J. Vijg (Jan); S. Imholz (Sandra); M.E.T. Dollé (Martijn); H. van Steeg (Harry); E. Reiling (Erwin); P. Hasty (Paul)

2014-01-01

textabstractKu70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB

GPM, DPR Level 2A Ku Precipitation V03

Data.gov (United States)

National Aeronautics and Space Administration — The 2AKu algorithm provides precipitation estimates from the Ku radar of the Dual-Frequency Precipitation Radar on the core GPM spacecraft. The product contains one...

Pohon pásového dopravníku pro transport uhlí

OpenAIRE

Kliš, Kamil

2013-01-01

Diplomová práce se zabývá návrhem pohonu pásového dopravníku pro transport uhlí. Práce obsahuje nezbytné výpočty dle norem potřebné k určení vhodných komponentů pásového dopravníku. Cílem diplomové práce bylo navrhnout pohon pásového dopravníku, všech jeho potřebných komponentů včetně návrhem rámu pohonu a vytvoření výkresové dokumentace. This diploma thesis deals with designing a drivetrain for a coal belt conveyor. Thesis contains necessary calculations according to norms needed for dete...

A Ku-band magnetically insulated transmission line oscillator with overmoded slow-wave-structure

Science.gov (United States)

Jiang, Tao; He, Jun-Tao; Zhang, Jian-De; Li, Zhi-Qiang; Ling, Jun-Pu

2016-12-01

In order to enhance the power capacity, an improved Ku-band magnetically insulated transmission line oscillator (MILO) with overmoded slow-wave-structure (SWS) is proposed and investigated numerically and experimentally. The analysis of the dispersion relationship and the resonant curve of the cold test indicate that the device can operate at the near π mode of the TM01 mode, which is useful for mode selection and control. In the particle simulation, the improved Ku-band MILO generates a microwave with a power of 1.5 GW and a frequency of 12.3 GHz under an input voltage of 480 kV and input current of 42 kA. Finally, experimental investigation of the improved Ku-band MILO is carried out. A high-power microwave (HPM) with an average power of 800 MW, a frequency of 12.35 GHz, and pulse width of 35 ns is generated under a diode voltage of 500 kV and beam current of 43 kA. The consistency between the experimental and simulated far-field radiation pattern confirms that the operating mode of the improved Ku-band MILO is well controlled in π mode of the TM01 mode. Project supported partly by the National Natural Science Foundation of China (Grant No. 61171021).

The Ku70/80 ring in Non-Homologous End-Joining: easy to slip on, hard to remove.

Science.gov (United States)

Kragelund, Birthe B; Weterings, Eric; Hartmann-Petersen, Rasmus; Keijzers, Guido

2016-01-01

Non-homologous end-joining (NHEJ) is an essential DNA double strand break repair pathway during all cell cycle stages. Deficiency in NHEJ factors can lead to accumulation of unrepaired DNA breaks or faulty DNA repair, which may ultimately result in cell death, senescence or carcinogenesis. The Ku70/80 heterodimer is a key-player in the NHEJ pathway and binds to DNA termini with high affinity, where it helps to protect DNA ends from degradation and to recruit other NHEJ factors required for repair. The mechanism of Ku70/80 detachment from the DNA helix after completion of DNA repair is incompletely understood. Some data suggest that certain DNA repair factors are ubiquitylated and targeted for proteasomal degradation after repair. Recent studies suggest that Ku80 is conjugated to lysine48-linked ubiquitin chains by the Skp1-Cullin-F-box (SCF) complex and/or the RING finger protein 8 (RNF8) ubiquitin-protein ligases, followed by rapid proteasomal degradation. In this review we address the structure and function of the Ku70/80 heterodimer and how ubiquitylation may affect the release of Ku70/80 from chromatin and its subsequent degradation via the ubiquitin-proteasome system.

An integrated Ka/Ku-band payload for personal, mobile and private business communications

Science.gov (United States)

Hayes, Edward J.; Keelty, J. Malcolm

1991-01-01

The Canadian Department of Communications has been studying options for a government-sponsored demonstration payload to be launched before the end of the century. A summary of the proposed system concepts and network architectures for providing an advanced private business network service at Ku-band and personal and mobile communications at Ka-band is presented. The system aspects addressed include coverage patterns, traffic capacity, and grade of service, multiple access options as well as special problems, such as Doppler in mobile applications. Earth terminal types and the advanced payload concept proposed in a feasibility study for the demonstration mission are described. This concept is a combined Ka-band/Ku-band payload which incorporates a number of advanced satellite technologies including a group demodulator to convert single-channel-per-carrier frequency division multiple access uplink signals to a time division multiplex downlink, on-board signal regeneration, and baseband switching to support packet switched data operation. The on-board processing capability of the payload provides a hubless VSAT architecture which permits single-hop full mesh interconnectivity. The Ka-band and Ku-band portions of the payload are fully integrated through an on-board switch, thereby providing the capability for fully integrated services, such as using the Ku-band VSAT terminals as gateway stations for the Ka-band personal and mobile communications services.

Coexposure to benzo[a]pyrene plus UVA induced DNA double strand breaks: visualization of Ku assembly in the nucleus having DNA lesions

International Nuclear Information System (INIS)

Toyooka, Tatsushi; Ibuki, Yuko; Koike, Manabu; Ohashi, Norio; Takahashi, Sentaro; Goto, Rensuke

2004-01-01

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant with potential carcinogenicity. It has been shown that BaP, upon UVA irradiation, synergistically induced oxidative DNA damage, but other DNA damage was not confirmed. In this study, we examined whether coexposure to BaP plus UVA induces double strand breaks (DSBs) using xrs-5 cells, deficient in the repair of DSBs (Ku80 mutant), and whether Ku translocates involving the formation of DSBs. BaP plus UVA had a significant cytotoxic effect on CHO-K1 cells and an even more drastic effect on Ku80-deficient, xrs-5 cells, suggesting that the DSBs were generated by coexposure to BaP plus UVA. The DSBs were repaired in CHO-K1 cells within 30 min, but not in xrs-5 cells, indicating the involvement of a non-homologous end joining, which needs Ku proteins. Furthermore, we succeeded in visualizing that Ku80 rapidly assembled to the exposed region, in which DSBs might be generated, and clarified that the presence of both Ku70 and Ku80 was important for their accumulation

Radiation effects on radiation-hardened KU and KS-4V optical fibres

International Nuclear Information System (INIS)

Ivanov, A.A.; Tugarinov, S.N.; Kaschuck, Y.A.; Krasilnikov, A.V.; Bender, S.E.

1999-01-01

The aim of this work was to test the un-pretreated and the hardened (H 2 -loaded and pre-irradiated) KS-4V and KU optical fibres in reactor environment by in-situ measurements of both the radiation-induced loss and the luminescence in the visible spectral region. Both the radio-luminescent and the transmission spectra were in-situ detected during irradiation by charge-coupled-device (CCD) linear detector in the visible spectral region of 400 to 700 nm. The radiation induced loss spectra at the fast neutron fluence of 2*10 6 n/cm 2 shows the hardened, H 2 -loading and pre-irradiating effects in the both KU and KS-4V fibres. KU un-pretreated fibre shows a big radiation absorption band of non-bridging oxygen centered at the wavelength of 630 nm. It appears that the KS-4V hardened fibre has a specific point in the loss spectrum in the vicinity of 460 nm. Other measurements were performed, particularly after reactor shutdown and at 3 different neutron fluences with constant neutron flux after restarting

Hypoxia downregulates Ku70/80 expression in cervical carcinoma tumors

International Nuclear Information System (INIS)

Lara, Pedro Carlos; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa Maria; Bordon, Elisa; Rey, Agustin; Falcon, Orlando; Alonso, Ana Ruiz; Belka, Claus

2008-01-01

Hypoxia may inhibits the NHEJ DNA repair through downregulating Ku70/80 expression and combined with an increased angiogenesis and altered p53 expression would be responsible for tumor progression in cervical carcinoma

Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

Directory of Open Access Journals (Sweden)

Mahvash Zakikhani

Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

Klimatizace líhně kuřat

OpenAIRE

Petr, Lukáš

2009-01-01

Diplomová práce se zabývá návrhem systému klimatizačního zařízení pro prostory s líhněmi kuřat. Práce v úvodu krátce přibližuje problematiku klimatizace, představuje dispozice objektu a nastiňuje požadavky na mikroklima pro správnou inkubaci vajec a líhnutí kuřat. Praktická část diplomové práce se dělí na dva základní úseky, a to výpočtový a návrhový. Výpočtová část se zabývá stanovením množství přiváděného čerstvého klimatizačního vzduchu, výpočtem tepelných ztrát, tepelné zátěže a psychrome...

Návrh zásobníku na sypký vápenný hydrát

OpenAIRE

Perna, Marek

2009-01-01

Tato diplomová práce řeší návrh hlubokého zásobníku na sypký vápenný hydrát pro technologická zařízení čistíren odpadních vod. Je zde proveden rozbor volby typu a konstrukce zásobníku, návrh rozměrů a pevnostní výpočet zásobníku. Je zde popsána možnost vzniku klenby při vyprazdňování a její potlačení pomocí aktivních a pasivních prvků napomáhající toku. Popis aktivních a pasivních stavů napjatosti materiálu v zásobníku. This diploma thesis is solving systems design of silo for a powdery li...

Loss of MLH1 sensitizes colon cancer cells to DNA-PKcs inhibitor KU60648.

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Hinrichsen, Inga; Ackermann, Anne; Düding, Tonja; Graband, Annika; Filmann, Natalie; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

2017-07-01

Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors. Therefore, we examined the expression of MLH1, MSH2, MSH6, and MSH3 in different MMR-deficient and proficient cell lines and determined their sensitivity to KU60648 by analyzing cell viability and survival. MLH1-dependent ability of double strand break (DSB) repair was monitored after irradiation via γH2AX detection. A panel of 12 colon cancer cell lines, two pairs of cells, where MLH1 knock down was compared to controls with the same genetic background, and one MLH1-deficient cell line where MLH1 was overexpressed, were included. In summary, we found that MLH1 and/or MSH3-deficient cells exhibited a significantly higher sensitivity to KU60648 than MMR-proficient cells and that overexpression of MLH1 in MLH1-deficient cells resulted in a decrease of cell sensitivity. KU60648 efficiency seems to be associated with reduced DSB repair capacity. Since the molecular testing of colon tumors for MLH1 expression is a clinical standard we believe that MLH1 is a much better marker and a greater number of patients would benefit from KU60648 treatment. © 2017 Wiley Periodicals, Inc.

Experimental research on Ku-band magnetically insulated transmission line oscillator

Energy Technology Data Exchange (ETDEWEB)

Jiang, Tao; Zhang, Jiande; He, Juntao; Li, Zhiqiang; Ling, Junpu [College of Optoelectric Science and Engineering, National University of Defense Technology, Hunan 410073 (China)

2015-10-15

An improved Ku-band magnetically insulated transmission line oscillator is proposed and investigated experimentally. In the particle-in-cell simulation, the Ku-band MILO generates the microwave with a power of 1.62 GW and a frequency of 13 GHz at the input voltage of 474 kV. The device is fabricated based on the simulation results, and an experiment system is designed. In the preliminary experiments, output microwave with frequency of 13.02 GHz, power of 150 MW, and pulse width of 17 ns is generated, under the diode voltage of 450 kV. Analysis on the experiment results shows that plasma produced due to the large current hitting to the outside of the collection tank is the essential cause for the low amplitude of the microwave power and short pulse width.

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

Science.gov (United States)

Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

2015-01-01

Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair.

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Sinha, Krishna Murari; Stephanou, Nicolas C; Gao, Feng; Glickman, Michael S; Shuman, Stewart

2007-05-18

Mycobacterium tuberculosis and other bacterial pathogens have a Ku-dependent nonhomologous end joining pathway of DNA double-strand break repair. Here we identify mycobacterial UvrD1 as a novel interaction partner for Ku in a genome-wide yeast two-hybrid screen. UvrD1 per se is a vigorous DNA-dependent ATPase but a feeble DNA helicase. Ku stimulates UvrD1 to catalyze ATP-dependent unwinding of 3'-tailed DNAs. UvrD1, Ku, and DNA form a stable ternary complex in the absence of ATP. The Ku binding determinants are located in the distinctive C-terminal segment of UvrD1. A second mycobacterial paralog, UvrD2, is a vigorous Ku-independent DNA helicase. Ablation of UvrD1 sensitizes Mycobacterium smegmatis to killing by ultraviolet and ionizing radiation and to a single chromosomal break generated by I-SceI endonuclease. The physical and functional interactions of bacterial Ku and UvrD1 highlight the potential for cross-talk between components of nonhomologous end joining and nucleotide excision repair pathways.

Low density lipoprotein receptor gene Ava II polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

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Wu Dong-Feng

2011-02-01

Full Text Available Abstract Background Several common genetic polymorphisms in the low density lipoprotein receptor (LDL-R gene have associated with modifications of serum total cholesterol (TC and low density lipoprotein cholesterol (LDL-C levels, but the results are not consistent in different populations. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LDL-R gene Ava Ⅱ polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum TC, high density lipoprotein cholesterol (HDL-C, LDL-C, apolipoprotein (Apo A1 and the ratio of ApoA1 to ApoB were lower in Bai Ku Yao than in Han (P - and A+ alleles was 65.5% and 34.5% in Bai Ku Yao, and 80.7% and 19.3% in Han (P -A-, A-A+ and A+A+ genotypes was 42.6%, 45.9% and 11.5% in Bai Ku Yao, and 64.9%, 31.6% and 3.5% in Han (P P 3.20 mmol/L subgroups in Bai Ku Yao (P P P P +A+ genotype had higher serum LDL-C, TC, HDL-C or ApoA1 levels than the subjects with A-A+ and A-A- genotypes. Spearman rank correlation analysis revealed that the levels of LDL-C in Bai Ku Yao and HDL-C in Han were correlated with genotypes (P P Conclusions The association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels is different between the Bai Ku Yao and Han populations. The discrepancy might partly result from different LDL-R gene Ava Ⅱ polymorphism or LDL-R gene-enviromental interactions.

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

Science.gov (United States)

Mujtaba, Muhammad Ahmad; Fridell, Jonathan; Book, Benita; Faiz, Sara; Sharfuddin, Asif; Wiebke, Eric; Rigby, Mark; Taber, Tim

2015-11-01

Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.

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Liu, Ying; Tan, Huiling; Tian, Hui; Liang, Chunyang; Chen, She; Liu, Qinghua

2011-11-04

The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. Copyright © 2011 Elsevier Inc. All rights reserved.

Oxidative DNA Damage in Neurons: Implication of Ku in Neuronal Homeostasis and Survival

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Daniela De Zio

2012-01-01

Full Text Available Oxidative DNA damage is produced by reactive oxygen species (ROS which are generated by exogenous and endogenous sources and continuously challenge the cell. One of the most severe DNA lesions is the double-strand break (DSB, which is mainly repaired by nonhomologous end joining (NHEJ pathway in mammals. NHEJ directly joins the broken ends, without using the homologous template. Ku70/86 heterodimer, also known as Ku, is the first component of NHEJ as it directly binds DNA and recruits other NHEJ factors to promote the repair of the broken ends. Neurons are particularly metabolically active, displaying high rates of transcription and translation, which are associated with high metabolic and mitochondrial activity as well as oxygen consumption. In such a way, excessive oxygen radicals can be generated and constantly attack DNA, thereby producing several lesions. This condition, together with defective DNA repair systems, can lead to a high accumulation of DNA damage resulting in neurodegenerative processes and defects in neurodevelopment. In light of recent findings, in this paper, we will discuss the possible implication of Ku in neurodevelopment and in mediating the DNA repair dysfunction observed in certain neurodegenerations.

Superconducting magnet for a Ku-band maser.

Science.gov (United States)

Berwin, R.; Wiebe, E.; Dachel, P.

1972-01-01

A superconducting magnet to provide a uniform magnetic field of up to 8000 G in a 1.14-cm gap for the 15.3-GHz (Ku-band) traveling wave maser is described. The magnet operates in a persistent mode in the vacuum environment of a closed-cycle helium refrigerator (4.5 K). The features of a superconducting switch, which has both leads connected to 4.5 K heat stations and thereby does not receive heat generated by the magnet charging leads, are described.

Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

International Nuclear Information System (INIS)

Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

2004-01-01

The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

DASCH ON KU Cyg: A ∼ 5 YEAR DUST ACCRETION EVENT IN ∼ 1900

International Nuclear Information System (INIS)

Tang Sumin; Grindlay, Jonathan; Los, Edward; Servillat, Mathieu

2011-01-01

KU Cyg is an eclipsing binary consisting of an F-type star accreting through a large accretion disk from a K5III red giant. Here we present the discovery of a 5 year dip around 1900 found from its 100 year DASCH light curve. It showed a ∼0.5 mag slow fading from 1899 to 1903 and brightened back around 1904 on a relatively shorter timescale. The light curve shape of the 1899-1904 fading-brightening event differs from the dust production and dispersion process observed in R Coronae Borealis stars, which usually has a faster fading and slower recovery, and for KU Cyg is probably related to the accretion disk surrounding the F star. The slow fading in KU Cyg is probably caused by increases in dust extinction in the disk, and the subsequent quick brightening may be due to the evaporation of dust transported inward through the disk. The extinction excess which caused the fading may arise from increased mass transfer rate in the system or from dust clump ejections from the K giant.

Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56

DEFF Research Database (Denmark)

Baek Sørensen, Rikke; Faurschou, Mikkel; Troelsen, Lone

2009-01-01

A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recentl...

Characterization of the roles of the catalytic domains of Mycobacterium tuberculosis ligase D in Ku-dependent error-prone DNA end joining.

Science.gov (United States)

Wright, Douglas; DeBeaux, Austin; Shi, Runhua; Doherty, Aidan J; Harrison, Lynn

2010-09-01

We previously established an Escherichia coli strain capable of re-circularizing linear plasmid DNA by expressing the Mycobacterium tuberculosis Ku (Mt-Ku) and Mycobacterium tuberculosis ligase D (Mt-LigD) proteins from the E.coli chromosome. Repair was predominately mutagenic due to deletions at the termini. We hypothesized that these deletions could be due to a nuclease activity of Mt-LigD that was previously detected in vitro. Mt-LigD has three domains: an N-terminal polymerase domain (PolDom), a central domain with 3'-phosphoesterase and nuclease activity and a C-terminal ligase domain (LigDom). We generated bacterial strains expressing Mt-Ku and mutant versions of Mt-LigD. Plasmid re-circularization experiments in bacteria showed that the PolDom alone had no re-circularization activity. However, an increase in the total and accurate repair was found when the central domain was deleted. This provides further evidence that this central domain does have nuclease activity that can generate deletions during repair. Deletion of only the PolDom of Mt-LigD resulted in a complete loss of accurate repair and a significant reduction in total repair. This is in agreement with published in vitro work indicating that the PolDom is the major Mt-Ku-binding site. Interestingly, the LigDom alone was able to re-circularize plasmid DNA but only in an Mt-Ku-dependent manner, suggesting a potential second site for Ku-LigD interaction. This work has increased our understanding of the mutagenic repair by Mt-Ku and Mt-LigD and has extended the in vitro biochemical experiments by examining the importance of the Mt-LigD domains during repair in bacteria.

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Science.gov (United States)

Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

2014-01-01

Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. PMID:24563225

Oil Slick Observation at Low Incidence Angles in Ku-Band

Science.gov (United States)

Panfilova, M. A.; Karaev, V. Y.; Guo, Jie

2018-03-01

On the 20 April 2010 the oil platform Deep Water Horizon in the Gulf of Mexico suffered an explosion during the final phases of drilling an exploratory well. As a result, an oil film covered the sea surface area of several thousand square kilometers. In the present paper the data of the Ku-band Precipitation Radar, which operates at low incidence angles, were used to explore the oil spill event. The two-scale model of the scattering surface was used to describe radar backscatter from the sea surface. The algorithm for retrieval of normalized radar cross section at nadir and the total slope variance of large-scale waves compared to the wavelength of electromagnetic wave (22 mm) was developed for the Precipitation Radar swath. It is shown that measurements at low incidence angles can be used for oil spill detection. This is the first time that the dependence of mean square slope of large-scale waves on wind speed has been obtained for oil slicks from Ku-band data, and compared to mean square slope obtained by Cox and Munk from optical data.

Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

Directory of Open Access Journals (Sweden)

Chaojun Hu

Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

Ku70 is required for late B cell development and immunoglobulin heavy chain class switching.

Science.gov (United States)

Manis, J P; Gu, Y; Lansford, R; Sonoda, E; Ferrini, R; Davidson, L; Rajewsky, K; Alt, F W

1998-06-15

Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1- or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921-929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325-332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have

'SON-GO-KU' : a dream of automated library

Science.gov (United States)

Sato, Mamoru; Kishimoto, Juji

In the process of automating libraries, the retrieval of books through the browsing of shelves is being overlooked. The telematic library is a document based DBMS which can deliver the content of books by simulating the browsing process. The retrieval actually simulates the process a person would use in selecting a book in a real library, where a visual presentation using a graphic display is substituted. The characteristics of prototype system "Son-Go-Ku" for such retrieval implemented in 1988 are mentioned.

Design of a Ku band miniature multiple beam klystron

Energy Technology Data Exchange (ETDEWEB)

Bandyopadhyay, Ayan Kumar, E-mail: ayan.bandyopadhyay@gmail.com; Pal, Debasish; Kant, Deepender [Microwave Tubes Division, CSIR-CEERI, Pilani, Rajasthan-333031 (India); Saini, Anil; Saha, Sukalyan; Joshi, Lalit Mohan

2016-03-09

The design of a miniature multiple beam klystron (MBK) working in the Ku-band frequency range is presented in this article. Starting from the main design parameters, design of the electron gun, the input and output couplers and radio frequency section (RF-section) are presented. The design methodology using state of the art commercial electromagnetic design tools, analytical formulae as well as noncommercial design tools are briefly presented in this article.

Analysis of metals in asphaltenes of KU-46 by PIXE analysis; Analisis de metales en asfaltenos de crudo mexicano KU-46 por PIXE

Energy Technology Data Exchange (ETDEWEB)

Navidad G, P.; Pina L, L.I.; Lopez M, J.; Ramirez T, J.J.; Aspiazu F, J.A.; Romero G, E.T. [Gerencia de Ciencias Basicas, Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

2002-07-01

The content of metals of the asphaltenes obtained from the KU-46 mexican crude with n-heptane was evaluated. The found metals in higher concentration are transition metals as well as the vanadium, nickel, copper and zinc. Moreover the sulfur in high concentrations was quantified. The metallic content of the asphaltenes revealed that the crude contains a lower quantity of metals unlike the vacuum residue previously analysed. (Author)

Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.

Science.gov (United States)

Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Asa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude

2009-03-17

Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

Analysis of a Compact Wideband Slotted Antenna for Ku Band Applications

Directory of Open Access Journals (Sweden)

M. R. Ahsan

2014-01-01

Full Text Available The design procedure and physical module of a compact wideband patch antenna for Ku band application are presented in this paper. Finite element method based on 3D electromagnetic field solver has been utilized for the designing and analyzing process of proposed microstrip line fed modified E-H shaped electrically small patch antenna. After successful completion of the design process through various simulations, the proposed antenna has been fabricated on printed circuit board (PCB and its characteristics have been studied. The parameters of the proposed antenna prototype have been measured in standard far-field rectangular shape anechoic measurement compartment. It is apparent from the measured antenna parameters that the proposed antenna achieved almost stable variation of radiation pattern over the entire operational band with 1380 MHz of -10 dB return loss bandwidth. The maximum gain of 7.8 dBi and 89.97% average efficiency within the operating band from 17.15 GHz to 18.53 GHz ensure the suitability of the proposed antenna for Ku band applications.

Kuřim–the largest small town in the South-Moravian Region (Czechia)

Czech Academy of Sciences Publication Activity Database

Vaishar, Antonín

2015-01-01

Roč. 8, č. 8 (2015), s. 135-147 ISSN 2084-5456 Institutional support: RVO:68145535 Keywords : small town * suburbanization * Kuřim Subject RIV: DE - Earth Magnetism, Geodesy, Geography http://annalesgeo.up.krakow.pl/article/view/2839/2502

SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis

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Mario Saare

2015-01-01

Full Text Available The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients.

Synergistic effects of methyl methanesulfonate and X rays in inducing somatic mutations in the stamen hairs of Tradescantia clones, KU 27 and BNL 4430

International Nuclear Information System (INIS)

Ichikawa, Sadao; Yamaguchi, Akihiko; Okumura, Mikiko

1993-01-01

Young influorescences of Tradescantia clones KU 27 and BNL 4430, the both of which are blue/pink heterozygotes and have been demonstrated to be highly sensitive to alkylating agents, were exposed either to aqueous solutions of methyl methanesulfonate (MMS) for 16 hr alone (at 0.005 to 0.02% for KU 27 and at 0.005% for BNL 4430) or to acute 150 kVp X rays alone (161 to 531 mGy for Ku 27 and 501 to 976 mGy for BNL 4430), or in combinations (134 to 448 mGy for KU 27 and 458 to 865 mGy for BNL 4430 after the 0.005% MMS treatment). The induced somatic pink mutation frequencies per hair-cell division were studied and compared, and clone BNL 4430 was found to be nearly two times more sensitive to MMS than clone KU 27, while the X-ray-induced mutation frequencies in the latter was about 1.5 times higher than those in the former. The lower sensitivity to MMS of clone KU 27 (as compared with BNL 4430) was nevertheless about 5.6 times higher as compared with the responses of clone BNL 02 to MMS reported earlier, proving the high sensitivities of the two clones used in the present study. Clear synergistic effects of MMS and X rays were observed in the both clones, indicating that the mechanisms of inducing mutations are common at least in part between MMS and X rays. (author)

Vecāku pedagoģiskās kompetences pilnveide pirmsskolas izglītības iestāde

OpenAIRE

Vītola, Aija

2015-01-01

Maģistra darba autore Aija Vītola. Maģistra darba nosaukums „Vecāku pedagoģiskās kompetences pilnveide pirmsskolas izglītības iestādē”. Maģistra darba mērķis: izpētīt vecāku pedagoģiskās kompetences pilnveides iespējas pirmsskolas izglītības iestādē. Darba zinātniski teorētisko daļu veido: 1,5 – 3 gadus vecu bērnu personības attīstības likumsakarības, problēmas, ar kurām vecāki sastopas, bērnam uzsākot gaitas pirmsskolas izglītības iestādē, kompetences jēdziens, būtība, veidi, vecāku ...

Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80. Analysis by cDNA microarray

International Nuclear Information System (INIS)

Chan, John Y.H.; Chen, Lung-Kun; Chang, Jui-Feng

2001-01-01

The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is defective in a DNA end-binding protein, Ku80, which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80- deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes. (author)

Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80. Analysis by cDNA microarray

Energy Technology Data Exchange (ETDEWEB)

Chan, John Y.H.; Chen, Lung-Kun; Chang, Jui-Feng [National Yang Ming Univ., Taipei, Taiwan (China). Inst. of Radiological Sciences] (and others)

2001-12-01

The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is defective in a DNA end-binding protein, Ku80, which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80- deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes. (author)

Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

International Nuclear Information System (INIS)

Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.; Gustafson, Carl; Gupta, Shiv K.; Riester, Scott M.; Maran, Avudaiappan; Galindo, Mario; Wijnen, Andre J. van; Sarkaria, Jann N.; Yaszemski, Michael J.

2017-01-01

Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK CS ), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PK CS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK CS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PK CS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PK CS inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively radiosensitizes osteosarcoma cells. • Combining KU60648 with radiation increases G2/M accumulation and DNA damage.

Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren’s Syndrome

Science.gov (United States)

Gourzi, V C; Kapsogeorgou, E K; Kyriakidis, N C; Tzioufas, A G

2015-01-01

The elevated tissue expression of Ro/SSA and La/SSB autoantigens appears to be crucial for the generation and perpetuation of autoimmune humoral responses against these autoantigens in Sjögren’s syndrome (SS). The mechanisms that govern their expression are not known. miRNAs, the post-transcriptional regulators of gene expression, might be implicated. We have identified previously the miRNAs let7b, miR16, miR181a, miR200b-3p, miR200b-5p, miR223 and miR483-5p that are predicted to target Ro/SSA [Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2)] and La/SSB mRNAs. To study possible associations with autoantigen mRNA expression and disease features, their expression was investigated in minor salivary gland (MSG) tissues, peripheral blood mononuclear cells (PBMC) and long-term cultured non-neoplastic salivary gland epithelial cells (SGEC) from 29 SS patients (20 of 29 positive for autoantibodies to Ro/SSA and La/SSB) and 24 sicca-complaining controls. The levels of miR16 were up-regulated in MSGs, miR200b-3p in SGECs and miR223 and miR483-5p in PBMCs of SS patients compared to sicca-complaining controls. The MSG levels of let7b, miR16, miR181a, miR223 and miR483-5p were correlated positively with Ro52/TRIM21-mRNA. miR181a and miR200b-3p were correlated negatively with Ro52/TRIM21 and Ro60/TROVE2 mRNAs in SGECs, respectively, whereas let7b, miR200b-5p and miR223 associated with La/SSB-mRNA. In PBMCs, let7b, miR16, miR181a and miR483-5p were correlated with Ro52/TRIM21, whereas let7b, miR16 and miR181a were also associated with La/SSB-mRNA expression. Significantly lower miR200b-5p levels were expressed in SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma compared to those without. Our findings indicate that miR16, miR200b-3p, miR223 and miR483-5p are deregulated in SS, but the exact role of this deregulation in disease pathogenesis and autoantigen expression needs to be elucidated. PMID:26201309

A novel coaxial Ku-band transit radiation oscillator without external guiding magnetic field

Energy Technology Data Exchange (ETDEWEB)

Ling, Junpu, E-mail: lingjunpu@163.com; Zhang, Jiande; He, Juntao; Jiang, Tao [College of Photoelectric Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-02-15

A novel coaxial transit radiation oscillator without external guiding magnetic field is designed to generate high power microwave at Ku-band. By using a coaxial structure, the space-charge potential energy is suppressed significantly, that is good for enhancing efficient beam-wave interaction. In order to improve the transmission stability of the unmagnetized intense relativistic electron beam, a Pierce-like cathode is employed in the novel device. By contrast with conventional relativistic microwave generators, this kind of device has the advantages of high stability, non-guiding magnetic field, and high efficiency. Moreover, with the coaxial design, it is possible to improve the power-handing capacity by increasing the radial dimension of the Ku-band device. With a 550 keV and 7.5 kA electron beam, a 1.25 GW microwave pulse at 12.08 GHz has been obtained in the simulation. The power conversion efficiency is about 30%.

PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF

Directory of Open Access Journals (Sweden)

Satish K. Tadi

2016-10-01

Full Text Available In mammalian cells, classical non-homologous end joining (c-NHEJ is critical for DNA double-strand break repair induced by ionizing radiation and during V(DJ recombination in developing B and T lymphocytes. Recently, PAXX was identified as a c-NHEJ core component. We report here that PAXX-deficient cells exhibit a cellular phenotype uncharacteristic of a deficiency in c-NHEJ core components. PAXX-deficient cells display normal sensitivity to radiomimetic drugs, are proficient in transient V(DJ recombination assays, and do not shift toward higher micro-homology usage in plasmid repair assays. Although PAXX-deficient cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound to DNA. Formation of this complex involves an interaction with Ku70 and requires a bare DNA extension for stability. Moreover, the relatively weak Ku-dependent stimulation of LIG4/XRCC4 activity by PAXX is unmasked by XLF ablation. Thus, PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF’s function.

Pirmsskolas vecuma bērnu vecāku emocionālais intelekts un stresa līmenis saistībā ar vecāku audzināšanas pieejām

OpenAIRE

Pastare, Ilze

2007-01-01

Rezumējums Pētījuma mērķis bija noskaidrot pirmsskolas vecuma bērnu vecāku emocionālā intelekta un stresa līmeņa rādītāju saistību ar audzināšanas pieejām. Kopā pētījumā piedalījās 41 māte. Vidējais vecums mātēm – 33 gadi, bērnu vidējais vecums – 5 gadi. Pētījumā tika izmantotas šādas metodes: “ Bar-On Emocionālā intelekta aptauja”, “Vecāku stresa indekss”, “ Alabamas audzināšanas aptaujas pirmsskolas versija”. Pētījumā tika noskaidrots, ka pastāv statistiski nozīmīga po...

Volba řešitelských strategií v závislosti na věku

Directory of Open Access Journals (Sweden)

Petr Eisenmann

2017-12-01

Full Text Available Příspěvek popisuje experiment, který byl součástí dlouhodobého výzkumu Rozvíjení kultury řešení matematických problémů ve školské praxi. Experiment byl proveden na vzorku celkem 584 respondentů ve věku 11–17 let a mapuje vývoj ve volbě řešitelských strategií matematických úloh u různých věkových skupin žáků. Žákům 6. a 8. ročníku základní školy, I. a III. ročníku střední školy byly předloženy tři úlohy, které se dají efektivně řešit pomocí heuristických strategií. Kromě úspěšnosti řešení úloh byla věnována pozornost také způsobu jejich řešení. Výsledkem experimentu je zjištění, že existují heuristické strategie, které žáci použili při řešení úloh i přesto, že s nimi ve výuce nebyli seznámeni. U některých z nich se jejich výskyt nemění v závislosti na věku.

Production of the main celiac disease autoantigen by transient expression in Nicotiana benthamiana

Directory of Open Access Journals (Sweden)

Vanesa Soledad Marin Viegas

2015-12-01

Full Text Available Celiac Disease (CD is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2, is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion and vacuolar (C-terminal KISIA fusion TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9 to 16 fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB were induced by the ELP, with a consequent 2 fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant

Analysis of metals in asphaltenes of KU-46 by PIXE analysis

International Nuclear Information System (INIS)

Navidad G, P.; Pina L, L.I.; Lopez M, J.; Ramirez T, J.J.; Aspiazu F, J.A.; Romero G, E.T.

2002-01-01

The content of metals of the asphaltenes obtained from the KU-46 mexican crude with n-heptane was evaluated. The found metals in higher concentration are transition metals as well as the vanadium, nickel, copper and zinc. Moreover the sulfur in high concentrations was quantified. The metallic content of the asphaltenes revealed that the crude contains a lower quantity of metals unlike the vacuum residue previously analysed. (Author)

Renewal of KU-FEL Facility

CERN Document Server

Kii, Toshiteru; Masuda, Kai; Murakami, Shio; Ohgaki, Hideaki; Yamazaki, Tetsuo; Yoshikawa, Kiyoshi; Zen, Heishun

2004-01-01

Users demands to a high power tunable IR laser are increasing in Japan in energy-related science, such as basic study of high-efficiency solar cells, generation of new energy source of alcohol and/or H2 from polluted gas, and separation of DNA and/or RNA. To satisfy these demands, we decided to renew our FEL facility more user friendly and to operate more flexibly. Construction and fundamental studies on the KU-FEL have been carried out at a building of Institute of Chemical Research where few other accelerators are operating. Therefore, available machine time for our experiments is quite limited. We are now modifying the room by adding concrete walls of 2-m thickness and some space for users will be available. The present FEL system will be moved to the room A photocathode RF-gun system will be nearly added to the system and the present thermionic RF-gun will be used ternatively according to the demands of users. The photocathode material will be Cs2Te. The room with the shielding will be completed in June, ...

Experimental demonstration of a Ku-band radial-line relativistic klystron oscillator based on transition radiation

Science.gov (United States)

Dang, Fangchao; Zhang, Xiaoping; Zhang, Jun; Ju, Jinchuan; Zhong, Huihuang

2017-03-01

We report on a radial-line relativistic klystron oscillator (RL-RKO), which is physically designed to generate gigawatt-level high power microwaves (HPMs) at Ku-band. The 3π/4 mode of a four-gap buncher is selected to highly modulate the radially propagating intense relativistic electron beam (IREB). A three-gap extractor operating at the π mode is employed to extract the radio-frequency energy efficiently. The Ku-band RL-RKO is investigated experimentally on an intense-current electron beam accelerator. The radially propagating IREB is well focused with an axial-width of 2 mm by a radial magnetic field of 0.4 T. Microwaves with a frequency of 14.86 GHz and a power of 1.5 GW are generated, corresponding to an efficiency of 24%, which indicates a significant advance for the research of radial-line HPM sources.

[Professor Wacław Kuśnierczyk (1908-1997)--Pro Memoria in the century of birthday].

Science.gov (United States)

Brozek, Krzysztof; Kozakiewicz, Jacek; Kierzek, Andrzej

2009-01-01

Wacław Kuśnierczyk was born in 1908 in Sniatyń. He received the degree in medicine at Jan Kazimierz University in Lwów in 1932. He did his PhD degree under Professor Zaleski supervision in 1938 at Jan Kazimierz University. At that time he concentrated his scientific activity on research on tuberculosis. In 1953 he obtained the title of second degree specialist in ear, nose and throat diseases. He became a chief of Otolaryngology at Urban Hospital No 4 in Katowice in 1960. Since then this eminent physician was working on tumours located in upper respiratory tract and the possibility of its endoscopic diagnosis at Silesian Academy of Medicine in Katowice. As one of the first he pointed out the negative influence of smoking cigarettes on cancer of larynx. It was Wacław Kuśnierczyk who implemented new priorities for integrated programs in patient care, research, education and cancer prevention. He has published widely in peer reviewed journals and has edited or contributed to many books. He has given many major lectures and is the recipient of numerous prestigious awards for his scientific accomplishments. The achievement of Professor Kuśnierczyk were the valuable source of information for the physicians. In 1997, on the 31st of January he died in Katowice.

Effect of Ku80 deficiency on mutation frequencies and spectra at a LacZ reporter locus in mouse tissues and cells.

Directory of Open Access Journals (Sweden)

Rita A Busuttil

Full Text Available Non-homologous end joining (NHEJ is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and gammaH2AX DNA damage foci in Ku80-/- as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements.

Ku-band electromagnetic wave absorbing properties of polysiloxane derived Si-O-C bulk ceramics

Science.gov (United States)

Ding, Donghai; Li, Zipei; Xiao, Guoqing; Yang, Shaoyu

2018-02-01

The bulk Si-O-C ceramics were prepared by polymer derived ceramics (PDCs) route using polysiloxane as precursor and their properties were investigated for electromagnetic wave absorbing in the frequency range of 12.4-18 GHz (Ku-band). It was found that the catalytic pyrolysis can enhance substantially the absorbing properties by in situ formation of turbostratic carbon network, ordered carbon, and multi-wall carbon nanotubes. The matching thickness of sample containing 1.5 wt% FeCl3 (FPSO-1.5) is 2.2 mm, and its reflection loss exceeds -10 dB in the whole Ku-band with an absorption peak of -35.48 dB at 14.16 GHz. For sample containing 1.5 wt% FeCl3, its absorption peak increases to -15.78 dB, but its matching thickness decreases significantly to 2.2 mm. The polymer derived Si-O-C ceramics could be used as excellent electromagnetic functional devices working in harsh environments.

Suppression of the asymmetric competition mode in the relativistic Ku-band coaxial transit-time oscillator

Energy Technology Data Exchange (ETDEWEB)

Ling, Junpu; He, Juntao; Zhang, Jiande; Jiang, Tao; Wang, Lei [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-10-15

A relativistic Ku-band coaxial transit-time oscillator has been proposed in our previous work. In the experiments, we find that the asymmetric competition mode in the device limits the microwave power with the increase of the input electric power. For solving such a problem, the methods for analysis and suppression of the asymmetric competition mode in the device are investigated theoretically and experimentally. It is shown that the structure and the material of the collector, the concentricity, and the electron emission uniformity play an important part in the suppression of the asymmetric competition mode in the relativistic Ku-band transit-time oscillator. In the subsequent experiments, the asymmetric mode was suppressed effectively. At a low guiding magnetic field of 0.7 T, a microwave pulse with power of 1 GW, frequency of 14.3 GHz close to the simulation one, and efficiency of 20% was generated.

Expression of Mycobacterium tuberculosis Ku and Ligase D in Escherichia coli results in RecA and RecB-independent DNA end-joining at regions of microhomology.

Science.gov (United States)

Malyarchuk, Svitlana; Wright, Douglas; Castore, Reneau; Klepper, Emily; Weiss, Bernard; Doherty, Aidan J; Harrison, Lynn

2007-10-01

Unlike Escherichia coli, Mycobacterium tuberculosis (Mt) expresses a Ku-like protein and an ATP-dependent DNA ligase that can perform non-homologous end-joining (NHEJ). We have expressed the Mt-Ku and Mt-Ligase D in E. coli using an arabinose-inducible promoter and expression vectors that integrate into specific sites in the E. coli chromosome. E. coli strains have been generated that express the Mt-Ku and Mt-Ligase D on a genetic background that is wild-type for repair, or deficient in either the RecA or RecB protein. Transformation of these strains with linearized plasmid DNA containing a 2bp overhang has demonstrated that expression of both the Mt-Ku and Mt-Ligase D is required for DNA end-joining and that loss of RecA does not prevent this double-strand break repair. Analysis of the re-joined plasmid has shown that repair is predominantly inaccurate and results in the deletion of sequences. Loss of RecB did not prevent the formation of large deletions, but did increase the amount of end-joining. Sequencing the junctions has revealed that the majority of the ligations occurred at regions of microhomology (1-4bps), eliminating one copy of the homologous sequence at the junction. The Mt-Ku and Mt-Ligase D can therefore function in E. coli to re-circularize linear plasmid.

Serial blood donations for intrauterine transfusions of severe hemolytic disease of the newborn with the use of recombinant erythropoietin in a pregnant woman alloimmunized with anti-Ku.

Science.gov (United States)

Lydaki, Evaggelia; Nikoloudi, Irene; Kaminopetros, Petros; Bolonaki, Irene; Sifakis, Stavros; Kikidi, Katerina; Koumantakis, Evgenios; Foundouli, Kaliopi

2005-11-01

The management of a pregnant woman with the rare Ko phenotype and anti-Ku is a special challenge, because matched blood is extremely rare and the possibility of severe hemolytic disease of the newborn is high. A 30-year-old woman with rare Ko (Knull) phenotype presented at 18 weeks of gestation with positive indirect agglutination test results. She had anti-Ku due to previous blood transfusion, one pregnancy, and two abortions. During this pregnancy, anti-Ku titers ranged from 1024 to 4096. At the 26th week of gestation ultrasound showed a hydropic fetus and urgent intrauterine exchange transfusion was performed with the maternal red blood cells (RBCs). Recombinant human erythropoietin (rHu-EPO) and intravenous (IV) iron were administered to the mother to ensure an adequate supply of matched RBCs for intrauterine transfusions and possible perinatal hemorrhage. Intrauterine transfusions were repeated every 1 to 3 weeks. By 35 weeks 2 days of gestation, the mother had donated 4 units of blood, and four intrauterine transfusions had been performed. Cesarean section was then decided and a healthy male newborn was born. He was treated with phototherapy but without exchange transfusions. By the 15th day of life rHu-EPO was administrated to the newborn because of anemia. The maternal RBCs completely disappeared from the child's blood by Day 100. As shown in this case, treatment with rHu-EPO and IV Fe has effectively increased the mother's capacity to donate RBCs for autologous use and intrauterine transfusions, with no adverse effects to the mother or the child.

Enterocin X, a novel two-peptide bacteriocin from Enterococcus faecium KU-B5, has an antibacterial spectrum entirely different from those of its component peptides.

Science.gov (United States)

Hu, Chih-Bo; Malaphan, Wanna; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

2010-07-01

Enterocin X, composed of two antibacterial peptides (Xalpha and Xbeta), is a novel class IIb bacteriocin from Enterococcus faecium KU-B5. When combined, Xalpha and Xbeta display variably enhanced or reduced antibacterial activity toward a panel of indicators compared to each peptide individually. In E. faecium strains that produce enterocins A and B, such as KU-B5, only one additional bacteriocin had previously been known.

Mammalian peptidylglycine alpha-amidating monooxygenase (PAM) mRNA expression can be modulated by the La autoantigen

DEFF Research Database (Denmark)

Brenet, Fabienne; Dussault, Nadège; Borch, Jonas

2005-01-01

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3' untranslated...... region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt...... downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most...

