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      • Identification of novel genes associated with HIV-1 latency by analysis of histone modifications

        Kim, Kyung-Chang,Lee, Sunyoung,Son, Junseock,Shin, Younghyun,Yoon, Cheol-Hee,Kang, Chun,Choi, Byeong-Sun HENRY STEWART PUBLICATIONS 2017 HUMAN GENOMICS Vol.11 No.1

        <P><B>Background</B></P><P>A reservoir of HIV-1 is a major obstacle in eliminating HIV-1 in patients because it can reactivate in stopping antiretroviral therapy (ART). Histone modifications, such as acetylation and methylation, play a critical role in the organization of chromatin domains and the up- or downregulation of gene expression. Although many studies have reported that an epigenetic mechanism is strongly involved in the maintenance of HIV-1 transcriptional latency, neither the epigenetic control of viral replication nor how HIV-1 latency is maintained is not fully understood.</P><P><B>Results</B></P><P>We re-analyzed a high throughput parallel DNA sequencing (ChIP-seq) data from previous work to investigate the effect of histone modifications, H3K4me3 and H3K9ac, on HIV-1 latency in terms of chromosome distribution. The outputs of ChIP-seq from uninfected CD4+ T cell lines and HIV-1 latently infected cells were aligned to hg18 using bowtie and then analyzed using various software packages. Certain chromosomes (16, 17, 19, and 22) were significantly enriched for histone modifications in both decreased and increased islands. In the same chromosomes in HIV-1 latently infected cells, 38 decreased and 41 increased islands from common islands of H3K4me3 and H3K9ac were selected for functional annotation. In Gene Ontology analysis, the 38 genes associated with decreased islands were involved in the regulation of biological process, regulation of cellular process, biological regulation, and purinergic receptor signaling pathway, while the 41 genes associated with increased islands were involved in nucleic acid binding, calcium-activated cation channel activity, DNA binding, and zinc ion binding. In Pathway Commons analysis, the 38 genes were strongly involved in the p63 transcription factor network, while the 41 genes were involved in the RNA polymerase III transcription termination pathway. Several genes such as Nuclear factor I X (<I>NFIX</I>) and TNF receptor association factor 4 (<I>TRAF4</I>) were selected as candidate genes for HIV latency. Especially, <I>NFIX</I> was highly expressed in HIV-1 latently infected cell lines and showed a dramatic reduction in expression after phorbol-13-myristate-12-acetate (PMA) treatment.</P><P><B>Conclusions</B></P><P>These results show that the unique enrichment of histone modifications and its linked genes in specific chromosomes might play a critical role in the establishment and maintenance of HIV-1 latency.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s40246-017-0105-7) contains supplementary material, which is available to authorized users.</P>

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        Detection and Isolation of SARS-CoV-2 in Serum, Urine, and Stool Specimens of COVID-19 Patients from the Republic of Korea

        Kim Jeong-Min,Kim Heui Man,Lee Eun Jung,Jo Hye Jun,Yoon Youngsil,Lee Nam-Joo,Son Junseock,Lee Ye-Ji,Kim Mi Seon,Lee Yong-Pyo,Chae Su-Jin,Park Kye Ryeong,Cho Seung-Rye,Park Sehee,Kim Su Jin,Wang Eunbye 질병관리본부 2020 Osong Public Health and Research Persptectives Vol.11 No.3

        Objectives Coronavirus Disease-19 (COVID-19) is a respiratory infection characterized by the main symptoms of pneumonia and fever. It is caused by the novel coronavirus severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), which is known to spread via respiratory droplets. We aimed to determine the rate and likelihood of SARS-CoV-2 transmission from COVID-19 patients through non-respiratory routes. Methods Serum, urine, and stool samples were collected from 74 hospitalized patients diagnosed with COVID-19 based on the detection of SARS-CoV-2 in respiratory samples. The SARS-CoV-2 RNA genome was extracted from each specimen and real-time reverse transcription polymerase chain reaction performed. CaCo-2 cells were inoculated with the specimens containing the SARS-COV-2 genome, and subcultured for virus isolation. After culturing, viral replication in the cell supernatant was assessed. Results Of the samples collected from 74 COVID-19 patients, SARS-CoV-2 was detected in 15 serum, urine, or stool samples. The virus detection rate in the serum, urine, and stool samples were 2.8% (9/323), 0.8% (2/247), and 10.1% (13/129), and the mean viral load was 1,210 ± 1,861, 79 ± 30, and 3,176 ± 7,208 copy/µL, respectively. However, the SARS-CoV-2 was not isolated by the culture method from the samples that tested positive for the SARS-CoV-2 gene. Conclusion While the virus remained detectable in the respiratory samples of COVID-19 patients for several days after hospitalization, its detection in the serum, urine, and stool samples was intermittent. Since the virus could not be isolated from the SARS-COV-2-positive samples, the risk of viral transmission via stool and urine is expected to be low.

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