RESUMO
Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice. B6 mice that are homozygous for 1a are highly susceptible to MHV-A59 infection, with a 50% lethal dose (LD(50)) of 10(2.5) PFU, while chimeric cB61ba mice and SJL mice homozygous for 1ba and 1b, respectively, survived following inoculation with 10(5) PFU. Unexpectedly, cB61ba mice were more resistant to MHV-A59 infection than SJL mice as measured by virus replication in target organs, including liver and brain. No infectious virus or viral RNA was detected in the organs of cB61ba mice, while viral RNA and infectious virus were detected in target organs of SJL mice. Furthermore, SJL mice produced antiviral antibodies after MHV-A59 inoculation with 10(5) PFU, but cB61ba mice did not. Thus, cB61ba mice are apparently completely resistant to MHV-A59 infection, while SJL mice permit low levels of MHV-A59 virus replication during self-limited, asymptomatic infection. When expressed on cultured BHK cells, the mCEACAM1b and mCEACAM1ba proteins had similar levels of MHV-A59 receptor activity. These results strongly support the hypothesis that although alleles of mCEACAM1 are the principal determinants of mouse susceptibility to MHV-A59, other as-yet-unidentified murine genes may also play a role in susceptibility to MHV.
Assuntos
Antígeno Carcinoembrionário/metabolismo , Glicoproteínas/metabolismo , Imunidade Inata , Vírus da Hepatite Murina/patogenicidade , Internalização do Vírus , Alelos , Animais , Antígeno Carcinoembrionário/genética , Moléculas de Adesão Celular , Glicoproteínas/genética , Homozigoto , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análise de SobrevidaRESUMO
BACKGROUND/AIM: Aldehyde dehydrogenase 1 (ALDH1) is known as a breast cancer stem cell (CSC) marker. This study aimed to identify genes associated with ALDH1. MATERIALS AND METHODS: ALDH1-positive and -negative breast cancer cells were isolated using laser capture microdissection from five tissue samples of ALDH1-positive breast cancer patients. Messenger RNA expression levels were compared between ALDH1-positive and -negative cells. RESULTS: We found 104 differentially expressed genes between ALDH1-positive and -negative cells. Gene ontology and pathway analysis revealed that these genes were correlated with CSC functions and pathways. Network analyses identified 10 genes that were closely associated with ALDH1. We validated these 10 genes utilizing The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium cohort, and found that they were associated with ALDH1 expression and correlated with Wnt pathway signaling. CONCLUSION: The 10 genes we identified could be potential targets for CSC therapy of breast cancer.
Assuntos
Aldeído Desidrogenase/metabolismo , Redes Reguladoras de Genes , Genes Neoplásicos , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/genética , Estudos de Coortes , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima/genéticaRESUMO
The 3' end region nucleotide sequence, including ORF7, of nine Japanese and two U.S.A. isolates of transmissible gastroenteritis virus (TGEV) were determined and compared. Nine Japanese TGEV strains have been isolated over the past 40 years (1956-1997). From the comparison of determined nucleotide sequences, we could divide the TGEV Japanese isolates into two groups and distinguish them from TGEV U.S.A. isolates.
Assuntos
Fases de Leitura Aberta/genética , Vírus da Gastroenterite Transmissível/genética , Animais , Sequência de Bases , Eletroforese em Gel de Ágar/veterinária , Japão , Dados de Sequência Molecular , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Homologia de Sequência do Ácido Nucleico , Suínos , Vírus da Gastroenterite Transmissível/isolamento & purificação , Estados UnidosRESUMO
A wide variety of 3-iodobenzo[b]furans were readily prepared by iodocyclization of 2-alkynyl-1-(1-ethoxyethoxy)benzenes with the I(coll)2PF6-BF3 x OEt2 combination. Aryl-, vinylic-, and alkyl-substituted alkynes undergo iodocyclization in good to excellent yields. The mechanism of the reaction is also discussed.