Initial assessment of an airborne Ku-band polarimetric SAR.

Energy Technology Data Exchange (ETDEWEB)

Raynal, Ann Marie; Doerry, Armin Walter

2013-02-01

Polarimetric synthetic aperture radar (SAR) has been used for a variety of dual-use research applications since the 1940s. By measuring the direction of the electric field vector from radar echoes, polarimetry may enhance an analysts understanding of scattering effects for both earth monitoring and tactical surveillance missions. Polarimetry may provide insight into surface types, materials, or orientations for natural and man-made targets. Polarimetric measurements may also be used to enhance the contrast between scattering surfaces such as man-made objects and their surroundings. This report represents an initial assessment of the utility of, and applications for, polarimetric SAR at Ku-band for airborne or unmanned aerial systems.

Izrada 3D modela kućišta centrifugalne pumpe

OpenAIRE

Hršak, Božidar; Golubić, Stjepan; Carek, Dalibor

2012-01-01

Prikazana je izrada 3D modela kućišta centrifugalne pumpe na temelju postojećeg 2D nacrta gotovog proizvoda primjenom sinkrone tehnologije 3D modeliranja, i reverzibilnog inženjeringa. Na temelju kreiranog 3D modela, predložene su moguće modifikacije postojeće izvedbe proizvoda. Provedene su analize zakrivljenosti površina, Bézierove krivulje modela i 3D geometrije. Prikazana je i mogućnost vizualizacije gotovog 3D modela na Web stranicama u cilju prezentiranja proizvoda budućim kupcima primj...

Enterocin X, a Novel Two-Peptide Bacteriocin from Enterococcus faecium KU-B5, Has an Antibacterial Spectrum Entirely Different from Those of Its Component Peptides▿

Science.gov (United States)

Hu, Chih-Bo; Malaphan, Wanna; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

2010-01-01

Enterocin X, composed of two antibacterial peptides (Xα and Xβ), is a novel class IIb bacteriocin from Enterococcus faecium KU-B5. When combined, Xα and Xβ display variably enhanced or reduced antibacterial activity toward a panel of indicators compared to each peptide individually. In E. faecium strains that produce enterocins A and B, such as KU-B5, only one additional bacteriocin had previously been known. PMID:20418437

Cloning human DNA repair genes

International Nuclear Information System (INIS)

Jeggo, P.A.; Carr, A.M.; Lehmann, A.R.

1994-01-01

Many human genes involved in the repair of UV damage have been cloned using different procedures and they have been of great value in assisting the understanding of the mechanism of nucleotide excision-repair. Genes involved in repair of ionizing radiation damage have proved more difficult to isolate. Positional cloning has localized the XRCC5 gene to a small region of chromosome 2q33-35, and a series of yeast artificial chromosomes covering this region have been isolated. Very recent work has shown that the XRCC5 gene encodes the 80 kDa subunit of the Ku DNA-binding protein. The Ku80 gene also maps to this region. Studies with fission yeast have shown that radiation sensitivity can result not only from defective DNA repair but also from abnormal cell cycle control following DNA damage. Several genes involved in this 'check-point' control in fission yeast have been isolated and characterized in detail. It is likely that a similar checkpoint control mechanism exists in human cells. (author)

EPR study of gamma and neutron irradiation effects on KU1, KS-4V and Infrasil 301 silica glasses

International Nuclear Information System (INIS)

Lagomacini, Juan C.; Bravo, David; Leon, Monica; Martin, Piedad; Ibarra, Angel; Martin, Agustin; Lopez, Fernando J.

2011-01-01

Electron paramagnetic resonance (EPR) studies have been carried out on KU1 and KS-4V high purity quartz glasses and commercial silica Infrasil 301, irradiated with gamma rays up to a dose of 11.6 MGy and neutron fluences of 10 21 and 10 22 n/m 2 . Gamma irradiations produce a much higher concentration of defect centres (mainly E', POR and NBOHC) for KU1 and I301 than for KS-4V silica. In contrast, neutron irradiation at the highest fluence produces similar concentrations in all silica types. These results agree to a good extent with those obtained in previous optical absorption measurements. Moreover, oxygen-related centres (POR and NBOHC) have been well characterized by means of electron paramagnetic resonance.

EPR study of gamma and neutron irradiation effects on KU1, KS-4V and Infrasil 301 silica glasses

Energy Technology Data Exchange (ETDEWEB)

Lagomacini, Juan C., E-mail: jc.lagomacini@uam.es [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Bravo, David [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Leon, Monica; Martin, Piedad; Ibarra, Angel [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain); Martin, Agustin [Dept. Fisica e Instalaciones, ETS Arquitectura UPM, E-28040 Madrid (Spain); Lopez, Fernando J. [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)

2011-10-01

Electron paramagnetic resonance (EPR) studies have been carried out on KU1 and KS-4V high purity quartz glasses and commercial silica Infrasil 301, irradiated with gamma rays up to a dose of 11.6 MGy and neutron fluences of 10{sup 21} and 10{sup 22} n/m{sup 2}. Gamma irradiations produce a much higher concentration of defect centres (mainly E', POR and NBOHC) for KU1 and I301 than for KS-4V silica. In contrast, neutron irradiation at the highest fluence produces similar concentrations in all silica types. These results agree to a good extent with those obtained in previous optical absorption measurements. Moreover, oxygen-related centres (POR and NBOHC) have been well characterized by means of electron paramagnetic resonance.

Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils.

Science.gov (United States)

Higa, Shinji; Hirano, Toru; Kotani, Mayumi; Matsumoto, Motonobu; Fujita, Akihito; Suemura, Masaki; Kawase, Ichiro; Tanaka, Toshio

2003-06-01

Activation of mast cells and basophils through allergen stimulation releases chemical mediators and synthesizes cytokines. Among these cytokines, IL-4, IL-13, and IL-5 have major roles in allergic inflammation. We sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) for the inhibition of cytokine expression and synthesis by human basophils. The inhibitory effect of flavonoids on cytokine expression by stimulated KU812 cells, a human basophilic cell line, and freshly purified peripheral blood basophils was measured by means of semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on transcriptional activation of the nuclear factor of activated T cells were assessed by means of electrophoretic mobility shift assays. Fisetin suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187-stimulated KU812 cells and basophils in response to cross-linkage of the IgE receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively) but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50) = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids examined, kaempferol and quercetin showed substantial inhibitory activities in cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812 cells. These results provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70.

Science.gov (United States)

Boboila, Cristian; Jankovic, Mila; Yan, Catherine T; Wang, Jing H; Wesemann, Duane R; Zhang, Tingting; Fazeli, Alex; Feldman, Lauren; Nussenzweig, Andre; Nussenzweig, Michel; Alt, Frederick W

2010-02-16

Class switch recombination (CSR) in B lymphocytes is initiated by introduction of multiple DNA double-strand breaks (DSBs) into switch (S) regions that flank immunoglobulin heavy chain (IgH) constant region exons. CSR is completed by joining a DSB in the donor S mu to a DSB in a downstream acceptor S region (e.g., S gamma1) by end-joining. In normal cells, many CSR junctions are mediated by classical nonhomologous end-joining (C-NHEJ), which employs the Ku70/80 complex for DSB recognition and XRCC4/DNA ligase 4 for ligation. Alternative end-joining (A-EJ) mediates CSR, at reduced levels, in the absence of C-NHEJ, even in combined absence of Ku70 and ligase 4, demonstrating an A-EJ pathway totally distinct from C-NHEJ. Multiple DSBs are introduced into S mu during CSR, with some being rejoined or joined to each other to generate internal switch deletions (ISDs). In addition, S-region DSBs can be joined to other chromosomes to generate translocations, the level of which is increased by absence of a single C-NHEJ component (e.g., XRCC4). We asked whether ISD and S-region translocations occur in the complete absence of C-NHEJ (e.g., in Ku70/ligase 4 double-deficient B cells). We found, unexpectedly, that B-cell activation for CSR generates substantial ISD in both S mu and S gamma1 and that ISD in both is greatly increased by the absence of C-NHEJ. IgH chromosomal translocations to the c-myc oncogene also are augmented in the combined absence of Ku70 and ligase 4. We discuss the implications of these findings for A-EJ in normal and abnormal DSB repair.

Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies

NARCIS (Netherlands)

Steenbakkers, Peter G. A.; Baeten, Dominique; Rovers, Eric; Veys, Eric M.; Rijnders, Antonius W. M.; Meijerink, Jan; de Keyser, Filip; Boots, Annemieke M. H.

2003-01-01

Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta

Peripheral blood mononuclear cells of patients with latent autoimmune diabetes secrete higher levels of pro- & anti-inflammatory cytokines compared to those with type-1 diabetes mellitus following in vitro stimulation with β-cell autoantigens

Directory of Open Access Journals (Sweden)

Darshan Badal

2017-01-01

Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.

YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

DEFF Research Database (Denmark)

Volck, B; Price, P A; Johansen, J S

1998-01-01

YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function...... of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a source of YKL-40. YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase...... YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential...

A wideband superconducting filter at Ku-band based on interdigital coupling

Science.gov (United States)

Jiang, Ying; Wei, Bin; Cao, Bisong; Li, Qirong; Guo, Xubo; Jiang, Linan; Song, Xiaoke; Wang, Xiang

2018-04-01

In this paper, an interdigital-type resonator with strong electric coupling is proposed for the wideband high-frequency (>10 GHz) filter design. The proposed microstrip resonator consists of an H-shaped main line part with its both ends installed with interdigital finger parts. Strong electric coupling is achieved between adjacent resonators. A six-pole high-temperature superconducting filter at Ku-band using this resonator is designed and fabricated. The filter has a center frequency of 15.11 GHz with a fractional bandwidth of 30%. The insertion loss of the passband is less than 0.3 dB, and the return loss is greater than 14 dB without any tuning.

Immuno-chemistry of hydroxyl radical modified GAD-65: A possible role in experimental and human diabetes mellitus.

Science.gov (United States)

Moinuddin; Ansari, Nadeem A; Shahab, Uzma; Habeeb, Safia; Ahmad, Saheem

2015-10-01

The repertoire of known auto-antigens is limited to a very small proportion of all human proteins, and the reason why only some proteins become auto-antigens is unclear. The 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD-65) is a major auto-antigen in type I diabetes, and in various neurological diseases. Most patients with type I diabetes (70-80%) have auto-antibodies against GAD-65, which often appear years before clinical onset of the autoimmune diabetes. Thus, the aim of the study is to focus on the immunogenicity of GAD65 and its reactive oxygen species (ROS) conformer in STZ-induced diabetic rats and on human diabetic patients. In the present study, GAD-65 was modified by hydroxyl radical following Fenton's reaction. The modifications in the structure of the GAD-65 are supported by UV-vis and fluorescence spectral studies. Immunogenicity of both native and hydroxyl radical modified GAD-65 (ROS-GAD-65) was studied in experimental rabbits and was confirmed by inducing type I diabetes in experimental male albino rats using streptozotocin (45 mg/kg). We found that ROS-GAD-65 was a better immunogen as compared to the native GAD-65. A considerable high binding to ROS-GAD-65 was observed as compared to native GAD-65 in both the serum antibodies from diabetes animal models and as well as in the serum samples of type I diabetes. Hydrogen peroxide under the exposure of UV light produces hydroxyl radical (·OH) which is most potent oxidant, and could cause protein damage (GAD-65) to the extent of generating neo-epitopes on the molecule, thus making it immunogenic. © 2015 International Union of Biochemistry and Molecular Biology.

A creative approach to the development of an agenda for knowledge utilization: outputs from the 11th international knowledge utilization colloquium (KU 11).

Science.gov (United States)

Wilkinson, Joyce E; Rycroft-Malone, Jo; Davies, Huw T O; McCormack, Brendan

2012-12-01

A group of researchers and practitioners interested in advancing knowledge utilization met as a colloquium in Belfast (KU 11) and used a "world café" approach to exploit the social capital and shared understanding built up over previous events to consider the research and practice agenda. We considered three key areas of relevance to knowledge use: (1) understanding the nature of research use, influence and impact; (2) blended and collaborative approaches to knowledge production and use; and (3) supporting sustainability and spread of evidence-informed innovations. The approach enabled the development of artifacts that reflected the three areas and these were analyzed using a creative hermeneutic approach. The themes that emerged and which are outlined in this commentary are not mutually exclusive. There was much overlap in the discussions and therefore of the themes, reflecting the complex nature of knowledge translation work. The agenda that has emerged from KU 11 also reflects the participatory and creative approach in which the meeting was structured and focused, and therefore emphasizes the processual, relational and contingent nature of some of the challenges we face. The past 20 years has seen an explosion in activity around understanding KU, and we have learned much about the difficulties. Whilst the agenda for the next decade may be becoming clearer, colloquia such as KU 11, using creative and engaging approaches, have a key role to play in dissecting, articulating and sharing that agenda. In this way, we also build an ever-expanding international community that is dedicated to working towards increasing the chances of success for better patient care. © 2012 Sigma Theta Tau International.

Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

Science.gov (United States)

Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

2013-01-01

Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

Study of sea-surface slope distribution and its effect on radar backscatter based on Global Precipitation Measurement Ku-band precipitation radar measurements

Science.gov (United States)

Yan, Qiushuang; Zhang, Jie; Fan, Chenqing; Wang, Jing; Meng, Junmin

2018-01-01

The collocated normalized radar backscattering cross-section measurements from the Global Precipitation Measurement (GPM) Ku-band precipitation radar (KuPR) and the winds from the moored buoys are used to study the effect of different sea-surface slope probability density functions (PDFs), including the Gaussian PDF, the Gram-Charlier PDF, and the Liu PDF, on the geometrical optics (GO) model predictions of the radar backscatter at low incidence angles (0 deg to 18 deg) at different sea states. First, the peakedness coefficient in the Liu distribution is determined using the collocations at the normal incidence angle, and the results indicate that the peakedness coefficient is a nonlinear function of the wind speed. Then, the performance of the modified Liu distribution, i.e., Liu distribution using the obtained peakedness coefficient estimate; the Gaussian distribution; and the Gram-Charlier distribution is analyzed. The results show that the GO model predictions with the modified Liu distribution agree best with the KuPR measurements, followed by the predictions with the Gaussian distribution, while the predictions with the Gram-Charlier distribution have larger differences as the total or the slick filtered, not the radar filtered, probability density is included in the distribution. The best-performing distribution changes with incidence angle and changes with wind speed.

Wpływ wysiłku fizycznego na funkcję układu oddechowego w twardzinie układowej

Directory of Open Access Journals (Sweden)

Stanisław Sierakowski

2010-12-01

Full Text Available Cel: Powikłania ze strony układu oddechowego stanowią główną przyczynę zgonów pacjentów z twardziną układową (TU. Tętniczenadciśnienie płucne i śródmiąższowa choroba płuc stanowią najistotniejszez nich. Pacjenci są jednak często zdiagnozowani dopierow późnym okresie choroby, dlatego też istotne jest opracowaniemetody diagnostycznej do wczesnego wykrywania tych powikłań.Celem pracy była ocena wpływu wysiłku fizycznego na zmiany parametrówoddechowych. Materiały i metody: Badania przeprowadzono wśród 32 pacjentów zezdiagnozowaną TU; 72% pacjentów miało postać ograniczoną TU,28% postać uogólnioną. Wykonywano pomiar zdolności dyfuzyjnejpłuc dla tlenku węgla (DLCO, natężonej pojemności życiowej (FVC,natężonej objętości wydechowej pierwszosekundowej (FEV1 orazcałkowitej pojemności płuc (TLC w spoczynku oraz bezpośrednio pozakończeniu wysiłku fizycznego. Wyniki: Pod wpływem wysiłku fizycznego obserwowano wzrostDLCO od 59,7% do 68,1% wartości należnej (p < 0,005. Nie stwierdzononatomiast istotnych statystycznie zmian wartości FVC, FEV1oraz TLC. Wnioski: U chorych na TU zdolność dyfuzyjna płuc dla tlenku węglapo wysiłku fizycznym uległa istotnej statystycznie poprawiew porównaniu z wartościami spoczynkowymi. Związane jest toz koniecznością zapewnienia właściwego utlenowania krwi tętniczeji wynika m.in. ze zwiększenia pojemności łożyska naczyniowego.W klinicznej interpretacji wartości DLCO należy uwzględniać opróczstężenia hemoglobiny i objętości pęcherzykowej także wpływ wysiłkuoraz związane z nim zmiany wielkości objętości rzutu serca.

Efficient gene replacements in ku70 disruption strain of Aspergillus chevalieri var. intermedius

Directory of Open Access Journals (Sweden)

Qingqing Huang

2017-01-01

Full Text Available Aspergillus chevalieri var. intermedius is a dominant filamentous fungal species in Fuzhuan tea and is associated with the quality and health benefits of this tea. The sexual or asexual reproduction of this fungus depends on the osmotic pressure of the tea. Efforts to enhance the beneficial effects of A. chevalieri var. intermedius are hampered by difficulties in disrupting its genes. To address this issue, we identified the A. chevalieri var. intermedius homolog (Acku70 of human Ku70 and generated an Acku70 disruption strain (ΔAcku70, aiming to improve the gene replacement efficiency. ΔAcku70 grew at a slightly lower rate in vitro than the wild-type strain; however, the two strains exhibited similar sensitivity to temperature, osmotic pressure and the effects of ethyl methane sulphonate and H2O2. The replacement efficiency of veA and flbA dramatically increased in ΔAcku70 compared to that in the wild type. The efficiency of flbA replacement increased from 2.6% to 80%, whereas the frequency of veA disruption increased from 15.2% to 83.9% and from 30.8% to 86.8%. Thus, ΔAcku70 is suitable for use as a type strain for large-scale functional genomic analysis of A. chevalieri var. intermedius.

Evaluation of genetic alteration induced by radon gas using the micronucleus test (Tradescantia sp. clone KU-20)

International Nuclear Information System (INIS)

Bruschi, Armando L.; Azevedo, Heliana de; Macacini, Jose F.; Roque, Claudio V.

2011-01-01

The first observations over the existence of radon gas (Rn), initially known as 'thorium emanation', were carried out between the end of 19 th and beginning of 20 th centuries. A result of uranium-238 (U 238 ) radioactive decay, radon is a tasteless, odorless and colorless gas under room temperature, with a 3.825-day half life and particle α emission in its decay, and as final product of its disintegration, the stable lead-206 isotope (Pb 206 ). Being it is the gas with the highest density known, closed and poor ventilated environments are favorable to its accumulation, with its inhalation being the highest health risk. The use of vegetal bioindicators has shown to be excellent on the monitoring of air quality and on mutagenic potential of various pollutants contained in the atmosphere. Within this context, the objective of this study was to evaluate the micronucleus test application potential utilizing the Tradescantia sp. clone KU-20, in order to evaluate genetic alterations induced by radon gas. Stems of Tradescantia sp. clone KU-20, previously immerse in Hoagland solution, were introduced in a radon detection equipment's calibration chamber (Alphaguard), containing radium salt. Afterwards, the accommodated stems were exposed to radon gas (the average radon concentration was 7.639 KBq/m3) for 24 hours. The results demonstrated an increase on micronucleus formation (39.23 + 2.143 MCN/100 tetrads) in stems exposed in relation to the negative control (18.00 + 1.396 MCN/100 tetrads). The difference between the values indicated a significant increase on micronucleus frequency in the inflorescences subjected to radon gas. The presented results demonstrated the micronucleus test application potential using Tradescantia clone KU-20 to evaluate genetic effects induced by radon gas. (author)

Improved foilless Ku-band transit-time oscillator for generating gigawatt level microwave with low guiding magnetic field

Energy Technology Data Exchange (ETDEWEB)

Ling, Junpu; He, Juntao, E-mail: hejuntao12@163.com; Zhang, Jiande; Jiang, Tao; Hu, Yi [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-09-15

An improved foilless Ku-band transit-time oscillator with low guiding magnetic field is proposed and investigated in this paper. With a non-uniform buncher and a coaxial TM{sub 02} mode dual-resonant reflector, this improved device can output gigawatt level Ku-band microwave with relatively compact radial dimensions. Besides the above virtue, this novel reflector also has the merits of high TEM reflectance, being more suitable for pre-modulating the electron beam and enhancing the conversion efficiency. Moreover, in order to further increase the conversion efficiency and lower the power saturation time, a depth-tunable coaxial collector and a resonant cavity located before the extractor are employed in our device. Main structure parameters of the device are optimized by particle in cell simulations. The typical simulation result is that, with a 380 kV, 8.2 kA beam guided by a magnetic field of about 0.6 T, 1.15 GW microwave pulse at 14.25 GHz is generated, yielding a conversion efficiency of about 37%.

Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80▿ †

Science.gov (United States)

Wei, Leizhen; Lan, Li; Hong, Zehui; Yasui, Akira; Ishioka, Chikashi; Chiba, Natsuko

2008-01-01

BRCA1 is the first susceptibility gene to be linked to breast and ovarian cancers. Although mounting evidence has indicated that BRCA1 participates in DNA double-strand break (DSB) repair pathways, its precise mechanism is still unclear. Here, we analyzed the in situ response of BRCA1 at DSBs produced by laser microirradiation. The amino (N)- and carboxyl (C)-terminal fragments of BRCA1 accumulated independently at DSBs with distinct kinetics. The N-terminal BRCA1 fragment accumulated immediately after laser irradiation at DSBs and dissociated rapidly. In contrast, the C-terminal fragment of BRCA1 accumulated more slowly at DSBs but remained at the sites. Interestingly, rapid accumulation of the BRCA1 N terminus, but not the C terminus, at DSBs depended on Ku80, which functions in the nonhomologous end-joining (NHEJ) pathway, independently of BARD1, which binds to the N terminus of BRCA1. Two small regions in the N terminus of BRCA1 independently accumulated at DSBs and interacted with Ku80. Missense mutations found within the N terminus of BRCA1 in cancers significantly changed the kinetics of its accumulation at DSBs. A P142H mutant failed to associate with Ku80 and restore resistance to irradiation in BRCA1-deficient cells. These might provide a molecular basis of the involvement of BRCA1 in the NHEJ pathway of the DSB repair process. PMID:18936166

Izrada 3D modela kućišta ravnog ventila DN 50

OpenAIRE

Hršak, Božidar; Golubić, Stjepan; Bošnjak, Matej

2012-01-01

Prikazana je izrada 3D modela kućišta centrifugalne pumpe na temelju postojećeg 2D nacrta gotovog proizvoda primjenom sinkrone tehnologije 3D modeliranja, i reverzibilnog inženjeringa. Na temelju kreiranog 3D modela, predložene su moguće modifikacije postojeće izvedbe proizvoda. Provedene su analize zakrivljenosti površina, Bézierove krivulje modela i 3D geometrije. Prikazana je i mogućnost vizualizacije gotovog 3D modela na Web stranicama u cilju prezentiranja proizvoda budućim kupcima primj...

Shuttle Ku-band bent-pipe implementation considerations. [for Space Shuttle digital communication systems

Science.gov (United States)

Batson, B. H.; Seyl, J. W.; Huth, G. K.

1977-01-01

This paper describes an approach for relay of data-modulated subcarriers from Shuttle payloads through the Shuttle Ku-band communications subsystem (and subsequently through a tracking and data relay satellite system to a ground terminal). The novelty is that a channel originally provided for baseband digital data is shown to be suitable for this purpose; the resulting transmission scheme is referred to as a narrowband bent-pipe scheme. Test results demonstrating the validity of the narrowband bent-pipe mode are presented, and limitations on system performance are described.

Detailed modeling of local anisotropy and transverse Ku interplay regarding hysteresis loop in FeCuNbSiB nanocrystalline ribbons

Science.gov (United States)

Geoffroy, Olivier; Boust, Nicolas; Chazal, Hervé; Flury, Sébastien; Roudet, James

2018-04-01

This article focuses on the modeling of the hysteresis loop featured by Fe-Cu-Nb-Si-B nanocrystalline alloys with transverse induced anisotropy. The magnetization reversal process of a magnetic correlated volume (CV), characterized by the induced anisotropy Ku, and a deviation of the local easy magnetization direction featuring the effect of a local incoherent anisotropy Ki, is analyzed, taking account of magnetostatic interactions. Solving the equations shows that considering a unique typical kind of CV does not enable accounting for both the domain pattern and the coercivity. Actually, the classical majority CVs obeying the random anisotropy model explains well the domain pattern but considering another kind of CVs, minority, mingled with classical ones, featuring a magnitude of Ki comparable to Ku, is necessary to account for coercivity. The model has been successfully compared with experimental data.

The orthologue of Sjögren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

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Helen P Price

Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens.

Science.gov (United States)

Lapierre, Pascal; Djilali-Saiah, Idriss; Vitozzi, Susana; Alvarez, Fernando

2004-04-01

Autoimmune hepatitis (AIH) is characterized by an immune-mediated injury of the hepatic parenchyma of unknown pathogenesis. Type 2 AIH is identified by the presence of anti-liver-kidney microsomes type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) autoantibodies. The current study shows that a murine model of AIH can be generated by DNA immunization against type 2 AIH self-antigens (P450 2D6 and formiminotransferase-cyclodeaminase). A pCMV plasmid containing the N-terminal region of mouse CTLA-4 and the antigenic region of human CYP2D6 (672-1,377 bp) and human formiminotransferase cyclodeaminase (FTCD; 1,232-1,668 bp) was used for DNA immunization of C57BL/6 female mice. Immunized mice showed elevated levels of alanine aminotransferase (ALT), with peaks at 4 and 7 months postinjection. Periportal, portal, and intralobular liver inflammatory infiltrates were observed at histology. Mainly CD4+ lymphocytes, but also CD8+ and B lymphocytes, were found in the liver. Cytotoxic-specific T cells were found in both the liver and spleen of these animals. Mice developed anti-LKM1 and anti-LC1 antibodies of immunoglobulin G2 (IgG2) subclass, against specific mouse autoantigens. The ALT levels correlated with both the presence of anti-LKM1/anti-LC1 antibodies and the presence of liver necroinflammation. In conclusion, in mice, DNA immunization against human autoantigens breaks tolerance and induces an autoimmune liver disease. Molecular mimicry between foreign and self-antigens explains the liver injury. This model of AIH resembles human type 2 AIH and will be helpful for the study of its pathogenesis.

Origin of absorption peaks in reflection loss spectrum in Ku- frequency band of Co-Zr substituted strontium hexaferrites prepared using sucrose precursor

Energy Technology Data Exchange (ETDEWEB)

Narang, Sukhleen Bindra, E-mail: sukhleen2@yahoo.com [Department of Electronics Technology, Guru Nanak Dev University, Amritsar (India); Pubby, Kunal, E-mail: kunalpubby02@gmail.com [Department of Electronics Technology, Guru Nanak Dev University, Amritsar (India); Chawla, S.K., E-mail: sschawla118@gmail.com [Department of Chemistry, Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar (India); Kaur, Prabhjyot, E-mail: prabhjyot.2525@gmail.com [Department of Chemistry, Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar (India)

2017-03-15

This study presents the detailed explanation of the factors, contributing towards the absorption peaks in reflection loss spectrum of hexaferrites. Cobalt-Zirconium substituted strontium hexaferrites, synthesized using sucrose precursor sol-gel technique, were analyzed in 12.4–18 GHz frequency range. The concepts of impedance matching through quarter wavelength condition, complex thickness, dielectric phase angle and attenuation constant have been used to determine the location as well as intensity of absorption peaks. This study also demonstrates the potential application of three compositions of this series with doping content (x)==0.0, 0.6 and 0.8 as an effective microwave absorbers in Ku-frequency band. - Highlights: • EM analysis of Sr Hexaferrites in Ku-band. • Factors towards absorption peak intensity & location.

Analysis of Standards Efficiency in Digital Television Via Satellite at Ku and Ka Bands

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Landeros-Ayala Salvador

2013-06-01

Full Text Available In this paper, an analysis on the main technical features of digital television standards for satellite transmission is carried out. Based on simulations and link budgets, the standard with the best operational performance is defined, based on simulations and link budget analysis, as well as a comparative efficiency analysis is conducted for the Ku and Ka bands for both transparent and regenerative transponders in terms of power, bandwidth, information rate and link margin, including clear sky, uplink rain, downlink rain and rain in both.

Investigation on the performance of an optically generated RF local oscillator signal in Ku-band DVB-S systems

NARCIS (Netherlands)

Khan, M.R.H.; Marpaung, D.A.I.; Burla, M.; Roeloffzen, C.G.H.; Bernhardi, Edward; de Ridder, R.M.

2011-01-01

We investigate a way to externally generate the local oscillator (LO) signal used for downconversion of the Ku-band (10.7 − 12.75 GHz) RF signal received from a phased array antenna (PAA). The signal is then translated to an intermediate frequency (950 − 2150 MHz) at the output of the mixer of

The pretreatment of corn stover with Gloeophyllum trabeum KU-41 for enzymatic hydrolysis

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Gao Ziqing

2012-05-01

Full Text Available Abstract Background Pretreatment is an essential step in the enzymatic hydrolysis of biomass for bio-ethanol production. The dominant concern in this step is how to decrease the high cost of pretreatment while achieving a high sugar yield. Fungal pretreatment of biomass was previously reported to be effective, with the advantage of having a low energy requirement and requiring no application of additional chemicals. In this work, Gloeophyllum trabeum KU-41 was chosen for corn stover pretreatment through screening with 40 strains of wood-rot fungi. The objective of the current work is to find out which characteristics of corn stover pretreated with G. trabeum KU-41 determine the pretreatment method to be successful and worthwhile to apply. This will be done by determining the lignin content, structural carbohydrate, cellulose crystallinity, initial adsorption capacity of cellulase and specific surface area of pretreated corn stover. Results The content of xylan in pretreated corn stover was decreased by 43% in comparison to the untreated corn stover. The initial cellulase adsorption capacity and the specific surface area of corn stover pretreated with G. trabeum were increased by 7.0- and 2.5-fold, respectively. Also there was little increase in the cellulose crystallinity of pretreated corn stover. Conclusion G. trabeum has an efficient degradation system, and the results indicated that the conversion of cellulose to glucose increases as the accessibility of cellulose increases due to the partial removal of xylan and the structure breakage of the cell wall. This pretreatment method can be further explored as an alternative to the thermochemical pretreatment method.

Study of the Effect of Simulated Rain on the Offset Parabolic Antenna at Ku-Band with Different Elevation Angles

Directory of Open Access Journals (Sweden)

H. Mostafa

2007-01-01

Full Text Available Effect of rain on the receiver antenna is a major factor to degrade the system performance in a frequency above 10 GHz. This paper deals with the wet antenna attenuation at Ku-band with three different frequencies at different rain rates. During the Ku-band propagation experiment, it was discovered that rain water on the antenna caused a significant attenuation. It is necessary to estimate the losses caused by water on the antenna in order to separate these losses from the atmospheric propagation losses. The experiment was done at USM Engineering Campus to study the attenuation for these physical parameters. A Ku-band RF signal was generated by a signal generator and transmitted via horn antenna. The signal was received using a smooth offset antenna of 60 cm by 54 cm (Astro dish and measured using spectrum analyzer. In order to simulate a rain, pipes with bores of a same distance were implemented. Three cases were considered: in the first case one pipe was used to simulate low rain rate, the second case two pipes were used to simulate medium rain rate, and the third case three pipes were used to simulate heavy rain rate. In addition, the tap was used to control the flow of water in order to get more values of rain rate. The total attenuation of RF signals due to water layer on the feed and on the reflector feed was found to be 3.1 dB at worst case. On the other hand, the attenuation of RF signal due to the feed only was 2.83 dB, so the major attenuation occur was due to feed.

New uranium chalcoantimonates, RbU{sub 2}SbS{sub 8} and KU{sub 2}SbSe{sub 8}, with a polar noncentrosymmetric structure

Energy Technology Data Exchange (ETDEWEB)

Choi, K S; Kanatzidis, M G

1999-09-01

The new compounds, RbU{sub 2}SbS{sub 8} and KU{sub 2}SbSe{sub 8}, were prepared as golden-black, blocklike crystals by the polychalcogenide molten flux method. RbU{sub 2}SbS{sub 8} has a two-dimensional character with layers running perpendicular to the c-axis. The coordination geometry around the U{sup 4+} atoms is best described as a bicapped trigonal prism. The trigonal prisms share triangular faces with neighboring prisms, forming one-dimensional columns along the a-axis. The columns are then joined to construct sheets by sharing capping S atoms. Sb{sup 3+} ions are sitting at the center of a slightly distorted seesaw coordination environment (CN = 4). Rb{sup +} ions are stabilized in 8-coordinate bicapped trigonal prismatic sites. KU{sub 2}SbSe{sub 8} has essentially the same structure as RbU{sub 2}SbS{sub 8}. However, Sb{sup 3+} and K{sup +} ions appear disordered in every other layer resulting in a different unit cell. RbU{sub 2}SbS{sub 8} is a semiconductor with a band gap of 1.38 eV. The band gap of KU{sub 2}SbSe{sub 8} could not be determined precisely due to the presence of overlapping intense f-f transitions in the region (0.5--1.1 eV). The Raman spectra show the disulfide stretching vibration in RbU{sub 2}SbS{sub 8} at 479 cm{sup {minus}1} and the diselenide stretching vibration in KU{sub 2}SbSe{sub 8} at 252 cm{sup {minus}1}. Magnetic susceptibility measurements indicate the presence of U{sup 4+} centers in the compounds. The compounds do not melt below 1,000 C under vacuum.

STS-79 Ku-band antenna, ODS and Spacehab module at PCR

Science.gov (United States)

1996-01-01

The orbiter Ku-band antenna looms large in this view of the Space Shuttle Atlantis' payload bay. Visible just past the antenna system -- stowed on the starboard side of the payload bay wall -- is the Orbiter Docking System (ODS), and connected to the ODS via a tunnel is the Spacehab Double Module in the aft area of the payload bay. This photograph was taken from the starboard wing platform on the fifth level of the Payload Changeout Room (PCR) at Launch Pad 39A. Work is under way in the PCR to close Atlantis' payload bay doors for flight. Atlantis currently is being targeted for liftoff on Mission STS-79, the fourth docking of the U.S. Shuttle to the Russian Space Station Mir, around September 12.

Analysis of Fade Dynamic at Ku-Band in Malaysia

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Siat Ling Jong

2014-01-01

Full Text Available This work investigates fade dynamics of satellite communication systems in equatorial heavy rain region based on a one year of Ku-band propagation measurement campaign carried out in Universiti Teknologi Malaysia (UTM, Johor, Malaysia. First order statistics of rain attenuation are deduced and the results are found to be in good agreement with those obtained from other beacon measurements gathered within the same area (Kuala Lumpur. Moreover, the fade duration and slope statistics of the satellite signal variations are also carefully derived and subsequently compared with the ITU-R recommendation model. Such information is useful for the system operator and radio communication engineer for the design of appropriate fade mitigation techniques as well as the quality of service that could be offered to the user (according to the time interval for a typical day. Further evaluation on the performances of several ITU-R models in the heavy rain region are needed based on the measurement database available of this climatic region.

55K isoform of CDK9 associates with Ku70 and is involved in DNA repair

International Nuclear Information System (INIS)

Liu, Hongbing; Herrmann, Christine H.; Chiang, Karen; Sung, Tzu-Ling; Moon, Sung-Hwan; Donehower, Lawrence A.; Rice, Andrew P.

2010-01-01

Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.

Leiomodins: larger members of the tropomodulin (Tmod) gene family

Science.gov (United States)

Conley, C. A.; Fritz-Six, K. L.; Almenar-Queralt, A.; Fowler, V. M.

2001-01-01

The 64-kDa autoantigen D1 or 1D, first identified as a potential autoantigen in Graves' disease, is similar to the tropomodulin (Tmod) family of actin filament pointed end-capping proteins. A novel gene with significant similarity to the 64-kDa human autoantigen D1 has been cloned from both humans and mice, and the genomic sequences of both genes have been identified. These genes form a subfamily closely related to the Tmods and are here named the Leiomodins (Lmods). Both Lmod genes display a conserved intron-exon structure, as do three Tmod genes, but the intron-exon structure of the Lmods and the Tmods is divergent. mRNA expression analysis indicates that the gene formerly known as the 64-kDa autoantigen D1 is most highly expressed in a variety of human tissues that contain smooth muscle, earning it the name smooth muscle Leiomodin (SM-Lmod; HGMW-approved symbol LMOD1). Transcripts encoding the novel Lmod gene are present exclusively in fetal and adult heart and adult skeletal muscle, and it is here named cardiac Leiomodin (C-Lmod; HGMW-approved symbol LMOD2). Human C-Lmod is located near the hypertrophic cardiomyopathy locus CMH6 on human chromosome 7q3, potentially implicating it in this disease. Our data demonstrate that the Lmods are evolutionarily related and display tissue-specific patterns of expression distinct from, but overlapping with, the expression of Tmod isoforms. Copyright 2001 Academic Press.

Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.

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Xiao-yu Jia

Full Text Available The autoantigen of anti-glomerular basement membrane (GBM disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IVNC1. Our previous study revealed a peptide on α3(IVNC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150. This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14.16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA.We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P<0.001. P14c was the core immunogenic region and the amino acid sequence (ISLWKGFSFIMFT was highly hydrophobic. Each amino acid residue in P14c was sequentially replaced by alanine. Three residues of glycine142, phenylalanine143, and phenylalanine145 were identified crucial for antibody binding based on the remarkable decline (P<0.001 of antibody reaction after each residue replacement.We defined GFxF (α3142, 143,145 as the critical motif of P14. It may provide some clues for understanding the etiology of anti-GBM disease.

Türkiye’de Çalışan Y Kuşağında İş Tatmini-Motivasyon İlişkisi

OpenAIRE

Saracel, Nüket; Taşseven, Özlem; Kaynak, Ece

2016-01-01

Bilgi çağı olarak nitelenen yirmi birinci yüzyılda, bilgi ve insan organizasyonların en önemli sermayesihaline gelmiştir. Üretim kaynakları içerisinde insanın öneminin artması şirketlerin yönetiminde insangücünün motivasyonu ve iş tatminine ilişkin konuların özel önem taşıyan konular olmasını beraberindegetirmiştir. Birbirlerine yakın zamanlarda doğan insanların benzer özellikler taşıması kuşak kavramınıortaya çıkarmıştır. Her bir kuşağın farklı özelliklerinin olması, organizasyonel sistemler...

Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells.

Directory of Open Access Journals (Sweden)

Cyndi Chen

Full Text Available BACKGROUND: Both naturally arising Foxp3(+ and antigen-induced Foxp3(- regulatory T cells (Treg play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel class II MHC tetramer, we have isolated a population of CD4(+ Foxp3(- T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells from diabetes-resistant non-obese resistant (NOR mice. These Foxp3(- NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. CONCLUSIONS/SIGNIFICANCE: These studies identified a unique population of autoantigen-specific Foxp3(- Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.

Impact of tropospheric scintillation in the Ku/K bands on the communications between two LEO satellites in a radio occultation geometry

DEFF Research Database (Denmark)

Martini, Enrica; Freni, A.; Facheris, L.

2006-01-01

A theoretical analysis of the impact of clear-air tropospheric scintillation on a radio occultation link between two low Earth orbit satellites in K- and Ku-bands is presented, with particular reference to differential approaches for the measure of the total content of water vapor. The troposphere...

Prokaryotic Homologs of the Eukaryotic 3-Hydroxyanthranilate 3,4-Dioxygenase and 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase in the 2-Nitrobenzoate Degradation Pathway of Pseudomonas fluorescens Strain KU-7†

OpenAIRE

Muraki, Takamichi; Taki, Masami; Hasegawa, Yoshie; Iwaki, Hiroaki; Lau, Peter C. K.

2003-01-01

The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase a...

Design of a Type-1 Diabetes Vaccine Candidate Using Edible Plants Expressing a Major Autoantigen

Directory of Open Access Journals (Sweden)

Edoardo Bertini

2018-05-01

Full Text Available Type-1 diabetes (T1D is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65. Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing. Here we combined edible plant systems, namely spinach (Spinacia oleracea cv Industra and red beet (Beta vulgaris cv Moulin Rouge, with the magnICON® expression system to develop a safe, cost-effective and environmentally sustainable platform for the large-scale production of GAD65. The superior red beet platform was extensively characterized in terms of recombinant protein yields and bioequivalence to wild-type plants, and the product was tested for its ability to resist simulated gastric digestion. Our results indicate that red beet plants are suitable for the production of a candidate oral vaccine based on GAD65 for the future preclinical and clinical testing of T1D immunotherapy approaches.

A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell

Science.gov (United States)

Hong, Zehui; Jiang, Jie; Lan, Li; Nakajima, Satoshi; Kanno, Shin-ichiro; Koseki, Haruhiko; Yasui, Akira

2008-01-01

DNA double-strand breaks (DSBs) represent the most toxic DNA damage arisen from endogenous and exogenous genotoxic stresses and are known to be repaired by either homologous recombination or nonhomologous end-joining processes. Although many proteins have been identified to participate in either of the processes, the whole processes still remain elusive. Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in gene silencing, cancer development and the maintenance of embryonic and adult stem cells. By screening proteins responding to DNA damage using laser micro-irradiation, we found that PHF1, a human homolog of Drosophila polycomb-like, Pcl, protein, was recruited to DSBs immediately after irradiation and dissociated within 10 min. The accumulation at DSBs is Ku70/Ku80-dependent, and knockdown of PHF1 leads to X-ray sensitivity and increases the frequency of homologous recombination in HeLa cell. We found that PHF1 interacts physically with Ku70/Ku80, suggesting that PHF1 promotes nonhomologous end-joining processes. Furthermore, we found that PHF1 interacts with a number of proteins involved in DNA damage responses, RAD50, SMC1, DHX9 and p53, further suggesting that PHF1, besides the function in PcG, is involved in genome maintenance processes. PMID:18385154

Chemical compatibility study of Cooley L18KU, Herculite, and Elephant Mat with Hanford tank waste

International Nuclear Information System (INIS)

Mercado, J.E.

1998-01-01

An independent chemical compatibility review of various wrapping and absorbent/padding materials was conducted to evaluate resistance to chemicals and constituents present in liquid waste from the Hanford underground tanks. These materials will be used to wrap long-length contaminated equipment when such equipment is removed from the tanks and prepared for transportation and subsequent disposal or storage. The materials studied were Cooley L18KU, Herculite, and Elephant Mat. The study concludes that these materials are appropriate for use in this application

In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

DEFF Research Database (Denmark)

Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

2008-01-01

in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

Room Temperature Thin Film Ba(x)Sr(1-x)TiO3 Ku-Band Coupled MicrostripPhase Shifters: Effects of Film Thickness, Doping, Annealing and Substrate Choice

Science.gov (United States)

VanKeuls, F. W.; Mueller, C. H.; Miranda, F. A.; Romanofsky, R. R.; Canedy, C. L.; Aggarwal, S.; Venkatesan, T.; Ramesh, R.; Horwitz, S.; Chang, W.

1999-01-01

We report on measurements taken on over twenty Ku-band coupled microstrip phase shifters (CMPS) using thin ferroelectric films of Ba(x)Sr(1-x)TiO3. This CMPS design is a recent innovation designed to take advantage of the high tunability and tolerate the high dielectric constant of ferroelectric films at Ku- and K-band frequencies. These devices are envisioned as a component in low-cost steerable beam phased area antennas, Comparisons are made between devices with differing film thickness, annealed vs unannealed, Mn-doped vs. undoped, and also substrates of LaAlO3 and MgO. A comparison between the CMPS structure and a CPW phase shifter was also made oil the same ferroelectric film.

PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.

Science.gov (United States)

Granito, Alessandro; Yang, Wei-Hong; Muratori, Luigi; Lim, Mark J; Nakajima, Ayako; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Bianchi, Francesco B; Bloch, Donald B; Muratori, Paolo

2010-01-01

Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identified using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients. We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies. Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific clinical feature of PBC. Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic significance of these reactivities, which are particularly useful in AMA-negative cases.

