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      • KCI등재

        Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients

        Ling Deng,Xuehua Zhu,Yun Sun,Jiemin Wang,Xiaorong Zhong,Jiayuan Li,Min Hu,Hong Zheng 대한암학회 2019 Cancer Research and Treatment Vol.51 No.1

        Purpose The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. Materials and Methods Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CAwere detected in freshfrozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. Results The AKT1mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2 status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2, Ki67 high), particularly with respect to overall survival. Conclusion A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.

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        The influence of endogenous cathepsin in different subcellular fractions on the quality deterioration of Northern pike (Esox lucius) fillets during refrigeration and partial freezing storage

        Hengheng Qiu,Xin Guo,Xiaorong Deng,Xiaobing Guo,Xiaoying Mao,Chengjian Xu,Jian Zhang 한국식품과학회 2020 Food Science and Biotechnology Vol.29 No.10

        The purpose of this study was to investigate theendogenous cathepsin activity in each subcellular fractionand the effect of this activity on myofibrillar protein andtexture during refrigeration and partial freezing storage ofnorthern pike (Esox lucius) fillets. The results showed thatfillets stored under the refrigerated condition were moresusceptible to oxidation than partial freezing. Endogenouscathepsin activity indicated that partial freezing destroysthe integrity of lysosomes more effectively than refrigerationand inhibits the increase in cathepsin B and B ? L inlysosomes. The activity of cathepsin B and B ? L inlysosomes, mitochondria and myofibrils under the partialfreezing conditions was always lower than that underrefrigeration. Texture analysis showed that refrigerationhad a negative impact on hardness and springiness. Inconclusion, the cathepsin activity in each subcellularfraction was effectively inhibited and better textural characteristicswere obtained with partial freezing thanrefrigeration.

      • <i>Arabidopsis</i> DET1 degrades HFR1 but stabilizes PIF1 to precisely regulate seed germination

        Shi, Hui,Wang, Xin,Mo, Xiaorong,Tang, Chao,Zhong, Shangwei,Deng, Xing Wang National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.12

        <P><B>Significance</B></P><P>How organisms respond to environment changes is a fundamental and intriguing question in biology. Light is the energy resource and a crucial environmental cue for plant major developmental switches, such as seed germination. Studying the underlying mechanism is important for us to understand the basic principles of plant development and improve crop productions. Here we identify DET1 as a novel central repressor of seed germination. We further reveal that seeds use a multilevel regulatory circuit of triple feed-forward loops to sensitively and precisely mediate light-regulated germination. This study provides a comprehensive framework of how light regulates seed germination.</P><P>Seed is an essential propagation organ and a critical strategy adopted by terrestrial flowering plants to colonize the land. The ability of seeds to accurately respond to light is vital for plant survival. However, the underlying mechanism is largely unknown. In this study, we reveal a circuit of triple feed-forward loops adopted by <I>Arabidopsis</I> seeds to exclusively repress germination in dark conditions and precisely initiate germination under diverse light conditions. We identify that de-etiolated 1 (DET1), an evolutionarily conserved protein, is a central repressor of light-induced seed germination. Genetic analysis demonstrates that DET1 functions upstream of long hypocotyl in far-red 1 (HFR1) and phytochrome interacting factor 1 (PIF1), the key positive and negative transcription regulators in seed germination. We further find that DET1 and constitutive photomorphogenic 10 (COP10) target HFR1 for protein degradation by assembling a COP10–DET1–damaged DNA binding protein 1–cullin4 E3 ligase complex. Moreover, DET1 and COP10 directly interact with and promote the protein stability of PIF1. Computational modeling reveals that phytochrome B (phyB)–DET1–HFR1–PIF1 and phyB–DET1–Protease–PIF1 are new signaling pathways, independent of the previously identified phyB-PIF1 pathway, respectively mediating the rapid and time-lapse responses to light irradiation. The model-simulated results are highly consistent with their experimental validations, suggesting that our mathematical model captures the essence of <I>Arabidopsis</I> seed germination networks. Taken together, this study provides a comprehensive molecular framework for light-regulated seed germination, improving our understanding of how plants respond to changeable environments.</P>

      • HFR1 Sequesters PIF1 to Govern the Transcriptional Network Underlying Light-Initiated Seed Germination in <i>Arabidopsis</i>

        Shi, Hui,Zhong, Shangwei,Mo, Xiaorong,Liu, Na,Nezames, Cynthia D.,Deng, Xing Wang American Society of Plant Biologists 2013 The Plant cell Vol.25 No.10

        <P>This study identifies the LONG HYPOCOTYL IN FAR-RED1 (HFR1)– PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) pair as the central transcriptional regulatory module for rapid light-initiated transcriptome changes in imbibed seeds. HFR1 interacts with PIF1 to prevent PIF1 from binding to DNA, promoting light-initiated germination. The functionally antagonistic HFR1–PIF1 pair constructs a fail-safe mechanism for fine-tuning seed germination under low-level illumination.</P>

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