ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-08-13
    Description: Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748827/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748827/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Itoh, Yasushi -- Shinya, Kyoko -- Kiso, Maki -- Watanabe, Tokiko -- Sakoda, Yoshihiro -- Hatta, Masato -- Muramoto, Yukiko -- Tamura, Daisuke -- Sakai-Tagawa, Yuko -- Noda, Takeshi -- Sakabe, Saori -- Imai, Masaki -- Hatta, Yasuko -- Watanabe, Shinji -- Li, Chengjun -- Yamada, Shinya -- Fujii, Ken -- Murakami, Shin -- Imai, Hirotaka -- Kakugawa, Satoshi -- Ito, Mutsumi -- Takano, Ryo -- Iwatsuki-Horimoto, Kiyoko -- Shimojima, Masayuki -- Horimoto, Taisuke -- Goto, Hideo -- Takahashi, Kei -- Makino, Akiko -- Ishigaki, Hirohito -- Nakayama, Misako -- Okamatsu, Masatoshi -- Takahashi, Kazuo -- Warshauer, David -- Shult, Peter A -- Saito, Reiko -- Suzuki, Hiroshi -- Furuta, Yousuke -- Yamashita, Makoto -- Mitamura, Keiko -- Nakano, Kunio -- Nakamura, Morio -- Brockman-Schneider, Rebecca -- Mitamura, Hiroshi -- Yamazaki, Masahiko -- Sugaya, Norio -- Suresh, M -- Ozawa, Makoto -- Neumann, Gabriele -- Gern, James -- Kida, Hiroshi -- Ogasawara, Kazumasa -- Kawaoka, Yoshihiro -- HHNSN266200700010C/NS/NINDS NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- HHSN272200800060C/AI/NIAID NIH HHS/ -- R01 AI069274/AI/NIAID NIH HHS/ -- R01 AI069274-04/AI/NIAID NIH HHS/ -- U19 AI070503/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1021-5. doi: 10.1038/nature08260.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga 520-2192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19672242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/immunology ; Antiviral Agents/pharmacology ; Cell Line ; Dogs ; Female ; Ferrets/virology ; HN Protein/metabolism ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/pathogenicity/*physiology ; Lung/immunology/pathology/virology ; Macaca fascicularis/immunology/virology ; Male ; Mice ; Mice, Inbred BALB C ; Neutralization Tests ; Orthomyxoviridae Infections/immunology/transmission/virology ; Primate Diseases/pathology/virology ; Swine/*virology ; Swine Diseases/pathology/virology ; Swine, Miniature/virology ; Virus Replication
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Characterization of H7N9 influenza A viruses isolated from humans (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-07-12
    Description: Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission, and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891892/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watanabe, Tokiko -- Kiso, Maki -- Fukuyama, Satoshi -- Nakajima, Noriko -- Imai, Masaki -- Yamada, Shinya -- Murakami, Shin -- Yamayoshi, Seiya -- Iwatsuki-Horimoto, Kiyoko -- Sakoda, Yoshihiro -- Takashita, Emi -- McBride, Ryan -- Noda, Takeshi -- Hatta, Masato -- Imai, Hirotaka -- Zhao, Dongming -- Kishida, Noriko -- Shirakura, Masayuki -- de Vries, Robert P -- Shichinohe, Shintaro -- Okamatsu, Masatoshi -- Tamura, Tomokazu -- Tomita, Yuriko -- Fujimoto, Naomi -- Goto, Kazue -- Katsura, Hiroaki -- Kawakami, Eiryo -- Ishikawa, Izumi -- Watanabe, Shinji -- Ito, Mutsumi -- Sakai-Tagawa, Yuko -- Sugita, Yukihiko -- Uraki, Ryuta -- Yamaji, Reina -- Eisfeld, Amie J -- Zhong, Gongxun -- Fan, Shufang -- Ping, Jihui -- Maher, Eileen A -- Hanson, Anthony -- Uchida, Yuko -- Saito, Takehiko -- Ozawa, Makoto -- Neumann, Gabriele -- Kida, Hiroshi -- Odagiri, Takato -- Paulson, James C -- Hasegawa, Hideki -- Tashiro, Masato -- Kawaoka, Yoshihiro -- AI058113/AI/NIAID NIH HHS/ -- AI099274/AI/NIAID NIH HHS/ -- HHSN266200700010C/AI/NIAID NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- T32 AI078985/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Sep 26;501(7468):551-5. doi: 10.1038/nature12392. Epub 2013 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23842494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/pharmacology ; Cells, Cultured ; Chickens/virology ; DNA-Directed RNA Polymerases/antagonists & inhibitors ; Dogs ; Enzyme Inhibitors/pharmacology ; Female ; Ferrets/virology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology ; *Influenza A virus/chemistry/drug effects/isolation & purification/pathogenicity ; Influenza, Human/drug therapy/*virology ; Macaca fascicularis/virology ; Madin Darby Canine Kidney Cells ; Male ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Monkey Diseases/pathology/virology ; Neuraminidase/antagonists & inhibitors ; Orthomyxoviridae Infections/pathology/transmission/*virology ; Quail/virology ; Swine/virology ; Swine, Miniature/virology ; *Virus Replication/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-06-23
    Description: Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388103/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388103/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imai, Masaki -- Watanabe, Tokiko -- Hatta, Masato -- Das, Subash C -- Ozawa, Makoto -- Shinya, Kyoko -- Zhong, Gongxun -- Hanson, Anthony -- Katsura, Hiroaki -- Watanabe, Shinji -- Li, Chengjun -- Kawakami, Eiryo -- Yamada, Shinya -- Kiso, Maki -- Suzuki, Yasuo -- Maher, Eileen A -- Neumann, Gabriele -- Kawaoka, Yoshihiro -- R01 AI069274/AI/NIAID NIH HHS/ -- R01 AI069274-05/AI/NIAID NIH HHS/ -- England -- Nature. 2012 May 2;486(7403):420-8. doi: 10.1038/nature10831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722205" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Animals ; Bioterrorism/prevention & control ; Birds/virology ; Body Fluids/virology ; Cell Line ; Dogs ; Evolution, Molecular ; Female ; Ferrets/*virology ; HEK293 Cells ; HeLa Cells ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/metabolism ; Hot Temperature ; Humans ; Influenza A Virus, H1N1 Subtype/genetics/pathogenicity/physiology ; Influenza A Virus, H5N1 Subtype/genetics/*pathogenicity/physiology ; Influenza in Birds/transmission/virology ; Influenza, Human/prevention & control/transmission/virology ; Molecular Epidemiology/methods ; Orthomyxoviridae Infections/*transmission/*virology ; Pandemics ; Population Surveillance/methods ; Protein Stability ; Reassortant Viruses/genetics/isolation & purification/*pathogenicity/physiology ; Receptors, Virus/chemistry/metabolism ; Respiratory System/anatomy & histology/*virology ; Security Measures ; Zoonoses/transmission/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...