The master two-dimensional gel database of human AMA cell proteins: towards linking protein and genome sequence and mapping information (update 1991)

DEFF Research Database (Denmark)

Celis, J E; Leffers, H; Rasmussen, H H

1991-01-01

autoantigens" and "cDNAs". For convenience we have included an alphabetical list of all known proteins recorded in this database. In the long run, the main goal of this database is to link protein and DNA sequencing and mapping information (Human Genome Program) and to provide an integrated picture......The master two-dimensional gel database of human AMA cells currently lists 3801 cellular and secreted proteins, of which 371 cellular polypeptides (306 IEF; 65 NEPHGE) were added to the master images during the last 10 months. These include: (i) very basic and acidic proteins that do not focus...

Focusing electrode and coaxial reflector used for reducing the guiding magnetic field of the Ku-band foilless transit-time oscillator

Energy Technology Data Exchange (ETDEWEB)

Ling, Junpu; Zhang, Jiande; He, Juntao, E-mail: hejuntao12@163.com; Wang, Lei; Deng, Bingfang [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-08-15

Based on the theoretical analysis of the intense relativistic electron beam propagation in the coaxial drift-tube, a focusing electrode and a coaxial reflector is proposed to lessen the demand of the coaxial Ku-band foilless transit-time oscillator (TTO) for the guiding magnetic field. Moreover, a Ku-band TTO with the focusing electrode and the coaxial reflector is designed and studied by particle in cell simulation. When the diode voltage is 390 kV, the beam current 7.8 kA, and the guiding magnetic field is only 0.3 T, the device can output 820 MW microwave pulse at 14.25 GHz by means of the simulation. However, for the device without them, the output power is only 320 MW. The primary experiments are also carried out. When the guiding magnetic field is 0.3 T, the output power of the device with the focusing electrode and the coaxial reflector is double that of the one without them. The simulation and experimental results prove that the focusing electrode and the coaxial reflector are effective on reducing the guiding magnetic field of the device.

Design studies of the Ku-band, wide-band Gyro-TWT amplifier

Science.gov (United States)

Jung, Sang Wook; Lee, Han Seul; Jang, Kwong Ho; Choi, Jin Joo; Hong, Yong Jun; Shin, Jin Woo; So, Jun Ho; Won, Jong Hyo

2014-02-01

This paper reports a Ku-band, wide band Gyrotron-Traveling-wave-tube(Gyro-TWT) that is currently being developed at Kwangwoon University. The Gyro-TWT has a two stage linear tapered interaction circuit to obtain a wide operating bandwidth. The linearly-tapered interaction circuit and nonlinearly-tapered magnetic field gives the Gyro-TWT a wide operating bandwidth. The Gyro-TWT bandwidth is 23%. The 2d-Particle-in-cell(PIC) and MAGIC2d code simulation results are 17.3 dB and 24.34 kW, respectively for the maximum saturated output power. A double anode MIG was simulated with E-Gun code. The results were 0.7 for the transvers to the axial beam velocity ratio (=alpha) and a 2.3% axial velocity spread at 50 kV and 4 A. A magnetic field profile simulation was performed by using the Poisson code to obtain the grazing magnetic field of the entire interaction circuit with Poisson code.

Impact of Surface Soil Moisture Variations on Radar Altimetry Echoes at Ku and Ka Bands in Semi-Arid Areas

Directory of Open Access Journals (Sweden)

Christophe Fatras

2018-04-01

Full Text Available Radar altimetry provides information on the topography of the Earth surface. It is commonly used for the monitoring not only sea surface height but also ice sheets topography and inland water levels. The radar altimetry backscattering coefficient, which depends on surface roughness and water content, can be related to surface properties such as surface soil moisture content. In this study, the influence of surface soil moisture on the radar altimetry echo and backscattering coefficient is analyzed over semi-arid areas. A semi-empirical model of the soil’s complex dielectric permittivity that takes into account that small-scale roughness and large-scale topography was developed to simulate the radar echoes. It was validated using waveforms acquired at Ku and Ka-bands by ENVISAT RA-2 and SARAL AltiKa respectively over several sites in Mali. Correlation coefficients ranging from 0.66 to 0.94 at Ku-band and from 0.27 to 0.96 at Ka-band were found. The increase in surface soil moisture from 0.02 to 0.4 (i.e., the typical range of variations in semi-arid areas increase the backscattering from 10 to 15 dB between the core of the dry and the maximum of the rainy seasons.

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

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Kostianets Olga

2012-11-01

Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

Zamyšlení nad charakterem vůdčí vrstvy městského obyvatelstva na příkladu Brna v raném novověku. Diskusní příspěvek

Czech Academy of Sciences Publication Activity Database

Sulitková, Ludmila

2004-01-01

Roč. 22, - (2004), s. 243-260, 383-384 ISSN 0231-7443. [Pražské městské elity středověku a raného novověku - jejich proměny, zázemí a kulturní profil. Praha, 01.10.2002-02.10.2002] Institutional research plan: CEZ:AV0Z8077915 Keywords : municipal elites * Early Modern Ages * Brno Subject RIV: AB - History

Low-loss negative index metamaterials for X, Ku, and K microwave bands

Directory of Open Access Journals (Sweden)

David A. Lee

2015-04-01

Full Text Available Low-loss, negative-index of refraction metamaterials were designed and tested for X, Ku, and K microwave frequency bands. An S-shaped, split-ring resonator was used as a unit cell to design homogeneous slabs of negative-index metamaterials. Then, the slabs of metamaterials were cut unto prisms to measure experimentally the negative index of refraction of a plane electromagnetic wave. Theoretical simulations using High-Frequency Structural Simulator, a finite element equation solver, were in good agreement with experimental measurements. The negative index of refraction was retrieved from the angle- and frequency-dependence of the transmitted intensity of the microwave beam through the metamaterial prism and compared well to simulations; in addition, near-field electromagnetic intensity mapping was conducted with an infrared camera, and there was also a good match with the simulations for expected frequency ranges for the negative index of refraction.

Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

Directory of Open Access Journals (Sweden)

Sandra M. McLachlan

2017-12-01

Full Text Available Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg, thyroid peroxidase (TPO, and the thyrotropin receptor (TSHR A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of spontaneously arising pathogenic TSHR antibodies in transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic form of TSHR A-subunit protein also provides evidence for original antigenic sin. From other studies, antigen presentation by B cells, not dendritic cells, is likely responsible for original antigenic sin. Recognition of restricted epitopes on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO, and 600-kDa Tg facilitates exploring the amino acid locations in the immunodominant regions. Epitope spreading has also been revealed by autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously develop autoimmunity to all three thyroid autoantigens, autoantibodies develop first to Tg and later to TPO and the TSHR A-subunit. The pattern of intermolecular epitope spreading is related in part to the thyroidal content of Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins. Importantly, the epitope spreading pattern provides a rationale for future antigen-specific manipulation to block the development of all thyroid autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade. Because of its abundance, Tg may be the autoantigen of choice to explore antigen-specific treatment, preventing the development of pathogenic TSHR antibodies.

Generation, Transformation and Place in Inga Iwasiów’s Novels Bambino (2008 and Ku słońcu (2010

Directory of Open Access Journals (Sweden)

Ursula PHILLIPS

2012-06-01

Full Text Available This chapter will discuss two novels by contemporary writer Inga Iwasiów (b. 1963, Bambino (2008 and Ku słońcu [Towards the Sun] (2010, in the context of geopolitical, ideological, social and psycho-cultural transformations as they specifically affect different generations of inhabitants of the Polish city of Szczecin (pre-1945 German Stettin from 1945 until the first decade of the 21st century. Bambino covers the years 1945–1981, but also contains flashbacksto pre-war memory of Stettin and to the suppressed experiences of the new post-war inhabitants, as well as ‘flash-forwards’ to post-1989, post-communist reality; Ku słońcu covers 1981 to the first decade of 2000s. It will show how the novels portray these transformations through the experience primarily of women (but not only — in Bambino, through the main protagonists: Ula (formerly Ulrike, Anna and Marysia, and through that of the hidden narrator Magda (Marysia’s daughter born in the same year as the author, Iwasiów, 1963; and in Ku słońcu, primarily through the experience of Magda herself, as well as through that of two generations of ‘feminist’ academics: Małgorzata and Sylwia (in which it is hard not to perceive the personal experience of the author, though she is at pains to emphasize elsewhere that her work is a collective biography of the city, not so much of herself. The analysis follows Katarzyna Chmielewska’s supposition that contemporary Polish fiction dealing with the past ‘constantly oscillates between memory and genealogy’, and that it raises raw issues not yet addressed by historians; it also derives inspiration from the new ‘postdependency’ studiesproposed by Hanna Gosk and Ryszard Nycz. It also attempts to capture the specific nature of Iwasiów’s use of language, her style of feminism, her method of portraying place, and the connections in her prose between place and memory.

Akadēmiskās pašregulācijas saistība ar pusaudžu personības iezīmēm un vecāku audzināšanas stiliem

OpenAIRE

Iliško, Judīte

2016-01-01

Maģistra darba pētījuma mērķis bija noskaidrot, kāda saistība pastāv starp pusaudžu pašnovērtēto akadēmisko pašregulāciju, vecāku audzināšanas stiliem un pusaudžu personības iezīmēm, kā arī, vai pastāv dzimuma atšķirības starp pusaudžu pašnovērtēto akadēmisko pašregulāciju, vecāku audzināšanas stiliem un personības iezīmēm, un, cik lielā mērā pusaudžu personības iezīmes un vecāku audzināšanas stili prognozē pusaudžu akadēmisko pašregulāciju. Pētījumā piedalījās 225 7.-8.klašu skolēni no vien...

Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders

International Nuclear Information System (INIS)

Perrot, A; Pionneau, C; Azar, N; Baillou, C; Lemoine, F M; Leblond, V; Merle-Béral, H; Béné, M-C; Herbrecht, R; Bahram, S; Vallat, L

2012-01-01

Waldenström's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative disorder (LPD) of post-germinal center nature. Despite the fact that the precise molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the disease is the absence of the immunoglobulin heavy chain class switch recombination. Using two-dimensional gel electrophoresis, we compared proteomic profiles of WM cells with that of other LPDs. We were able to demonstrate that WM constitutes a unique proteomic entity as compared with chronic lymphocytic leukemia and marginal zone lymphoma. Statistical comparisons of protein expression levels revealed that a few proteins are distinctly expressed in WM in comparison with other LPDs. In particular we observed a major downregulation of the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and RNA levels in an independent cohort of patients. Hence, we define a distinctive proteomic profile for WM where the downregulation of Ku70—a component of the non homologous end-joining pathway—might be relevant in disease pathophysiology

Reduction of intergranular exchange coupling and grain size for high Ku CoPt-based granular media: Metal-oxide buffer layer and multiple oxide boundary materials

Science.gov (United States)

Tham, Kim Kong; Kushibiki, Ryosuke; Kamada, Tomonari; Hinata, Shintaro; Saito, Shin

2018-05-01

Investigation of magnetic properties and microstructure of granular media with various multiple oxides as the grain boundary material is reported. Saturation magnetization (Ms), uniaxial magnetocrystalline anisotropy (Ku), and magnetic grain diameter (GD) of the granular media show linear correlation with volume weighted average for melting point (Tm) of each oxides (Tmave). Ku of magnetic grains (Kugrain) shows a trade-off relation with GD that it is a big challenge to satisfy both high Kugrain and small GD by only controlling Tmave. To obtain a granular medium with appropriate Kugrain, GD, and low degree of intergranular exchange coupling, the combination of Tmave control of grain boundary material by mixing oxides and employment of a buffer layer are required. Here the degree of intergranular exchange coupling is estimated from the slope of M-H loop at around coercivity (α). By applying this technique, a typical granular medium with Kugrain of 1.0×107 erg/cm3, GD of 5.1 nm, and α of 1.2 is realized.

A high efficiency Ku-band radial line relativistic klystron amplifier

Energy Technology Data Exchange (ETDEWEB)

Dang, Fangchao; Zhang, Xiaoping, E-mail: zhangxiaoping@nudt.edu.cn; Zhong, Huihuang; Zhang, Jun; Ju, Jinchuan [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2016-07-15

To achieve the gigawatt-level microwave amplification output at Ku-band, a radial-line relativistic klystron amplifier is proposed and investigated in this paper. Different from the annular electron beam in conventional axial relativistic klystron amplifiers, a radial-radiated electron beam is employed in this proposed klystron. Owing to its radially spreading speciality, the electron density and space charge effect are markedly weakened during the propagation in the radial line drift tube. Additionally, the power capacity, especially in the output cavity, is enhanced significantly because of its large volume, which is profitable for the long pulse operation. Particle-in-cell simulation results demonstrate that a high power microwave with the power of 3 GW and the frequency of 14.25 GHz is generated with a 500 kV, 12 kA electron beam excitation and the 30 kW radio-frequency signal injection. The power conversion efficiency is 50%, and the gain is about 50 dB. Meanwhile, there is insignificant electron beam self-excitation in the proposed structure by the adoption of two transverse electromagnetic reflectors. The relative phase difference between the injected signals and output microwaves keeps stable after the amplifier saturates.

Effects of surface roughness on sea ice freeboard retrieval with an Airborne Ku-Band SAR radar altimeter

DEFF Research Database (Denmark)

Hendricks, Stefan; Stenseng, Lars; Helm, Veit

2010-01-01

to investigate sea ice volume changes on an Arctic wide scale. Freeboard retrieval requires precise radar range measurements to the ice surface, therefore we investigate the penetration of the Ku-Band radar waves into the overlying snow cover as well as the effects of sub-footprint-scale surface roughness using...... airborne radar and laser altimeters. We find regional variable penetration of the radar signal at late spring conditions, where the difference of the radar and the reference laser range measurement never agrees with the expected snow thickness. In addition, a rough surface can lead to biases...

Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer.

Science.gov (United States)

Nguyen, Huy; Loustaunau, Cristy; Facista, Alexander; Ramsey, Lois; Hassounah, Nadia; Taylor, Hilary; Krouse, Robert; Payne, Claire M; Tsikitis, V Liana; Goldschmid, Steve; Banerjee, Bhaskar; Perini, Rafael F; Bernstein, Carol

2010-07-28

In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia. Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia. We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas

Recognition of lyso-phospholipids by human natural killer T lymphocytes.

Directory of Open Access Journals (Sweden)

Lisa M Fox

2009-10-01

Full Text Available Natural killer T (NKT cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC. Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

60 kD Ro and nRNP A frequently initiate human lupus autoimmunity.

Directory of Open Access Journals (Sweden)

Latisha D Heinlen

2010-03-01

Full Text Available Systemic lupus erythematosus (SLE is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%. However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%, nRNP A (24%, anti-phospholipids (18% or rheumatoid factor (15%. We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98% or anti-52 kD Ro (95%. The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns.

Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils.

Science.gov (United States)

Hirano, Toru; Arimitsu, Junsuke; Higa, Shinji; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Kawase, Ichiro; Tanaka, Toshio

2006-01-01

We have previously shown that flavonoids such as luteolin, apigenin and fisetin inhibit interleukin 4 and interleukin 13 production. In this study, we investigated whether luteolin can suppress CD40 ligand expression by basophils. A human basophilic cell line, KU812, was stimulated with A23187 and phorbol myristate acetate (PMA) with or without various concentrations of luteolin or other flavonoids for 12 h, and CD40 ligand expression was analyzed by FACS. The effect of luteolin on CD40 ligand mRNA expression was studied by semiquantitative reverse transcription PCR analysis. In addition, CD40 ligand expression was also measured in purified basophils that had been stimulated for 12 h with A23187 plus PMA with or without various concentrations of luteolin. CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 microM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression. The incubation of purified basophils with A23187 plus PMA significantly enhanced CD40 ligand expression, and the presence of luteolin again had an inhibitory effect. Luteolin inhibits CD40 ligand expression by activated basophils.

Resistance to Sri Lankan Cassava Mosaic Virus (SLCMV) in Genetically Engineered Cassava cv. KU50 through RNA Silencing

KAUST Repository

Ntui, Valentine Otang

2015-04-22

Cassava ranks fifth among the starch producing crops of the world, its annual bioethanol yield is higher than for any other crop. Cassava cultivar KU50, the most widely grown cultivar for non-food purposes is susceptible to Sri Lankan cassava mosaic virus (SLCMV). The objective of this work was to engineer resistance to SLCMV by RNA interference (RNAi) in order to increase biomass yield, an important aspect for bioethanol production. Here, we produced transgenic KU50 lines expressing dsRNA homologous to the region between the AV2 and AV1 of DNA A of SLCMV. High level expression of dsRNA of SLCMV did not induce any growth abnormality in the transgenic plants. Transgenic lines displayed high levels of resistance to SLCMV compared to the wild-type plants and no virus load could be detected in uninoculated new leaves of the infected resistant lines after PCR amplification and RT-PCR analysis. The agronomic performance of the transgenic lines was unimpaired after inoculation with the virus as the plants presented similar growth when compared to the mock inoculated control plants and revealed no apparent reduction in the amount and weight of tubers produced. We show that the resistance is correlated with post-transcriptional gene silencing because of the production of transgene specific siRNA. The results demonstrate that transgenic lines exhibited high levels of resistance to SLCMV. This resistance coupled with the desirable yield components in the transgenic lines makes them better candidates for exploitation in the production of biomass as well as bioethanol.

Resistance to Sri Lankan Cassava Mosaic Virus (SLCMV) in Genetically Engineered Cassava cv. KU50 through RNA Silencing

KAUST Repository

Ntui, Valentine Otang; Kong, Kynet; Khan, Raham Sher; Igawa, Tomoko; Janavi, Gnanaguru Janaky; Rabindran, Ramalingam; Nakamura, Ikuo; Mii, Masahiro

2015-01-01

Cassava ranks fifth among the starch producing crops of the world, its annual bioethanol yield is higher than for any other crop. Cassava cultivar KU50, the most widely grown cultivar for non-food purposes is susceptible to Sri Lankan cassava mosaic virus (SLCMV). The objective of this work was to engineer resistance to SLCMV by RNA interference (RNAi) in order to increase biomass yield, an important aspect for bioethanol production. Here, we produced transgenic KU50 lines expressing dsRNA homologous to the region between the AV2 and AV1 of DNA A of SLCMV. High level expression of dsRNA of SLCMV did not induce any growth abnormality in the transgenic plants. Transgenic lines displayed high levels of resistance to SLCMV compared to the wild-type plants and no virus load could be detected in uninoculated new leaves of the infected resistant lines after PCR amplification and RT-PCR analysis. The agronomic performance of the transgenic lines was unimpaired after inoculation with the virus as the plants presented similar growth when compared to the mock inoculated control plants and revealed no apparent reduction in the amount and weight of tubers produced. We show that the resistance is correlated with post-transcriptional gene silencing because of the production of transgene specific siRNA. The results demonstrate that transgenic lines exhibited high levels of resistance to SLCMV. This resistance coupled with the desirable yield components in the transgenic lines makes them better candidates for exploitation in the production of biomass as well as bioethanol.

Destruction of gel sulfonated cation-exchangers of the KU-2 type under the influence of hydrogen peroxide

Energy Technology Data Exchange (ETDEWEB)

Roginskaya, B.S.; Zavadovskaya, A.S.; Znamenskii, Yu.P.; Paskhina, N.A.; Dobrova, E.I.

1988-10-20

The purpose of this work was to study the mechanism of interaction of Soviet sulfonated cation-exchangers of the KU-2 type with hydrogen peroxide. It is shown that under the influence of hydrogen peroxide sulfonated cation-exchangers begin, after a certain induction period, to lose capacity and to release destruction products into water; the length of the induction period increases with the degree of cross-linking. In a given time of contact between the resin and the solution the degree of destruction falls with increase of cross-linking. The principal product of destruction of sulfonated cation-exchangers is an aromatic sulfonic acid containing oxidized groups in the side chains.

Reduction of intergranular exchange coupling and grain size for high Ku CoPt-based granular media: Metal-oxide buffer layer and multiple oxide boundary materials

Directory of Open Access Journals (Sweden)

Kim Kong Tham

2018-05-01

Full Text Available Investigation of magnetic properties and microstructure of granular media with various multiple oxides as the grain boundary material is reported. Saturation magnetization (Ms, uniaxial magnetocrystalline anisotropy (Ku, and magnetic grain diameter (GD of the granular media show linear correlation with volume weighted average for melting point (Tm of each oxides (Tmave. Ku of magnetic grains (Kugrain shows a trade-off relation with GD that it is a big challenge to satisfy both high Kugrain and small GD by only controlling Tmave. To obtain a granular medium with appropriate Kugrain, GD, and low degree of intergranular exchange coupling, the combination of Tmave control of grain boundary material by mixing oxides and employment of a buffer layer are required. Here the degree of intergranular exchange coupling is estimated from the slope of M-H loop at around coercivity (α. By applying this technique, a typical granular medium with Kugrain of 1.0×107 erg/cm3, GD of 5.1 nm, and α of 1.2 is realized.

Teplovodní výměník pro krbovou vložku

OpenAIRE

Kněžínek, Petr

2012-01-01

Diplomová práce je zaměřena na problematiku zapojení krbových kamen a krbových vložek do teplovodních vytápěcích systémů. Práce obsahuje stručný popis krbů a otopných soustav. Konkrétně se zabývá návrhem teplovodního výměníku pro krbová kamna. Poslední část práce je věnována experimentálnímu ověření provozních parametrů a vyhodnocení získaných výsledků. The diploma thesis is focused on problems connecting of fireplace with water heating systems. The thesis comprises concise description of ...

A technical writing programme implemented in a first-year engineering course at KU Leuven

Science.gov (United States)

Heylen, Christel; Vander Sloten, Jos

2013-12-01

Technical communication and technical writing are important skills for the daily work-life of every engineer. In the first-year engineering programme at KU Leuven, a technical writing programme is implemented within the project-based course 'Problem Solving and Engineering Design'. This paper describes a case study for implementing a writing programme based on active learning methods and situated learning in large classes. The programme consists of subsequent cycles of instructions, learning by doing and reflection on received feedback. In addition, a peer-review assignment, together with an interactive lecture using clicking devices, is incorporated within the assignments of the second semester. A checklist of desired writing abilities makes it easier to grade the large number of papers. Furthermore, this ensures that all staff involved in the evaluation process uses the same criteria to grade and for providing feedback.

Hemşirelerin Bireysel ve Profesyonel Değerlerinde Kuşaklararası Farklılıklar / Personal and Professional Difference between the Generation of Nurses

OpenAIRE

IŞIK, Gülşen; EĞELİOĞLU CETİŞLİ, Nuray; TOKEM, Yasemin; YILMAZ, Dilan; İLHAN, Aylin

2018-01-01

Amaç: Buaraştırmanın amacı hemşirelerin bireysel ve profesyonel değerleri arasındakikuşaklararası farklılıkları belirlemektir. Gereçve Yöntem: Tanımlayıcı ve karşılaştırmalı tipteki bu çalışma, İzmir’dekibir üniversite hastanesinde çalışan, X kuşağındaki 85(doğum tarihi 1965-1979yılları arasında olanlar) ve Y kuşağındaki 79 (doğum tarihi 1980-1999 yıllarıarasında olanlar) olmak üzere toplam 164 hemşire ile yürütülmüştür. Veriler, araştırmacılar tarafından 30 dakikalık süreiçerisinde yüz yüze ...

8 – 11 gadus vecu bērnu pašcieņas saistība ar vecāku audzināšanas stilu un tehnoferenci

OpenAIRE

Ērmane, Linda

2017-01-01

Ir izvirzīts pētījuma mērķis teorētiski un praktiski izpētīt 8 – 11 gadus vecu bērnu pašcieņas saistību ar vecāku audzināšanas stilu un tehnoferenci. Pētījumā ir viena hipotēze par to, ka pastāv saistība starp vecāku audzināšanas stilu, bērnu pašcieņu un tehoferenci. Pētījuma izlasi veido 15 bērni (M = 9,6 gadi; SD = 1,12; 8 meitenes un 7 zēni) un 30 vecāki (M = 36,8 gadi; SD = 5,74; 15 vīrieši un 15 sievietes). Ir izmantoti 3 instrumenti: Audzināšanas pieeju aptauja, Tehnoloģijas ierīču ieja...

A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIVKU-1bMC33) susceptible to rimantadine

International Nuclear Information System (INIS)

Hout, David R.; Gomez, Lisa M.; Pacyniak, Erik; Miller, Jean-Marie; Hill, M. Sarah; Stephens, Edward B.

2006-01-01

Previous studies from our laboratory have shown that the transmembrane domain (TM) of the Vpu protein of human immunodeficiency virus type 1 (HIV-1) contributes to the pathogenesis of SHIV KU-1bMC33 in macaques and that the TM domain of Vpu could be replaced with the M2 protein viroporin from influenza A virus. Recently, we showed that the replacement of the TM domain of Vpu with that of the M2 protein of influenza A virus resulted in a virus (SHIV M2 ) that was sensitive to rimantadine [Hout, D.R., Gomez, M.L., Pacyniak, E., Gomez, L.M., Inbody, S.H., Mulcahy, E.R., Culley, N., Pinson, D.M., Powers, M.F., Wong, S.W., Stephens, E.B., 2006. Substitution of the transmembrane domain of Vpu in simian human immunodeficiency virus (SHIV KU-1bMC33 ) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques. Virology 344, 541-558]. Based on previous studies of the M2 protein which have shown that the His-X-X-X-Trp motif within the M2 is essential to the function of the M2 proton channel, we have constructed a novel SHIV in which the alanine at position 19 of the TM domain was replaced with a histidine residue resulting in the motif His-Ile-Leu-Val-Trp. The SHIV VpuA19H replicated with similar kinetics as the parental SHIV KU-1bMC33 and pulse-chase analysis revealed that the processing of viral proteins was similar to SHIV KU-1bMC33 . This SHIV VpuA19H virus was found to be more sensitive to the M2 ion channel blocker rimantadine than SHIV M2 . Electron microscopic examination of SHIV VpuA19H -infected cells treated with rimantadine revealed an accumulation of viral particles at the cell surface and within intracellular vesicles, which was similar to that previously observed to SHIV M2 -infected cells treated with rimantadine. These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the alteration of one amino acid and provide

Contribution of defective PS recognition and efferocytosis to chronic inflammation and autoimmunity

Directory of Open Access Journals (Sweden)

Stanley Gititu Kimani

2014-11-01

Full Text Available Rapid and efficient clearance of apoptotic cells results in elimination of auto-antigens and provides a strong anti-inflammatory and immunosuppressive signal to prevent autoimmunity. While professional and non-professional phagocytes utilize a wide array of surface receptors to recognize apoptotic cells, recognition of phosphatidylserine (PS on apoptotic cells by PS receptors on phagocytes is emblematic signal for efferocytosis in metazoans. PS-dependent efferocytosis is associated with production of anti-inflammatory factors such as IL-10 and TGF-β that function, in part, to maintain tolerance to auto-antigens. In contrast, when apoptotic cells fail to be recognized and processed for degradation, auto-antigens persist, which can trigger immune activation leading to autoantibody production and autoimmunity. Despite the fact that genetic mouse models clearly demonstrate that loss of PS receptors can lead to age-dependent autoimmune diseases reminiscent of systemic lupus erythematosus (SLE, link between PS and defective clearance in chronic inflammation and human autoimmunity is not well delineated. In this hypothesis and theory, we review emerging questions developing in the field that may be of relevance to SLE and human autoimmunity.

Structural profiles of human miRNA families from pairwise clustering

DEFF Research Database (Denmark)

Kaczkowski, Bogumil; Þórarinsson, Elfar; Reiche, Kristin

2009-01-01

secondary structure already predicted, little is known about the patterns of structural conservation among pre-miRNAs. We address this issue by clustering the human pre-miRNA sequences based on pairwise, sequence and secondary structure alignment using FOLDALIGN, followed by global multiple alignment...... of obtained clusters by WAR. As a result, the common secondary structure was successfully determined for four FOLDALIGN clusters: the RF00027 structural family of the Rfam database and three clusters with previously undescribed consensus structures. Availability: http://genome.ku.dk/resources/mirclust...

Wideband Array for C, X, and Ku-Band Applications with 5.3:1 Bandwidth

Science.gov (United States)

Novak, Markus H.; Volakis, John L.; Miranda, Felix A.

2015-01-01

Planar arrays that exploit strong intentional coupling between elements have allowed for very wide bandwidths in low-profile configurations. However, such designs also require complex impedance matching networks that must also be very compact. For many space applications, typically occurring at C-, X-, Ku-, and most recently at Ka-band, such designs require specialized and expensive fabrication techniques. To address this issue, a novel ultra-wideband array is presented, using a simplified feed network to reduce fabrication cost. The array operates from 3.5-18.5 GHz with VSWR less than 2.4 at broadside, and is of very low profile, having a total height of lambda/10 at the lowest frequency of operation. Validation is provided using a 64-element prototype array, fabricated using common Printed Circuit Board (PCB) technology. The low size, weight, and cost of this array make it attractive for space-borne applications.

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

Emocionālā intelekta attīstība 16 -18 gadus veciem pusaudžiem un tā saistība ar vecāku audzināšanas stilu.

OpenAIRE

Poļakova, Anželika

2011-01-01

Šī pētījuma mērķis ir noskaidrot, vai vecāku izvēlētais audzināšanas stils ir saistīts ar emocionālā intelekta attīstību. Pētījumā piedalījās 64 respondenti: 32 sievietes no 16 līdz 18 gadiem un 32 vīrieši no 16 līdz 18 gadiem. Respondenti pārstāv dažādas sociāli ekonomiskas grupas. Tika izmantotas šādas metodes: Bar-Ona emocionālā intelekta aptauja (Bar-On Emotional Quotient Inventory (EQ-i), Bar-On, 1999) un Buri Vecāku audzināšanas stila aptauju (Buri Parental Authority Questionnaire- PAQ...

Non-homologous end-joining genes are not inactivated in human radiation-induced sarcomas with genomic instability

International Nuclear Information System (INIS)

Lefevre, S.H.; Coquelle, A.; Gonin-Laurent, N.

2005-01-01

DNA double-strand break (DSB) repair pathways are implicated in the maintenance of genomic stability. However the alterations of these pathways, as may occur in human tumor cells with strong genomic instability, remain poorly characterized. We analyzed the loss of heterozygosity (LOH) and the presence of mutations for a series of genes implicated in DSB repair by non-homologous end-joining in five radiation-induced sarcomas devoid of both active Tp53 and Rb1. LOH was recurrently observed for 8 of the 9 studied genes (KU70, KU80, XRCC4, LIG4, Artemis, MRE11, RAD50, NBS1) but not for DNA-PKcs. No mutation was found in the remaining allele of the genes with LOH and the mRNA expression did not correlate with the allelic status. Our findings suggest that non-homologous end-joining repair pathway alteration is unlikely to be involved in the high genomic instability observed in these tumors. (author)

Pusaudžu problemātiskas uzvedības saistības ar viņu piesaistes stilu un vecāku audzināšanas stilu ģimenē

OpenAIRE

Zamberga, Zane

2006-01-01

Maģistra darba pētījuma mērķis bija noskaidrot pusaudžu uzvedības traucējumu, piesaistes stilu un vecāku audzināšanas stilu savstarpējo saistību pusaudžu pašnovērtējumā, un, kāda ir savstarpējā ietekme (multiplās regresijas analīzes rezultātā) piesaistes stilam un vecāku audzināšanas stilam, iepretim uzvedības pašnovērtējumam. Pētījuma izlasi veido 60 pusaudži vcecumā no 14 – 16 gadiem. Tika aptaujāti Latvijas vispārizglītojošo skolu 7. un 8. klases skolēni: 30 meitenes un 30 zēni. Pētījumā...

Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

Science.gov (United States)

McLachlan, Sandra M; Aliesky, Holly A; Chen, Chun-Rong; Chong, Gao; Rapoport, Basil

2012-01-01

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a "double-edged sword". On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the

Breaking Tolerance in Transgenic Mice Expressing the Human TSH Receptor A-Subunit: Thyroiditis, Epitope Spreading and Adjuvant as a ‘Double Edged Sword’

Science.gov (United States)

McLachlan, Sandra M.; Aliesky, Holly A.; Chen, Chun-Rong; Chong, Gao; Rapoport, Basil

2012-01-01

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a “double-edged sword”. On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the

Wpływ wysiłku fizycznego na funkcję układu oddechowego w twardzinie układowej

OpenAIRE

Stanisław Sierakowski; Ewa Gińdzieńska-Sieśkiewicz; Maciej Kaczmarski; Zenon Siergiejko; Grzegorz Siergiejko; Piotr Siergiejko; Justyna Fryc

2010-01-01

Cel: Powikłania ze strony układu oddechowego stanowią główną przyczynę zgonów pacjentów z twardziną układową (TU). Tętniczenadciśnienie płucne i śródmiąższowa choroba płuc stanowią najistotniejszez nich. Pacjenci są jednak często zdiagnozowani dopierow późnym okresie choroby, dlatego też istotne jest opracowaniemetody diagnostycznej do wczesnego wykrywania tych powikłań.Celem pracy była ocena wpływu wysiłku fizycznego na zmiany parametrówoddechowych. Materiały i metody: Badania przeprowadzono...

Microwave absorption in X and Ku band frequency of cotton fabric coated with Ni–Zn ferrite and carbon formulation in polyurethane matrix

International Nuclear Information System (INIS)

Gupta, K.K.; Abbas, S.M.; Goswami, T.H.; Abhyankar, A.C.

2014-01-01

The present study highlights various microwave properties, i.e. reflection, transmission, absorption and reflection loss, of the coated cotton fabric [formulation: Ni–Zn ferrite (Ni 0.5 Zn 0.5 Fe 2 O 4 ) and carbon black (acetylene black) at concentrations of 30, 40, 50, 60 and70 g of ferrite and 5 g carbon in each 100 ml polyurethane] evaluated at 8–18 GHz frequency. The uniform density of filling materials in coated fabrics (dotted marks in SEM micrograph) indicates homogeneous dispersion of conducting fillers in polyurethane and the density of filling material cluster increases with increase in ferrite concentration. SEM images also show uniform coating of conducting fillers/resin system over individual fibers and interweave spaces. The important parameters governing the microwave properties of coated fabrics i.e. permittivity and permeability, S-parameters, reflection loss, etc. were studied in a HVS free space microwave measurement system. The lossy character of coated fabric is found to increase with increase of ferrite content; the ferrite content decreases the impedance and increases the permittivity and permeability values. The 1.6–1.8 mm thick coated fabric sample (40 wt% ferrite, 3 wt% carbon and 57 wt% PU) has shown about 40% absorption, 20% transmission and 40% reflectance in X (8.2–12.4 GHz) and Ku (12–18 GHz) frequency bands. The reflection loss at 13.5 GHz has shown the highest peak value (22.5 dB) due to coated sample optical thickness equal to λ/4 and more than 7.5 dB in entire Ku band. Owing to its thin and flexible nature, the coated fabric can be used as apparel in protecting human being from hazardous microwaves and also as radar camouflage covering screen in defense. - Highlights: • Ni–Zn ferrite (Ni 0.5 Zn 0.5 Fe 2 O 4 ) with acetylene black found effective coating for microwave absorption. • Coating formulation containing 40 wt% ferrite, 3 wt% carbon and 57 wt% PU offered 40% absorption, 20% transmission and 40% reflection

Microwave absorption in X and Ku band frequency of cotton fabric coated with Ni–Zn ferrite and carbon formulation in polyurethane matrix

Energy Technology Data Exchange (ETDEWEB)

Gupta, K.K., E-mail: krishna62@rediffmail.com [Defence Materials and Stores Research and Development Establishment, Kanpur PO, GT Road, Kanpur 208013 (India); Abbas, S.M.; Goswami, T.H. [Defence Materials and Stores Research and Development Establishment, Kanpur PO, GT Road, Kanpur 208013 (India); Abhyankar, A.C. [Defence Institute of Advanced Technology( DIAT), Giri Nagar, Pune 411025 (India)

2014-08-01

The present study highlights various microwave properties, i.e. reflection, transmission, absorption and reflection loss, of the coated cotton fabric [formulation: Ni–Zn ferrite (Ni {sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4}) and carbon black (acetylene black) at concentrations of 30, 40, 50, 60 and70 g of ferrite and 5 g carbon in each 100 ml polyurethane] evaluated at 8–18 GHz frequency. The uniform density of filling materials in coated fabrics (dotted marks in SEM micrograph) indicates homogeneous dispersion of conducting fillers in polyurethane and the density of filling material cluster increases with increase in ferrite concentration. SEM images also show uniform coating of conducting fillers/resin system over individual fibers and interweave spaces. The important parameters governing the microwave properties of coated fabrics i.e. permittivity and permeability, S-parameters, reflection loss, etc. were studied in a HVS free space microwave measurement system. The lossy character of coated fabric is found to increase with increase of ferrite content; the ferrite content decreases the impedance and increases the permittivity and permeability values. The 1.6–1.8 mm thick coated fabric sample (40 wt% ferrite, 3 wt% carbon and 57 wt% PU) has shown about 40% absorption, 20% transmission and 40% reflectance in X (8.2–12.4 GHz) and Ku (12–18 GHz) frequency bands. The reflection loss at 13.5 GHz has shown the highest peak value (22.5 dB) due to coated sample optical thickness equal to λ/4 and more than 7.5 dB in entire Ku band. Owing to its thin and flexible nature, the coated fabric can be used as apparel in protecting human being from hazardous microwaves and also as radar camouflage covering screen in defense. - Highlights: • Ni–Zn ferrite (Ni{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4}) with acetylene black found effective coating for microwave absorption. • Coating formulation containing 40 wt% ferrite, 3 wt% carbon and 57 wt% PU offered 40% absorption, 20

Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

Science.gov (United States)

Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

1991-04-01

A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

Science.gov (United States)

Jansen, Manon A A; Spiering, Rachel; Broere, Femke; van Laar, Jacob M; Isaacs, John D; van Eden, Willem; Hilkens, Catharien M U

2018-01-01

Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens. © 2017 John Wiley & Sons Ltd.

The impact of the snow cover on sea-ice thickness products retrieved by Ku-band radar altimeters

Science.gov (United States)

Ricker, R.; Hendricks, S.; Helm, V.; Perovich, D. K.

2015-12-01

Snow on sea ice is a relevant polar climate parameter related to ocean-atmospheric interactions and surface albedo. It also remains an important factor for sea-ice thickness products retrieved from Ku-band satellite radar altimeters like Envisat or CryoSat-2, which is currently on its mission and the subject of many recent studies. Such satellites sense the height of the sea-ice surface above the sea level, which is called sea-ice freeboard. By assuming hydrostatic equilibrium and that the main scattering horizon is given by the snow-ice interface, the freeboard can be transformed into sea-ice thickness. Therefore, information about the snow load on hemispherical scale is crucial. Due to the lack of sufficient satellite products, only climatological values are used in current studies. Since such values do not represent the high variability of snow distribution in the Arctic, they can be a substantial contributor to the total sea-ice thickness uncertainty budget. Secondly, recent studies suggest that the snow layer cannot be considered as homogenous, but possibly rather featuring a complex stratigraphy due to wind compaction and/or ice lenses. Therefore, the Ku-band radar signal can be scattered at internal layers, causing a shift of the main scattering horizon towards the snow surface. This alters the freeboard and thickness retrieval as the assumption that the main scattering horizon is given by the snow-ice interface is no longer valid and introduces a bias. Here, we present estimates for the impact of snow depth uncertainties and snow properties on CryoSat-2 sea-ice thickness retrievals. We therefore compare CryoSat-2 freeboard measurements with field data from ice mass-balance buoys and aircraft campaigns from the CryoSat Validation Experiment. This unique validation dataset includes airborne laser scanner and radar altimeter measurements in spring coincident to CryoSat-2 overflights, and allows us to evaluate how the main scattering horizon is altered by the

Gözeli yöresindeki (Elazığ meşe (Quercus sp . ormanlarına asılan yapay yuvalardaki böcekçil kuşların kuluçka faaliyetleri

Directory of Open Access Journals (Sweden)

Özden YALÇIN

2015-12-01

Full Text Available Elazığ Orman Bölge Müdürlüğü sınırları içerisinde yer alan Elazığ ili Sivrice ilçesi Gözeli mevkiinde bulunan meşe ormanlarında, 2009-2013 yılları arasında gerçekleştirilen bu çalışma ile farklı bakılara asılan farklı renkteki küçük ve büyük yuva sandıklarında yuva yapan kuş türleri ve bu türlerin kuluçka faaliyetlerinin saptanması amaçlanmıştır. Kuluçkalarını başarı ile tamamlayan kuş türlerinin Otus scops haricindeki türlerin hepsi, hem küçük hem de büyük yuvaları kullanmıştır. Öncelikli yuva tercihleri şu şekilde olmuştur: Parus major küçük yuvaların %66,4’ünde, Cyanistes caeruleus büyük yuvaların %16,3’ünde, Sitta europaea büyük yuvaların %23,2’sinde, Petronia petronia küçük yuvaların %15,2’sinde, Passer domesticus büyük yuvaların %27,9’unda, Otus scops ise sadece büyük yuvaların %7’sinde yuvalanmıştır. Asılan yuvalarda başarılı kuluçka durumunun farklı kuş türlerine göre bakı tercihleri arasında farklılıklar bulunmaktadır. Büyük yuvalarda güney (%39,5, doğu (%34,9, kuzey (%16,3 ve batı (%9,3’dır. Küçük yuvalarda ise güney (%33,2, doğu (%27,2, batı (%20,8 ve kuzey (%18,8’dir.Farklı renklerde asılan kuş yuvalarında başarılı kuluçka yapan kuş türlerinin renk tercihleri değişmektedir. Büyük yuvalarda, Parus major yeşil yuvaları, Cyanistes caeruleus sarı yuvaları, Sitta europaea turuncu yuvaları, Petronia petronia sarı ve mavi yuvaları, Passer domesticus sarı, mavi ve boyanmamış yuvaları daha fazla tercih etmişlerdir. Kuşların yuva tercihinde yuva boyutu, renk ve bakının türler arası farklılık gösterdiği ortaya çıkmıştır. Bir türün daha yoğun bulunduğu alanda, o türe uygun yuva tercihinin gerçekleştirilerek asılması biyolojik mücadele kapsamında daha verimli sonuçlar elde edilmesini sağlayacaktır.

Ida-1, the Caenorhabditis elegans orthologue of mammalian diabetes autoantigen IA-2, potentially acts as a common modulator between Parkinson's disease and Diabetes: role of Daf-2/Daf-16 insulin like signalling pathway.

Science.gov (United States)

Fatima, Soobiya; Haque, Rizwanul; Jadiya, Pooja; Shamsuzzama; Kumar, Lalit; Nazir, Aamir

2014-01-01

The lack of cure to age associated Parkinson's disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing "human" alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes.

Expression of the transcription factor Evi-1 in human erythroleukemia cell lines and in leukemias.

Science.gov (United States)

Fontenay-Roupie, M; Bouscary, D; Melle, J; Viguié, F; Picard, F; Guesnu, M; Dreyfus, F

1997-02-01

The Evi-1 proto-oncogene is a zinc finger DNA binding protein. Although activation of the Evi-1 gene has been associated with chromosomal rearrangements of the 3q25-q28 region, ectopic expression of Evi-1 could also be observed in acute myelogenous leukemias and myelodysplastic syndromes without cytogenetic abnormalities of the 3q26 locus. In this study, human erythroleukemic cell lines were screened for the expression of Evi-1 mRNA by northern blotting. Evi-1 was expressed in all the erythroid cell lines, whether undifferentiated (K 562, HEL, LAMA 84) or exhibiting spontaneous terminal erythroid differentiation (KU 812, JK-1). Evi-1 mRNA levels were constant or elevated in hemoglobin-synthesizing KU 812 or K 562 cells in response to erythropoietin or hemin treatment, respectively. In human acute myeloblastic leukemias (AML), 11/30 expressed Evi-1 by RT-PCR. Among these cases, 4/6 erythroleukemias without abnormalities of the 3q25-q28 region were found positive. The presence of acidophilic erythroblasts (15-47% of bone marrow cells) accounted for the existence of a terminal erythroid differentiation in all Evi-1-positive AML M6, whereas one negative case was poorly differentiated and referred to as AML M6 variant. These results suggest that Evi-1 mRNA expression can coexist with erythroid differentiation.

Exposure to power frequency magnetic fields suppresses X-ray-induced apoptosis transiently in Ku80-deficient xrs5 cells

International Nuclear Information System (INIS)

Tian, Furong; Nakahara, Takehisa; Yoshida, Masami; Honda, Naoko; Hirose, Hideki; Miyakoshi, Junji

2002-01-01

In an attempt to determine whether exposure to extremely low frequency (ELF) electromagnetic fields can affect cells, Ku80-deficient cells (xrs5) and Ku80-proficient cells (CHO-K1) were exposed to ELF electromagnetic fields. Cell survival, and the levels of the apoptosis-related genes p21, p53, phospho-p53 (Ser 15 ), caspase-3 and the anti-apoptosis gene bcl-2 were determined in xrs5 and CHO-K1 cells following exposure to ELF electromagnetic fields and X-rays. It was found that exposure of xrs5 and CHO-K1 cells to 60 Hz ELF electromagnetic fields had no effect on cell survival, cell cycle distribution and protein expression. Exposure of xrs5 cells to 60 Hz ELF electromagnetic fields for 5 h after irradiation significantly inhibited G 1 cell cycle arrest induced by X-rays (1 Gy) and resulted in elevated bcl-2 expression. A significant decrease in the induction of p53, phospho-p53, caspase-3 and p21 proteins was observed in xrs5 cells when irradiation by X-rays (8 Gy) was followed by exposure to 5 mT ELF magnetic fields. Exposure of xrs5 cells to the ELF electromagnetic fields for 10 h following irradiation significantly decreased X-ray-induced apoptosis from about 1.7% to 0.7%. However, this effect was not found in CHO-K1 cells within 24 h of irradiation by X-rays alone and by X-rays combined with ELF electromagnetic fields. Exposure of xrs5 cells to 60 Hz ELF electromagnetic fields following irradiation can affect cell cycle distribution and transiently suppress apoptosis by decreasing the levels of caspase-3, p21, p53 and phospho-p53 and by increasing bcl-2 expression

USP22 Induces Cisplatin Resistance in Lung Adenocarcinoma by Regulating γH2AX-Mediated DNA Damage Repair and Ku70/Bax-Mediated Apoptosis

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Aman Wang

2017-05-01

Full Text Available Resistance to platinum-based chemotherapy is one of the most important reasons for treatment failure in advanced non-small cell lung cancer, but the underlying mechanism is extremely complex and unclear. The present study aimed to investigate the correlation of ubiquitin-specific peptidase 22 (USP22 with acquired resistance to cisplatin in lung adenocarcinoma. In this study, we found that overexpression of USP22 could lead to cisplatin resistance in A549 cells. USP22 and its downstream proteins γH2AX and Sirt1 levels are upregulated in the cisplatin- resistant A549/CDDP cell line. USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A. In addition, USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax-mediated apoptosis and inducing cisplatin resistance. The cisplatin sensitivity in cisplatin-resistant A549/CDDP cells was restored by USP22 inhibition in vivo and vitro. In summary, our findings reveal the dual mechanism of USP22 involvement in cisplatin resistance that USP22 can regulate γH2AX-mediated DNA damage repair and Ku70/Bax-mediated apoptosis. USP22 is a potential target in cisplatin-resistant lung adenocarcinoma and should be considered in future therapeutic practice.

Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.

Science.gov (United States)

Wolff, Anette S B; Kärner, Jaanika; Owe, Jone F; Oftedal, Bergithe E V; Gilhus, Nils Erik; Erichsen, Martina M; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S

2014-10-15

Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG, thymoma, or both for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and we assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including chronic mucocutaneous candidiasis, AI, and asplenia, respectively, in 49 of 121 (40%) and 10 of 121 (8%) thymoma patients, but clinical features seldom occurred together with the corresponding autoantibodies. Both were rare in other MG subgroups (n = 126). In 38 patients with APS-I, by contrast, we observed neither autoantibodies against muscle Ags nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected underexpression in thymomas, levels were increased for four of the five TSAgs most frequently targeted by these patients' autoantibodies. Therefore, the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and hypoparathyroidism. Copyright © 2014 by The American Association of Immunologists, Inc.

The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

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Hassan Mziaut

2016-08-01

Full Text Available Objective: Insulin release from pancreatic islet β cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512 (also known as islet antigen 2/Ptprn. Here we investigated how Ica512 modulates SG trafficking and exocytosis. Methods: Transcriptomic changes in Ica512−/− mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. Results: The F-actin modifier villin was consistently downregulated in Ica512−/− mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of β cells and dispersed villin−/− islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. Keywords: F-actin, Granules, Ica512, Insulin, Secretion, Villin

Ocena poziomu lęku i depresji u rodziców dzieci z zespołem nerczycowym – sposoby radzenia sobie z nimi i metody wsparcia

Directory of Open Access Journals (Sweden)

Monika Pawlak-Bratkowska

2013-06-01

Full Text Available Wstęp i cele pracy: Idiopatyczny zespół nerczycowy w wieku rozwojowym przebiega nawrotowo i trwale zmie‑ nia życie dzieci oraz ich rodziców. Celem badania była ocena poziomu lęku i depresji u rodziców dzieci z zespo‑ łem nerczycowym. Materiał i metodyka: Badanie zaplanowano jako przekrojową próbę kliniczną wśród rodzi‑ ców dzieci chorujących na zespół nerczycowy w odniesieniu do rodziców dzieci zdrowych. Wszyscy badani (46 rodziców wypełniali: ankietę dotyczącą przebiegu choroby u dziecka, kwestionariusz STAI (Inwentarz stanu i cechy lęku, kwestionariusz Skali depresji Becka, kwestionariusz Skali kontroli emocji (CECS. Grupę kontrolną stanowiło 20 rodziców dzieci zdrowych. Wyniki: Rodzice dzieci z zespołem nerczycowym charakteryzowali się istotnie wyższym poziomem depresji (Skala depresji Becka 8,7 vs 4,9, t = 2,18, p < 0,05. U ojców zaobserwo‑ wano wyższe subiektywne uczucie kontrolowania własnych reakcji w porównaniu z matkami – wyższy wynik CECS, suma u ojców (55,1 vs 47,2, t = 2,53, p < 0,05. U matek odnotowano wyższe wskaźniki zarówno w ska‑ lach mierzących poziom lęku jako cechy (STAI – cecha 45,7 vs 36,1, t = 3,19, p < 0,05 i stanu (STAI – stan 42,8 vs 33,4, t = 2,8, p < 0,05, jak i w kwestionariuszu badającym poziom depresji (10,62 vs 4,86, t = 2,66, p < 0,05. Rodzice, którzy wykazywali tendencję do obwiniania się o chorobę dziecka, podczas jej pierwszego epizodu uzyskali statystycznie istotny wyższy wynik w testach badających poziom depresji. Wnioski: Rodzice dzieci cierpiących na zespół nerczycowy charakteryzowali się istotnie wyższym poziomem depresji niż rodzice dzieci zdrowych. Ważne wydaje się objęcie szczególną opieką matek, mającą na celu obniżenie poziomu lęku i objawów depresji, oraz ojców skłonnych do tłumienia przeżywanych emocji.

Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1

Science.gov (United States)

Wolff, Anette S. B.; Kärner, Jaanika; Owe, Jone F.; Oftedal, Bergithe E.V.; Gilhus, Nils Erik; Erichsen, Martina M.; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S.

2014-01-01

Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG and/or thymoma for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including CMC, AI and asplenia, respectively in 49/121 (40%) and 10/121 (8%) thymoma patients, but clinical features seldom co-occurred with the corresponding autoantibodies. Both were rare in other MG subgroups (N=126). In 38 APS-I patients, by contrast, we observed neither autoantibodies against muscle antigens nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected under-expression in thymomas, levels were increased for 4 of the 5 TSAgs most frequently targeted by these patients’ autoAbs. Hence the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and HP. PMID:25230752

Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity

NARCIS (Netherlands)

Amedei, Amedeo; Bergman, Mathijs P.; Appelmelk, Ben J.; Azzurri, Annalisa; Benagiano, Marisa; Tamburini, Carlo; van der Zee, Ruurd; Telford, John L.; Vandenbroucke-Grauls, Christina M. J. E.; D'Elios, Mario M.; del Prete, Gianfranco

2003-01-01

Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells

Some clastic rocks as parent rocks in beech forests of Brezovica - Južni Kučaj

Directory of Open Access Journals (Sweden)

Joksimović Vesna

2003-01-01

Full Text Available On the large forest areas, where the measures of soil quality improvement are absent or rarely undertaken, the rocks are the sources of a great number of elements in plant nutrition and one of the factors affecting the contents of some elements in plants. The aim of the study is to determine the differences in the contents of Cu, Zn, Mn, Ni, Fe, Cd, Co, Pb and Cr in the beech leaves developed in the same climate conditions, on morphologically similar terrains, composed of different types of sedimentary rocks. This paper presents the study results of the contents of the above elements in argillites, sandstones (grauwackes and microconglomerates occurring as the parent rocks in high beech forests in the region of GJ Bogovina (Brezovica Južni Kučaj and in the leaves of beech developed on these rocks.

Substitution of the transmembrane domain of Vpu in simian-human immunodeficiency virus (SHIVKU1bMC33) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques

International Nuclear Information System (INIS)

Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Fegley, Barbara; Mulcahy, Ellyn R.; Hill, M. Sarah; Culley, Nathan; Pinson, David M.; Nothnick, Warren; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

2006-01-01

The Vpu protein of human immunodeficiency virus type 1 has been shown to shunt the CD4 receptor molecule to the proteasome for degradation and to enhance virus release from infected cells. The exact mechanism by which the Vpu protein enhances virus release is currently unknown but some investigators have shown that this function is associated with the transmembrane domain and potential ion channel properties. In this study, we determined if the transmembrane domain of Vpu could be functionally substituted with that of the prototypical viroporin, the M2 protein of influenza A virus. We constructed chimeric vpu gene in which the transmembrane domain of Vpu was replaced with that of the M2 protein of influenza. This chimeric vpu gene was substituted for the vpu gene in the genome of a pathogenic simian human immunodeficiency virus, SHIV KU-1bMC33 . The resulting virus, SHIV M2 , synthesized a Vpu protein that had a slightly different M r compared to the parental SHIV KU-1bMC33 , reflecting the different sizes of the two Vpu proteins. The SHIV M2 was shown to replicate with slightly reduced kinetics when compared to the parental SHIV KU-1bMC33 but electron microscopy revealed that the site of maturation was similar to the parental virus SHIV KU1bMC33 . We show that the replication and spread of SHIV M2 could be blocked with the antiviral drug rimantadine, which is known to target the M2 ion channel. Our results indicate a dose dependent inhibition of SHIV M2 with 100 μM rimantadine resulting in a >95% decrease in p27 released into the culture medium. Rimantadine did not affect the replication of the parental SHIV KU-1bMC33 . Examination of SHIV M2 -infected cells treated with 50 μM rimantadine revealed numerous viral particles associated with the cell plasma membrane and within intracytoplasmic vesicles, which is similar to HIV-1 mutants lacking a functional vpu. To determine if SHIV M2 was as pathogenic as the parental SHIV KU-1bMC33 virus, two pig-tailed macaques

Motorické projevy laterality u osob středního věku a starších

OpenAIRE

Habartová, Lucie

2008-01-01

Název dielomové eráce: Motorické projevy laterality u osob středního věku a starších. Název v gnglickém jazyce: The Manifestations of Motoric Laterality of Middle-aged People and Elderly. Cíle eráce: Definovat, popsat lateralitu, zjistit stupeň laterality horní končetiny, dolní končetiny a oka. Zjistit vztah laterality horních končetin a očí, horních končetin a dolních končetin. Metoda: Lateralitu budeme zjišťovat na základě dotazníků a motorických testů. Testovaný soubor čítá 50 probandů ve ...

Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

Science.gov (United States)

Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

2014-04-01

Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.

Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

Science.gov (United States)

Fridkis-Hareli, Masha

2008-02-15

of human disease-associated HLA determinants and T or B cell receptors, as well as in vitro binding studies employing purified HLA proteins, synthetic peptides, and cellular assays with antigen-presenting cells and patient's lymphocytes. Indisputably, a bioinformatics-based search for peptide motifs and the modeling of the conformation of bound autoantigenic peptides associated with their respective HLA alleles will reveal some of these important processes. The elucidation of HLA-restricted immune recognition mechanisms prompting the production of two or more disease-specific autoantibodies holds significant clinical ramifications and implications for the development of more effective treatment protocols.

Y Kuşağı Turistlerin Destinasyon İmaj Algıları Üzerine Bir Araştırma A Research On Generation Y Tourists Perceptions Of Destination Image

Directory of Open Access Journals (Sweden)

Aslı ALBAYRAK

2013-07-01

Full Text Available This study has been performed on the purposed of determiningeffects of the destination image composing factors on deciding tovacation resort of Y Generation tourists who show differentcharacterists in comparison to the previous and the next generation,and making recommendations related to destination marketing for thegeneration by examining the relationship between destinationperception and structural features of Y Generation tourist.In this study, questionnaire technique which is one thequantitative research method, were used and questionnaire study weremade face to face with 384 people who were determined by quotasampling method and represent the generation in Istanbul. On analysisobtained from data were used descriptive statistics, t-test, and Anovaanalysis.According to results of research, destination image differs fromdepending on gender, level of educaiton, also income levels ofparticipants. On the other other hand, it can be said that Y Generationtourists act at the request of seeing new places, leisure, andentertainment and are the individuals who look for quality and luxuryholiday with affordable price.Touristic purchase process is shaped by many factors. One of thefactors affecting this process is image of destination. The mostgenerational definition about destination image is as an individual’soverall perception and these perceptions ınfluenced by many factorssuch as age, education, income and culture. There are several studieshave been conducted about tourists’ perceptions of destination image inpast and generally these studies about effects of tourists’ characteristicssuch as age, education, culture income to perception of destinationimage but there are no studies about different generations’ destinationimage perceptions. Therefore ıt’s thought that the results obtained fromthis study could contribute to the tourism marketers. Bu çalışma, kendinden önceki ve sonraki kuşaklardan farklı özellikler gösteren Y ku

Contribution of dot-blot assay to the diagnosis and management of myositis: a three-year practice at a university hospital centre.

Science.gov (United States)

Martel, Clothilde; Vignaud, Guillaume; Liozon, Eric; Magy, Laurent; Gallouedec, Gael; Ly, Kim; Bezanahary, Holly; Cypierre, Anne; Lapébie, François-Xavier; Palat, Sylvain; Gondran, Guillaume; Jauberteau, Marie-Odile; Fauchais, Anne-Laure

2016-01-01

Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases with wide clinical spectrum that may lead to delayed diagnosis. The aim of this study was to examine the impact of IIM-specific dot-blot assay on diagnostic process of patients presenting with muscular or systemic symptoms evocating of IIM. We collected all the prescriptions of an IIM specific dot-blot assay (8 autoantigens including Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, PM/Scl and Scl-70) over a 38-month period. 316 myositis dot-blot assays (MSD) were performed in 274 patients (156 women, mean age 53±10.6 years) referring for muscular and/or systemic symptoms suggesting IIM. The timing of dot prescription through the diagnostic process was highly variable: without (35%), concomitantly (16%) or after electromyographic studies (35%). Fifty-nine patients (22%) had IIM according to Bohan and Peter's criteria. Among them, 29 (49%) had positive dot (8 Jo-1, 6 PM-Scl, 5 PL-12, 5 SRP, 2 Mi-2, 2 PL-7 and 1 Ku). Various other diagnoses were performed including 35 autoimmune disease or granulomatosis (12%), 19 inflammatory rheumatic disease (7%), 16 non inflammatory muscular disorders (6%), 10 drug-induced myalgia (4%), 11 infectious myositis (4%). Except 11 borderline SRP results and one transient PM-Scl, MSD was positive only in one case of IIM. Dot allowed clinicians to correct diagnosis in 4 cases and improved the diagnosis of IIM subtypes in 4 cases. This study reflects the interest of myositis dot in the rapid diagnosis process of patients with non-specific muscular symptoms leading to various diagnoses including IIM.

A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines

DEFF Research Database (Denmark)

Jensen, Bettina Margrethe; Dissing, S; Skov, P S

2005-01-01

Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation......, FcepsilonRIalpha protein stability and the mRNA level of FcepsilonRIalpha-, beta- and the truncated beta-chain (beta(T)), and thereby determine the utility of these cell lines in investigations of the FcepsilonRI biology....

A Small Ku-Band Polarization Tracking Active Phased Array for Mobile Satellite Communications

Directory of Open Access Journals (Sweden)

Wei Shi

2013-01-01

Full Text Available A compact polarization tracking active phased array for Ku-band mobile satellite signal reception is presented. In contrast with conventional mechanically tracking antennas, the approach presented here meets the requirements of beam tracking and polarization tracking simultaneously without any servo components. The two-layer stacked square patch fed by two probes is used as antenna element. The impedance bandwidth of 16% for the element covers the operating frequency range from 12.25 GHz to 12.75 GHz. In the presence of mutual coupling, the dimensional parameters for each element of the small 7 × 7 array are optimized during beam scanning and polarization tracking. The compact polarization tracking modules based on the low-temperature cofired ceramic (LTCC system-in-package (SiP technology are proposed. A small active phased array prototype with the size of 120 mm (length × 120 mm (width × 55 mm (height is developed. The measured polarization tracking patterns of the prototype are given. The polarization tracking beam can be steered in the elevation up to 50°. The gain of no less than 16.0 dBi and the aperture efficiency of more than 50% are obtained. The measured and simulated polarization tracking patterns agreed well.

Pusaudžu agresivitātes saistība ar vecāku audzināšanas stilu.

OpenAIRE

Dambe, Agnese

2007-01-01

Šajā darbā tiek apskatīta viena no mūsdienu būtiskākajām problēmām- pusaudžu agresivitāte. Pētījuma mērķis bija noskaidrot, vai pastāv statistiski nozīmīgas saistības starp vecāku audzināšanas stilu un pusaudžu agresivitāti. Pētījuma izlasi veido 60 pusaudži (30 jaunietes un 30 jaunieši) no pilnām ģimenēm, vecumposmā no 15-17 gadiem. Pētījumā tika izmantotas divas pētījuma metodes- A.H. Bassa (A.H. Buss)- A. Darki (A. Durkee) aptaujas anketa agresīvu reakciju noteikšanai un ...

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

Science.gov (United States)

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

Oxygen Isotope Records in Modern Oyster Shells from Chi Ku, Tainan and Their Implication of Seasonality

Science.gov (United States)

Chen, Y. C.; Mii, H. S.; Li, K. T.

2015-12-01

To exam whether oxygen isotope records of Crassostrea gigasoysters can be used as proxies of environment, 133 cultivated oysters and 21 water samples were collected from Chi Ku area, Tainan City, southern Taiwan in December of 2012, and from March, 2013 to July, 2014. Instrumental air and water temperatures and precipitation records were obtained from a nearest Central Weather Bureau (CWB) station roughly 16 km north of Chi Ku. The oxygen and carbon isotope values of the ligamental area of the modern oyster shells are from -6.92‰ to -0.08‰ (-3.05 ± 1.17‰, N = 2280; 1σ; VPDB) and from -5.57‰ to 0.63‰ (-1.88 ± 0.81‰), respectively. Oxygen isotope values of the water samples are mainly between -0.28‰ and 0.74‰ (0.18 ± 0.29‰, N = 20; 1σ; VSMOW). However, water oxygen isotope value of -2.75‰ was observed for the water sample collected immediately after a typhoon heavy rainfall. Seasonal temperature fluctuation pattern of estimated oxygen isotope temperatures from modern shells is similar to that of CWB instrumental records. However, the oxygen isotope temperatures are respectively about 3 °C and 10°C higher than those of instrumental records for winter and summer. Higher estimated oxygen isotope temperatures are most likely caused by underestimated fraction of freshwater. We analyzed 5 archaeological oyster shells of Siraya culture (500~250B.P.) collected from Wu Chien Tuso North (WCTN) archaeological site of Tainan branch of Southern Taiwan Science Park to infer the harvest season of mollusks. Oxygen isotope values of the ligamental area of the archaeological oyster shells are between -5.98‰ and -1.26‰ (-3.34 ± 1.37‰, N = 60; 1σ), and carbon isotope values are between -3.21‰ and 0.60‰ (-2.04‰ ± 0.55‰). The oxygen isotope records of archaeological oyster shells also showed clear seasonality. Most of the oysters were collected in autumn and winter. Oxygen isotope values of archaeological oyster shells was 1‰ greater than that

Tracking- and Scintillation-Aware Channel Model for GEO Satellite to Land Mobile Terminals at Ku-Band

Directory of Open Access Journals (Sweden)

Ali M. Al-Saegh

2015-01-01

Full Text Available Recent advances in satellite to land mobile terminal services and technologies, which utilize high frequencies with directional antennas, have made the design of an appropriate model for land mobile satellite (LMS channels a necessity. This paper presents LMS channel model at Ku-band with features that enhance accuracy, comprehensiveness, and reliability. The effect of satellite tracking loss at different mobile terminal speeds is considered for directional mobile antenna systems, a reliable tropospheric scintillation model for an LMS scenario at tropical and temperate regions is presented, and finally a new quality indicator module for different modulation and coding schemes is included. The proposed extended LMS channel (ELMSC model is designed based on actual experimental measurements and can be applied to narrow- and wide-band signals at different regions and at different speeds and multichannel states. The proposed model exhibits lower root mean square error (RMSE and significant performance observation compared with the conventional model in terms of the signal fluctuations, fade depth, signal-to-noise ratio (SNR, and quality indicators accompanied for several transmission schemes.

Cave bear (Ursus spelaeus Rosenmüller & Heinroth males' den from Velika Pećina in Duboka Near Kučevo, Eastern Serbia

Directory of Open Access Journals (Sweden)

Dimitrijević Vesna M.

2002-01-01

Full Text Available More a 100 years after the first research in the cave Velika pećina in Duboka near Kučevo cave bear remains were discovered in a small chamber cut off from the passable channels by a 7 m high slope. A whole skull, bones of a forearm in articulation, and other skeleton parts were laying on the cave floor encrusted in travertine cover and in some places overgrown by stalagmites. Bones belonged to adult males, which found there the shelter to hibernate, in a short epizode that ended by closing the channels that once linked this part of the cave to a surface.

Analysis and comparison model for measuring tropospheric scintillation intensity for Ku-band frequency in Malaysia

Directory of Open Access Journals (Sweden)

Mandeep JS

2011-06-01

Full Text Available This study has been based on understanding local propagation signal data distribution characteristics and identifying and predicting the overall impact of significant attenuating factors regarding the propagation path such as impaired propagation for a signal being transmitted. Predicting propagation impairment is important for accurate link budgeting, thereby leading to better communication network system designation. This study has thus used sample data for one year concerning beacon satellite operation in Malaysia from April 2008 to April 2009. Data concerning 12GHz frequency (Ku-band and 40° elevation angle was collected and analysed, obtaining average signal amplitude value, ÷ and also standard deviation ó which is normally measured in dB to obtain long-term scintillation intensity distribution. This analysis showed that scintillation intensity distribution followed Gaussian distribution for long-term data distribution. A prediction model was then selected based on the above; Karasawa,
ITU-R, Van de Kamp and Otung models were compared to obtain the best prediction model performance for selected data regarding specific meteorological conditions. This study showed that the Karasawa model had the best performance for predicting scintillation intensity for the selected da ta.

Y Kuşağının Mobil Öğrenme Uygulama Tercihini Etkileyen Faktörlerin İncelenmesi

OpenAIRE

ALTUNTAŞ, Başar

2017-01-01

Mobilteknolojilerin öğrenme ortamlarına dâhil edilmesiyle birlikte öğrenme faaliyetifiziksel sınırların dışına çıkmış ve farklı bir boyuta evrilmiştir. Tasarlanan öğrenmeuygulamaları kullanıcılarına zamandan ve mekândan bağımsız öğrenme fırsatısunarken, yeni ve farklı deneyimleri de beraberinde getirmiştir. Bu çalışmada,Y kuşağının mobil öğrenme uygulamalarını tercih etmesini ve kullanmasınıetkileyen faktörler incelenmiştir. Teknoloji kabul modeli ile beklenti-kabul modelitemelinde tasarlanan...

Kuş Gölü (Bandırma Makrobentik Omurgasız Faunası Hakkında Bir Ön Araştırma.

Directory of Open Access Journals (Sweden)

Süleyman Balık

2015-12-01

Full Text Available Kuş Gölü’nün makrobentik omurgasız faunasını belirlemek amacıyla 1987 ve 1988 yılları arasında aylık periyotlar halinde, bir yıl süre ile 5 istasyonda arazi çalışması yapılmıştır. Ekman grab ile alınan çamur örnekleri 500 μm göz açıklığındaki elekten geçirilmiş ve örnekler %4’lük formaldehit solüsyonunda tespit edilmiştir. Araştırma sonucunda, Oligochaeta sınıfından 10, Chironomidae familyasından 5 ve Ceratopogonidae familyasından 1 olmak üzere toplam 16 takson tespit edilmiştir. Kuş gölü’nde metrekarede ortalama 6759 birey tespit edilmiş, grupların oransal dağılımında %81,94 ile Oligochaeta bireylerinin en baskın grubu oluşturduğu, bu grubu Chironomidae (%17,90 ve Ceratopogonidae (%0,16 larvalarının takip ettiği saptanmıştır. Tespit edilen grupların istasyonlara göre oransal dağılımlarında ise, 1. istasyonun en zengin (%28,71, 4. istasyonun en fakir (%12,77 istasyon olduğu gözlenmiştir

Pusaudžu - hokeja spēlētāju sasniegumu stratēģijas un apmierinātības izjūta, spēlējot hokeju, saistībā ar vecāku audzināšanas stiliem.

OpenAIRE

Stālmane, Liene

2014-01-01

Maģistra darba mērķis bija izpētīt saistības starp pusaudžu, kuri trenējas hokejā jau no agrīna vecuma, sasniegumu stratēģijām, apmierinātības izjūtu, spēlējot hokeju, un viņu vecāku audzināšanas stilus. Pētījumā tika iekļauti 53 respondenti latviešu tautības zēni, vecumā no 9 – 14 gadiem, kuri trenējas hokejā. Par pētījuma instrumentāriju izmantotas: 1)Vecāku audzināšanas stila aptauja. (Parental Authority Questionnaire (PAQ), Buri, 1991); 2) Sasniegumu stratēģiju aptauja....

Vecāku audzināšanas stilu saistība ar pašcieņu pusaudžu vecumā

OpenAIRE

Miķelsone-Ježaka, Dace

2008-01-01

Darba mērķis ir izpētīt pašcieņas saistību ar mātes un tēvu audzināšanas stilu bērnībā. Pētījumā piedalījās 105 pusaudži no dažādām skolām vecumā no 16 līdz 18 gadiem, kas dzīvo pilnās ģimenēs. Tika izmantotas 2 aptaujas: 1. Vecāku autoritātes novērtējuma aptauja (The Parental Authority Questionnaire, Buri, 1991; Griškina, 2002). 2. Rozenberga pašcieņas aptauja (The Rosenberg Self – esteem Scale, Rosenberg, 1965).

Scrambling of the amino acids within the transmembrane domain of Vpu results in a simian-human immunodeficiency virus (SHIVTM) that is less pathogenic for pig-tailed macaques

International Nuclear Information System (INIS)

Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Inbody, Sarah H.; Mulcahy, Ellyn R.; Culley, Nathan; Pinson, David M.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

2005-01-01

Previous studies have shown that the transmembrane (TM) domain of the subtype B Vpu enhances virion release from cells and some studies have shown that this domain may form an oligomeric structure with properties of an ion channel. To date, no studies have been performed to assess the role of this domain in virus pathogenesis in a macaque model of disease. Using a pathogenic molecular clone of simian human immunodeficiency virus (SHIV KU-1bMC33 ), we have generated a novel virus in which the transmembrane domain of the Vpu protein was scrambled but maintained hydrophobic in nature (SHIV TM ), which presumably would disrupt any ion channel TM properties of this protein. Vectors expressing the Vpu as a fusion protein with the enhanced green fluorescent protein (Vpu TM EGFP) indicate that it was transported to the same intracellular compartment as the unmodified Vpu protein but did not down-regulate cell surface expression of CD4. To assess the pathogenicity of SHIV TM , three pig-tailed macaques were inoculated with the SHIV TM and monitored for 6-8 months for CD4 + T cell levels, viral loads and the stability of the sequence of the vpu gene. Our results indicated that unlike the parental SHIV KU-1bMC33 , inoculation of macaques with SHIV TM did not cause a severe CD4 + T cell loss over the course of their infections. Sequence analysis of the vpu gene analyzed from sequential PBMC samples derived from macaques revealed that the scrambled TM was stable during the course of infection. At necropsy, examination of tissues revealed low viral loads and none of the pathology commonly observed in lymphoid and non-lymphoid tissues following inoculation with the pathogenic parental SHIV KU-1bMC33 virus. Thus, these results show for the first time that the TM domain of Vpu contributes to the pathogenicity of SHIV KU-1bMC33 in pig-tailed macaques

Vecāku audzināšanas stila saistība ar pusaudžu vientulības izjūtu

OpenAIRE

Vlasova, Iveta

2013-01-01

Pētījuma jautājums: Vai starp mātes audzināšanas stilu un vientulības līmeni pusaudžiem pastāv saistība? Pētījuma dalībnieki. Viena izlase, pēc pieejamības principa. Dalībnieku vecums: 12-16 gadi, 31 meitene, 23 zēni. Dzīvojoši pilnās ģimenēs. Pētījuma metode. 1.Lieto, lai noteiktu kopējo vientulības izjūtas līmeni, tika izmantota Vientulības skala (UCLA Loneliness Scale/UCLA LS/, VERSION 3; Russel, D.W. 1996).– visu jautājumu summa. 2.Vecāku audzināšanas stila aptauja (Parental...

Comparison of neutron and gamma irradiation effects on KU1 fused silica monitored by electron paramagnetic resonance

Energy Technology Data Exchange (ETDEWEB)

Bravo, D. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)], E-mail: david.bravo@uam.es; Lagomacini, J.C. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Leon, M.; Martin, P. [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain); Martin, A. [Department Fisica e Instalaciones, ETS Arquitectura UPM, E-28040 Madrid (Spain); Lopez, F.J. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Ibarra, A. [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain)

2009-06-15

Electron paramagnetic resonance (EPR) studies have been carried out on KU1 fused silica irradiated with neutrons at fluences 10{sup 21} and 10{sup 22} n/m{sup 2}, and gamma-ray doses up to 12 MGy. The effects of post-irradiation thermal annealing treatments, up to 850 deg. C, have also been investigated. Paramagnetic oxygen-related defects (POR and NBOHC) and E'-type defects have been identified and their concentration has been measured as a function of neutron fluence, gamma dose and post-irradiation annealing temperature. It is found that neutrons at the highest fluence generate a much higher concentration of defects (mainly E' and POR, both at concentrations about 5 x 10{sup 18} spins/cm{sup 3}) than gamma irradiations at the highest dose (mainly E' at a concentration about 4 x 10{sup 17} spins/cm{sup 3}). Moreover, for gamma-irradiated samples a lower treatment temperature (about 400 deg. C) is required to annihilate most of the observed defects than for neutron-irradiated ones (about 600 deg. C)

Faktorová analýza antropometrických charakteristik u mladých plavců ve věku 11 a 12 let Factor analysis of anthropometric characteristics in young swimmers aged 11 and 12

Directory of Open Access Journals (Sweden)

Zofia Ignasiak

2006-02-01

Full Text Available Cílem této práce bylo popsat vybrané somatické charakteristiky typické pro mladé plavce. Faktorová analýza umožnila úměrné snížení somatických ukazatelů a umožnila vypočítat hlavní strukturální faktory typické pro mladé plavce. Do výzkumného souboru bylo zařazeno 80 žáků (11 a 12letých přijatých ke studiu na základní sportovní škole ve Wroclawi. Sledovaní probandi trénovali po dobu 2–3 let a jejich průměrný tréninkový čas byl 12 až 18 hodin týdně. Byly měřeny následující parametry: tělesná výška a hmotnost, délka horních a dolních končetin, obvod stehen, lýtka, paží, předloktí, hrudníku v klidu, hrudníku po nádechu a po výdechu, obvod pasu a boků, šířka ramen, šířka boků, šířka hrudníku, hloubka hrudníku a Rohrerův index. K dosažení cíle této studie byla použita metoda faktorové analýzy. Analýza výsledků ukázala, že pouze některé zvláštnosti mezi sledovanými parametry jsou pro mladé plavce charakteristické. Jsou spojeny do 2 trsů somatických charakteristik: kubický obsah (zahrnuje tělesnou hmotnost, svalstvo, trup a obvod horních a dolních končetin a vertikální rozměr (zahrnuje tělesnou výšku a délku horních a dolních končetin. Tyto parametry signalizují formování postavy typické pro plavce, charakteristické specifickými proporcemi tělesné hmotnosti a výšky, hrudníku a boků a obvykle delšími končetinami. Výsledky naznačují, že antropometrické charakteristiky lze použít pro optimalizaci tréninkového procesu mladých plavců. The aim of this study was to describe the set of somatic characteristics, which significantly discriminate young swimmers. The factor analysis let us reduce the number of somatic traits mostly correlated and to calculate the main structural factors typical for young swimmers. There were 80 pupils (11 and 12 years old from the primary sport school in Wroclaw recruited for the study

A Novel Ku-Band/Ka-Band and Ka-Band/E-Band Multimode Waveguide Couplers for Power Measurement of Traveling-Wave Tube Amplifier Harmonic Frequencies

Science.gov (United States)

Wintucky, Edwin G.; Simons, Rainee N.

2015-01-01

This paper presents the design, fabrication and test results for a novel waveguide multimode directional coupler (MDC). The coupler, fabricated from two dissimilar frequency band waveguides, is capable of isolating power at the second harmonic frequency from the fundamental power at the output port of a traveling-wave tube (TWT) amplifier. Test results from proof-of-concept demonstrations are presented for a Ku-band/Ka-band MDC and a Ka-band/E-band MDC. In addition to power measurements at harmonic frequencies, a potential application of the MDC is in the design of a satellite borne beacon source for atmospheric propagation studies at millimeter-wave (mm-wave) frequencies (Ka-band and E-band).

Beretning for undersøgelse af bopladsområde med værkstedsaktivitet fra yngre jernalder/vikingetid, neolitiske anlæg fortrinsvis fra MN A III og en grav fra MN B II. Kalmergården (KU) 2000

DEFF Research Database (Denmark)

Bican, Josefine Franck

2001-01-01

anlæggelse er omtalt nedenfor i en separat beretning ved Lone Gebauer Thomsen (se bilag 2). Yngre jernalder/vikingetid er den periode, der var bedst repræsenteret på pladsen. Her var spor efter en markeds-/produktionsplads, der er registreret vha. 3735 detektorfund, hvor især sølvskatten (KU 2337) skal...

Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage

International Nuclear Information System (INIS)

Park, Jung Wook; Nickel, Kwangok P.; Torres, Alexandra D.; Lee, Denis; Lambert, Paul F.; Kimple, Randall J.

2014-01-01

Background and purpose: Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV−) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV− HNC cells. However, roles of HPV oncogenes in regulating the response of DNA damage repair remain unknown. Material and methods: Using immortalized normal oral epithelial cell lines, HPV+ HNC derived cell lines, and HPV16 E7-transgenic mice we assessed the repair of DNA damage using γ-H2AX foci, single and split dose clonogenic survival assays, and immunoblot. The ability of E7 to modulate expression of proteins associated with DNA repair pathways was assessed by immunoblot. Results: HPV16 E7 increased retention of γ-H2AX nuclear foci and significantly decreased sublethal DNA damage repair. While phospho-ATM, phospho-ATR, Ku70, and Ku80 expressions were not altered by E7, Rad51 was induced by E7. Correspondingly, HPV+ HNC cell lines showed retention of Rad51 after γ-radiation. Conclusions: Our findings provide further understanding as to how HPV16 E7 manipulates cellular DNA damage responses that may underlie its oncogenic potential and influence the altered sensitivity to radiation seen in HPV+ HNC as compared to HPV− HNC

Styl radzenia sobie ze stresem jako moderator związku lęku z neurotyzmem u osób z reumatoidalnym zapaleniem stawów

Directory of Open Access Journals (Sweden)

Michał Ziarko

2011-06-01

Full Text Available Lęk stanowi jedną z konsekwencji chorób przewlekłych, w tymreumatoidalnego zapalenia stawów (RZS. Wysoki poziom lękuobniża jakość życia pacjentów, prowadzi do zachowań antyzdrowotnychoraz może wpływać na gorszy przebieg choroby. Związekneurotyzmu z lękiem został dotąd dobrze udokumentowany. Neurotyzmstanowi cechę temperamentu, a więc w niewielkim stopniumożna ją modyfikować. Redukcja kosztów psychicznych ponoszonychprzez osoby o wysokim poziomie neurotyzmu wymagapoznania czynników, które mogłyby ograniczać wpływ neurotyzmuna poziom lęku (czynniki moderujące relację neurotyzm–lęk.Celem badania było określenie zmiennych moderujących relacjępomiędzy neurotyzmem a lękiem.W badaniach wzięło udział 100 osób chorujących na RZS (78 ko -biet i 22 mężczyzn. Zostali oni przebadani za pomocą kwestionariuszymierzących: poziom lęku, style radzenia sobie ze stresemoraz wymiary osobowości. Obliczono współczynniki korelacjir Pearsona pomiędzy mierzonymi zmiennymi oraz wykonano analizęmoderacji związku pomiędzy neurotyzmem a lękiem jakostanem za pośrednictwem stylów radzenia sobie ze stresem.Testowanie interakcji przeprowadzono metodą najmniejszych kwadratówi regresji logistycznej.Ustalono, że istnieje wprost proporcjonalny związek pomiędzyneurotyzmem a lękiem rozumianym jako stan (r = 0,63; p < 0,01(tab. I. Zaobserwowano, że związek ten nie zachodzi w przypadkuosób o wysokim neurotyzmie posługujących się unikowym stylem radzenia sobie ze stresem (R2 = 0,19; F = 7,00; p < 0,001 (ryc. 1oraz u osób poszukujących kontaktów towarzyskich (R2 = 0,22;F = 8,70; p < 0,001 (ryc. 2, tab. II.Wyniki wskazują, że silny neurotyzm zwiększa prawdopodobieństworeagowania podwyższonym poziomem lęku w obliczu pojawiającychsię objawów oraz zagrożeń będących konsekwencjąchoroby. Zaobserwowane zależności potwierdzają hipotezę, żetemperament jest czynnikiem ryzyka w rozwoju zaburze

Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses.

Science.gov (United States)

Tu, Xiaoning; Li, Shan; Zhao, Lijuan; Xiao, Ran; Wang, Xiuling; Zhu, Fan

2017-08-01

Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201 + restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLA-A*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A*0201 + donors with each of these peptides induced peptide-specific CD8 + T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

Bot podobný člověku

OpenAIRE

Dufek, Jan

2012-01-01

The main goal of my thesis is to create a bot for Unreal Tournament 2004 whose behaviour will be as similar as possible to human controlled players. At the beginning, I measured game play data from both humans and bots. Then, I chose one initial bot and I did five iterations of comparing bot data with humans data, selecting one difference, improving the bot with the aim to eliminate the difference and measuring data again. The successful improvements I made were removing rotations during runn...

Use of combined ion exchangers on the basis of KU-23 and KM-2p cation exchangers for purification of ammonium molybdate and tungstate solutions from phosphate, arsenate, and silicate impurities

International Nuclear Information System (INIS)

Blokhin, A.A.; Majorov, D.Yu.; Kopyrin, A.A.; Taushkanov, V.P.

2002-01-01

Using the Tracer technique ( 32 P) and elementary analysis, potentiality of using combined ionites on the basis of macroporous cation-exchange resins KU-23 or KM-2p and hydrated zirconium oxide for purification of concentrated solutions of ammonium molybdate and tungstate from phosphate-, arsenate-, and silicate-ions impurities was studied. High selectivity of the combined ionites towards impurity ions was ascertained, which permits reducing the content of impurities by a factor of 50-100 compared with the initial one [ru

Extracted atmospheric impairments on earth-sky signal quality in tropical regions at Ku-band

Science.gov (United States)

Al-Saegh, Ali Mohammed; Sali, Aduwati; Mandeep, J. S.; Ismail, Alyani

2013-11-01

Atmospheric condition variations were shown to have a major effect on the earth sky signal quality at Ku band. Moreover, such variations increased in the tropical regions as compared to temperate areas due to their different weather parameters. With the increase of recent satellite communication technology applications throughout the tropical countries and lack of information regarding the atmospheric impairments analysis, simulation and mitigation techniques, there is an ever increasing need for extracting a unique and accurate performance of the signal quality effects during highly natural tropical weather impairments. This paper presents a new method developed for proper analysis with distinctive and highly realistic performance evaluation for signal quality during the atmospheric conditions variations in 14 tropical areas from the four continents analyzed based on actual measured parameters. The method implementation includes signal attenuation, carrier to noise ratio, symbol energy to noise ratio, and symbol error rate at different areas and different modulation schemes. Furthermore, for improvement in analysis in terms of covering more remarkable regions in tropics, the paper provides new measurements data with analysis for certain region in tropics used as a test bed and to add measurement data of such area to the world's data base for future researchers. The results show a significant investigation and performance observation in terms of weather impairments in tropical regions in general and each region in that area in particular regarding the signal attenuation and error rates accompanied for several transmission schemes.

Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis.

Directory of Open Access Journals (Sweden)

Amal Elfaitouri

Full Text Available Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome, a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60 occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM immune response was studied in 69 ME patients and 76 blood donors (BD (the Training set with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients, a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24% of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001. IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

Human neutrophils in auto-immunity.

Science.gov (United States)

Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

2016-04-01

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

Science.gov (United States)

Rapoport, Basil

2014-01-01

Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

Kinetics of destruction of KU-2 x 8 and AV-17 x 8 ion-exchange resins by the joint action of heating and irradiation

International Nuclear Information System (INIS)

Tulupov, P.E.; Butenko, T.Yu.

1982-01-01

Experimental data indicates a decrease of the exchange capacity of AV-17 x 8 (OH) resin in ion-exchange beds at various temperatures. Losses of exchange of the resin in hydroxyl form after 10,000h of continuous heating at 60, 70, and 80 0 C are 24, 44, and 78% respectively. Partial replacement of the hydroxyl by the salt form is accomplished by appreciable lowering of capacity losses. The trimethlyamine evolved during deamination of AV-17 x 8 anion exchange resin, and only methanol, enters the coolant. Under the influence of ionizing radiation in the active zone the methanol will be converted successively into formaldehyde, formic acid and CO 2 . Thus the maximum temperature of use of the hydroxyl form of te anion-exchange resin AV-17 x 8 (OH) in nuclear power plants can be raised to 70-75 0 C. Brief changes of temperature at 100 0 C do not cause any appreciable losses of exchange capacity either. Physicochemical properties of ion-exchange resins after use in nuclear power plants leads to excessive and unjustified restriction of their service life in the course of a single cycle. Joint action of heating and irradiation on AV-17 anion-exchange resin was studied. It was found that rate constants of the processes of thermal radiation decreases the exchange capacities of the resins in the temperature ranges of interest with relation to nuclear power plants. Calculation of the stability of KU-2 x 8 cation-exchange resin shows that even after a year of use at 100 0 C the loss of its exchange capacity is less than 0.1%. Therefore, under the conditions of use in a nuclear power plant KU-2 x 8 resin can be regarded as absolutely stable. The loss of exchange capacity of AV-17 x 8 resin in C1 form at 100 0 C is of similar magnitude

Pašvērtējuma, apmierinātības ar dzīvi un agresijas atšķirības pieaugušajiem ar un bez bērnībā pieredzētas vecāku šķiršanās

OpenAIRE

Ekarte, Marika

2013-01-01

Pētījuma mērķis ir noskaidrot vai pastāv atšķirības starp uzrādītajiem pašvērtējuma, apmierinātības ar dzīvi un agresijas rādītājiem respondentiem ar bērnībā pieredzētu vecāku šķiršanos un respondentiem bez vecāku šķiršanās pieredzes, kontrolējot dzimumu. Pētījuma mērķa noskaidrošanā pielietota pašvērtējuma aptauja (Rosenberg Self-Esteem Scale, RSE, Rosenberg, 1965), apmierinātības ar dzīvi aptauja (Satisfaction with life scales. Diener, 1985), agresijas līmeņa noteikšanai - agre...

Autoimmunity due to molecular mimicry as a cause of neurological disease.

Science.gov (United States)

Levin, Michael C; Lee, Sang Min; Kalume, Franck; Morcos, Yvette; Dohan, F Curtis; Hasty, Karen A; Callaway, Joseph C; Zunt, Joseph; Desiderio, Dominic; Stuart, John M

2002-05-01

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.

10- 12 gadus vecu bērnu ar atkārtotu nesekmību iemācītās bezpalīdzības saistība ar vecāku iemācīto bezpalīdzību

OpenAIRE

Lamstere, Jolanta

2006-01-01

Darbā tika pētīta iemācītās bezpalīdzības saistība bērniem ar vecāku iemācīto bezpalīdzību. Pētījuma gaitā tika izvirzīti pētījuma jautājumi: vai pastāv statistiski nozīmīgas sakarības starp iemācītās bezpalīdzības rādītājiem 10- 12 gadus veciem bērniem ar atkārtotu nesekmību un viņu vecāku iemācītās bezpalīdzības rādītājiem; vai pastāv statistiski nozīmīgas atšķirības starp iemācītās bezpalīdzības rādītājiem bērniem ar atkārtotu nesekmību un sekmīgiem bērniem; vai pastāv statistiski nozīmīga...

Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid.

Science.gov (United States)

Banda, Kalyan; Gregg, Christopher J; Chow, Renee; Varki, Nissi M; Varki, Ajit

2012-08-17

Although N-acetyl groups are common in nature, N-glycolyl groups are rare. Mammals express two major sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic acid (Neu5Gc). Although humans cannot produce Neu5Gc, it is detected in the epithelial lining of hollow organs, endothelial lining of the vasculature, fetal tissues, and carcinomas. This unexpected expression is hypothesized to result via metabolic incorporation of Neu5Gc from mammalian foods. This accumulation has relevance for diseases associated with such nutrients, via interaction with Neu5Gc-specific antibodies. Little is known about how ingested sialic acids in general and Neu5Gc in particular are metabolized in the gastrointestinal tract. We studied the gastrointestinal and systemic fate of Neu5Gc-containing glycoproteins (Neu5Gc-glycoproteins) or free Neu5Gc in the Neu5Gc-free Cmah(-/-) mouse model. Ingested free Neu5Gc showed rapid absorption into the circulation and urinary excretion. In contrast, ingestion of Neu5Gc-glycoproteins led to Neu5Gc incorporation into the small intestinal wall, appearance in circulation at a steady-state level for several hours, and metabolic incorporation into multiple peripheral tissue glycoproteins and glycolipids, thus conclusively proving that Neu5Gc can be metabolically incorporated from food. Feeding Neu5Gc-glycoproteins but not free Neu5Gc mimics the human condition, causing tissue incorporation into human-like sites in Cmah(-/-) fetal and adult tissues, as well as developing tumors. Thus, glycoproteins containing glycosidically linked Neu5Gc are the likely dietary source for human tissue accumulation, and not the free monosaccharide. This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids.

Pusaudžu tipiskās reakcijas pēc vecāku laulības šķiršanas.

OpenAIRE

Steļmaha, Elza

2011-01-01

Rezumējums Pētījuma „Pusaudžu depresija un uzvedības problēmas pēc vecāku laulības šķiršanas” mērķis bija noskaidrot kādas ir pusaudžu uzvedības un depresijas atšķirības starp šķirtajām un pilnajām ģimenēm.. Pētījuma papildus daļas mērķis bija noskaidrot kādas ir atšķirības depresijas izpausmēm un uzvedības problēmām, meitenēm un zēniem gan šķirto, gan pilno ģimeņu izlasē. Pētījumā piedalījās 60 respondenti vecuma grupā no 13-16 gadiem, 30 pusaudžiem vecāki ir šķiršanās procesā vai šķīr...

Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype

International Nuclear Information System (INIS)

Mendlovic, S.; Brocke, S.; Meshorer, A.; Mozes, E.; Shoenfeld, Y.; Bakimer, R.; Ben-Bassat, M.

1988-01-01

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. The authors report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE

128 | P a g e

African Journals Online (AJOL)

Fr. Ikenga

1Office of the High Commissioner for Human Rights, (OHCHR) 'Migration and Human .... led states to reduce their services in areas of social welfare, education and ... murder of black families by members of the Ku Klux Klan (KKK); Indian caste .... emphasis here will be on crime against humanity as provided for under the ...

From Resident to President: The Sinuous Participation of Paraguayan Women in Politics and the Emergence of the Feminist Political Movement Kuña Pyrenda

Directory of Open Access Journals (Sweden)

Sarah Cerna Villarga

2015-07-01

Full Text Available Paraguayan women have transcended history as the mothers of the “Guarani breed”, as The Resident Woman Residentas, the social role of these has been undeniable, but in other scopes, such as the political area, its social and historical role is still invisible, because the policy has historically been considered a male activity. However, many women have contributed to the construction of the history of this nation, and although the asymmetries in the real access to power between men and women are notorious today, Paraguayan want power and will seek, as it was found in the last two presidential elections of 2008 and 2013. On this basis, this paper aims to describe what has been the impact of feminism in Paraguayan politics and, in turn, explain the factors that have influenced raid Kuña Pyrenda feminist movement in the elections of 2013.

The presence of the casein kinase II phosphorylation sites of Vpu enhances the CD4+ T cell loss caused by the simian-human immunodeficiency virus SHIVKU-lbMC33 in pig-tailed macaques

International Nuclear Information System (INIS)

Singh, Dinesh K.; Griffin, Darcy M.; Pacyniak, Erik; Jackson, Mollie; Werle, Michael J.; Wisdom, Bo; Sun, Francis; Hout, David R.; Pinson, David M.; Gunderson, Robert S.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

2003-01-01

The simian-human immunodeficiency virus (SHIV)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of Vpu in lentivirus pathogenesis. In this report, we have mutated the two phosphorylated serine residues of the HIV-1 Vpu to glycine residues and have reconstructed a SHIV expressing this nonphosphorylated Vpu (SHIV S52,56G ). Expression studies revealed that this protein was localized to the same intracellular compartment as wild-type Vpu. To determine if this virus was pathogenic, four pig-tailed macaques were inoculated with SHIV S52,56G and virus burdens and circulating CD4 + T cells monitored up to 1 year. Our results indicate that SHIV S52,56G caused rapid loss in the circulating CD4 + T cells within 3 weeks of inoculation in one macaque (CC8X), while the other three macaques developed no or gradual numbers of CD4 + T cells and a wasting syndrome. Histological examination of tissues revealed that macaque CC8X had lesions in lymphoid tissues (spleen, lymph nodes, and thymus) that were typical for macaques inoculated with pathogenic parental SHIV KU-1bMC33 and had no lesions within the CNS. To rule out that macaque CC8X had selected for a virus in which there was reversion of the glycine residues at positions 52 and 56 to serine residues and/or compensating mutations occurred in other genes associated with CD4 down-regulation, sequence analysis was performed on amplified vpu sequences isolated from PBMC and from several lymphoid tissues at necropsy. Sequence analysis revealed a reversion of the glycine residues back to serine residues in this macaque. The other macaques maintained low virus burdens, with one macaque (P003) developing a wasting syndrome between months 9 and 11. Histological examination of tissues from this macaque revealed a thymus with severe atrophy that was similar to that of a previously reported macaque inoculated with a SHIV lacking vpu (Virology 293, 2002, 252). Sequence analysis revealed no

Diagnostic performance of a commercial immunoblot assay for myositis antibody testing.

Science.gov (United States)

Bundell, Chris; Rojana-Udomsart, Arada; Mastaglia, Frank; Hollingsworth, Peter; McLean-Tooke, Andrew

2016-06-01

The objective of this study was to establish a population based reference range for a commercial immunoblot assay detecting myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs), and to assess the diagnostic performance of this reference range against the manufacturer's recommended ranges in a myositis patient cohort. A total of 124 patients from a myositis cohort and 197 healthy controls were serologically assessed using a commercial immunoblot containing eleven autoantigens (Jo-1, EJ, OJ, PL7, PL12, Mi-2, SRP, Ku, PMScl75, PMScl100 and Ro52) according to the manufacturer's instructions. Use of the manufacturer's reference ranges resulted in detection of MSAs in 19.4% of myositis patients and 9.1% of controls; MAAs were detected in 41.1% of myositis patients and 14.2% of controls. Reference values derived from the healthy control population resulted in significant differences in cut-off values for some autoantibodies, particularly Ro52 and PMScl75. Use of local reference ranges reduced detection of MSAs to 16.9% of myositis patients and 3% of healthy controls, with MAAs 23.4% of patients and 2% of healthy controls. Application of population based reference ranges resulted in significant differences in detection of MSAs and MAAs compared to the manufacturer's recommended ranges. Cut-off levels should be assessed to ensure suitability for the population tested. Copyright © 2016. Published by Elsevier B.V.

Kinetic modelling and optimisation of antimicrobial compound production by Candida pyralidae KU736785 for control of Candida guilliermondii.

Science.gov (United States)

Mewa-Ngongang, Maxwell; du Plessis, Heinrich W; Hutchinson, Ucrecia F; Mekuto, Lukhanyo; Ntwampe, Seteno Ko

2017-06-01

Biological antimicrobial compounds from yeast can be used to address the critical need for safer preservatives in food, fruit and beverages. The inhibition of Candida guilliermondii, a common fermented beverage spoilage organism, was achieved using antimicrobial compounds produced by Candida pyralidae KU736785. The antimicrobial production system was modelled and optimised using response surface methodology, with 22.5 ℃ and pH of 5.0 being the optimum conditions. A new concept for quantifying spoilage organism inhibition was developed. The inhibition activity of the antimicrobial compounds was observed to be at a maximum after 17-23 h of fermentation, with C. pyralidae concentration being between 0.40 and 1.25 × 10 9 CFU ml -1 , while its maximum specific growth rate was 0.31-0.54 h -1 . The maximum inhibitory activity was between 0.19 and 1.08 l contaminated solidified media per millilitre of antimicrobial compound used. Furthermore, the antimicrobial compound formation rate was 0.037-0.086 l VZI ml -1 ACU h -1 , respectively. The response surface methodology analysis showed that the model developed sufficiently described the antimicrobial compound formation rate 1.08 l VZI ml -1 ACU, as 1.17 l VZI ml -1 ACU, predicted under the optimum production conditions.

Mycobacterium tuberculosis and Mycobacterium marinum non-homologous end-joining proteins can function together to join DNA ends in Escherichia coli.

Science.gov (United States)

Wright, Douglas G; Castore, Reneau; Shi, Runhua; Mallick, Amrita; Ennis, Don G; Harrison, Lynn

2017-03-01

Mycobacterium tuberculosis and Mycobacterium smegmatis express a Ku protein and a DNA ligase D and are able to repair DNA double strand breaks (DSBs) by non-homologous end-joining (NHEJ). This pathway protects against DNA damage when bacteria are in stationary phase. Mycobacterium marinum is a member of this mycobacterium family and like M. tuberculosis is pathogenic. M. marinum lives in water, forms biofilms and infects fish and frogs. M. marinum is a biosafety level 2 (BSL2) organism as it can infect humans, although infections are limited to the skin. M. marinum is accepted as a model to study mycobacterial pathogenesis, as M. marinum and M. tuberculosis are genetically closely related and have similar mechanisms of survival and persistence inside macrophage. The aim of this study was to determine whether M. marinum could be used as a model to understand M. tuberculosis NHEJ repair. We identified and cloned the M. marinum genes encoding NHEJ proteins and generated E. coli strains that express the M. marinum Ku (Mm-Ku) and ligase D (Mm-Lig) individually or together (LHmKumLig strain) from expression vectors integrated at phage attachment sites in the genome. We demonstrated that Mm-Ku and Mm-Lig are both required to re-circularize Cla I-linearized plasmid DNA in E. coli. We compared repair of strain LHmKumLig with that of an E. coli strain (BWKuLig#2) expressing the M. tuberculosis Ku (Mt-Ku) and ligase D (Mt-Lig), and found that LHmKumLig performed 3.5 times more repair and repair was more accurate than BWKuLig#2. By expressing the Mm-Ku with the Mt-Lig, or the Mt-Ku with the Mm-Lig in E. coli, we have shown that the NHEJ proteins from M. marinum and M. tuberculosis can function together to join DNA DSBs. NHEJ repair is therefore conserved between the two species. Consequently, M. marinum is a good model to study NHEJ repair during mycobacterial pathogenesis. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen

European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease

DEFF Research Database (Denmark)

Husby, S; Koletzko, S; Korponay-Szabó, I R

2012-01-01

Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather...... uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved....

Uticaj povećanja dometa na dinamičku stabilnost artiljerijskih raketa sa olučastim krilima / Influence of range extension on dynamic stability for artillery rockets with wrap around fins

Directory of Open Access Journals (Sweden)

Danilo Ćuk

2007-07-01

Full Text Available U radu su prikazani efekti povećanja dometa artiljerijske rakete sa olučastim krilima na njenu dinamičku stabilnost. Totalni impuls raketnog motora, uvećan za 50% i let rakete kroz slojeve atmosfere sa malom gustinom vazduha povećavaju domet rakete za više od 75% od nominalnog dometa. Međutim, let rakete kroz razređeni vazduh proizvodi teškoće koje se odnose na dinamičku stabilnost. Male promene bočnog momenta indukovanog napadnim uglom i Magnusovog momenta mogu proizvesti nestabilnost kretanja i nedozvoljeni rast napadnog ugla. Određene su tolerancije bočnog momenta za osnovnu i poboljšanu varijantu rakete radi sprečavanja nestabilnog leta. Analiziran je, takođe uticaj povećanja dometa na verovatna odstupanja rakete po dometu i pravcu. / This paper presents the effects of the range extension of an artillery rocket with wrap around fins on its dynamic stability. The increased total impulse of the rocket engine for 50% and flight through the atmosphere layers with low air density extend the range for more than 75% of the nominal range. However, the flight of the unguided rocket through the rarefied air produces difficulties related to the dynamic stability. The small changes in the side moment which is induced by the angle of attack and Magnus moment of the improved rocket can produce instabilities in flight and increasement the angle of attack. The tolerances of the side moment were determined for both basic and improved type of the rocket in order to prevent instable flight. The influence of the range extension on the probable errors in range and cross-range was analyzed as well.

A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk.

Science.gov (United States)

González, Silvia; Fló, Martín; Margenat, Mariana; Durán, Rosario; González-Sapienza, Gualberto; Graña, Martín; Parkinson, John; Maizels, Rick M; Salinas, Gustavo; Alvarez, Beatriz; Fernández, Cecilia

2009-09-17

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H(+)-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 - EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (K(I) (*)) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection.

Rainfall measurement from the opportunistic use of an Earth–space link in the Ku band

Directory of Open Access Journals (Sweden)

L. Barthès

2013-08-01

Full Text Available The present study deals with the development of a low-cost microwave device devoted to the measurement of average rain rates observed along Earth–satellite links, the latter being characterized by a tropospheric path length of a few kilometres. The ground-based power measurements, which are made using the Ku-band television transmissions from several different geostationary satellites, are based on the principle that the atmospheric attenuation produced by rain encountered along each transmission path can be used to determine the path-averaged rain rate. This kind of device could be very useful in hilly areas where radar data are not available or in urban areas where such devices could be directly placed in homes by using residential TV antenna. The major difficulty encountered with this technique is that of retrieving rainfall characteristics in the presence of many other causes of received signal fluctuation, produced by atmospheric scintillation, variations in atmospheric composition (water vapour concentration, cloud water content or satellite transmission parameters (variations in emitted power, satellite pointing. In order to conduct a feasibility study with such a device, a measurement campaign was carried out over a period of five months close to Paris. The present paper proposes an algorithm based on an artificial neural network, used to identify dry and rainy periods and to model received signal variability resulting from effects not related to rain. When the altitude of the rain layer is taken into account, the rain attenuation can be inverted to obtain the path-averaged rain rate. The rainfall rates obtained from this process are compared with co-located rain gauges and radar measurements taken throughout the full duration of the campaign, and the most significant rainfall events are analysed.

Rainfall measurement from the opportunistic use of an Earth-space link in the Ku band

Science.gov (United States)

Barthès, L.; Mallet, C.

2013-08-01

The present study deals with the development of a low-cost microwave device devoted to the measurement of average rain rates observed along Earth-satellite links, the latter being characterized by a tropospheric path length of a few kilometres. The ground-based power measurements, which are made using the Ku-band television transmissions from several different geostationary satellites, are based on the principle that the atmospheric attenuation produced by rain encountered along each transmission path can be used to determine the path-averaged rain rate. This kind of device could be very useful in hilly areas where radar data are not available or in urban areas where such devices could be directly placed in homes by using residential TV antenna. The major difficulty encountered with this technique is that of retrieving rainfall characteristics in the presence of many other causes of received signal fluctuation, produced by atmospheric scintillation, variations in atmospheric composition (water vapour concentration, cloud water content) or satellite transmission parameters (variations in emitted power, satellite pointing). In order to conduct a feasibility study with such a device, a measurement campaign was carried out over a period of five months close to Paris. The present paper proposes an algorithm based on an artificial neural network, used to identify dry and rainy periods and to model received signal variability resulting from effects not related to rain. When the altitude of the rain layer is taken into account, the rain attenuation can be inverted to obtain the path-averaged rain rate. The rainfall rates obtained from this process are compared with co-located rain gauges and radar measurements taken throughout the full duration of the campaign, and the most significant rainfall events are analysed.

Estimating Snow Water Equivalent with Backscattering at X and Ku Band Based on Absorption Loss

Directory of Open Access Journals (Sweden)

Yurong Cui

2016-06-01

Full Text Available Snow water equivalent (SWE is a key parameter in the Earth’s energy budget and water cycle. It has been demonstrated that SWE can be retrieved using active microwave remote sensing from space. This necessitates the development of forward models that are capable of simulating the interactions of microwaves and the snow medium. Several proposed models have described snow as a collection of sphere- or ellipsoid-shaped ice particles embedded in air, while the microstructure of snow is, in reality, more complex. Natural snow usually forms a sintered structure following mechanical and thermal metamorphism processes. In this research, the bi-continuous vector radiative transfer (bi-continuous-VRT model, which firstly constructs snow microstructure more similar to real snow and then simulates the snow backscattering signal, is used as the forward model for SWE estimation. Based on this forward model, a parameterization scheme of snow volume backscattering is proposed. A relationship between snow optical thickness and single scattering albedo at X and Ku bands is established by analyzing the database generated from the bi-continuous-VRT model. A cost function with constraints is used to solve effective albedo and optical thickness, while the absorption part of optical thickness is obtained from these two parameters. SWE is estimated after a correction for physical temperature. The estimated SWE is correlated with the measured SWE with an acceptable accuracy. Validation against two-year measurements, using the SnowScat instrument from the Nordic Snow Radar Experiment (NoSREx, shows that the estimated SWE using the presented algorithm has a root mean square error (RMSE of 16.59 mm for the winter of 2009–2010 and 19.70 mm for the winter of 2010–2011.

WRN Exonuclease Structure, Molecular Mechanism, and DNA EndProcessing Role

Energy Technology Data Exchange (ETDEWEB)

Perry, J. Jefferson P.; Yannone, Steven M.; Holden, Lauren G.; Hitomi, Chiharu; Asaithamby, Aroumougame; Han, Seungil; Cooper, PriscillaK.; Chen, David J.; Tainer, John A.

2006-02-15

WRN is unique among the five human RecQ DNA helicases by having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end-joining. Metal ion complex structures, active site mutations and activity assays reveal a two-metal-ion mediated nuclease mechanism. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end-joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ family replicative proofreading exonucleases, with WRN-specific adaptations consistent with dsDNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support analogous proof-reading activities that are stimulated by Ku70/80 with implications for WRN functions in age related pathologies and maintenance of genomic integrity.

The determinants of long-term care utilization and equity of access to care among older adults in Dong-Ku of Incheon Metropolitan city, South Korea.

Science.gov (United States)

Park, J M

2005-01-01

Under the current health care system, around three percent of the elderly remain uninsured. Based on the 2003 Dong-Ku Health Status Survey and the Aday and Andersen Access Framework, the present study examined the social and behavioral determinants of long-term care utilization and the extent to which equity in the use of long-term care services for the elderly has been achieved. The results indicate that universal health insurance system has not yielded a fully equitable distribution of services. Type of coverage and resource availability do not remain predictors of long-term care utilization. The data suggest that a universal health insurance system exists in South Korea with significant access problems for the population without insurance. Access differences also arise from obstacles in expanding the scope and level of plan benefits due to financial disparity among insurers. Health policy reforms must continue to concentrate on extending insurance coverage to the uninsured and establishing long-term insurance system for the elderly.

Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes.

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Bertolini, Marta; Uchida, Youhei; Paus, Ralf

2015-11-01

Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the-as yet elusive-key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.

Effects of Snow/ Soil Interface on Microwave Backscatter of Terrestrial Snowpack at X- and Ku- Band

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Kang, D. H.; Tan, S.; Zhu, J.; Gu, W.; Tsang, L.; Kim, E. J.

2017-12-01

Recent advances in monitoring and modeling capabilities to support remote sensing of terrestrial snow is encouraging to develop satellite mission concept in monitoring cold-region hydrological processes on global scales. However, it is still challenging to link back the active microwave backscattering signals to physical snowpack parameters. One of the limitations resides in the ignorance of the vegetation and soil conditions beneath the snowpack in the microwave scattering/ emission modeling and the snow water equivalent (SWE) retrieval algorithm. During the SnowEx 2017 winter campaign in Grand Mesa, CO, a particular effort has been made on comprehensive measurements of the underlying vegetation and soil characteristics from the snowpit measurements. Besides conducting standard snow core sampling, we have made additional protocols to record the background information beneath the snowpack. Recent works on active SWE retrieval algorithm using backscatters at X- (9.6 GHz) and Ku- (17.2 GHz) band suggest the significant signals from the background scattering characterization. The background scattering arising from the rough snow/ soil interface and the buried vegetation inside and beneath the snowpack modifies the sensitivity of the total backscatter to SWE. In this paper, we summarize the snow/ soil interface conditions as observed in the SnowEx campaign. We also develop standards for future in-situ snowpit measurements to include regular snow/ soil interface observations to accommodate the interpretation of microwave backscatter both for modeling and observation of microwave signatures. These observations first provide inputs to the microwave scattering models to predict the backscattering contribution from background, which is one of the key factors to be included to improve the SWE retrieval performance.

X ve Y Kuşağı: Hemşirelerin Meslek Dayanışması İle İş Doyumu Arasındaki İlişki

OpenAIRE

KARASU, Fatma; AYLAZ, Rukuye

2017-01-01

Amaç:Bu araştırma, X ve Y kuşağındaki hemşirelerin meslek dayanışması ile iş doyumuarasındaki ilişkisini belirlemek amacıyla yapılmıştır. Gereç ve Yöntem: Kesitsel nitelikteki araştırmanın evrenini devlethastanesinde çalışan hemşireler oluşturmuş, örneklem seçimine gidilmeyerekevrenin tamamı örnekleme dahil edilmiş ve 01.02.2017-01.03.2017 tarihleriarasında çalışmayı kabul eden toplamda 145 hemşireye ulaşılmıştır. Veri toplamaformunda, hemşirelerin sosyo-demografik özellikleri, Hemşirelerde M...

High-performance 16-way Ku-band radial power combiner based on the TE01-circular waveguide mode

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Montejo-Garai, José R.; Saracho-Pantoja, Irene O.; Ruiz-Cruz, Jorge A.; Rebollar, Jesús M.

2018-03-01

This work presents a 16-way Ku-band radial power combiner for high power and high frequency applications, using the very low loss TE01 circular waveguide mode. The accomplished design shows an excellent performance: the experimental prototype has a return loss better than 30 dB, with a balance for the amplitudes of (±0.15 dB) and (±2.5°) for the phases, in a 16.7% fractional bandwidth (2 GHz centered at 12 GHz). For obtaining these outstanding specifications, required, for instance, in high-frequency amplification or on plasma systems, a rigorous step-by-step procedure is presented. First, a high-purity mode transducer has been designed, from the TE10 mode in the rectangular waveguide to the TE01 mode in the circular waveguide, with very high attenuation (>50 dB) for the other propagating and evanescent modes in the circular waveguide. This transducer has been manufactured and measured in a back-to-back configuration, validating the design process. Second, an E-plane 16-way radial power divider has been designed, where the power is coupled from the 16 non-reduced-height radial standard waveguides into the TE01 circular waveguide mode, improving the insertion loss response and removing the usual tapered transformers of previous designs limiting the power handling. Finally, both the transducer and the divider have been assembled to make the final radial combiner. The prototype has been carefully manufactured, showing very good agreement between the measurements and the full-wave simulations.

CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses.

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Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J

2018-05-15

Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.

Wybrane zagadnienia dotyczące wpływu wysiłku fizycznego na organizm człowieka=Selected issues concerning the impact of physical exercise on the human organism

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Wojciech Wojtasik

2015-10-01

3      Instytut Kultury Fizycznej, Uniwersytet Kazimierza Wielkiego w Bydgoszczy   Słowa kluczowe: aktywność fizyczna, wysiłek fizyczny, geny i aktywności fizyczna Keywords: physical activity, physical effort, genes and physical activity   Cel i zakres pracy Ludzie, już w starożytnej Grecji, przywiązywali dużą wagę do zdrowego trybu życia, którego wyznacznikami są m. in.: siła mięśniowa, koordynacja nerwowo-mięśniowa, wydolność krążeniowo-oddechowa. Wysiłek fizyczny oddziałuje na poszczególne układy organizmu człowieka, w tym szczególnie na układ ruchu, krwionośny i oddechowy, neuro-hormonalny, a przez to na funkcjonowanie wielu narządów wewnętrznych. Od wieków prowadzone są liczne badania mające na celu poznanie zmian zachodzących w organizmie na skutek aktywności fizycznej. Zmiany w funkcjonowaniu organizmu poddanemu określonemu wysiłkowi fizycznemu (zarówno statycznemu jak i dynamicznemu określane są poprzez zastosowanie diagnostyki medycznej, praw fizycznych oraz diagnostyki sportowej. W pracy opisano zmiany, jakie zachodzą w organizmie człowieka w czasie wysiłku fizycznego, w takich układach jak: kostno-stawowy, mięśniowy, krwionośny, czy też oddechowy. Opisano także procesy przystosowawcze organizmu i wykazano korzystne oraz niekorzystne działanie (fizyczne, psychiczne i społeczne aktywności fizycznej na organizm człowieka. Sklasyfikowano również wysiłek fizyczny w zależności od przyjętych obecnie kryteriów. Artykuł stanowi częściowe podsumowanie zainteresowań naukowych autorów w latach 2014-2015.

Pituitary autoantibodies in endocrine disorders

OpenAIRE

Bensing, Sophie

2005-01-01

Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid...

Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica.

Science.gov (United States)

Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José; Dolz, Gaby

2017-01-01

One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs.

Rapid induction of autoantibodies during ARDS and septic shock

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Meduri G Umberto

2010-10-01

Full Text Available Abstract Background Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction. Methods Using Luciferase Immunoprecipitation Systems (LIPS, a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time. Results From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected. Conclusion The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.

Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma

OpenAIRE

Barghash, Ahmad; Golob-Schwarzl, Nicole; Helms, Volkhard; Haybaeck, Johannes; Kessler, Sonja M.

2016-01-01

Esophageal adenocarcinoma (EAC) represents the sixth leading cause of cancer-related deaths and develops in Barret's esophagus affected tissues. The IGF2 mRNA binding protein IMP2/IGF2BP2/p62 was originally identified as an autoantigen in hepatocellular carcinoma. Aim of this study was to investigate the expression and prognostic role of IMP2 in EAC. Human EAC and Barret's esophagus tissue showed overexpression of IMP2, particularly in tumors of increased size and in metastatic tissues. Molec...

Gaistošo organisko savienojumu emisijas no kuņģa vēža audiem un to potenciālā bioloģiskā saistība

OpenAIRE

Aronsson, Dan Erik

2018-01-01

Gaistošā organiskā savienojuma (VOC) emisija, ko var novērot izelpā, ir strauji augoša diagnostikas metode audzēju izmeklēšanā. VOC ir savienojums, kam istabas temperatūrā ir augsts tvaika spiediens, kas veicina tā iztvaikošanu gāzes formā. Šo gāzi var noteikt cilvēka audos un šķidrumos.( Haick et al 2014) Galvenokārt ir pētīta VOC saistība ar plaušu vēzi. Taču aizvien vairāk tiek veikti pētījumi, lai noteiktu, kādas ir iespējas VOC pielietot arī kuņģa audzēja gadījumā. Tā kā VOC molekula sp...

A Ku band pulsed electron paramagnetic resonance spectrometer using an arbitrary waveform generator for quantum control experiments at millikelvin temperatures

Energy Technology Data Exchange (ETDEWEB)

Yap, Yung Szen, E-mail: yungszen@utm.my [Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka-shi, Osaka 560-8531 (Japan); Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor (Malaysia); Tabuchi, Yutaka [Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Negoro, Makoto; Kagawa, Akinori; Kitagawa, Masahiro, E-mail: kitagawa@ee.es.osaka-u.ac.jp [Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka-shi, Osaka 560-8531 (Japan)

2015-06-15

We present a 17 GHz (Ku band) arbitrary waveform pulsed electron paramagnetic resonance spectrometer for experiments down to millikelvin temperatures. The spectrometer is located at room temperature, while the resonator is placed either in a room temperature magnet or inside a cryogen-free dilution refrigerator; the operating temperature range of the dilution unit is from ca. 10 mK to 8 K. This combination provides the opportunity to perform quantum control experiments on electron spins in the pure-state regime. At 0.6 T, spin echo experiments were carried out using γ-irradiated quartz glass from 1 K to 12.3 mK. With decreasing temperatures, we observed an increase in spin echo signal intensities due to increasing spin polarizations, in accordance with theoretical predictions. Through experimental data fitting, thermal spin polarization at 100 mK was estimated to be at least 99%, which was almost pure state. Next, to demonstrate the ability to create arbitrary waveform pulses, we generate a shaped pulse by superposing three Gaussian pulses of different frequencies. The resulting pulse was able to selectively and coherently excite three different spin packets simultaneously—a useful ability for analyzing multi-spin system and for controlling a multi-qubit quantum computer. By applying this pulse to the inhomogeneously broadened sample, we obtain three well-resolved excitations at 8 K, 1 K, and 14 mK.

Problemas de los grupos *k(hi̭, *kṷ(hi̭, *t(hi̭ y *tṷ en griego

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M.ª Luisa del Barrio Vega

1990-12-01

Full Text Available In this research the author studies a series of problems related to the evolution of the groups *k(hi̭, *kṷ(hi̭, *t(hi̭ and *tṷ in Greek. After a brief description of the palatalization process undergone by these groups and considering the different results from *t(hi̭ in the Ionic-Attic and Arcadian-Cypriot dialects which were swept twice by a wave of palatalization as well as the possible influence by analogy of the development undergone by *k(hi̭, the author examines in great depth the state of these groups at the time of the Mycenaean tablets analyzing the different values proposed for the series z- and s-. For z- an occlusive palatal and for s- an affricate articulation are considered the most likely ones. The author further suggests that the s- series followed an evolution parallel to that of the complex syllabograms of the type raz, roz, etc. Subsequently the author analyzes the graphic issues related to the evolution of the phonemic groups under study: The use of a special graphical notation in some Ionic and Pamphylian σσ/ττ in the dialects during the first millennium are due to the influence derived from the graphic representation of the state *ts. Finally the author suggests the Boeotian dialect as a starting point for the change *ts > tt, as in this dialect tt has a corresponding voiced series dd.

The Effect of the Unique Features of Y Generation on Organizational Commitment / Y Kuşağının Belirleyici Özelliklerinin Örgütsel Bağlılık Üzerindeki Etkisi

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Mustafa Emre Civelek

2017-12-01

Full Text Available ABSTRACT In this research, the determinants of the generations and unique characteristics of Generation Y are examined and the effect of this unique characteristics on organizational commitment is investigated. In the introduction part of the research, different features separating the generations from each other were mentioned and the studies done in this subject were examined and the studies and findings of different researchers were evaluated. In the final part of the survey, there is the analysis result of the survey collected from overall Turkey from 8 corporations. Sample size of this research is 267.  In order to measure organizational commitment, the scale developed by Allen and Meyer was used (Allen & Meyer, 1993. In order to measure team working, the scale developed by Levi and Slem was used (Levi & Slem, 1995. In order to measure playful spirit at work, the scale developed by Berg was used (Berg, 2011. According to the test results, there is a positive and significant relationship between Workplace fun and Team Working and between Team Working and Organizational Commitment. Contrary to expectation, there is not directly relation between organizational commitment and workplace fun. But work place fun positively effects organizational commitment through team working indirectly. The results of this research are to confirm that employees will be more likely to work in teams if organization environments are established to make them happy and entertained, thereby increasing their organizational commitment. ÖZ Bu araştırmada Kuşakların belirleyici özellikleri incelenerek Y kuşağını diğer kuşaklardan ayıran özelliklerin neler olduğu ve bu özelliklerin örgütsel bağlılık üzerinde ne gibi bir etkisi olduğu araştırılmaktadır. Araştırmanın giriş kısmında kuşakları birbirinden ayrıştıran farklı özelliklere değinilmiş ve bu konuda yapılan çalışmalar incelenerek farklı araştırmacıların �

Inflammatory etiopathogenesis of systemic lupus erythematosus: an update

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Podolska MJ

2015-08-01

Full Text Available Malgorzata J Podolska, Mona HC Biermann, Christian Maueröder, Jonas Hahn, Martin Herrmann Department of Internal Medicine 3, Institute for Clinical Immunology and Rheumatology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany Abstract: The immune system struggles every day between responding to foreign antigens and tolerating self-antigens to delicately maintain tissue homeostasis. If self-tolerance is broken, the development of autoimmunity can be the consequence, as it is in the case of the chronic inflammatory autoimmune disease systemic lupus erythematosus (SLE. SLE is considered to be a multifactorial disease comprising various processes and cell types that act abnormally and in a harmful way. Oxidative stress, infections, or, in general, tissue injury are accompanied by massive cellular demise. Several processes such as apoptosis, necrosis, or NETosis (formation of Neutrophil Extracellular Traps [NETs] may occur alone or in combination. If clearance of dead cells is insufficient, cellular debris may accumulate and trigger inflammation and leakage of cytoplasmic and nuclear autoantigens like ribonucleoproteins, DNA, or histones. Inadequate removal of cellular remnants in the germinal centers of secondary lymphoid organs may result in the presentation of autoantigens by follicular dendritic cells to autoreactive B cells that had been generated by chance during the process of somatic hypermutation (loss of peripheral tolerance. The improper exposure of nuclear autoantigens in this delicate location is consequently prone to break self-tolerance to nuclear autoantigens. Indeed, the germline variants of autoantibodies often do not show autoreactivity. The subsequent production of autoantibodies plays a critical role in the development of the complex immunological disorder fostering SLE. Immune complexes composed of cell-derived autoantigens and autoantibodies are formed and get deposited in various tissues, such as the

Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

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Jacques C Mbongue

Full Text Available Dendritic cells (DC interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS. Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1. Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention

SERANGAN BENALU PADA BEBERAPA KELAS UMUR TANAMAN JATI DI WILAYAH HUTAN BKPH BEGAL, KPH NGAWI, JAWA TIMUR (An Attact of Parasitic Plant on Several Ages of Teak Plantation In Begal Forest Sub-District, Ngawi Forest District, East Java

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Soewarno Hasanbahri

2014-10-01

The objectives of the study were to determine the relationship of teak plantation age class with the frequency and severity of teak trees due to an attack of parasitic plant (mistletoe, and parasitic plant distribution patterns horizontally. The sampling method in this study was the Multistage Sampling, i.e. at each age group classe (KU represented one compartment and each compartment made an individual sampling tree as much as 10 % for KU V and up (old age classes, 5 % for KU III – IV (middle age classes and 1 % for KU I - II (young age classes to the total trees populations. Age class relationship with the frequency and degree of tree damage due to an attack of parasitic plant were analyzed by correlation test formula and for the parasitic plant distribution were analysed by the Poisson distribution formula and the Binomial Test Statistically Reversed. The conclusions of this study that were found two species of parasitic plants of Dendrophthoe pentandra and Scurula parasitiaca of the Loranthaceae family members, sub-family Viscoidae. The frequency of teak trees that were attacted by parasitic plants ranged from 12.88 % for KU II and  followed by 15.55 % for KU I, 15.72 % for KU V, 18.06 % for KU IV and VI, up  to 19.73 % for KU III. The correlation between an attack of parasitic plants and the teak forest age classes have proven that significant relationship to the level of the proximal health. In another part, proved that age class does not have a significant relationship to the distal extent of damage. Nevertheless , the teak tree damage suffered an attack of parasitic plants were more prevalent on trees in the younger age classes. It was shown by a comparison of proximal and distal branches in each age class, namely: -23.81 cm for KU I, -1.56 cm for KU II, 14.66 cm for KU III, 24.13 cm for KU IV, 22.40 cm for KU V and 54.94 cm for KU VI. With the loss of future growth faced by teak trees in the young age classes become very vulnerable in the presence of

Simulation study for ground-based Ku-band microwave observations of ozone and hydroxyl in the polar middle atmosphere

Science.gov (United States)

Newnham, David; Clilverd, Mark; Kosch, Michael; Verronen, Pekka

2017-04-01

Commercial satellite TV broadcasting is possible due to remarkable advances in microwave electronics, enabling weak signals transmitted over 36,000 km from geostationary orbit to be received by inexpensive rooftop dishes. The Ku band satellite frequencies (10.70-14.25 GHz) overlap microwave emissions from ozone (O3) at 11.072 GHz and hydroxyl radical (OH) at 13.44 GHz. These important chemical species in the polar middle atmosphere respond strongly to solar variability and, at high latitudes, geomagnetic activity associated with space weather. Atmospheric model calculations predict that energetic electron precipitation (EEP) driven by magnetospheric substorms produces large changes in polar mesospheric O3 and OH. The EEP typically peaks at geomagnetic latitudes ˜65˚ (e.g. Kilpisjärvi, Finland and Syowa station, Antarctica) and evolves rapidly with time eastwards and over the geomagnetic latitude range 60˚ -80˚ (e.g. reaching Halley, Antarctica). During the substorms OH can increase by more than 1000% at 64-84 km. The substorms leave footprints of 5-55% O3 loss lasting many hours of local time, with strong altitude and seasonal dependences. An atmospheric simulation and retrieval study is performed to determine the specification and design requirements for microwave radiometers capable of measuring O3 and OH profiles from Arctic and Antarctic locations using accessible satellite TV receiver technology. The proposed observations are highly applicable to studies of EEP, atmospheric dynamics, planetaryscale circulation, chemical transport, and the representation of these processes in polar and global climate models. They would provide a lowcost, reliable alternative to increasingly sparse satellite measurements, extending long-term data records and also providing "ground truth" calibration data.

Agrobacterium tumefaciens T-DNA Integration and Gene Targeting in Arabidopsis thaliana Non-Homologous End-Joining Mutants

Directory of Open Access Journals (Sweden)

Qi Jia

2012-01-01

Full Text Available In order to study the role of AtKu70 and AtKu80 in Agrobacterium-mediated transformation and gene targeting, plant lines with a T-DNA insertion in AtKu80 or AtKu70 genes were functionally characterized. Such plant lines lacked both subunits, indicating that heterodimer formation between AtKu70 and AtKu80 is needed for the stability of the proteins. Homozygous mutants were phenotypically indistinguishable from wild-type plants and were fertile. However, they were hypersensitive to the genotoxic agent bleomycin, resulting in more DSBs as quantified in comet assays. They had lower end-joining efficiency, suggesting that NHEJ is a critical pathway for DSB repair in plants. Both Atku mutants and a previously isolated Atmre11 mutant were impaired in Agrobacterium T-DNA integration via floral dip transformation, indicating that AtKu70, AtKu80, and AtMre11 play an important role in T-DNA integration in Arabidopsis. The frequency of gene targeting was not significantly increased in the Atku80 and Atku70 mutants, but it was increased at least 10-fold in the Atmre11 mutant compared with the wild type.

effect of plant biomass, manure and inorganic fertiliser on maize

African Journals Online (AJOL)

Administrator

1Kenyatta University (KU), School of Environmental Studies and Human ... own innovations where they combined organic resources and generally ... to differences in management practices arising from partial adoption of recommended rates. ... RÉSUMÉ. La dégradation de la fertilité de sol reste la cause biophysique ...

The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation

International Nuclear Information System (INIS)

Alao, John P; Sunnerhagen, Per

2009-01-01

The ataxia telangiectasia mutated (ATM) and the ATM- related (ATR) kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933) or ATM and ATR (CGK733) have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB). Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles

Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes

DEFF Research Database (Denmark)

Andersen, Marie Louise M; Vaziri-Sani, Fariba; Delli, Ahmed

2012-01-01

The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D.......The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D....

Multi-Satellite MIMO Communications at Ku-Band and Above: Investigations on Spatial Multiplexing for Capacity Improvement and Selection Diversity for Interference Mitigation

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Liolis Konstantinos P

2007-01-01

Full Text Available This paper investigates the applicability of multiple-input multiple-output (MIMO technology to satellite communications at the Ku-band and above. After introducing the possible diversity sources to form a MIMO matrix channel in a satellite environment, particular emphasis is put on satellite diversity. Two specific different topics from the field of MIMO technology applications to satellite communications at these frequencies are further analyzed: (i capacity improvement achieved by MIMO spatial multiplexing systems and (ii interference mitigation achieved by MIMO diversity systems employing receive antenna selection. In the first case, a single-user capacity analysis of a satellite MIMO spatial multiplexing system is presented and a useful analytical closed form expression is derived for the outage capacity achieved. In the second case, a satellite MIMO diversity system with receive antenna selection is considered, adjacent satellite cochannel interference on its forward link is studied and an analytical model predicting the interference mitigation achieved is presented. In both cases, an appropriate physical MIMO channel model is assumed which takes into account the propagation phenomena related to the frequencies of interest, such as clear line-of-sight operation, high antenna directivity, the effect of rain fading, and the slant path lengths difference. Useful numerical results obtained through the analytical expressions derived are presented to compare the performance of multi-satellite MIMO systems to relevant single-input single-output (SISO ones.

Mouse but not human embryonic stem cells are deficient in rejoining of ionizing radiation-induced DNA double-strand breaks.

Science.gov (United States)

Bañuelos, C A; Banáth, J P; MacPhail, S H; Zhao, J; Eaves, C A; O'Connor, M D; Lansdorp, P M; Olive, P L

2008-09-01

Mouse embryonic stem (mES) cells will give rise to all of the cells of the adult mouse, but they failed to rejoin half of the DNA double-strand breaks (dsb) produced by high doses of ionizing radiation. A deficiency in DNA-PK(cs) appears to be responsible since mES cells expressed strand breaks more rapidly. Consistent with more rapid dsb rejoining, H2AX(-/-) mES cells also expressed 6 times more DNA-PK(cs) than wild-type mES cells. Similar results were obtained for ATM(-/-) mES cells. Differentiation of mES cells led to an increase in DNA-PK(cs), an increase in dsb rejoining rate, and a decrease in Ku70/80. Unlike mouse ES, human ES cells were proficient in rejoining of dsb and expressed high levels of DNA-PK(cs). These results confirm the importance of homologous recombination in the accurate repair of double-strand breaks in mES cells, they help explain the chromosome abnormalities associated with deficiencies in H2AX and ATM, and they add to the growing list of differences in the way rodent and human cells deal with DNA damage.

microRNA-145 promotes differentiation in human urothelial carcinoma through down-regulation of syndecan-1

International Nuclear Information System (INIS)

Fujii, Tomomi; Shimada, Keiji; Tatsumi, Yoshihiro; Hatakeyama, Kinta; Obayashi, Chiho; Fujimoto, Kiyohide; Konishi, Noboru

2015-01-01

A new molecular marker of carcinoma in the urinary bladder is needed as a diagnostic tool or as a therapeutic target. Potential markers include microRNAs (miRNAs), which are short, low molecular weight RNAs 19–24 nt long that regulate genes associated with cell proliferation, differentiation, and development in various cancers. In this study, we investigated the molecular mechanisms by which miR-145 promotes survival of urothelial carcinoma cells and differentiation into multiple lineages. We found miR-145 to regulate expression of syndecan-1, a heparin sulfate proteoglycan. Cell proliferation in the human urothelial carcinoma cell lines T24 and KU7 was assessed by MTS assay. Cellular senescence and apoptosis were measured by senescence-associated β-galactosidase (SA-β-gal) and TUNEL assay, respectively. Quantitative RT-PCR was used to measure mRNA expression of various genes, including syndecan-1, stem cell factors, and markers of differentiation into squamous, glandular, or neuroendocrine cells. Overexpression of miR-145 induced cell senescence, and thus significantly inhibited cell proliferation in T24 and KU7 cells. Syndecan-1 expression diminished, whereas stem cell markers such as SOX2, NANOG, OCT4, and E2F3 increased. miR-145 also up-regulated markers of differentiation into squamous (p63, TP63, and CK5), glandular (MUC-1, MUC-2, and MUC-5 AC), and neuroendocrine cells (NSE and UCHL-1). Finally, expression of miR-145 was down-regulated in high-grade urothelial carcinomas, but not in low-grade tumors. Results indicate that miR-145 suppresses syndecan-1 and, by this mechanism, up-regulates stem cell factors and induces cell senescence and differentiation. We propose that miR-145 may confer stem cell-like properties on urothelial carcinoma cells and thus facilitate differentiation into multiple cell types. The online version of this article (doi:10.1186/s12885-015-1846-0) contains supplementary material, which is available to authorized users

The University of Kansas High-Throughput Screening laboratory. Part I: meeting drug-discovery needs in the heartland of America with entrepreneurial flair.

Science.gov (United States)

McDonald, Peter R; Roy, Anuradha; Chaguturu, Rathnam

2011-05-01

The University of Kansas High-Throughput Screening (KU HTS) core is a state-of-the-art drug-discovery facility with an entrepreneurial open-service policy, which provides centralized resources supporting public- and private-sector research initiatives. The KU HTS core applies pharmaceutical industry project-management principles in an academic setting by bringing together multidisciplinary teams to fill critical scientific and technology gaps, using an experienced team of industry-trained researchers and project managers. The KU HTS proactively engages in supporting grant applications for extramural funding, intellectual-property management and technology transfer. The KU HTS staff further provides educational opportunities for the KU faculty and students to learn cutting-edge technologies in drug-discovery platforms through seminars, workshops, internships and course teaching. This is the first instalment of a two-part contribution from the KU HTS laboratory.

Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

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Vazhappilly Cijo George

2017-01-01

Full Text Available Scope. Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4 against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. Methods and Results. AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK, NNK acetate (NNK-Ae, methotrexate (MTX, and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage. Furthermore, phosphorylated histone (γ-H2AX and proteins involved in DNA damage (ATM/ATR, Chk1, Chk2, and p53 and repair (DNA-PKcs and Ku80 mechanisms were evaluated by immunofluorescence and western blotting, respectively. The results revealed that AF4-pretreated cells showed lower cytotoxicity, total ROS generation, and DNA fragmentation along with consequent inhibition of DNA tail moment. An increased level of γ-H2AX and DNA damage proteins was observed in carcinogen-treated cells and that was significantly (p≤0.05 inhibited in AF4-pretreated cells, in an ATR-dependent manner. AF4 pretreatment also facilitated the phosphorylation of DNA-PKcs and thus initiation of repair mechanisms. Conclusion. Apple flavonoids can protect in vitro oxidative DNA damage and facilitate repair mechanisms.

Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

OpenAIRE

Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

2003-01-01

In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

International Nuclear Information System (INIS)

Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

2013-01-01

Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

KUŞAKLARIN SİYASAL İLETİŞİM KÜLTÜR VE LİDERLİK AÇISINDAN DEĞERLENDİRİLMESİ

OpenAIRE

GÖKTAŞ, Pınar; ÇARIKÇI, İlker Hüseyin

2018-01-01

Kuşaklararası farklılıklar; bireylerin iletişim tarzını vearzu edilen liderlik tarzını etkilemektedir. Tipik kuşak çatışmalarının çoğuiletişimsizlikten kaynaklanmaktadır. Bu sorunu çözmek için hedef kitleye yönelikiletişim tarzı seçilmelidir. Liderlik tarzı açısından ise kuşaklar inandırıcı vegüvenilir bir lider arzusu içindedir. Araştırma kapsamında aynı zamandaaralarındaki farka da değinebilmek adına sessiz kuşak, patlama kuşağı, X, Y ve Zkuşaklarına yer verilmiştir. Bu bağlamda kuşaklar il...

Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array.

Directory of Open Access Journals (Sweden)

Songliu Hu

Full Text Available To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, Ku heterodimeric regulatory complex 70-KD subunit (Ku70 and ataxia-telangiectasia mutated (ATM.The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC.The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009 and lymph node status (P = 0.004. The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012 and DNA-PKcs (P = 0.02. Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001 and Ku70 expression (P<0.001.Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.

PM1-Alpha ELISA: the assay of choice for the detection of anti-PM/Scl autoantibodies?

Science.gov (United States)

Mahler, Michael; Fritzler, Marvin J

2009-03-01

A characteristic serological feature of patients suffering from the overlap polymyositis and scleroderma (PM/Scl) syndrome are antibodies to the human counterpart of the yeast exosome referred to as the PM/Scl complex. Historically, the detection of anti-PM/Scl antibodies was laborious and relied largely on indirect immunofluorescence and immunodiffusion techniques. In 1992 the major autoantigen PM/Scl-100 was identified and cloned. Subsequently, the major epitopes were mapped and one of these, termed PM1-Alpha, became the antigen for a novel ELISA exhibiting high sensitivity and specificity for the detection of anti-PM/Scl antibodies. Comparative studies with other methods using other PM/Scl autoantigens have shown that the PM1-Alpha ELISA has higher sensitivity and specificity than assays that employed recombinant PM/Scl-75c and PM/Scl-100. Anti-PM1-Alpha antibodies were identified in 55.0% of sera from PM/Scl overlap syndrome patients, but were also seen in 7.9% of SSc and in 7.5% of PM patients. The frequency in other systemic autoimmune diseases and in infectious diseases was significant lower. In summary, the data derived from individual studies suggest that PM1-Alpha may become the "gold standard" for the detection of anti-PM/Scl antibodies.

A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses

Science.gov (United States)

Kanno, Shin-ichiro; Kuzuoka, Hiroyuki; Sasao, Shigeru; Hong, Zehui; Lan, Li; Nakajima, Satoshi; Yasui, Akira

2007-01-01

DNA damage causes genome instability and cell death, but many of the cellular responses to DNA damage still remain elusive. We here report a human protein, PALF (PNK and APTX-like FHA protein), with an FHA (forkhead-associated) domain and novel zinc-finger-like CYR (cysteine–tyrosine–arginine) motifs that are involved in responses to DNA damage. We found that the CYR motif is widely distributed among DNA repair proteins of higher eukaryotes, and that PALF, as well as a Drosophila protein with tandem CYR motifs, has endo- and exonuclease activities against abasic site and other types of base damage. PALF accumulates rapidly at single-strand breaks in a poly(ADP-ribose) polymerase 1 (PARP1)-dependent manner in human cells. Indeed, PALF interacts directly with PARP1 and is required for its activation and for cellular resistance to methyl-methane sulfonate. PALF also interacts directly with KU86, LIGASEIV and phosphorylated XRCC4 proteins and possesses endo/exonuclease activity at protruding DNA ends. Various treatments that produce double-strand breaks induce formation of PALF foci, which fully coincide with γH2AX foci. Thus, PALF and the CYR motif may play important roles in DNA repair of higher eukaryotes. PMID:17396150

The Comparison of Canopy Height Profiles Extracted from Ku-band Profile Radar Waveforms and LiDAR Data

Directory of Open Access Journals (Sweden)

Hui Zhou

2018-05-01

Full Text Available An airborne Ku-band frequency-modulated continuous waveform (FM-CW profiling radar, Tomoradar, records the backscatter signal from the canopy surface and the underlying ground in the southern boreal forest zone of Finland. The recorded waveforms are transformed into canopy height profiles (CHP with a similar methodology utilized in large-footprint light detection and ranging (LiDAR. The point cloud data simultaneously collected by a Velodyne® VLP-16 LiDAR on-board the same platform represent the frequency of discrete returns, which are also applied to the extraction of the CHP by calculating the gap probability and incremental distribution. To thoroughly explore the relationships of the CHP derived from Tomoradar waveforms and LiDAR data we utilized the effective waveforms of one-stripe field measurements and comparison them with four indicators, including the correlation coefficient, the root-mean-square error (RMSE of the difference, and the coefficient of determination and the RMSE of residuals of linear regression. By setting the Tomoradar footprint as 20 degrees to contain over 95% of the transmitting energy of the main lobe, the results show that 88.17% of the CHPs derived from Tomoradar waveforms correlated well with those from the LiDAR data; 98% of the RMSEs of the difference ranged between 0.002 and 0.01; 79.89% of the coefficients of determination were larger than 0.5; and 98.89% of the RMSEs of the residuals ranged from 0.001 to 0.01. Based on the investigations, we discovered that the locations of the greatest CHP derived from the Tomoradar were obviously deeper than those from the LiDAR, which indicated that the Tomoradar microwave signal had a stronger penetration capability than the LiDAR signal. Meanwhile, there are smaller differences (the average RMSEs of differences is only 0.0042 when the total canopy closure is less than 0.5 and better linear regression results in an area with a relatively open canopy than with a denser

Pilot testing of the Czech versions of the Coaching Behavior Assessment Questionnaire structure [Pilotní testování struktury české verze dotazníku Coaching Behavior Assessment Questionnaire

Directory of Open Access Journals (Sweden)

Martin Musálek

2012-03-01

Martin a Kelly Barnes vytvořili v roce 1999 dotazník Coaching Behavior Assessment Questionnaire, který vychází z CBAS (Smith a kol., 1977 a LSS (Chelladurai & Saleh, 1978, 1980. V současné době není v České republice podobný diagnostický nástroj pro hodnocení chování trenéra. CÍLE: Cílem této pilotní studie bylo přeložit a ohodnotit strukturu dotazníku CBAQ metodou strukturálního modelování pro populaci dětí ve věku 10 – 16 let. METODIKA: Pro účel překladu dotazníku byla použita modifikovaná metoda přímého překladu (Behling & Law, 2000. Dotazník vyplnilo 100 účastníků ve věku 10 – 16 let, 63 děvčat (průměrný věk 13,02; SD = 2,10, 37 chlapců (průměrný věk 13,27; SD = 1,37. Pro analýzu dat byla použita exploratorní a konfirmační faktorová analýza. VÝSLEDKY: Původní model byl testován za účelem ověření struktury a diagnostické kvality tohoto nástroje. Výsledky původního 12-faktorového modelu CBAQ ukázaly slabý fit modelu s podprůměrnými hodnotami indexů fitu RMSEA = 0,082, CFI = 0,600 a také nízké koeficienty generické reliability. Z tohoto důvodu jsme se rozhodli pro re-analýzu dat, ze které byla vytvořena modifikovaná 5-faktorová struktura CBAQ. Tento 5-faktorový model s omezeným počtem položek ukázal nejlepší hodnoty indexů fitu RMSEA = 0,056; CFI = 0.964 a také akceptovatelné hodnoty generické reliability. ZÁVĚRY: Tato studie měla pilotní charakter, uvědomujeme si proto, že snížení velkého počtu položek u této modifikované verze vedlo ke ztrátě informace. Přesto se domníváme, že by tato finální 5-faktorová verze s 15 položkami mohla tvořit základ pro budoucí připravovanou plně standardizovanou českou verzi CBAQ.

Mechanický návrh průběžného zásobníku příze a jeho realizace

OpenAIRE

Klusoň, Vladimír

2014-01-01

Práce se zabývá vývojem zařízení Průběžného zásobníku příze pro textilní stroj. Průběžný zásobník přízeobsahuje poháněný navíjecí válec s rotačním kompenzátorem napětí příze, flyerem. Poháněný otočný zásobník je spřažen s prvním pohonem tvořeným elektrickým motorem a rotační kompenzátor je spřažen s druhým pohonem tvořeným elektrickým motorem, přičemž oba motory jsou napojeny na řídicí systém. Zařízení Průběžný zásobník příze efektivně zvyšuje stupeň automatizace textilního stroje. This th...

Prohibitin Is Involved in Patients with IgG4 Related Disease.

Directory of Open Access Journals (Sweden)

Hongwu Du

Full Text Available IgG4-related disease (IgG4-RD is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%, Mikulicz's disease (8/15; 53.3%, retroperitoneal fibrosis (6/11; 54.5%, other probable IgG4-RD (26/29; 89.7% and Sjögren's syndrome (4/30; 13.3% but not in apparently healthy donors (1/70; 1.4%.An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz's disease and retroperitoneal fibrosis.

Vecāku prombūtnes un klātesošā vecāka audzināšanas pieejas saistība ar pusaudžu depresijas pazīmēm

OpenAIRE

Ločmele, Renāte

2014-01-01

Pētījuma mērķis bija noskaidrot, kādas ir saistības starp vecāku prombūtni, klātesošā vecāka audzināšanas pieeju un pusaudžu depresijas pazīmēm. Pētījumā piedalījās 62 respondenti – 37 meitenes un 25 zēni vecumā no 11 līdz 16 gadiem. Respondentu vidējais vecums bija 14 gadi. Tie tika sadalīti divās grupās: vienā grupā bija pusaudži, kuriem viens no vecākiem atrodas prombūtnē (n=31), otrā grupā bija pusaudži, kas dzīvo kopā ar abiem vecākiem ( n=31). Datu ievākšanai tika izmantotas sekojoš...

Tetraploidization or autophagy: The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.

Science.gov (United States)

Borodkina, Aleksandra V; Shatrova, Alla N; Deryabin, Pavel I; Grukova, Anastasiya A; Nikolsky, Nikolay N; Burova, Elena B

2016-01-01

Previously we demonstrated that endometrium-derived human mesenchymal stem cells (hMESCs) via activation of the ATM/p53/p21/Rb pathway enter the premature senescence in response to oxidative stress. Down regulation effects of the key components of this signaling pathway, particularly ATM and p53, on a fate of stressed hMESCs have not yet been investigated. In the present study by using the specific inhibitors Ku55933 and Pifithrin-α, we confirmed implication of both ATM and p53 in H(2)O(2)-induced senescence of hMESCs. ATM or p53 down regulation was shown to modulate differently the cellular fate of H(2)O(2)-treated hMESCs. ATM inhibition allowed H(2)O(2)-stimulated hMESCs to escape the permanent cell cycle arrest due to loss of the functional ATM/p53/p21/Rb pathway, and induced bypass of mitosis and re-entry into S phase, resulting in tetraploid cells. On the contrary, suppression of the p53 transcriptional activity caused a pronounced cell death of H(2)O(2)-treated hMESCs via autophagy induction. The obtained data clearly demonstrate that down regulation of ATM or p53 shifts senescence of human endometrial stem cells toward tetraploidization or autophagy.

Ku to V-band 4-bit MEMS phase shifter bank using high isolation SP4T switches and DMTL structures

Science.gov (United States)

Dey, Sukomal; Koul, Shiban K.; Poddar, Ajay K.; Rohde, Ulrich L.

2017-10-01

This work presents a micro-electro-mechanical system (MEMS) based on a wide-band 4-bit phase shifter using two back-to-back single-pole-four-throw (SP4T) switches and four different distributed MEMS transmission line (DMTL) structures that are implemented on 635 µm alumina substrate using surface micromachining process. An SP4T switch is designed with a series-shunt configuration and it demonstrates an average return loss of  >17 dB, an insertion loss of  28 dB up to 60 GHz. A maximum area of the SP4T switch is ~0.76 mm2. Single-pole-single-throw and SP4T switches are capable of handling 1 W of radio frequency (RF) power up to  >100 million cycles at 25° C; they can even sustained up to  >70 million cycles with 1 W at 85 °C. The proposed wide-band phase shifter works at 17 GHz (Ku-band), 25 GHz (K-band), 35 GHz (Ka-band) and 60 GHz (V-band) frequencies. Finally,a 4-bit phase shifter demonstrates an average insertion loss of  10 dB and maximum phase error of ~3.8° at 60 GHz frequency over 500 MHz bandwidth. Total area of the fabricated device is ~11 mm2. In addition, the proposed device works well up to  >107 cycles with 1 W of RF power. To the best of the author’s knowledge, this is the best reported wide-band MEMS 4-bit phase shifter in the literature that works with a constant resolution.

Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT in DNA repair, apoptosis and necrosis after cisplatin

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Calkins Anne S

2011-06-01

Full Text Available Abstract Background Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK binds to DNA double strand breaks (DSBs through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity. Results Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1, Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT. The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis. Conclusions DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and

Morusin induces apoptosis and suppresses NF-κB activity in human colorectal cancer HT-29 cells

International Nuclear Information System (INIS)

Lee, J.-C.; Won, S.-J.; Chao, C.-L.; Wu, F.-L.; Liu, H.-S.; Ling Pin; Lin, C.-N.; Su, C.-L.

2008-01-01

Morusin is a pure compound isolated from root bark of Morusaustralis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G 1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-α, IKK-β and IκB-α, increased expression of IκB-α, and suppressed nuclear translocation of NF-κB and its DNA binding activity. Dephosphorylation of NF-κB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-κB

Hard X-Ray Properties of the Merging Cluster Abell 3667 as Observed with Suzaku

Science.gov (United States)

2008-08-01

3667 as Observed with Suzaku Kazuhiro NAKAZAWA Department of Physics, The University of Tokyo, 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 nakazawa...of Tokyo, 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 Kazuo MAKISHIMA Department of Physics, The University of Tokyo, 7-3-1 Hongo , Bunkyo-ku, Tokyo 113

Wpływ terapii BEMER na wybrane wskaźniki krwi w ramach procesu odnowy biologicznej po wysiłku wytrzymałościowym. Studium przypadku = Effect of BEMER therapy on selected indicators of blood in the process of wellness after exercise endurance. Case study

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Mirosław Mrozkowiak

2015-04-01

-6 dekadzie życia może być uzasadnione i jako przygotowanie do wysiłku fizycznego.     Abstract   The principal vesels are forming capillary microcirculation. A single capillary has a diameter of about 6 pm, the total cross sectional area of the capillary is about 3000 cm2. For every cubic millimeter of the human body is an average of 600 capillaries. BEMR therapy system using the complex or complement excellent basic physiological processes angiokinesis microcirculation bringing nutrients and oxygen to muscle cells. With specific modulation biorhythmical synergistic effect is achieved also into primary and secondary, slightly larger vessels. Materials and methods. Tested man pursuing a healthy lifestyle surrendered twice selected indicators measure the blood and the vascular system: after exercise endurance during physiological restitution and renewal BEMER assisted therapy. The obtained results. The most significant changes in selected indicators of blood after endurance exercise was observed in the total amount of hemoglobin smallest hydrocarbyl ion concentration. Significant changes occurred during early recovery in the indicators: partial pressure of oxygen (PO2, arterial oxygen saturation (SO2 (c, oxyhemoglobin (O2Hb, carboxyhemoglobin (HbCO, methemoglobin (MeHb and hydroxyhemoglobin (HHB. Conclusions. Methodology and profile BEMER signal variation affects the size of the selected features of the blood. BEMER pacing in rejuvenating the efforts of strength in men in 5-6 decade of life may be justified, and in preparation for exercise.

The effect of MRN complex and ATM kinase inhibitors on Zebrafish embryonic development

Science.gov (United States)

Kumaran, Malina; Fazry, Shazrul

2018-04-01

Zebrafish is an ideal animal model to study developmental biology due to its transparent embryos and rapid development stages of embryogenesis. Here we investigate the role of DNA damage proteins, specifically Mre11/Rad50/NBN (MRN) complex and ataxia-telangiectasia mutated (ATM) kinase during embryogenesis by inhibiting its function using specific MRN complex (Mirin) and ATM Kinase inhibitors (Ku60019 and Ku55933). Zebrafish embryos at midblastula transition (MBT) stage are treated with Mirin, Ku60019 and Ku55933. The embryonic development of the embryos was monitored at 24 hours-post fertilisation (hpf), 48 hpf and 72 hpf. We observed that at the lowest concentrations (3 µM of Mirin, 1.5 nM of Ku60019 and 3 nM of Ku55933), the inhibitors treated embryos have 100% survivability. However, with increasing inhibitor concentration, the survivability drops. Control or mock treatment of all embryos shows 100 % survivability rate. This study suggests that DNA damage repair proteins may be crucial for normal zebrafish embryo development and survival.

Lastedisain ehk kodumaine disainerlooming lastele / Dagmar Reinolt

Index Scriptorium Estoniae

Reinolt, Dagmar

2015-01-01

Eesti disainerite poolt toodetud lastepärased esemed - võileivaalus (VarmCountry), tapeet "Värvi ise" (Anni Varm), söögitool "Mari" (Julia Maria Künnap), nööpsadul (Liisa Elken), öökullipadi (Ann Lutter), kiikhobu "Fox" (Maile Grünberg), KuKuJuKu helkurid (Okeiko) ja Dadamora lasteriided (Mariliis Oksaar,Tõnis Kenkmaa)

Structural Modification of Egyptian Kaolinite for Paper Coating

International Nuclear Information System (INIS)

Mohamed, H.F.; Hassan, M.S.; Morsy, F.A.; El-Sherbiny, S.

2013-01-01

The aim of this work is surface modification of Egyptian kaolinite for paper coating. Kaolinite < 2 fraction (KF) obtained using sedimentation and centrifuging techniques. Organo-kaolinite was prepared via inserting Urea (NH 2 CO NH 2 ) within the gallery of kaolinite using grinding technique for different times. Nano kaolinite was prepared from dispersion of organo-kaolinite in paper coating. The kaolinite (K), kaolinite /urea (KU) and kaolinite urea with binder (KU/Binder) were characterized using X-ray diffractometry (XRD), Infrared spectroscopy (IR) and Scanning Electron Microscopy (SEM). XRD studies revealed shifting of basal space of kaolinite from 0.714 to 1.11 nm upon grinding of kaolinite with urea for 5 h. On the other hand, the characteristic peak of kaolinite completely disappeared during dispersion of KU in paper coating suspension, which revealed the exfoliation of organo-kaolinite layers through the binder. Meanwhile, IR spectra show that NH-CO molecule exists in the intercalated kaolinite. The SEM images of KU revealed that kaolinite is intercalated U and fully exfoliation of KU achieved in KU/Binder and revealed by thin flakes with particle size ranged from 500 nm and 300 nm respectively. The modified kaolinite for paper coating increased the optical properties in terms of ISO brightness, opacity and gloss of the coated paper. There was a significant decrease in coated paper roughness compared to untreated kaolinite. Air permeance of the KF decreased in comparison with K sample, but increased sharply by intercalation of kaolinite (KU). Burst strength also started to increase with untreated kaolinite but decreased sharply with urea KU.

Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

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Saimul Islam

Full Text Available Human papillomavirus (HPV causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT and Neo-adjuvant chemotherapy (NACT patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0% and NACT (71.0% cases with significant association with younger (20-45 yrs PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21, fibro adenomas (30%, 3/10 to tumors (64.8%, 203/313 samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0% followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839 in the LCR region and two (KT020836 and KT020837 in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314 and E6^E7*II (KU199315 fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

Safety Evaluation Report related to the renewal of the operating license for the research reactor at the University of Kansas (Docket No. 50-148)

International Nuclear Information System (INIS)

1984-05-01

This Safety Evaluation Report for the application filed by the University of Kansas (KU) for a renewal of Operating License R-78 to continue to operate the KU 250-kW open-pool training reactor has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. The facility is owned and operated by the University of Kansas and is located on the KU campus in Lawrence, Douglas County, Kansas. The staff concludes that the reactor facility can continue to be operated by KU without endangering the health and safety of the public. 17 references, 11 figures, 4 tables

Lie. kū́nas

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Simas Karaliūnas

2011-12-01

Full Text Available LIТН. kū́nas “BODY”SummaryThe cognates of Lith. kū́nas “body” and Latv. kûnis (kи̃пе, kũņа “body; chrysalis; caterpil­lar of a butterfly; bee pupae” are supposed to be Lith. kūпа “carrion”, pa-kū́nė “sore, furuncle; upper lamella, a layer under the roots”, Latv. kипа “wart, excrescence”, kunis “bottom of a sheaf” and others. Lith. kū́nas, kūпа may represent substantivized forms of the adjective Latv. kûns“round, obese, stout”, while Latv. kûnis, kũņа, kūne seem to be derivatives of the suffixes *-o-*-ā-, *-ē-.

Toll-like receptor 3 stimulation promotes Ro52/TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway

Science.gov (United States)

Kyriakidis, N C; Kapsogeorgou, E K; Gourzi, V C; Konsta, O D; Baltatzis, G E; Tzioufas, A G

2014-01-01

Up-regulated expression of Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2) and lupus LA protein/Sjögren's syndrome antigen B (La/SSB) autoantigens has been described in the salivary gland epithelial cells (SGEC) of patients with Sjögren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional Toll-like receptor (TLR)-3, whereas Ro52/TRIM21 negatively regulates TLR-3-mediated inflammation. Herein, we investigated the effect of TLR-3-signalling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs. The effect of TLR-3 or TLR-4 stimulation on autoantigen expression was evaluated by polyI:C or lipopolysaccharide (LPS) treatment, respectively, of SGEC lines (10 from SS patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold increment at 6 h followed by a 2·5-fold increment at 24–48 h, whereas it induced a late two-fold up-regulation of Ro60/TROVE2 and La/SSB mRNAs at 48 h. Although protein expression levels were not affected significantly, the late up-regulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout the nucleus. These late phenomena were mediated significantly by interferon (IFN)-β production, as attested by cognate secretion and specific inhibition experiments and associated with IFN regulatory factor (IRF)3 degradation. TLR-3-signalling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. TLR-3 signalling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their over-expression in inflamed tissues and possibly in their exposure to the immune

Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic Mimicry

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Silvia Rodriguez-Fernandez

2018-02-01

Full Text Available Type 1 diabetes (T1D is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC generation. These liposomes contained phosphatidylserine (PS—the main signal of the apoptotic cell membrane—and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-liposomes displayed decreased ability to stimulate autologous T cell proliferation. Moreover, transcriptional changes in DCs from patients with T1D after PS-liposomes phagocytosis pointed to an immunoregulatory prolife. Bioinformatics analysis showed 233 differentially expressed genes. Genes involved in antigen presentation were downregulated, whereas genes pertaining to tolerogenic/anti-inflammatory pathways were mostly upregulated. In conclusion, PS-liposomes phagocytosis mimics efferocytosis and leads to phenotypic and functional changes in human DCs, which are accountable for tolerance induction. The herein reported results reinforce the potential of this novel immunotherapy to re-establish immunological

Radiometallating antibodies and biologically active peptides

International Nuclear Information System (INIS)

Mercer-Smith, J.A.; Roberts, J.C.; Lewis, D.; Newmyer, S.L.; Schulte, L.D.; Burns, T.P.; Mixon, P.L.; Jeffery, A.L.; Schreyer, S.A.; Cole, D.A.; Figard, S.D.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

1990-01-01

We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N-benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have on functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies, and we have also developed methods to label smaller biologically active molecules, such as autoantigenic peptides. The autoantigenic peptides, fragments of the acetylcholine receptor, are under investigation for myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules and the radiometallation chemistry will be discussed

Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

International Nuclear Information System (INIS)

He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

2011-01-01

Highlights: → A new anti-cancer effect of an antibiotics, asperlin, is exploited. → Asperlin induced human cervical cancer cell apoptosis through ROS generation. → Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. → Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A.

Science.gov (United States)

Ito, Yuki; Ito, Takumi; Karasawa, Satoki; Enomoto, Teruya; Nashimoto, Akihiro; Hase, Yasuyoshi; Sakamoto, Satoshi; Mimori, Tsuneyo; Matsumoto, Yoshihisa; Yamaguchi, Yuki; Handa, Hiroshi

2012-01-01

Bisphenol A (BPA) forms the backbone of plastics and epoxy resins used to produce packaging for various foods and beverages. BPA is also an estrogenic disruptor, interacting with human estrogen receptors (ER) and other related nuclear receptors. Nevertheless, the effects of BPA on human health remain unclear. The present study identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel BPA-binding protein. DNA-PKcs, in association with the Ku heterodimer (Ku70/80), is a critical enzyme involved in the repair of DNA double-strand breaks. Low levels of DNA-PK activity are previously reported to be associated with an increased risk of certain types of cancer. Although the Kd for the interaction between BPA and a drug-binding mutant of DNA-PKcs was comparatively low (137 nM), high doses of BPA were required before cellular effects were observed (100-300 μM). The results of an in vitro kinase assay showed that BPA inhibited DNA-PK kinase activity in a concentration-dependent manner. In M059K cells, BPA inhibited the phosphorylation of DNA-PKcs at Ser2056 and H2AX at Ser139 in response to ionizing radiation (IR)-irradiation. BPA also disrupted DNA-PKcs binding to Ku70/80 and increased the radiosensitivity of M059K cells, but not M059J cells (which are DNA-PKcs-deficient). Taken together, these results provide new evidence of the effects of BPA on DNA repair in mammalian cells, which are mediated via inhibition of DNA-PK activity. This study may warrant the consideration of the possible carcinogenic effects of high doses of BPA, which are mediated through its action on DNA-PK.

Repair of DNA DSB in higher eukaryotes

International Nuclear Information System (INIS)

Wang, H.; Perrault, A.R.; Takeda, Y.; Iliakis, G.

2003-01-01

Cells of higher eukaryotes process within minutes double strand breaks (DSBs) in their genome using a NHEJ apparatus that engages DNA-PKcs, Ku, DNA ligase IV, XRCC4, and other as of yet unidentified factors. Although chemical inhibition, or mutation, in any of these factors delays processing, cells ultimately remove the majority of DNA DSBs using an alternative pathway operating with slower kinetics. This alternative pathway is active in mutants deficient in genes of the RAD52 epistasis group. We proposed, therefore, that it reflects an alternative form of NHEJ that operates as a backup (B-NHEJ) to the DNA-PK- dependent (D-NHEJ) pathway, rather than homology directed repair of DSBs. We studied the role of Ku and DNA-PKcs in the coordination of these pathways using as a model end joining of restriction endonuclease linearized plasmid DNA in whole cell extracts. Efficient error-free endjoining observed in such in-vitro reactions is strongly inhibited by anti-Ku antibodies. The inhibition requires DNA-PKcs, despite that fact that Ku efficiently binds DNA ends in the presence of antibodies, or in the absence of DNA-PKcs. Strong inhibition of DNA endjoining is also mediated by wortmannin, an inhibitor of DNA-PKcs, in the presence but not in the absence of Ku, and this inhibition can be rescued by pre-incubating the reaction with double stranded oligonucleotides. The results are compatible with a role of Ku in directing endjoining to a DNA-PK dependent pathway, mediated by efficient end binding and productive interactions with DNA-PKcs. On the other hand, efficient end joining is observed in extracts of cells lacking DNA-PKcs, as well as in Ku-depleted extracts sugggesting the operation of alternative pathways. Extracts depleted of Ku and DNA-PKcs rejoin blunt ends, as well as homologous ends with 3' or 5' protruding single strands with similar efficiency, but addition of Ku suppresses joining of blunt ends and homologous ends with 3' overhangs. We propose that the

Identification of a Common Epitope between Enterovirus 71 and Human MED25 Proteins Which May Explain Virus-Associated Neurological Disease

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Peihu Fan

2015-03-01

Full Text Available Enterovirus 71 (EV71 is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. To date, the pathogenesis of EV71 in the central neurons system has remained unclear. Cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. To further study the pathogenesis, we identified a common epitope (co-epitope between EV71 VP1 and human mediator complex subunit 25 (MED25 highly expressed in brain stem. A monoclonal antibody (2H2 against the co-epitope was prepared, and its interaction with MED25 was examined by ELISA, immunofluorescence assay and Western blot in vitro and by live small animal imaging in vivo. Additionally, 2H2 could bind to both VP1 and MED25 with the affinity constant (Kd of 10−7 M as determined by the ForteBio Octet System. Intravenously injected 2H2 was distributed in brain stem of mice after seven days of EV71 infection. Interestingly, 2H2-like antibodies were detected in the serum of EV71-infected patients. These findings suggest that EV71 infection induces the production of antibodies that can bind to autoantigens expressed in nervous tissue and maybe further trigger autoimmune reactions resulting in neurological disease.

Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis

DEFF Research Database (Denmark)

Bäcklund, Johan; Treschow, Alexandra; Bockermann, Robert

2002-01-01

Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA......). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII......, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactose at position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII...

Volcanology of Tuzo pipe (Gahcho Kué cluster) — Root-diatreme processes re-interpreted

Science.gov (United States)

Seghedi, I.; Maicher, D.; Kurszlaukis, S.

2009-11-01

The Middle Cambrian (~ 540 Ma) Gahcho Kué Kimberlite Field is situated about 275 km ENE of Yellowknife, NWT, Canada. The kimberlites were emplaced into 2.6 Ga Archean granitic rocks of the Yellowknife Supergroup. Four larger kimberlite bodies (5034, Tesla, Tuzo, and Hearne) as well as a number of smaller pipes and associated sheets occur in the field. In plan view, the Tuzo pipe has a circular outline at the surface, and it widens towards deeper levels. The pipe infill consists of several types of coherent and fragmental kimberlite facies. Coherent or apparent coherent (possibly welded) kimberlite facies dominate at depth, but also occur at shallow levels, as dikes intruded late in the eruptive sequence or individual coherent kimberlite clasts. The central and shallower portions of the pipe consist of several fragmental kimberlite varieties that are texturally classified as Tuffisitic Kimberlites. The definition, geometry and extent of the geological units are complex and zones controlled by vertical elements are most significant. The fluidal outlines of some of the coherent kimberlite clasts suggest that at least some are the product of disruption of magma that was in a semi-plastic state or even of welded material. Ragged clasts at low levels are inferred to form part of a complex peperite-like system that intrudes the base of the root zone. A variable, often high abundance of local wall-rock xenoliths between and within the kimberlite phases is observed, varying in size from sub-millimeter to several tens of meters. Wall-rock fragments are common at all locations within the pipe but are especially frequent in a domain with a belt-like geometry between 120 and 200 m depth in the pipe. Steeply outward-dipping bedded deposits made up of wall-rock fragments occur in deep levels of the pipe and are especially common under the downward-widening roof segments. The gradational contact relationships of these deposits with the surrounding kimberlite-bearing rocks as well

Beyond repair foci: DNA double-strand break repair in euchromatic and heterochromatic compartments analyzed by transmission electron microscopy.

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Yvonne Lorat

Full Text Available DNA double-strand breaks (DSBs generated by ionizing radiation pose a serious threat to the preservation of genetic and epigenetic information. The known importance of local chromatin configuration in DSB repair raises the question of whether breaks in different chromatin environments are recognized and repaired by the same repair machinery and with similar efficiency. An essential step in DSB processing by non-homologous end joining is the high-affinity binding of Ku70-Ku80 and DNA-PKcs to double-stranded DNA ends that holds the ends in physical proximity for subsequent repair.Using transmission electron microscopy to localize gold-labeled pKu70 and pDNA-PKcs within nuclear ultrastructure, we monitored the formation and repair of actual DSBs within euchromatin (electron-lucent and heterochromatin (electron-dense in cortical neurons of irradiated mouse brain.While DNA lesions in euchromatin (characterized by two pKu70-gold beads, reflecting the Ku70-Ku80 heterodimer are promptly sensed and rejoined, DNA packaging in heterochromatin appears to retard DSB processing, due to the time needed to unravel higher-order chromatin structures. Complex pKu70-clusters formed in heterochromatin (consisting of 4 or ≥ 6 gold beads may represent multiple breaks in close proximity caused by ionizing radiation of highly-compacted DNA. All pKu70-clusters disappeared within 72 hours post-irradiation, indicating efficient DSB rejoining. However, persistent 53BP1 clusters in heterochromatin (comprising ≥ 10 gold beads, occasionally co-localizing with γH2AX, but not pKu70 or pDNA-PKcs, may reflect incomplete or incorrect restoration of chromatin structure rather than persistently unrepaired DNA damage.Higher-order organization of chromatin determines the accessibility of DNA lesions to repair complexes, defining how readily DSBs are detected and processed. DNA lesions in heterochromatin appear to be more complex, with multiple breaks in spatial vicinity inducing

Two haplotype clusters of Echinococcus granulosus sensu stricto in northern Iraq (Kurdistan region) support the hypothesis of a parasite cradle in the Middle East.

Science.gov (United States)

Hassan, Zuber Ismael; Meerkhan, Azad Abdullah; Boufana, Belgees; Hama, Abdullah A; Ahmed, Bayram Dawod; Mero, Wijdan Mohammed Salih; Orsten, Serra; Interisano, Maria; Pozio, Edoardo; Casulli, Adriano

2017-08-01

Human cystic echinococcosis (CE) caused by Echinococcus granulosus s.s. is a major public health problem in Iraqi Kurdistan with a reported surgical incidence of 6.3 per 100,000 Arbil inhabitants. A total of 125 Echinococcus isolates retrieved from sheep, goats and cattle were used in this study. Our aim was to determine species/genotypes infecting livestock in Iraqi Kurdistan and examine intraspecific variation and population structure of Echinococcus granulosus s.s. in this region and relate it to that of other regions worldwide. Using nucleotide sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox 1) we identified E. granulosus s.s. as the cause of hydatidosis in all examined animals. The haplotype network displayed a double-clustered topology with two main E. granulosus s.s. haplotypes, (KU05) and (KU33). The 'founder' haplotype (KU05) confirmed the presence of a common lineage of non-genetically differentiated populations as inferred by the low non-significant fixation index values. Overall diversity and neutrality indices indicated demographic expansion. We used E. granulosus s.s. nucleotide sequences from GenBank to draw haplotype networks for the Middle East (Iran, Jordan and Turkey), Europe (Albania, Greece, Italy, Romania and Spain), China, Mongolia, Russia, South America (Argentina, Brazil, Chile and Mexico) and Tunisia. Networks with two haplotype clusters like that reported here for Iraqi Kurdistan were seen for the Middle East, Europe, Mongolia, Russia and Tunisia using both 827bp and 1609bp cox1 nucleotide sequences, whereas a star-like network was observed for China and South America. We hypothesize that the double clustering seen at what is generally assumed to be the cradle of domestication may have emerged independently and dispersed from the Middle East to other regions and that haplotype (KU33) may be the main haplotype within a second cluster in the Middle East from where it has spread into Europe, Mongolia, Russia and North

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy

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Howard R. Seay

2017-03-01

Full Text Available Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR. Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

He, Long; Nan, Mei-Hua [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Oh, Hyun Cheol [College of Medical and Life Sciences, Silla University, 100 Silladaehak-gil, Sasang-gu, Busan 617-736 (Korea, Republic of); Kim, Young Ho [College of Pharmacy, ChungNam National University, Yuseong, Daejeon, 305-764 (Korea, Republic of); Jang, Jae Hyuk [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Erikson, Raymond Leo [Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 (United States); Ahn, Jong Seog, E-mail: jsahn@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Kim, Bo Yeon, E-mail: bykim@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); World Class Institute, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of)

2011-06-10

Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

Näitus nagu kuu / Anders Härm

Index Scriptorium Estoniae

Härm, Anders, 1977-

2005-01-01

Näitusest "Expat-Art-Centre" Tallinna Kunstihoone fuajees, Ku fassaadil ja Ku-Ku kohvikus kuni 12. I. Näituse ja sellega kaasneva ajakirja on koostanud Mathieu Copeland, osalevad Brian Eno, Pierre Huyghe (sünd. 1962), Ben Kinmont, Claude Leveque (sünd. 1953), Didier Marcel, Olivier Mosset (sünd. 1933), Shimabuku (sünd. 1969), Dan Walsh (sünd. 1962), Ian Wilson (sünd. 1940)

Natural course of sensitization to hen's egg in children not previously exposed to egg ingestion.

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de Boissieu, D; Dupont, C

2006-04-01

Clinical adverse reactions to egg may occur in infants or children who have never eaten egg. They may be sensitized or even react at first egg ingestion. Few studies are available concerning the reality of egg white allergy in such sensitized children, the natural evolution of this condition and the appropriate decisions to make. To analyze the actuality and natural course of egg allergy in children sensitized without previous of hen's egg ingestion. We set up a clinical decision tree based on clinical history and specific egg white IgE to manage patients who had never ingested egg but were sensitized as demonstrated by a positive SPT and report a cohort of 30 such children The mean level of egg white specific IgE at first analysis, i.e. before 12 months, was high, 28.3 KU(A) /L, with a large range, from 0.6 to >100 KU(A) /L, below 6 KU(A) /L in only 8 patients. In 6 children ("no challenge" group), IgE values remained >8 KU(A) /L by the end of the survey and the oral challenge with egg was always denied. Their mean + SD IgE level was at 51.7 + 38 KU(A) /L at 1 year and 19.7 + 13 KU(A) /L at a mean age of 34 + 5 months. All had an associated anaphylactic reaction with milk and 5 were still allergic to milk by the end of the survey. In the remaining 24 infants, egg was given for the first time at a mean age of 30 + 9 months, by error in 4 cases, all exhibiting an immediate reaction, and in a hospital setting in 20, among whom 14 reacted. Among those 18, with a specific IgE level at 9.1 + 10 KU(A) /L at 28 + 9 months, 4 became tolerant between 3 and 4 years, with specific IgE levels below 1.3 KU(A) /L and a 5th one with specific IgE >100 KU(A) /L at 6 months tolerated scrambled eggs at age 7 year, with specific IgE at 2.6 KU(A) /L. In the 6 others, labeled "non allergic", egg white specific IgE levels were significantly lower, whatever the age, than in the "no challenge" group. The age at challenge was 35 + 8 months, with a mean specific IgE level at 1.0 + 0.9 KU

DNA-PK dependent targeting of DNA-ends to a protein complex assembled on matrix attachment region DNA sequences

International Nuclear Information System (INIS)

Mauldin, S.K.; Getts, R.C.; Perez, M.L.; DiRienzo, S.; Stamato, T.D.

2003-01-01

Full text: We find that nuclear protein extracts from mammalian cells contain an activity that allows DNA ends to associate with circular pUC18 plasmid DNA. This activity requires the catalytic subunit of DNA-PK (DNA-PKcs) and Ku since it was not observed in mutants lacking Ku or DNA-PKcs but was observed when purified Ku/DNA-PKcs was added to these mutant extracts. Competition experiments between pUC18 and pUC18 plasmids containing various nuclear matrix attachment region (MAR) sequences suggest that DNA ends preferentially associate with plasmids containing MAR DNA sequences. At a 1:5 mass ratio of MAR to pUC18, approximately equal amounts of DNA end binding to the two plasmids were observed, while at a 1:1 ratio no pUC18 end-binding was observed. Calculation of relative binding activities indicates that DNA-end binding activities to MAR sequences was 7 to 21 fold higher than pUC18. Western analysis of proteins bound to pUC18 and MAR plasmids indicates that XRCC4, DNA ligase IV, scaffold attachment factor A, topoisomerase II, and poly(ADP-ribose) polymerase preferentially associate with the MAR plasmid in the absence or presence of DNA ends. In contrast, Ku and DNA-PKcs were found on the MAR plasmid only in the presence of DNA ends. After electroporation of a 32P-labeled DNA probe into human cells and cell fractionation, 87% of the total intercellular radioactivity remained in nuclei after a 0.5M NaCl extraction suggesting the probe was strongly bound in the nucleus. The above observations raise the possibility that DNA-PK targets DNA-ends to a repair and/or DNA damage signaling complex which is assembled on MAR sites in the nucleus

Validitas dan Reliabilitas Konstruk Pengukuran Perpustakaan Ideal Berbasis Pemakai dengan Pendekatan LIBQUAL

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Yulyanti Fahruna

2017-08-01

Full Text Available This study aims to measure the validity and reliability construct satisfaction and quality of library services based on the user using LIBQUAL (library quality method with a touch of marketing management. Data analysis by Cronbach Alpha and Pearson Correlation. The research was conducted in Tanjungpura University (UNTAN by taking samples of visitors (students at six (6 faculty libraries namely three (3 social faculty of 150 people and three (3 science faculty of 150 people. The sample is chosen by purposive sampling method. Reliability test results show that the five US, IC, LP, LQ and KU variables show high instrument reliability. The result of pearson correlation test shows that the measurement instrument used has problem validity on some question items. At minimum service item with correlation value smaller than 0.30 is IC2, IC5 and LQ5 so it is declared invalid. At service expectation items with correlation value smaller than 0.30 ie AS8, IC1, IC2, IC4, LP1, KU1, KU2, KU4, and KU8. And at present service items with correlation values smaller than 0.30 ie IC1, IC3, LP1, LP3, LQ1, LQ3, LQ4 and KU1.

Regulation of DNA repair mechanism in human glioma xenograft cells both in vitro and in vivo in nude mice.

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Ponnala, Shivani; Veeravalli, Krishna Kumar; Chetty, Chandramu; Dinh, Dzung H; Rao, Jasti S

2011-01-01

Glioblastoma Multiforme (GBM) is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR) are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ) repair mechanism plays a major role in double strand break (DSB) repair in mammalian cells. Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU) and MMP9-cathepsin B (pMC) shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls. Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential of MMP9, uPAR and cathepsin B shRNA in the treatment of glioma from clinical stand

Regulation of DNA repair mechanism in human glioma xenograft cells both in vitro and in vivo in nude mice.

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Shivani Ponnala

Full Text Available Glioblastoma Multiforme (GBM is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ repair mechanism plays a major role in double strand break (DSB repair in mammalian cells.Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU and MMP9-cathepsin B (pMC shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls.Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential of MMP9, uPAR and cathepsin B shRNA in the treatment of glioma from

Novel autoantigens immunogenic in COPD patients

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Stephan Bernhard

2009-03-01

Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.

Siim Nestor soovitab : Odessa Pop. Neoandertals / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2007-01-01

Indieüritusest Odessa Pop 17. veebr. Tallinnas baar-klubis Juuksur. Ultrabrutaalse death-metali duo Neoandertals heliplaadi "Neoandertals Were Master Butchers" esitluskontserdist 17. veebr. Tallinnas KuKu klubis

ONR Far East Scientific Bulletin, Volume 12, Number 4, October-December 1987,

Science.gov (United States)

1987-12-01

magnetic Japan Control Engineers Measurements (CPEM󈨜) 1-35-28-303 Hongo , Bunkyo-ku, Tokyo 113 June The 7th International Kyoto, Professor Isao Yamada...Physics-Material Japan Faculty of Engineering, 0 Research Society) Inter- Tokyo University national Conference on 7-3-1 Hongo , Bunkyo-ku, Tokyo 113...o Department of Psychological 39-FlOO-J200 Chemistry and Nutrition, Faculty of Medicine, University of Tokyo 7-3-1 Hongo , Bunkyo-ku, Tokyo 113

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

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Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

A novel method for calculating the energy cost of turning during running

OpenAIRE

Hatamoto, Yoichi; Yamada,Yosuke; Higaki,Yasuki; Kiyonaga,Akira; Tanaka,Hiroaki; Fujii,Tatsuya

2013-01-01

Yoichi Hatamoto,1 Yosuke Yamada,2 Tatsuya Fujii,3 Yasuki Higaki,3 Akira Kiyonaga,3 Hiroaki Tanaka31Graduate School of Sports and Health Science, Fukuoka University, Nanakuma Jonan-ku Fukuoka, Japan; 2The Fukuoka University Institute for Physical Activity, Nanakuma Jonan-ku Fukuoka, Japan; 3Faculty of Sports and Health Science, Fukuoka University, Nanakuma Jonan-ku Fukuoka, JapanAbstract: Although changes of direction are one of the essential locomotor patterns in ball sports, the physiologica...

Evaluation of mutagenic potential of contaminated atmosphere at Ibirapuera Park, Sao Paulo - SP, Brazil, using the Tradescantia stamen-hair assay

International Nuclear Information System (INIS)

Ferreira, Maria Izildinha; Domingos, Marisa; Gomes, Heliana de A; Saldiva, Paulo H.N.; Assuncao, Joao V. de

2007-01-01

Trad-SHM assay was used to check mutagenic potential of atmospheric contamination at Ibirapuera Park, located in Sao Paulo city, Brazil, and variation of risk along the year, besides determining which Tradescantia clone, BNL 4430 or KU-20, better indicates risk. Thirty pots of both clones were exposed during one-year period (September, 2002-August, 2003). Twenty inflorescences were taken from each clone twice a month in the morning, in order to estimate the frequency of mutations in stamen hairs. Results were compared to air pollution and climatic data measured next to the exposure site. KU-20 showed stamen-hair mutations greater than BNL 4430. Greatest mutation rates in KU-20 were observed in condition of high monthly mean of NO 2 and average peak concentrations of NO during the day, indicating that mutagenic effects originated from vehicular pollution. Clone KU-20 revealed to be more appropriate for biomonitoring purposes at the Park. - Clone KU-20 showed to be more appropriate than clone BNL 4430 to indicate vehicular pollution mutagenic risks in Trad-SHM assay

Kunstnike Liidu volikogu koosolek toimus 20. X Ku-Ku klubis

Index Scriptorium Estoniae

2003-01-01

Kinnitati EKLi 2004. a. eelarve, selle toetustest. Harry Liivrand tutvustas Kunstihoone ja selle galerii, Reet Varblane Linnagalerii, Elin Kard Hobusepea ja Draakoni galerii 2004. a. näituseplaane. Ateljee Vabaduse väljak 6-35 otsustati anda rendile Ülle Marksile, ateljee Ristiku 27 müüa Rafael Arutjunjanile. EKLi uued liikmed: Andrus Joonas, Alice Kask, Hermes Sarapuu, Epp Viires, Kristel Sibul

Properties of Extreme Precipitation and Their Uncertainties in 3-year GPM Precipitation Radar Data

Science.gov (United States)

Liu, N.; Liu, C.

2017-12-01

Extreme high precipitation rates are often related to flash floods and have devastating impacts on human society and the environments. To better understand these rare events, 3-year Precipitation Features (PFs) are defined by grouping the contiguous areas with nonzero near-surface precipitation derived using Global Precipitation Measurement (GPM) Ku band Precipitation Radar (KuPR). The properties of PFs with extreme precipitation rates greater than 20, 50, 100 mm/hr, such as the geographical distribution, volumetric precipitation contribution, seasonal and diurnal variations, are examined. In addition to the large seasonal and regional variations, the rare extreme precipitation rates often have a larger contribution to the local total precipitation. Extreme precipitation rates occur more often over land than over ocean. The challenges in the retrieval of extreme precipitation might be from the attenuation correction and large uncertainties in the Z-R relationships from near-surface radar reflectivity to precipitation rates. These potential uncertainties are examined by using collocated ground based radar reflectivity and precipitation retrievals.

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

Science.gov (United States)

Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

Science.gov (United States)

Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

2016-01-01

Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

Somatic mutation frequencies in the stamen hairs of stable and mutable clones of Tradescantia after acute gamma-ray treatments with small doses

International Nuclear Information System (INIS)

Ichikawa, Sadao; Takahashi, C.S.

1977-01-01

Young inflorescences of two different Tradescantia clones heterozygous for flower and stamen-hair color, one stable (KU 9) and the other spontaneously mutable (KU 20), were irradiated acutely with small doses (approx. 3 to 50 R) of 60 Co gamma-rays. Somatic mutation frequencies from blue to pink in the stamen hairs scored on post-irradiation days 10 to 16 increased essentially linearly with increasing gamma-ray dose in both clones. Despite about a 5-fold difference in spontaneous mutation frequency per hair found between the two clones, the dose-response curves of pink mutations determined were similar to each other, giving average mutation frequencies of 1.51 and 1.41 pink-mutant events per 1000 hairs per R for KU 9 and KU 20, respectively. These frequencies are comparable to earlier results obtained from acute irradiation treatments of other clones with higher doses. The doubling dose of pink mutation (the radiation dose making the mutation frequency double the spontaneous level) was calculated to be 2.09 R for KU 9, and this low doubling dose must be given full attention. On the other hand, the doubling dose for KU 20 (calculated to be 10.4 R) is of questionable value, being greatly subject to change because of the diversely variable spontaneous mutation frequency of this clone

Endothelin-A-receptor antagonism with atrasentan exhibits limited activity on the KU-19-19 bladder cancer cell line in a mouse model.

Science.gov (United States)

Herrmann, Edwin; Tiemann, Arne; Eltze, Elke; Bolenz, Christian; Bremer, Christoph; Persigehl, Thorsten; Hertle, Lothar; Wülfing, Christian

2009-10-01

The endothelin axis consists of endothelin-1 (ET-1) and its two receptors, ET(A)- and ET(B)-receptor (ET(A)-R and ET(B)-R). In several tumor entities, the ET(A)-R plays a significant role as a drug target. In our study, we investigated whether inhibition of ET(A)-R with atrasentan leads to an antitumor effect in urinary bladder carcinoma as well. Twenty nude mice with thymic aplasia were subcutaneously administered 2 x 10(6) KU-19-19 bladder cancer cells in the right flank. Starting on the 22nd day after the injection, ten animals were treated with atrasentan (2.5 mg/kg BW intraperitoneally), and another ten animals were treated with placebo. During treatment, absolute tumor growth and relative growth rate over time were determined. After the end of treatment, the mitosis and necrosis rates, microvessel density, and receptor density in the tumor tissue were analyzed by immunohistochemistry. In addition, the expression intensities of ET-1, ET(A)-R, and ET(B)-R were evaluated semiquantitatively and compared between the groups. No significant differences between the active-treatment and placebo groups were detected, either with respect to absolute tumor growth (P = 0.333) or mitosis rate (P = 0.217). In the analysis of the necrosis rate and receptor density for ET(A)-R, a trend toward higher values in the active-treatment group (mean necrosis rate = 63.67%, receptor density: 1.417) than in the placebo group (mean necrosis rate = 46.25%, receptor density: 1.270) was found; however, neither difference was statistically significant (P = 0.08 and 0.219, respectively). ET(A)-R blockade with atrasentan in a bladder cancer xenograft model shows no significant antitumor effect.

Proteomic definition of a desmoglein linear determinant common to Pemphigus vulgaris and Pemphigus foliaceous

Directory of Open Access Journals (Sweden)

Sinha Animesh A

2006-08-01

Full Text Available Abstract Background A number of autoimmune diseases have been clinically and pathologically characterized. In contrast, target antigens have been identified only in a few cases and, in these few cases, the knowledge of the exact epitopic antigenic sequence is still lacking. Thus the major objective of current work in the autoimmunity field is the identification of the epitopic sequences that are related to autoimmune reactions. Our labs propose that autoantigen peptide epitopes able to evoke humoral (autoimmune response are defined by the sequence similarity to the host proteome. The underlying scientific rationale is that antigen peptides acquire immunoreactivity in the context of their proteomic similarity level. Sequences uniquely owned by a protein will have high potential to evoke an immune reaction, whereas motifs with high proteomic redundancy should be immunogenically silenced by the tolerance phenomenon. The relationship between sequence redundancy and peptide immunoreactivity has been successfully validated in a number of experimental models. Here the hypothesis has been applied to pemphigus diseases and the corresponding desmoglein autoantigens. Methods Desmoglein 3 sequence similarity analysis to the human proteome followed by dot-blot/NMR immunoassays were carried out to identify and validate possible epitopic sequences. Results Computational analysis led to identifying a linear immunodominant desmoglein-3 epitope highly reactive with the sera from Pemphigus vulgaris as well as Pemphigus foliaceous. The epitopic peptide corresponded to the amino acid REWVKFAKPCRE sequence, was located in the extreme N-terminal region (residues 49 to 60, and had low redundancy to the human proteome. Sequence alignment showed that human desmoglein 1 and 3 share the REW-KFAK–RE sequence as a common motif with 75% residue identity. Conclusion This study 1 validates sequence redundancy to autoproteome as a main factor in shaping desmoglein peptide

Agresijas un vecāku audzināšanas stila saistība jauniešiem no profesionālās vidējās izglītības iestādēm

OpenAIRE

Stikāne, Austra

2012-01-01

Pētījuma jautājumi ir vai pastāv saistība starp agresijas rādītājiem un vecāku audzināšanas stilu profesionālās vidējās izglītības iestāžu audzēkņiem, kuri ikdienā dzīvo ar vecākiem un audzēkņiem, kuri ikdienā nedzīvo ģimenē, kā arī vai pastāv atšķirības agresijas skalās starp jauniešiem, kuri dzīvo ar vecākiem ikdienā un jauniešiem, kuri ikdienā nedzīvo ar vecākiem. Pētījumā piedalījās 95 respondenti (55 studenti, kuri ikdienā dzīvo ar vecākiem, 40 studenti, kuri ikdienā nedzīvo ģimenē)...

National Security and the Right to Information in Europe

DEFF Research Database (Denmark)

Jacobsen, Amanda Lynn

2013-01-01

Full text available at: http://cast.ku.dk/pdf/National_Security_and_the_Right_to_Information.pdf/......Full text available at: http://cast.ku.dk/pdf/National_Security_and_the_Right_to_Information.pdf/...

Organizational Analysis of the United States Army Contracting Command-Kuwait

National Research Council Canada - National Science Library

Orr, Kristine R

2008-01-01

This study of the U.S. Army Contracting Command - Kuwait (USACC-KU) used an organizational systems framework to analyze factors related to strategy structure, processes and results experienced at USACC-KU during 2006-2008...

Siim Nestor soovitab : Tallinn Doom Night vol.1. Odessa Pop / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2006-01-01

Soome doom-metal ansambel Reverend Bizarre üritusel "Tallinn Doom Night vol.1" 8. dets. klubis Rockstar's. Indipoppi viljelev Rootsi duo My Darling Yoy! üritusel "Odessa Pop" 9. dets. Tallinnas klubis KuKu

Ginsbergi vennaskond, värskelt ühendatud / Marko Mägi

Index Scriptorium Estoniae

Mägi, Marko

2005-01-01

Poetry slami laadis luuleõhtul "Poesie United" esinesid 21. mail KuKu klubis Wehwalt Koslovsky, Tobias Hoffmann (Saksamaa), Ben Porter Lewis, Milo Martin (USA), Antoine Faure (Prantsusmaa), fs, Asko Künnap, Jürgen Rooste

Uudised : "Odessa Pop uuel ringil". Neoandertals jõuab plaadile. "Xanadu" Hollandis muusikalilaval

Index Scriptorium Estoniae

2007-01-01

Kontsertõhtust sarja Odessa Pop raames 17. veebr. Tallinnas baar-klubis Juuksur. Ultrabrutaalse deathmetali duo Neoandertals heliplaadi "Neanderthals Were Master Butchers" esitluskontserdist 17. veebr. Tallinnas KuKu klubis. 1980. aastal valminud diskofilmi "Xanadu" muusikaliversioonist

Immunochemical and autoantigenic properties of the globular domain of basement membrane collagen (type IV).

Science.gov (United States)

von der Mark, H; Oberbäumer, I; Timpl, R; Kemler, R; Wick, G

1985-02-01

Polyclonal rabbit antibodies raised against the globular domain NC1 of collagen IV from human placenta and a mouse tumor react with conformational antigenic determinants present on the NC1 hexamers and also with the three major subunits obtained after dissociation. The antibodies recognized unique structures within basement membranes and showed a broad tissue reactivity but only limited species cross-reactivity. Using these antibodies, it was possible to detect small amounts of collagen IV antigens from cell cultures and in serum. Monoclonal rat antibodies against mouse NC1 revealed a similar reaction potential. Autoantibodies could be produced in mice against mouse NC1 which react with kidney and lung basement membranes in a pathological manner, mimicking Goodpasture syndrome.

Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

Science.gov (United States)

Casciola-Rosen, L; Rosen, A

1997-01-01

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

PERAN HEAT SHOCK PROTEINS (HSP DALAM PATOGENESIS PENYAKIT OTOIMUN DI DALAM RONGGA MULUT

Directory of Open Access Journals (Sweden)

Endang W. Bachtiar

2015-08-01

Full Text Available Heat Shock Proteins (HSP are highly conserved immunoreactive group of proteins found in microorganisms and animal/human tissue. In addition to heat, other stressful conditiions also induce stressed proteins, especially anorexia, heavy metal ion, exposure to H2O2 and infection by DNA or RNA viruses. Recent studies suggest the involvement of HSPs as autoantigens in autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Bechet's syndrome, recurrent oral uclers, oral lichen planus and other. The HSPs 60 - 65 KDa might be involved in the pathogenesis of autoimmune diseases such as Bechet's syndrome, recurrent oral ulcers, and oral lichen planus. This paper will discuss the immunopathogenesis mechanism of those diseases induced by HSPs.

Siim Nestor soovitab : Back2Bass Helsinki. Teenage Kicks / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2002-01-01

Soome trummi-ja-bassi klubi Back2Bass 28. septembril KuKu klubis Tallinnas. 28. sept. Von Krahlis toimuvast live-üritusest Teenage Kicks, kus ansambel Claire's Birthaday esitleb ka oma uut singlit "Do You Remember"

Uudised : Depeche Mode'i maailmaturnee peaaegu välja müüdud. Easy Listening esitleb : Villu Tamme diskorina

Index Scriptorium Estoniae

2001-01-01

Ans. Depeche Mode maailmaturnee "Exciter" Euroopa ja Ameerika kontserdid on peaaegu välja müüdud. 11. mail KuKu klubis toimuval muusikapeol sarjas 'The Easy Listening Sessions' astub diskorina üles V.Tamme

Chance Discovery with Data Crystallization: A Basic Research for Discovering Unobservable Events

Science.gov (United States)

2006-05-10

Ohsawa y School of Engineering, The University of Tokyo, 7-3-1 Hongo , Bunkyo-ku, 113-8563, Japan y.ohsawa@gmail.com Received 17 June 2005 This paper...this study as the software developer of data crystallization. y School of Engineering, The University of Tokyo, 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-8653...University of Tokyo, 7-3-1 Hongo , Bunkyo-ku, Tokyo, 113-8563 Japan, ohsawa@q.t.u-tokyo.ac.jp Abstract. There are invisible events which play an important role

In vitro studies of the cellular response to boron neutron capture therapy (BNCT) in thyroid carcinoma

International Nuclear Information System (INIS)

Rodriguez, C; Carpano, M; Perona, M; Thorp, S; Curotto, P; Pozzi, E; Casal, M; Juvenal, G; Pisarev, M; Dagrosa, A

2012-01-01

Background: Previously, we have started to study the mechanisms of DNA damage and repair induced by BNCT in thyroid carcinoma some years ago. We have shown different genotoxic patterns for tumor cells irradiated with gamma rays, neutrons alone or neutrons plus different compounds, boronophenylalanine (BPA) or α, β - dihydroxyethyl)-deutero-porphyrin IX (BOPP). In the present study we analyzed the expression of Ku70, Rad51 and Rad54 components of non homologous end-joing (NHEJ) and homologous recombination repair (HRR) pathways, respectively, induced by BNCT in human cells of thyroid carcinoma. Methods: A human cell line of follicular thyroid carcinoma (WRO) in exponential growth phase was distributed into the following groups: 1) Gamma Radiation, 2) Radiation with neutrons beam (NCT), 3) Radiation with n th in presence of BPA (BNCT). A control group for each treatment was added. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux= 1.10 10 n/cm 2 sec) or with a source of 60 Co. The irradiations were performed during different lapses in order to obtain a total physical dose of 3 Gy (±10%). The mRNA expressions of Ku70, Rad 51 and Rad 54 were analysed by reverse transcription-polymerase chain reaction (RT-PCR) at different times post irradiation (2, 4, 6, 24 and 48 h). DNA damage was evaluated by immunofluorescence using an antibody against the phosphorylation of histone H2AX, which indicates double strand breaks in the DNA. Results: The expression of Rad51 increased at 2 h post-irradiation and it lasted until 6 h only in the neutron and neutron + BPA groups (p<0.05). Rad54 showed an up-regulation from 2 to 24 h in both groups irradiated with the neutron beam (with and without BPA) (p<0.05). On the other hand, Ku70 mRNA did not show a modification of its expression in the irradiated groups respect to the control group. Conclusion: these results would indicate an activation of the HRR pathway in the thyroid carcinoma cells treated by

Gridded 5-day mean sea surface height anomaly and significant wave height from Jason-1 and OSTM/Jason-2 satellites (NODC Accession 0065055)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains the gridded 5-day mean sea surface height anomaly (SSHA) and Ku Band significant wave height (SWH-KU) observed from Jason-1 and OSTM/Jason-2...

Siim Nestor soovitab : Eddie Amador Vibe'i neljandal sünnipäeval. Aasta hiphop.ee-d / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2002-01-01

Ameeriklane Eddy Amador külas Vibe neljandal sünnipäeval 11.okt. Internetiaadressi www.hiphop.ee esimese aastapäeva tähistamisest Tartus Club-Tallinnas 11. okt. ja Tallinnas KuKu klubis 12. oktoobril

What Determines Labour Movement from Turkey to Europe? Extent of the Situation and Implications

OpenAIRE

İNCE YENİLMEZ, Meltem

2017-01-01

There are several different issues affecting migration on the global scale, which are commonly interconnected. These include work migration, lifestyle migration, ecological migration, workers’ wages abroad, transit migration, irregular global migration, forced and forced humanitarian migration, human trafficking, refugees, and the safety of displaced populations. This study analyzes causation and consequences of Turkish workforce migration. Aim: Bu çalışma hayatlarını iyileştirmek amacıyla ku...

KU24 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

Ku dydaktyce afirmatywnej

Directory of Open Access Journals (Sweden)

Monika Rogowska-Stangret

2016-11-01

Full Text Available "Towards affirmative didactics" The article “Towards affirmative didactics” is a description of a project reflecting on the experience of teaching and learning in a systematic and complex manner. It is also an effort to define the conditions that could encourage values such as inclusiveness, tolerance, mindfulness, joint responsibility, as well as engagement in and support for actions undertaken to strengthen the above-mentioned values. The project is a work in progress and it consists of two parts. The first one is critical and it describes the given situation by pointing the main threats involved. The second – affirmative one – was created with the effort to develop positive guidelines that would encourage transformations in the approach to didactics.

Siim Nestor soovitab : Turbodisko. Camouflage / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2006-01-01

Üritusest "Turbodisko" 2. dets. Tallinnas KuKu klubis, indieansambli Bad Apples heliplaadi "When Colours Become Day and Night" (plaadifirmalt Seksound) esitluskontserdist. Saksamaa futuelektroonika ansambli Camouflage albumi "Relocated" esitluskontserdist 3. dets klubis Hollywood (kontserti soojendab läti ansambel STandArt)

Analysis artefacts of the INS-IGF2 fusion transcript

DEFF Research Database (Denmark)

Wernersson, Rasmus; Frogne, Thomas; Rescan, Claude

2015-01-01

Background: In gene expression analysis, overlapping genes, splice variants, and fusion transcripts are potential sources of data analysis artefacts, depending on how the observed intensity is assigned to one, or more genes. We here exemplify this by an in-depth analysis of the INS-IGF2 fusion...... transcript, which has recently been reported to be among the highest expressed transcripts in human pancreatic beta cells and its protein indicated as a novel autoantigen in Type 1 Diabetes. Results: Through RNA sequencing and variant specific qPCR analyses we demonstrate that the true abundance of INS-IGF2...... is >20,000 fold lower than INS in human beta cells, and we suggest an explanation to the nature of the artefacts which have previously led to overestimation of the gene expression level in selected studies. We reinvestigated the previous reported findings of detection of INS-IGF2 using antibodies both...

Environmental radiation status in Bunkyo-ku, Tokyo, after the TEPCO Fukushima Dai-ichi Nuclear Power Plant disaster

International Nuclear Information System (INIS)

Ebisawa, Takao; Hirose, Seiichi; Furuta, Etsuko; Kusama, Keiji; Iimoto, Takeshi

2013-01-01

Bunkyo-ku is located in the eastern part of the metropolitan area of Tokyo, Japan, and is roughly 220 km south of the TEPCO Fukushima Dai-ichi Nuclear Power Plant. The population of the city was 201,079 as of August 1, 2012, and its area is 11.31 km"2. The local government has officially been surveying the environmental radiation status after the disaster in response to numerous requests from its citizens. The radiation surveillance in this area has been technically guided by radiation protection specialists. The two main targets for surveillance are (1) the ambient radiation dose (microsieverts per hour) at all the school yards, public parks, and representative measurement points selected by the local government, and (2) the specific radioactivity (becquerels per kilogram) present in school lunch. These data have been reported to the citizens through the city website as well as in a bi-monthly report in the public relations magazine of the local government. This report presents the background status and technical information of the related activities, as well as the measured environmental radiation data. The ambient radiation dose in the city has been surveyed since July 2011. In the 1st period of surveillance (from July to August, 2012), over a total of 304 measurement points, the highest recorded value of the ambient radiation dose was 0.22 μSv h"-"1 at the height of 1 m from the ground, the lowest was 0.05 μSv h"-"1, and the average was around 0.09 μSv h"-"1. These values include the natural background dose rate detected by the energy compensation type surveymeters. In the most recent surveillance records, the maximum value recorded was 0.10, the minimum was 0.05, and 0.07 μSv h"-"1 was the average value. The specific radioactivity of drinking water has been monitored at local purification plants since the accident occurred. No water sample supplied to the city has exceeded the national limits for intake dose. The specific radioactivity of school lunch was

Variability of selected indicators of physical activity in a randomized sample of the Czech population between the years 2003–2006: Results from the short and long self administered format of the IPAQ questionnaire [Variabilita vybraných indikátorů pohybové aktivity u randomizovaných souborů české populace v letech 2003–2006: Výsledky z krátké a dlouhé administrativní verze IPAQ dotazníku

Directory of Open Access Journals (Sweden)

Erik Sigmund

2009-06-01

MET–minutes/week for walking and sitting on working days. The long self administered format of the IPAQ provides more detailed results on PA. However, the value of total PA is significantly higher than that obtained using the short self administered format of the IPAQ. In order to obtain more exact data on PA, we recommend using the long self administered format of the IPAQ simultaneously with pedometer or accelerometer PA monitoring. [VÝCHODISKA: Snaha o získání celosvětově srovnatelných výsledků o úrovni pohybové aktivity (PA různých populačních skupin vyústila ve vytvoření a standardizaci Mezinárodního dotazníku o pohybové aktivitě (IPAQ. CÍLE: Hlavním cílem této studie bylo zjistit variabilitu vybraných proměnných PA ze dvou ekvivalentních forem českých administrativních verzí IPAQ dotazníku aplikovaných u randomizovaných souborů české populace v letech 2003–2006. METODIKA: Ve studii byla použita data od 11277 obyvatel České republiky (5683 žen a 5594 mužů ve věku 15–69 let. Krátká administrativní verze IPAQ byla u 2066 žen a 1976 mužů aplikována na podzim 2003 a jaře 2004. Dlouhá administrativní verze IPAQ (resp. jako součást ANEWS dotazníku byla použita u 1688 žen a 1689 mužů na podzim 2004 a jaře 2005 (resp. u 1929 žen a 1929 mužů na podzim 2005 a jaře 2006. Jednotlivé soubory účastníků byly randomizovány podle pohlaví, věku a velikosti místa bydliště v souladu s údaji Českého statistického úřadu (www.czso.cz. VÝSLEDKY: Mezi samostatně aplikovanou dlouhou verzí IPAQ a ANEWS dotazníkem (obsahujícím dlouhou verzi IPAQ nenacházíme u mužů ani žen výrazné rozdíly v MET–minut/týden v celkové PA, transportní PA, PA v zaměstnání a chůzi. U krátké verze IPAQ zaznamenáváme u mužů i žen nižší hodnoty celkové PA (p < 0,0001 než v dlouhé verzi IPAQ (resp. ANEWS dotazníku. Bez rozdílu mezi jednotlivými ekvivalentními formami IPAQ dotazníku jsou

Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

Science.gov (United States)

Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

1993-09-01

Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases

International Nuclear Information System (INIS)

Fukui, Hiroyuki; Kashiwagi, Toru; Kasahara, Akinori

1991-01-01

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-galactosyl-human-serum-albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver disease. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images were not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku, and PT values were more significantly decreased or prolonged in the patients with chronic hepatitis. Kd, Ku, and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degree of hepatic fibrosis. On the other hand, the indices obtained using Tc-99m-PMT or Tc-99m-sn-phytate did not have correlations with the histological degrees of hepatic fibrosis. It is concluded that the liver scintigraphy using Tc-99m-GSA may be useful and give different information from those with conventional liver scintigraphies in evaluating chronic liver diseases. (author)

High LET Radiation Amplifies Centrosome Overduplication Through a Pathway of γ-Tubulin Monoubiquitination

Energy Technology Data Exchange (ETDEWEB)

Shimada, Mikio [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan); Hirayama, Ryoichi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Komatsu, Kenshi, E-mail: komatsu@house.rbc.kyoto-u.ac.jp [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan)

2013-06-01

Purpose: Radiation induces centrosome overduplication, leading to mitotic catastrophe and tumorigenesis. Because mitotic catastrophe is one of the major tumor cell killing factors in high linear energy transfer (LET) radiation therapy and long-term survivors from such treatment have a potential risk of secondary tumors, we investigated LET dependence of radiation-induced centrosome overduplication and the underlying mechanism. Methods and Materials: Carbon and iron ion beams (13-200 keV/μm) and γ-rays (0.5 keV/μm) were used as radiation sources. To count centrosomes after IR exposure, human U2OS and mouse NIH3T3 cells were immunostained with antibodies of γ-tubulin and centrin 2. Similarly, Nbs1-, Brca1-, Ku70-, and DNA-PKcs-deficient mouse cells and their counterpart wild-type cells were used for measurement of centrosome overduplication. Results: The number of excess centrosome-containing cells at interphase and the resulting multipolar spindle at mitosis were amplified with increased LET, reaching a maximum level of 100 keV/μm, followed by sharp decrease in frequency. Interestingly, Ku70 and DNA-PKcs deficiencies marginally affected the induction of centrosome overduplication, whereas the cell killings were significantly enhanced. This was in contrast to observation that high LET radiation significantly enhanced frequencies of centrosome overduplication in Nbs1- and Brca1-deficient cells. Because NBS1/BRCA1 is implicated in monoubiquitination of γ-tubulin, we subsequently tested whether it is affected by high LET radiation. As a result, monoubiquitination of γ-tubulin was abolished in 48 to 72 hours after exposure to high LET radiation, although γ-ray exposure slightly decreased it 48 hours postirradiation and was restored to a normal level at 72 hours. Conclusions: High LET radiation significantly reduces NBS1/BRCA1-mediated monoubiquitination of γ-tubulin and amplifies centrosome overduplication with a peak at 100 keV/μm. In contrast, Ku70 and DNA

ВПЛИВ ПОРОГОВИХ УМОВ ITU НА ЕФЕКТИВНІСТЬ ВИКОРИСТАННЯ ГЕОСТАЦІОНАРНОЇ ОРБІТИ В Ku ДІАПАЗОНІ

OpenAIRE

Kolomytsev, M. A.; Lipatov, A.; Synepolski, Y.

2014-01-01

The article is devoted to the estimation of threshold values, regulated by ITU, which determine the necessity of satellite networks coordination in the Ku band. Maximum capacity of geostationary orbit (GEO) for different diameters ofearth station antennas, operating in standard DVB-S2 accounting the limitations caused by the parameters of existing satellite networks equipment, is determined. Optimal values of satellites’ orbital separation, relative increase in allowablenoise / and the signal...

Arabidopsis CDS blastp result: AK105677 [KOME

Lifescience Database Archive (English)

Full Text Available AK105677 001-201-B01 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediab...etic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting co

Arabidopsis CDS blastp result: AK119376 [KOME

Lifescience Database Archive (English)

Full Text Available AK119376 001-132-A09 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediab...etic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting co

Arabidopsis CDS blastp result: AK101105 [KOME

Lifescience Database Archive (English)

Full Text Available AK101105 J033025D11 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediabe...tic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting com

Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from isolated human islets of Langerhans.

Science.gov (United States)

Cooper, E Jane; Hudson, Alan L; Parker, Christine A; Morgan, Noel G

2003-12-15

It is well known that certain imidazoline compounds can stimulate insulin secretion and this has been attributed to the activation of imidazoline I(3) binding sites in the pancreatic beta-cell. Recently, it has been proposed that beta-carbolines may be endogenous ligands having activity at imidazoline sites and we have, therefore, studied the effects of beta-carbolines on insulin secretion. The beta-carbolines harmane, norharmane and pinoline increased insulin secretion two- to threefold from isolated human islets of Langerhans. The effects of harmane and pinoline were dose-dependent (EC(50): 5 and 25 microM, respectively) and these agents also blocked the inhibitory effects of the potassium channel agonist, diazoxide, on glucose-induced insulin release. Stimulation of insulin secretion by harmane was glucose-dependent but, unlike the imidazoline I(3) receptor agonist efaroxan, it increased the rate of insulin release beyond that elicited by 20 mM glucose (20 mM glucose alone: 253+/-34% vs. basal; 20 mM glucose plus 100 microM harmane: 327+/-15%; P<0.01). Stimulation of insulin secretion by harmane was attenuated by the imidazoline I(3) receptor antagonist KU14R (2 (2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole) and was reduced when islets were treated with efaroxan for 18 h, prior to the addition of harmane. The results reveal that beta-carbolines can potentiate the rate of insulin secretion from human islets and suggest that these agents may be useful prototypes for the development of novel insulin secretagogues.

Homme kell 19 algab EKA galeriis Norra eri väljapanek "(A guide to) constructing the universe"

Index Scriptorium Estoniae

2005-01-01

Kuraatoriduo Rakett koosseisus Karolin Tampere ja Ase Lovgren norra noorema kunsti ja muusikaga.12. III toimuva norra video- ja performance'i-õhtu esinejad loetletud, vt. ka lk. 24. Projekti II osa 19. märtsil Ku-Ku klubis (bändid ja dj-d)

TAS-116, a novel Hsp90 inhibitor, selectively enhances radio-sensitivity of human cancer cells to X-rays and carbon ion radiation

Science.gov (United States)

Lee, Younghyun; Sunada, Shigeaki; Hirakawa, Hirokazu; Fujimori, Akira; Nickoloff, Jac A.; Okayasu, Ryuichi

2016-01-01

Hsp90 inhibitors have been investigated as cancer therapeutics in mono-therapy and to augment radiotherapy, however serious adverse effects of early generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here we investigated the radio-sensitizing effects of TAS-116 in low LET X-ray, and high LET carbon ion irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of non-cancerous human fibroblasts. TAS-116 increased the number of radiation-induced γ-H2AX foci, and delayed the repair of DNA double-strand breaks (DSBs). TAS-116 reduced the expression of proteins that mediate repair of DSBs by homologous recombination (RAD51) and non-homologous end joining (Ku, DNA-PKcs), and suppressed formation of RAD51 foci and phosphorylation/activation of DNA-PKcs. TAS-116 also decreased expression of the cdc25 cell cycle progression marker, markedly increasing G2/M arrest. Combined treatment of mouse tumor xenografts with carbon ions and TAS-116 showed promising delay in tumor growth compared to either individual treatment. These results demonstrate that TAS-116 radio-sensitizes human cancer cells to both X rays and carbon ions by inhibiting the two major DSB repair pathways, and these effects were accompanied by marked cell cycle arrest. The promising results of combination TAS-116 + carbon ion radiation therapy of tumor xenografts justify further exploration of TAS-116 as an adjunct to radiotherapy using low or high LET radiation. PMID:28062703

Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia.

Science.gov (United States)

Strickland, Stephen A; Raptis, Anastasios; Hallquist, Allan; Rutledge, James; Chernick, Michael; Perree, Mathieu; Talbott, Mahsa S; Presant, Cary A

2013-03-01

Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. A total of 109 patients with untreated AML had blood and/or bone marrow aspirate samples analyzed for anthracycline-induced apoptosis using the MiCK assay. The amount of apoptosis observed over 48 h was determined and expressed as kinetic units of apoptosis (KU). Complete remission (CR) was significantly higher (72%) in patients with high idarubicin-induced apoptosis >3 KU compared to patients with apoptosis ≤ 3 KU (p = 0.01). Multivariate analysis showed the only significant variables to be idarubicin-induced apoptosis and karyotype. Median overall survival of patients with idarubicin-induced apoptosis >3 KU was 16.1 months compared to 4.5 months in patients with apoptosis ≤ 3 KU (p = 0.004). Multivariate analysis showed the only significant variable to be idarubicin-induced apoptosis. Chemotherapy-induced apoptosis measured by the MiCK assay demonstrated significant correlation with outcomes and appears predictive of complete remission and overall survival for patients receiving standard induction chemotherapy.

Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

OpenAIRE

Oe, Mariko; Sakai, Seigo; Yoshida, Hideto; Okado, Nao; Kaneda, Haruna; Masuda, Yasunobu; Urushibata, Osamu

2017-01-01

Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW...

Lactococcus lactis As a Versatile Vehicle for Tolerogenic Immunotherapy

Science.gov (United States)

Cook, Dana P.; Gysemans, Conny; Mathieu, Chantal

2018-01-01

Genetically modified Lactococcus lactis bacteria have been engineered as a tool to deliver bioactive proteins to mucosal tissues as a means to exert both local and systemic effects. They have an excellent safety profile, the result of years of human consumption in the food industry, as well as a lack of toxicity and immunogenicity. Also, containment strategies have been developed to promote further application as clinical protein-based therapeutics. Here, we review technological advancements made to enhanced the potential of L. lactis as live biofactories and discuss some examples of tolerogenic immunotherapies mediated by mucosal drug delivery via L. lactis. Additionally, we highlight their use to induce mucosal tolerance by targeted autoantigen delivery to the intestine as an approach to reverse autoimmune type 1 diabetes. PMID:29387056

Targeting inflammation with autoantigen-specific T cells

NARCIS (Netherlands)

Guichelaar, T.

2008-01-01

Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin

International Nuclear Information System (INIS)

Lee, Y.-J.; Sheu, T.-J.; Keng, Peter C.

2005-01-01

Cofilin is an actin-associated protein that belongs to the actin depolymerization factor/cofilin family and is important for regulation of actin dynamics. Cofilin can import actin monomers into the nucleus under certain stress conditions, however the biological effects of nuclear transport are unclear. In this study, we found that over-expression of cofilin led to increased radiation sensitivity in human non-small lung cancer H1299 cells. Cell survival as determined by colony forming assay showed that cells over-expressing cofilin were more sensitive to ionizing radiation (IR) than normal cells. To determine whether the DNA repair capacity was altered in cofilin over-expressing cells, comet assays were performed on irradiated cells. Repair of DNA damage caused by ionizing radiation was detected in cofilin over-expressing cells after 24 h of recovery. Consistent with this observation, the key components for repair of DNA double-strand breaks, including Rad51, Rad52, and Ku70/Ku80, were down-regulated in cofilin over-expressing cells after IR exposure. These findings suggest that cofilin can influence radiosensitivity by altering DNA repair capacity

Disease: H00082 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 0:397-409 (2004) DOI:10.1046/j.1365-2265.2004.01978.x ... PMID:12734493 (gene, env_factor, marker, autoantigen) ... AUTHORS ... Ai J, Leonha...rdt JM, Heymann WR. ... TITLE ... Autoimmune thyroid diseases: etiology, pathogenesis

ONR Far East Scientific Bulletin, Volume 7, Number 4, October-December 1982,

Science.gov (United States)

1982-12-01

Japan Professor D. Kunii June 3 on Fluidization Department of ChemicalEngineering Faculty of Engineering University of Tokyo 7-3-1, Hongo , Bunkyo-ku...tentative) Conference on Raman Department of Chemistry Spectroscopy Faculty of Science University of Tokyo 7-3-1, Hongo Bunkyo-ku, Tokyo 113 September

WhichCyp

DEFF Research Database (Denmark)

Rostkowski, Michal; Spjuth, Ola; Rydberg, Patrik

2013-01-01

. AVAILABILITY: The WhichCyp server is freely available for use on the web at http://drug.ku.dk/whichcyp, where the WhichCyp Java program and source code is also available for download. CONTACT: pry@sund.ku.dk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online....

Endemic pemphigus over a century: Part II.

Science.gov (United States)

Abréu-Vélez, Ana María; Roselino, Ana Maria; Howard, Michael S; Reason, Iara J de Messias

2010-03-01

Endemic pemphigus foliaceus (EPF) is an autoimmune disease, classically occurring in a restricted geographic area. Foci of EPF have been described in several Central and South American countries, often affecting young people and Amerindians, with some female predilection. Although most American EPF cases have been documented in Brazil, cases have been reported in Peru, Paraguay, El Salvador and Venezuela. An additional variant of EPF has been described in El Bagre, Colombia, (El Bagre-EPF) affecting older men and a few post-menopausal females. Finally, one additional type of EPF has been described in nomadic tribes affecting females of child bearing age in Tunisia, Africa. The main aim of this review is to summarize current knowledge about autoantigens, and immunologic and genetic studies in EPF. We utilized a retrospective review of the literature, aiming to compile and compare the multiple geographic foci of EPF. The primary autoantigens in EPF are still considered to be desmogleins in the case of the Tunisian and all American cases, in contradistinction to plakins and desmogleins in El Bagre-EPF. Although several autoantigens are been suggested, their biochemical nature needs further elucidation. Current knowledge still supports the concept that an antibody mediated immune response represents the principal pathophysiology in all variants of EPF. A strong genetic susceptibility appears to contribute to disease development in several people affected by these diseases; however, no specific genes have been confirmed at present. We conclude that further investigation is necessary to define these disorders immunologically and genetically.

Spin Electronics

Science.gov (United States)

2003-08-01

Site: University of Tokyo Department of Physics Graduate School of Science 7-3-1 Hongo , Bunkyo-ku Tokyo 113-0033, Japan Date April 5, 2001...University of Tokyo Department of Electrical Engineering 7-3-1, Hongo , Bunkyo-ku Tokyo 113, Japan Date: April 5, 2001 WTEC Attendees: D

Development of a Charged-particle Accumulator Using an RF Confinement Method II

Science.gov (United States)

2006-08-24

Ryugo Hayano, Ph.D., Professor Department of Physics, Graduate School of Science University of Tokyo 7-3-1 Hongo , Bunkyo-ku...NAME(S) AND ADDRESS(ES) University of Tokyo,7-3-1 Hongo , Bunkyo-ku,Tokyo 113-0033,Japan,JP,113-0033 8. PERFORMING ORGANIZATION REPORT NUMBER AOARD

Siim Nestor soovitab : Scratch Perverts. Q-Boy. Sümpaatsed väiksed peod / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2005-01-01

Üritustest 11. veebr. Tallinnas: klubis Hip Hop Café diskorid Tony Vegas, Prime Cuts, Plus One, Paul Oja ja Critical; klubis BonBon inglise räppar Q-Boy ja MC Ms Fontaine; klubis Võitlev Sõna üritus "Lift" ja 12. veebr. klubis KuKu üritus "Turbodisko"

Making the Road While Walking It: A Conversation with Richard Simpson

Science.gov (United States)

Zabel, Robert H.; Kaff, Marilyn; Teagarden, James

2016-01-01

Richard Simpson is professor of special education at the University of Kansas (KU). Dr. Simpson's duties at KU have included roles of staff psychologist, teaching associate, assistant professor, project director, associate professor, professor, and chairperson for the Department of Special Education. He has directed numerous University of Kansas…

Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.

Science.gov (United States)

Green, Nathaniel M; Moody, Krishna-Sulayman; Debatis, Michelle; Marshak-Rothstein, Ann

2012-11-16

The key step in the activation of autoreactive B cells is the internalization of nucleic acid containing ligands and delivery of these ligands to the Toll-like Receptor (TLR) containing endolysosomal compartment. Ribonucleoproteins represent a large fraction of autoantigens in systemic autoimmune diseases. Here we demonstrate that many uridine-rich mammalian RNA sequences associated with common autoantigens effectively activate autoreactive B cells. Priming with type I IFN increased the magnitude of activation, and the range of which RNAs were stimulatory. A subset of RNAs that contain a high degree of self-complementarity also activated B cells through TLR3. For the RNA sequences that activated predominantly through TLR7, the activation is proportional to uridine-content, and more precisely defined by the frequency of specific uridine-containing motifs. These results identify parameters that define specific mammalian RNAs as ligands for TLRs.

Content of Diabetes-Associated Autoantibodies against Islet Autoantigens (IA-2A, GADA, IAA and the Level of Different Cytokines in Children and Adolescents on the Pre-Clinical and Early Clinical Stages of Type 1 Diabetes Mellitus Development

Directory of Open Access Journals (Sweden)

V.V. Popova

2015-03-01

Full Text Available The article provides the data on the immunological mechanisms of type 1 diabetes mellitus (T1DM on the preclinical and early clinical stages of disease formation on the basis of studying the features of T1DM pathogenesis, monitoring the process of autoimmune destruction of insulin-producing β-cells by determining the content of diabetes-associated auto-antibodies (the incidence and titers dynamics, the study of the characteristics of cytokine secretion on the pre-clinical stage of T1DM development in children and adolescents. Introduction of new approaches to pre-clinical diagnosis of T1DM allowed determine the group of marker-positive children with burdened heredity and predictable risk of disease development. The study involved 450 healthy normoglycemic children and adolescents aged from 7 to 15 years old. It was revealed that 94 (26.7 % of 366 children with burdened hereditary by at least two-fold determination of DAAb had an increased DAAb titer, mainly GADA and IA-2A, the clinical debut of T1DM manifested in 49 (52.1 % of them from 6 months to 12 years (30.9 ± 3.2 months. T1DM developed in the same period in a child, that was 0.8 % of the 272 (73.3 % DAAb-negative children. There was determined a formula of combined incidence and values of simultaneously elevated DAAb titers to islet autoantigens, namely IA-2A + GADA, which are predictor of the duration of T1DM pre-clinical stage and debut occurrence. It has been also established a disturbance of cytokine production (increased level of pro-inflammatory cytokines IL-1α, IL-6 and FNO-α, IL-8 and IL-16 while reduced concentration of IL-4 in blood plasma as a key factor in the T1DM pathogenesis that causes the debut occurrence, and aggressiveness of its course.

Domain structure of a NHEJ DNA repair ligase from Mycobacterium tuberculosis.

Science.gov (United States)

Pitcher, Robert S; Tonkin, Louise M; Green, Andrew J; Doherty, Aidan J

2005-08-19

A prokaryotic non-homologous end-joining (NHEJ) system for the repair of DNA double-strand breaks (DSBs), composed of a Ku homodimer (Mt-Ku) and a multidomain multifunctional ATP-dependent DNA ligase (Mt-Lig), has been described recently in Mycobacterium tuberculosis. Mt-Lig exhibits polymerase and nuclease activity in addition to DNA ligation activity. These functions were ascribed to putative polymerase, nuclease and ligase domains that together constitute a monomeric protein. Here, the separate polymerase, nuclease and ligase domains of Mt-Lig were cloned individually, over-expressed and the soluble proteins purified to homogeneity. The polymerase domain demonstrated DNA-dependent RNA primase activity, catalysing the synthesis of unprimed oligoribonucleotides on single-stranded DNA templates. The polymerase domain can also extend DNA in a template-dependent manner. This activity was eliminated when the catalytic aspartate residues were replaced with alanine. The ligase domain catalysed the sealing of nicked double-stranded DNA designed to mimic a DSB, consistent with the role of Mt-Lig in NHEJ. Deletion of the active-site lysine residue prevented the formation of an adenylated ligase complex and consequently thwarted ligation. The nuclease domain did not function independently as a 3'-5' exonuclease. DNA-binding assays revealed that both the polymerase and ligase domains bind DNA in vitro, the latter with considerably higher affinity. Mt-Ku directly stimulated the polymerase and nuclease activities of Mt-Lig. The polymerase domain bound Mt-Ku in vitro, suggesting it may recruit Mt-Lig to Ku-bound DNA in vivo. Consistent with these data, Mt-Ku stimulated the primer extension activity of the polymerase domain, suggestive of a functional interaction relevant to NHEJ-mediated DSB repair processes.

RENAL VASCULITIS IN 2012 Reclassification and the introduction of biologicals

NARCIS (Netherlands)

Kallenberg, Cees G. M.

2012 saw the classification of the systemic vasculitides revised. Genetic studies showed that granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are different diseases with aberrant immune responses to different autoantigens. B-cell depletion with rituximab also acquired a

The University of Kansas High-Throughput Screening Laboratory. Part II: enabling collaborative drug-discovery partnerships through cutting-edge screening technology.

Science.gov (United States)

McDonald, Peter R; Roy, Anuradha; Chaguturu, Rathnam

2011-07-01

The University of Kansas High-Throughput Screening (KU HTS) core is a state-of-the-art drug-discovery facility with an entrepreneurial open-service policy, which provides centralized resources supporting public- and private-sector research initiatives. The KU HTS core was established in 2002 at the University of Kansas with support from an NIH grant and the state of Kansas. It collaborates with investigators from national and international academic, nonprofit and pharmaceutical organizations in executing HTS-ready assay development and screening of chemical libraries for target validation, probe selection, hit identification and lead optimization. This is part two of a contribution from the KU HTS laboratory.

Quantification of Forecasting and Change-Point Detection Methods for Predictive Maintenance

Science.gov (United States)

2015-08-19

University of Tokyo 7-3-1 Hongo , Bunkyo-ku, Ttokyo 113-8645, Japan 3 Air Force Research Laboratory, 2977 Hobson Way, Bldg 653 Rm 427 Wright...AFB OH 45433-7734 *** University of Tokyo 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-8645, Japan Abstract This work investigates the application of the

Proceedings of 16th Nordic Semiconductor Meeting Held in Laugarvatn, Iceland on 12-15 June 1994

Science.gov (United States)

1995-01-10

7-3-1 Hongo , Bunkyo-ku, Tokyo 113, Japan Received May 4, 1994; accepted June 16, 1994 Abstract described in detail in a previous work [5]. The...Henrik Stubb, Dept. of Physics, KTH Electrum 229, Badenerstr. 569, VTT Electronics, 7-3-1 Hongo , Bunkyo-ku, Dept. of Electronics, CH-8048 Ziirich

Rozbor morfologie nohy u chlapců a dívek ve věku Infans 2 a Juvenis Analysis of morphology of foot in Moravian male and female students in the age Infans 2 and Juvenis

Directory of Open Access Journals (Sweden)

Michaela Peštuková

2005-02-01

Full Text Available U 106 studentů a 162 studentek z Gymnázia ve Šternberku a Střední integrované školy v Ostravě ve věku 12–18 let byl sledován morfologický typ nohy, index nohy pro hodnocení podélné klenby nožní, vyosení palce a malíku, úhel paty a stav svalstva dolních končetin. U chlapců i dívek byla nalezena výrazně vyšší frekvence výskytu nohy egyptské (71,69 % a 70,99 %. Noha kvadratická se vyskytovala u chlapců ve velmi nízkém procentu (2,83 % s určitou individuální asymetrií, u dívek nalezena nebyla. Diagnostika plochonoží metodou Chippauxe–Šmiřáka poskytla velmi příznivé výsledky (4,94–10,38 % výskytu ploché nohy, metoda podle Szritera–Godunova naopak nález podstatně horší (38,2–43,21 % výskytu ploché nohy. S nulovým stavem vyosení palce jsme se setkali u necelé čtvrtiny souborů. U souboru chlapců byla četnost projevu valgozity a varozity palce téměř vyrovnána, věcně převažovalo varózní postavení palce vpravo. U souboru dívek dominovalo signifikantně valgózní postavení. Průměrné hodnoty se pohybovaly v rozmezí 4 až 7 stupňů. Průměrná hodnota úhlu malíku, charakterizující vbočený malík, byla vysoká (17,73 až 21,90 stupně. Průměrný úhel paty byl diagnostikován v rozmezí 15 až 18 stupňů. Při hodnocení vztahů mezi zkrácením svalů dolní končetiny a poruchami funkčního stavu klenby nožní (pouze u mužů jsme nalezli potvrzení statistické významnosti závislosti u vyosení paty a zkrácení m. triceps surae sin. a signifikantní závislost mezi úhlem paty a zkrácením flexorů kolen sin. Morphological foot type, foot index for longitudinal foot vault, misalignment of the big and little toes, heel angle and lower limb muscles condition were monitored in 106 male students and 162 female students from the Gymnasium school in Šternberk and the Integrated secondary school in Ostrava ranging in age from 12 to 18 years. A considerably

Either non-homologous ends joining or homologous recombination is required to repair double-strand breaks in the genome of macrophage-internalized Mycobacterium tuberculosis.

Science.gov (United States)

Brzostek, Anna; Szulc, Izabela; Klink, Magdalena; Brzezinska, Marta; Sulowska, Zofia; Dziadek, Jaroslaw

2014-01-01

The intracellular pathogen Mycobacterium tuberculosis (Mtb) is constantly exposed to a multitude of hostile conditions and is confronted by a variety of potentially DNA-damaging assaults in vivo, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or reactive oxygen species causes different types of DNA damage, including oxidation, depurination, methylation and deamination, that can result in single- or double-strand breaks (DSBs). These breaks affect the integrity of the whole genome and, when left unrepaired, can lead to cell death. Here, we investigated the role of the DSB repair pathways, homologous recombination (HR) and non-homologous ends joining (NHEJ), in the survival of Mtb inside macrophages. To this end, we constructed Mtb strains defective for HR (ΔrecA), NHEJ [Δ(ku,ligD)], or both DSB repair systems [Δ(ku,ligD,recA)]. Experiments using these strains revealed that either HR or NHEJ is sufficient for the survival and propagation of tubercle bacilli inside macrophages. Inhibition of nitric oxide or superoxide anion production with L-NIL or apocynin, respectively, enabled the Δ(ku,ligD,recA) mutant strain lacking both systems to survive intracellularly. Complementation of the Δ(ku,ligD,recA) mutant with an intact recA or ku-ligD rescued the ability of Mtb to propagate inside macrophages.

Either non-homologous ends joining or homologous recombination is required to repair double-strand breaks in the genome of macrophage-internalized Mycobacterium tuberculosis.

Directory of Open Access Journals (Sweden)

Anna Brzostek

Full Text Available The intracellular pathogen Mycobacterium tuberculosis (Mtb is constantly exposed to a multitude of hostile conditions and is confronted by a variety of potentially DNA-damaging assaults in vivo, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or reactive oxygen species causes different types of DNA damage, including oxidation, depurination, methylation and deamination, that can result in single- or double-strand breaks (DSBs. These breaks affect the integrity of the whole genome and, when left unrepaired, can lead to cell death. Here, we investigated the role of the DSB repair pathways, homologous recombination (HR and non-homologous ends joining (NHEJ, in the survival of Mtb inside macrophages. To this end, we constructed Mtb strains defective for HR (ΔrecA, NHEJ [Δ(ku,ligD], or both DSB repair systems [Δ(ku,ligD,recA]. Experiments using these strains revealed that either HR or NHEJ is sufficient for the survival and propagation of tubercle bacilli inside macrophages. Inhibition of nitric oxide or superoxide anion production with L-NIL or apocynin, respectively, enabled the Δ(ku,ligD,recA mutant strain lacking both systems to survive intracellularly. Complementation of the Δ(ku,ligD,recA mutant with an intact recA or ku-ligD rescued the ability of Mtb to propagate inside macrophages.

Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Shintani, Satoru; Mihara, Mariko; Li, Chunnan; Nakahara Yuuji; Hino, Satoshi; Nakashiro, Koh-ichi; Hamakawa, Hiroyuki

2003-01-01

DNA-PK is a nuclear protein with serine/threonine kinase activity and forms a complex consisting of the DNA-PKcs and a heterodimer of Ku70 and Ku80 proteins. Recent laboratory experiments have demonstrated that the DNA-PK complex formation is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. In this study, we evaluated the relationship between expression levels of DNA-PKcs, Ku70 and Ku80 proteins and radiation sensitivity in oral squamous cell carcinoma (OSCC) cell lines and in OSCC patients treated with preoperative radiation therapy. The OSCC cell lines greatly differed in their response to irradiation, as assessed by a standard colony formation assay. However, the expression levels of the DNA-PK complex proteins were all similar, and there was no association between the magnitude of their expression and the tumor radiation sensitivity. Expression of DNA-PK complex proteins increased after radiation treatment, and the increased values correlated with the tumor radiation resistance. Expression of DNA-PKcs and Ku70 after irradiation was increased in the surviving cells of OSCC tissues irradiated preoperatively. These results suggest that up-regulation of DNA-PK complex protein, especially DNA-PKcs, after radiation treatment correlates to radiation resistance. DNA-PKcs might be a molecular target for a novel radiation sensitization therapy of OSCC. (author)

Parenteral formulation of an antileishmanial drug candidate--tackling poor solubility, chemical instability, and polymorphism.

Science.gov (United States)

Kupetz, Eva; Preu, Lutz; Kunick, Conrad; Bunjes, Heike

2013-11-01

The paullon chalcone derivative KuRei300 is active against Leishmania donovani, the protozoans causing visceral leishmaniasis. The aim of this study was the development of a parenteral formulation of the virtually water insoluble compound in order to enable future studies in mice. Mixed lecithin/bile salt micelles, liposomes, supercooled smectic cholesterol myristate nanoparticles, cubic phase nanoparticles and a triglyceride emulsion were screened for their solubilizing properties. Due to the limited available amount of KuRei300 a passive loading approach with pre-formulated carriers that were incubated with drug substance deposited onto the walls of glass vials was used. The loading capacities of the nanocarriers, the influence of the solid state properties of the drug and its deposits on the loading results and chemical stability aspects of KuRei300 were investigated. Employed methods included HPLC, UV spectroscopy, (1)H NMR, XRPD, and DSC. All nanocarriers substantially improved the solubility of KuRei300; the mixed micelles exhibited the highest drug load. Related to the lipid matrix, however, the smectic nanoparticles solubilized the significantly highest amount of drug. Loading from physically altered drug deposits improved the obtainable concentration to the threefold compared with untreated drug powder. Formulations with KuRei300 must be stored excluded from light under a nitrogen atmosphere as the substance is susceptible to photoisomerization and decomposition. Copyright © 2013 Elsevier B.V. All rights reserved.

Gclust Server: 97794 [Gclust Server

Lifescience Database Archive (English)

Full Text Available 97794 CEL_B0244.2_25143920 Cluster Sequences Related Sequences(171) 767 ida-1: related to Islet cell Diabete...ida-1: related to Islet cell Diabetes Autoantigen family member (ida-1) Number of Sequences 1 Homologs 1 Clu

Characteristics of Prevotella intermedia-specific CD4+ T cell clones from peripheral blood of a chronic adult periodontitis patient

NARCIS (Netherlands)

Wassenaar, A.; Reinhardus, C.; Abraham-Inpijn, L.; Snijders, A.; Kievits, F.

1998-01-01

Periodontitis is a chronic destructive inflammatory disease associated with periodontopathic bacteria. In addition, autoantigens such as collagen and heat shock proteins (hsp) have been suggested to play a role. Established periodontal lesions are characterized by dense infiltrations of immune cells

A NEW ELISA FOR THE DETECTION OF ANTI-HEPARAN SULFATE REACTIVITY, USING PHOTOBIOTINYLATED ANTIGEN

NARCIS (Netherlands)

HYLKEMA, MN; KRAMERS, C; VANDERWAL, TJ; VANBRUGGEN, MCJ; SWAAK, AJG; BERDEN, JHM; SMEENK, RJT; Hylkema, Machteld

1994-01-01

Autoantibodies reacting with a great variety of autoantigens are characteristic for the autoimmune disease systemic lupus erythematosus (SLE). Although reactivity with heparan sulfate (HS) in sera of patients with SLE is found in association with the occurrence of nephritis, the aetiological

Antiplectin autoantibodies in subepidermal blistering diseases

NARCIS (Netherlands)

Buijsrogge, J. J. A.; de Jong, M. C. J. M.; Kloosterhuis, G. J.; Vermeer, M. H.; Koster, J.; Sonnenberg, A.; Jonkman, M. F.; Pas, H. H.

2009-01-01

Background Hemidesmosomal proteins may become targets of autoimmunity in subepidermal blistering diseases. Well-known recognized autoantigens are the intracellular plaque protein BP230, the transmembrane BP180 and its shed ecto-domain LAD-1. Objectives To establish the prevalence of autoimmunity

Dendritic cells and veiled accessory macrophages : hormonal influences and autoimmune thyroid disease

NARCIS (Netherlands)

M.O. Canning (Martha)

2005-01-01

textabstractImmune responses to thyroid specific autoantigens form the basis of autoimmune thyroid disease pathogenesis. Two polar forms of autoimmune reactivity of the thyroid gland exist in this disease spectrum: a catabolic form characterized by gradual inflammatory destruction of thyroid

The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells

Directory of Open Access Journals (Sweden)

Melissa García-Caballero

2017-11-01

Full Text Available Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells. In this work, human myeloid leukemia cells (HL60, U937 and KU812F were treated with AD0157 ranging from 1 to 10 μM and an experimental battery was applied to evaluate its apoptogenic potential. We report here that AD0157 was highly effective to inhibit cell growth by promotion of apoptosis in human myeloid leukemia cells, and provide evidence of its mechanisms of action. The apoptogenic activity of AD0157 on leukemia cells was verified by an increased chromatin condensation and DNA fragmentation, and confirmed by an augmentation in the apoptotic subG1 population, translocation of the membrane phosphatidylserine from the inner face of the plasma membrane to the cell surface and by cleavage of the apoptosis substrates PARP and lamin-A. In addition, AD0157 in the low micromolar range significantly enhanced the activities of the initiator caspases-8 and -9, and the effector caspases-3/-7 in a dose-dependent manner. Results presented here throw light on the apoptogenic mechanism of action of AD0157, mediated through caspase-dependent cascades, with an especially relevant role played by mitochondria. Altogether, these results suggest the therapeutic potential of this compound for the treatment of human myeloid leukemia.

Non-liberal subjectivities

DEFF Research Database (Denmark)

Sonnichsen, André

2014-01-01

Paper presented at the one-day exploratory workshop on 'Sovereignty and Social Orders in the Postcolony", co-funded by Faculty of Social Sciences, KU, and Danida.......Paper presented at the one-day exploratory workshop on 'Sovereignty and Social Orders in the Postcolony", co-funded by Faculty of Social Sciences, KU, and Danida....

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

International Nuclear Information System (INIS)

Eskew, Jeffery D; Rajewski, Roger A; Blagg, Brian SJ; Manjarrez, Jacob R; Matts, Robert L; Holzbeierlein, Jeffrey M; Vielhauer, George A; Sadikot, Takrima; Morales, Pedro; Duren, Alicia; Dunwiddie, Irene; Swink, Megan; Zhang, Xiaoying; Hembruff, Stacey; Donnelly, Alison

2011-01-01

The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

Directory of Open Access Journals (Sweden)

Eskew Jeffery D

2011-10-01

Full Text Available Abstract Background The molecular chaperone, heat shock protein 90 (Hsp90 has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. Methods PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. Results KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. Conclusions Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer.

Balance og stofskifte

DEFF Research Database (Denmark)

2011-01-01

Udstilling på Medicinsk Museion. Baseret på bevilling fra Assens Fond. Se mere på http://www.museion.ku.dk/whats-on/exhibitions/balance-and-metabolism/......Udstilling på Medicinsk Museion. Baseret på bevilling fra Assens Fond. Se mere på http://www.museion.ku.dk/whats-on/exhibitions/balance-and-metabolism/...

Siim Nestor soovitab : Stereo ÖÖ. Mutant Disco. Beats from the Vault. Turbodisko / Siim Nestor

Index Scriptorium Estoniae

Nestor, Siim, 1974-

2006-01-01

Oma debüütalbumit "Migration" tutvustav ameerika diskor Alex Attias üritustel "Stereo ÖÖ" 19. mail Tallinnas Von Krahlis. Üritustest "Mutant Disco" 19. mail Tallinnas klubis Privé ja Tartus 20. mail klubis Illusion, "Beats from the Vault" 19. mail Tallinnas klubis Võit ja "Turbodisko" 20. mail Tallinnas klubis KuKu

TDRSS S-shuttle unique receiver equipment

Science.gov (United States)

Weinberg, A.; Schwartz, J. J.; Spearing, R.

1985-01-01

Beginning with STS-9, the Tracking and Date Relay Satellite system (TDRSS) will start providing S- and Ku-band communications and tracking support to the Space Shuttle and its payloads. The most significant element of this support takes place at the TDRSS White Sands Ground Terminal, which processes the Shuttle return link S- and Ku-band signals. While Ku-band hardware available to other TDRSS users is also applied to Ku-Shuttle, stringent S-Shuttle link margins have precluded the application of the standard TDRSS S-band processing equipment to S-Shuttle. It was therfore found necessary to develop a unique S-Shuttle Receiver that embodies state-of-the-art digital technology and processing techniques. This receiver, developed by Motorola, Inc., enhances link margins by 1.5 dB relative to the standard S-band equipment and its bit error rate performance is within a few tenths of a dB of theory. An overview description of the Space Shuttle Receiver Equipment (SSRE) is presented which includes the presentation of block diagrams and salient design features. Selected, measured performance results are also presented.

The Joint Venture Model of Knowledge Utilization: a guide for change in nursing.

Science.gov (United States)

Edgar, Linda; Herbert, Rosemary; Lambert, Sylvie; MacDonald, Jo-Ann; Dubois, Sylvie; Latimer, Margot

2006-05-01

Knowledge utilization (KU) is an essential component of today's nursing practice and healthcare system. Despite advances in knowledge generation, the gap in knowledge transfer from research to practice continues. KU models have moved beyond factors affecting the individual nurse to a broader perspective that includes the practice environment and the socio-political context. This paper proposes one such theoretical model the Joint Venture Model of Knowledge Utilization (JVMKU). Key components of the JVMKU that emerged from an extensive multidisciplinary review of the literature include leadership, emotional intelligence, person, message, empowered workplace and the socio-political environment. The model has a broad and practical application and is not specific to one type of KU or one population. This paper provides a description of the JVMKU, its development and suggested uses at both local and organizational levels. Nurses in both leadership and point-of-care positions will recognize the concepts identified and will be able to apply this model for KU in their own workplace for assessment of areas requiring strengthening and support.

Heat exchanger design

OpenAIRE

Vítek, Tomáš

2017-01-01

Tato bakalářská práce řeší návrh výměníku tepla pro teplovodní kotel se zplyňovací komorou pro předehřev spalovacího vzduchu odpadním teplem spalin. Hodnoty pro výpočet byly experimentálně naměřeny. Práce obsahuje stručný popis trubkového výměníku tepla, stechiometrický vypočet spalování, návrh geometrických rozměrů výměníku, výpočet tlakových ztrát a výpočet výkonu. Její součástí je také výkresová dokumentace navrženého výměníku. This bachelor thesis solves design of a heat exchanger for ...

Substitution of Pichia pastoris-derived recombinant proteins with mannose containing O- and N-linked glycans decreases specificity of diagnostic tests

NARCIS (Netherlands)

van Oort, Erica; Lerouge, Patrice; de Heer, Pleuni G.; Séveno, Martial; Coquet, Laurent; Modderman, Piet W.; Faye, Loïc; Aalberse, Rob C.; van Ree, Ronald

2004-01-01

Background: Recombinant proteins from Pichia pastoris need to be fully evaluated before used as diagnostic tools. Objective: The objective of this study was to investigate whether glycosylation by P. pastoris interferes with the specificity of diagnostic tests. Methods: An autoantigen involved in

Hypersensitivity Responses in the Central Nervous System

DEFF Research Database (Denmark)

Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

2015-01-01

of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

International Nuclear Information System (INIS)

Sanli, Toran; Rashid, Ayesha; Liu Caiqiong

2010-01-01

Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells. Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. Results: IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK α subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21 waf/cip as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further. Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21 waf/cip and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21 waf/cip pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.

Direct Ex Vivo Analysis of Activated, Fas-sensitive Autoreactive T Cells in Human Autoimmune Disease

Science.gov (United States)

Bieganowska, Katarzyna D.; Ausubel, Lara J.; Modabber, Yalda; Slovik, Elissa; Messersmith, Wells; Hafler, David A.

1997-01-01

The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor (TCR)-α and -β chains found in T cell clones previously isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to frequencies of 1 in 105–106 as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99–associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor α–positive T cells which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data demonstrate that at least a subpopulation of patients with MS can have a very high frequency of activated autoreactive T cells. PMID:9151896

Development of a Charged-Particle Accumulator Using an RF Confinement Method VI

Science.gov (United States)

2010-08-10

PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) University of Tokyo,7-3-1 Hongo , Bunkyo-ku...Department of Physics 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 - Phone : 03-5841-4235 - Fax : 03-4496-4043 Period of Performance: 2/9/2009 – 3/8/2010

TAM receptor knockout mice are susceptible to retinal autoimmune induction.

Science.gov (United States)

Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

2011-06-16

TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

Science.gov (United States)

Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

2012-05-10

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis

OpenAIRE

Jette, Nicholas; Lees-Miller, Susan P.

2014-01-01

The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and the Ku70/80 heterodimer. Over the past two decades, significant progress has been made in elucidating the role of DNA-PK in non-homologous end joining (NHEJ), the major pathway for repair of ionizing radiation-induced DNA double strand breaks in human cells and recently, additional roles for DNA-PK have been reported. In this review, we will describe the biochemi...

Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune Addison's disease.

Science.gov (United States)

Brozzetti, Annalisa; Alimohammadi, Mohammad; Morelli, Silvia; Minarelli, Viviana; Hallgren, Åsa; Giordano, Roberta; De Bellis, Annamaria; Perniola, Roberto; Kämpe, Olle; Falorni, Alberto

2015-05-01

NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects. NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P < .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies. NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.

Chronic malaria revealed by a new fluorescence pattern on the antinuclear autoantibodies test.

Directory of Open Access Journals (Sweden)

Benjamin Hommel

Full Text Available BACKGROUND: Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA. METHODS: We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. RESULTS: We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. CONCLUSION: In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.

Multiple and variable NHEJ-like genes are involved in resistance to DNA damage in Streptomyces ambofaciens

Directory of Open Access Journals (Sweden)

Grégory Hoff

2016-11-01

Full Text Available Non homologous end-joining (NHEJ is a double strand break (DSB repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing and ligation of the broken ends. In silico analyses performed in the 38 sequenced genomes of Streptomyces species revealed the existence of a large panel of NHEJ-like genes. Indeed, ku genes or ligD domain homologues are scattered throughout the genome in multiple copies and can be distinguished in two categories: the core NHEJ gene set constituted of conserved loci and the variable NHEJ gene set constituted of NHEJ-like genes present in only a part of the species. In Streptomyces ambofaciens ATCC 23877, not only the deletion of core genes but also that of variable genes led to an increased sensitivity to DNA damage induced by electron beam irradiation. Multiple mutants of ku, ligase or polymerase encoding genes showed an aggravated phenotype compared to single mutants. Biochemical assays revealed the ability of Ku-like proteins to protect and to stimulate ligation of DNA ends. RT-qPCR and GFP fusion experiments suggested that ku-like genes show a growth phase dependent expression profile consistent with their involvement in DNA repair during spores formation and/or germination.

Natural antibodies related to metabolic and mammary health in dairy cows

NARCIS (Netherlands)

Knegsel, van A.T.M.; Hostens, M.; Vries Reilingh, de G.; Lammers, A.; Kemp, B.; Opsomer, G.; Parmentier, H.K.

2012-01-01

Natural antibodies (NAb) are defined as antibodies that circulate in normal healthy individuals under the absence of deliberate antigenic stimulation. Two types of NAb are distinguished: NAb towards exogenous antigens and NAb towards autoantigens (N(A)Ab). The objectives of the current study were

Thyroid peroxidase autoantibodies in euthyroid subjects

NARCIS (Netherlands)

Prummel, Mark F.; Wiersinga, Wilmar M.

2005-01-01

Thyroid peroxidase (TPO) is a key enzyme in the formation of thyroid hormones and a major autoantigen in autoimmune thyroid diseases. Titers of TPO antibodies also correlate with the degree of lymphocytic infiltration in euthyroid subjects, and they are frequently present in euthyroid subjects

Výzkum církve a náboženského života v raně novověkých městech

Czech Academy of Sciences Publication Activity Database

Mikulec, Jiří

2013-01-01

Roč. 32, č. 2 (2013), s. 139-151 ISSN 0231-7443. [Města ve středověku a raném novověku jako badatelské téma posledních dvou desetiletí. Praha, 10.10.2011-11.10.2011] Institutional support: RVO:67985963 Keywords : Early Modern period * towns * church * religious life Subject RIV: AB - History

Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

Science.gov (United States)

Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

2013-01-01

Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

Digital Humanities – zpřístupňování, uchovávání a záchrana pramenů v digitálním věku

Czech Academy of Sciences Publication Activity Database

Šícha, Vojtěch

-, č. 1 (2016) E-ISSN 1805-2800 Institutional research plan: CEZ:AV0Z7083919 Institutional support: RVO:67985971 Keywords : Academy of Sciences Library * digital humanities * web portals * science and research Subject RIV: AF - Documentation, Librarianship, Information Studies https://www.lib.cas.cz/casopis-informace/digital-humanities/

A Detailed Examination of the GPM Core Satellite Gridded Text Product

Science.gov (United States)

Stocker, Erich Franz; Kelley, Owen A.; Kummerow, C.; Huffman, George; Olson, William S.; Kwiatowski, John M.

2015-01-01

The Global Precipitation Measurement (GPM) mission quarter-degree gridded-text product has a similar file format and a similar purpose as the Tropical Rainfall Measuring Mission (TRMM) 3G68 quarter-degree product. The GPM text-grid format is an hourly summary of surface precipitation retrievals from various GPM instruments and combinations of GPM instruments. The GMI Goddard Profiling (GPROF) retrieval provides the widest swath (800 km) and does the retrieval using the GPM Microwave Imager (GMI). The Ku radar provides the widest radar swath (250 km swath) and also provides continuity with the TRMM Ku Precipitation Radar. GPM's Ku+Ka band matched swath (125 km swath) provides a dual-frequency precipitation retrieval. The "combined" retrieval (125 km swath) provides a multi-instrument precipitation retrieval based on the GMI, the DPR Ku radar, and the DPR Ka radar. While the data are reported in hourly grids, all hours for a day are packaged into a single text file that is g-zipped to reduce file size and to speed up downloading. The data are reported on a 0.25deg x 0.25 deg grid.

Radiation-induced apoptosis of chicken lymphocyte B-cell line DT40

International Nuclear Information System (INIS)

Furusawa, Y.; Aoki, M.; Takakura, K.

2003-01-01

Full text: Ionizing radiation causes lesions of DNA, cell cycle arrest, induced cell death, and apoptosis in the irradiated cells. Then it is easy to expect that those events would be increased in a cell line which is defective in DNA repair system. However, induction of apoptosis by irradiation takes so complicated process when the cells are defective of DNA repair system. Indeed by many recent studies it has been clarified that DNA repair gene is also concerned with apoptotic event and some study shows the contrary data. Thus, the relationship between the genetics of apoptosis and that of DNA repair is still unclear. In this study two kinds of DNA repair proteins, Rad54 and Ku70, were focused. Proteins of Rad54 and Ku70 have important role at two type of DNA repair systems called homologous recombination repair and non-homologous end joining repair, respectively. 4 phenotypes of DT40, parent type, ku70-/-, rad54-/- and ku70-/-/rad54-/- were used to study the radiation-induced apoptosis (Previous study shows that survival fraction of 4 phenotypes of DT40 is decreased in the cell line, in which DNA repair gene is defective). From the results in this study, two things are clarifies. One is that the dependence of apoptotic index on phenotypes is so different between at low dose and at high dose irradiation. The other is that Ku70 has effective role to induce apoptosis in DT40 irradiated with high dose X-rays

Designating Domestic Terrorist Individuals or Groups

Science.gov (United States)

2010-09-01

These individuals and groups include the Black Panther Party, Weather Underground, Covenant Sword and the Arm of the Lord, Ku Klux Klan, Earth...based and left wing and right wing groups such as the Covenant Sword and the Arm of the Lord, Ku Klux Klan, Black Panther Party, and the Weather...TERMS Watch list, domestic terrorism, validation, designation, domestic terrorism organization, material support, domestic surveillance, SHAC, animal

Mistrz i miasto Mirona Pietrowskiego w ujęciu postkolonialnym

OpenAIRE

Korcz, Karolina

2008-01-01

Recenzja książki: M. Pietrowski, Mistrz i Miasto. Kijowskie konteksty Michaiła Bułhakowa. Tłum. I. Kuźmina, A. Jezierska. Wydawnictwo „Bonami”, Poznań 2004, ss. 319. Review of book: Miron Pietrowski, Mistrz i Miasto. Kijowskie konteksty Michaiła Bułhakowa. Tłum. I. Kuźmina, A. Jezierska. Wydawnictwo „Bonami”, Poznań 2004, pp. 319.

20. X avati arhitektuuri- ja disainigaleriis...

Index Scriptorium Estoniae

2004-01-01

Väljapanek "Vaateaken Eesti ekspositsioonile Veneetsia arhitektuuribiennaalil". Eestit esindab 9. Veneetsia arhitektuuribiennaalil Eesti Arhitektide Liidu projekt "Aeg-maha-arhitektuur", idee autor Kristjan Holm, kaasautorid Liina Jänes ja Pille Epner. Kabli rannast Veneetsiasse teisaldatud puust hobusekujulise välikäimla on loonud Agu Külm ja Jukka-Pekka Jalovaara. Ku-Ku klubis esilinastus Marianne Kõrveri, Rain Tolgi ja Andres Maimiku dokumentaalfilm "Surm Veneetsias"

Divergent frequencies of IGF-I receptor-expressing blood lymphocytes in monozygotic twin pairs discordant for Graves' disease: evidence for a phenotypic signature ascribable to nongenetic factors

DEFF Research Database (Denmark)

Douglas, Raymond S; Brix, Thomas H; Hwang, Catherine J

2009-01-01

CONTEXT: Graves' disease (GD) is an autoimmune process of the thyroid and orbital connective tissues. The fraction of T and B cells expressing IGF-I receptor (IGF-IR) is increased in GD. It is a potentially important autoantigen in GD. Susceptibility to GD arises from both genetic and acquired...

Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

Science.gov (United States)

Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

2014-05-13

Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Clusterin: an IR-inducible protein determining life and death

Energy Technology Data Exchange (ETDEWEB)

DAVID A. BOOTHMAN, Ph.D.

2006-07-11

The roles of ionizing radiation (IR)-inducible genes/proteins are now being elucidated and the research team will focus on the functions of the clusterin (CLU) proteins after low dose IR exposures. With funding from the DOE, we discovered that x-ray-inducible transcript/protein #8 (xip8) bound to the Ku70 DNA double strand break repair protein using various molecular biology techniques. We showed that translation of the CLU/xip8 transcript was complicated, leading to two classes of proteins separated by their intracellular processing. One set of CLU proteins (a secreted and precursor protein, sCLU and psCLU, respectively) were induced by very low doses of IR (>2.0 cGy) and subsequently secreted from the cell. The functions of sCLU, particularly in bystander effects, are not known; sCLU does not bind Ku70, but can interact with the TGF-ß II receptor. Another intracellular class of CLU proteins was targeted to the cytoplasm and existed in a dormant precursor nuclear form (pnCLU). After higher IR doses (>1.0 Gy), pnCLU was activated via post-translational modification, and translocated to the nucleus, where nuclear CLU (nCLU) interacted with Ku70/Ku80, and signaled cell death. The mechanism(s) of how cells die following nCLU accumulation are unknown. Recent data from our lab indicate that CLU gene transcription is also complicated. Thus far, the data suggest that: (a) p53 is a negative regulator of CLU transcription, however, the mechanisms by which it exerts this negative pressure are not known; and (b) IR induces transcription of the CLU promoter, independent of p53, at regulatory elements that lie between -1403 and -325 bps 5'-from the TATAA box. In this renewal, the research team will investigate three separate, but interrelated hypotheses: (1) p53 negatively regulates the CLU promoter via distinct head to tail p53 half sites, and induction is mediated by the combination of retinoblatoma control elements (RCEs) and NF-∫B sites; (2) sCLU is cytoprotective

Clusterin: an IR-inducible protein determining life and death

International Nuclear Information System (INIS)

DAVID A. BOOTHMAN

2006-01-01

The roles of ionizing radiation (IR)-inducible genes/proteins are now being elucidated and the research team will focus on the functions of the clusterin (CLU) proteins after low dose IR exposures. With funding from the DOE, we discovered that x-ray-inducible transcript/protein No.8 (xip8) bound to the Ku70 DNA double strand break repair protein using various molecular biology techniques. We showed that translation of the CLU/xip8 transcript was complicated, leading to two classes of proteins separated by their intracellular processing. One set of CLU proteins (a secreted and precursor protein, sCLU and psCLU, respectively) were induced by very low doses of IR (>2.0 cGy) and subsequently secreted from the cell. The functions of sCLU, particularly in bystander effects, are not known; sCLU does not bind Ku70, but can interact with the TGF-? II receptor. Another intracellular class of CLU proteins was targeted to the cytoplasm and existed in a dormant precursor nuclear form (pnCLU). After higher IR doses (>1.0 Gy), pnCLU was activated via post-translational modification, and translocated to the nucleus, where nuclear CLU (nCLU) interacted with Ku70/Ku80, and signaled cell death. The mechanism(s) of how cells die following nCLU accumulation are unknown. Recent data from our lab indicate that CLU gene transcription is also complicated. Thus far, the data suggest that: (a) p53 is a negative regulator of CLU transcription, however, the mechanisms by which it exerts this negative pressure are not known; and (b) IR induces transcription of the CLU promoter, independent of p53, at regulatory elements that lie between -1403 and -325 bps 5'-from the TATAA box. In this renewal, the research team will investigate three separate, but interrelated hypotheses: (1) p53 negatively regulates the CLU promoter via distinct head to tail p53 half sites, and induction is mediated by the combination of retinoblatoma control elements (RCEs) and NF-?B sites; (2) sCLU is cytoprotective and

Expression of Toll-like receptors and their detection of nuclear self-antigen leading to immune activation in JSLE.

Science.gov (United States)

Midgley, Angela; Thorbinson, Colin; Beresford, Michael W

2012-05-01

Toll-like receptors (TLRs) essential in the functioning of the immune system have been implicated in the development of autoimmunity. TLR3, 7, 8 and 9 are capable of recognizing nucleic autoantigens typical of SLE. Their expression correlates positively with disease activity in adult-onset SLE. This study aimed to determine the role of TLRs in JSLE and whether apoptotic neutrophils are a source of nuclear autoantigen being detected through TLR3, 7, 8 and 9, leading to an inflammatory response. TLR3, 7, 8 and 9 mRNA and protein expression were measured in peripheral blood mononuclear cells (PBMCs) in JSLE patients compared with JIA and non-inflammatory controls. Activation of the TLRs by JSLE serum-induced apoptotic neutrophils was detected by measuring IFN-α mRNA and protein expression, and confirmed using myeloid differentiation factor 88 (MyD88) and TIR domain-containing adapter-inducing IFN-β (TRIF) inhibitors. JSLE patients have increased TLR3, 8 and 9 mRNA and protein expression compared with controls (P < 0.05). Incubation of PBMCs with apoptotic neutrophils demonstrated a dose-response relationship for IFN-α mRNA expression. Inhibition of TLR signalling by blocking MyD88 and TRIF signalling decreased IFN-α mRNA expression in PBMCs incubated with apoptotic neutrophils (P < 0.05). This study demonstrated significantly increased TLR expression in JSLE compared with controls. Our data indicate that apoptotic neutrophils trigger TLR activation through their presentation of autoantigens. The role of TLRs in this inflammatory response was demonstrated by a dose-response relationship to apoptotic neutrophil concentration and confirmed by a decrease in IFN-α production after inhibition of TLR signalling.

Artvin yöresinin iklim, toprak yapısı, orman alanları, ağaç serveti ve ormancılık çalışmalarıyla ilgili genel bir değerlendirme

OpenAIRE

Yüksek, Turan; Ölmez, Zafer

2002-01-01

Çalışma konusu olan Artvin, Kuzeydoğu Karadeniz Bölgesinde yer almaktadır. Artvin ormanları ılıman iklim kuşağından, sert-karasal iklim kuşağına kadar farklı kuşaklarda yayılış göstermektedir. Artvin yöresi 390471 hektar orman alanına sahiptir. Orman alanlarının 276883 hektarı (%70.91’i) doğal ormanlar, 113588 hektarı (% 29.09’u) baltalık ormanlardan oluşmaktadır. Toplam arazinin % 54.77’si ormanlarla kaplıdır. Artvin Orman Bölge Müdürlüğü ormanları, Picea ssp., Pinus ssp., Abies ...

Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is stimulated by ATM inhibition

International Nuclear Information System (INIS)

Toulany, Mahmoud; Mihatsch, Julia; Holler, Marina; Chaachouay, Hassan; Rodemann, H. Peter

2014-01-01

Background and purpose: Cisplatin activates ataxia-telangiectasia-mutated (ATM), a protein with roles in DNA repair, cell cycle progression and autophagy. We investigated the radiosensitizing effect of cisplatin with respect to its effect on ATM pathway activation. Material and methods: Non-small cell lung cancer cells (NSCLC) cell lines (A549, H460) and human fibroblast (ATM-deficient AT5, ATM-proficient 1BR3) cells were used. The effects of cisplatin combined with irradiation on ATM pathway activity, clonogenicity, DNA double-strand break (DNA-DSB) repair and cell cycle progression were analyzed with Western blotting, colony formation and γ-H2AX foci assays as well as FACS analysis, respectively. Results: Cisplatin radiosensitized H460 cells, but not A549 cells. Radiosensitization of H460 cells was not due to impaired DNA-DSB repair, increased apoptosis or cell cycle dysregulation. The lack of radiosensitization demonstrated for A549 cells was associated with cisplatin-mediated stimulation of ATM (S1981) and AMPKα (T172) phosphorylation and autophagy. However, in both cell lines inhibition of ATM and autophagy by KU-55933 and chloroquine diphosphate (CQ) respectively resulted in a significant radiosensitization. Combined treatment with the AMPK inhibitor compound-C led to radiosensitization of A549 but not of H460 cells. As compared to the treatment with KU-55933 alone, radiosensitivity of A549 cells was markedly stimulated by the combination of KU-55933 and cisplatin. However, the combination of CQ and cisplatin did not modulate the pattern of radiation sensitivity of A549 or H460 cells. In accordance with the results that cisplatin via stimulation of ATM activity can abrogate its radiosensitizing effect, ATM deficient cells were significantly sensitized to ionizing radiation by cisplatin. Conclusion: The results obtained indicate that ATM targeting can potentiate cisplatin-induced radiosensitization

Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase

DEFF Research Database (Denmark)

Maurer, Marcus; Altrichter, Sabine; Bieber, Thomas

2011-01-01

BACKGROUND: A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate whether such patients with CU with IgE against TPO benefit from treatment with omalizumab......, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. OBJECTIVES: We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. METHODS: In this multicenter, randomized, double-blind, placebo......-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table...

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

DEFF Research Database (Denmark)

Iversen, Rasmus; Mysling, Simon; Hnida, Kathrin

2014-01-01

The multifunctional enzyme transglutaminase 2 (TG2) is the target of autoantibodies in the gluten-sensitive enteropathy celiac disease. In addition, the enzyme is responsible for deamidation of gluten peptides, which are subsequently targeted by T cells. To understand the regulation of TG2 activity...... and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca(2+) binding, which is necessary for TG2 activity, induces structural changes in the catalytic core...... domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed...