RISS 학술연구정보서비스

검색
다국어 입력

http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.

변환된 중국어를 복사하여 사용하시면 됩니다.

예시)
  • 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
  • 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
닫기
    인기검색어 순위 펼치기

    RISS 인기검색어

      검색결과 좁혀 보기

      선택해제

      오늘 본 자료

      • 오늘 본 자료가 없습니다.
      더보기
      • 무료
      • 기관 내 무료
      • 유료
      • KCI등재

        A brain somatic RHEB doublet mutation causes focal cortical dysplasia type II

        Shanshan Zhao,Zhenghui Li,Muxian Zhang,Lingliang Zhang,Honghua Zheng,Jinhuan Ning,Yanyan Wang,Feng-Peng Wang,Xiaobin Zhang,Hexia Gan,Yuanqing Wang,Xian Zhang,Hong Luo,Guojun Bu,Huaxi Xu,Yi Yao,Yun-wu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

        Focal cortical dysplasia type II (FCDII) is a cerebral cortex malformation characterized by local cortical structure disorganization, neuronal dysmorphology, and refractory epilepsy. Brain somatic mutations in several genes involved in the PI3K/AKT/mTOR pathway are associated with FCDII, but they are only found in a proportion of patients with FCDII. The genetic causes underlying the development FCDII in other patients remain unclear. Here, we carried out whole exome sequencing and targeted sequencing in paired brain–blood DNA from patients with FCDII and identified a brain somatic doublet mutation c.(A104T, C105A) in the Ras homolog, mTORC1 binding (RHEB) gene, which led to the RHEB p.Y35L mutation in one patient with FCDII. This RHEB mutation carrier had a dramatic increase of ribosomal protein S6 phosphorylation, indicating mTOR activation in the region of the brain lesion. The RHEB p.Y35L mutant protein had increased GTPλS-binding activity compared with wild-type RHEB. Overexpression of the RHEB p. Y35L variant in cultured cells also resulted in elevated S6 phosphorylation compared to wild-type RHEB. Importantly, in utero electroporation of the RHEB p.Y35L variant in mice induced S6 phosphorylation, cytomegalic neurons, dysregulated neuron migration, abnormal electroencephalogram, and seizures, all of which are found in patients with FCDII. Rapamycin treatment rescued abnormal electroencephalograms and alleviated seizures in these mice. These results demonstrate that brain somatic mutations in RHEB are also responsible for the pathogenesis of FCDII, indicating that aberrant activation of mTOR signaling is a primary driver and potential drug target for FCDII.

      • KCI등재

        Intracellular trafficking of TREM2 is regulated by presenilin 1

        Yingjun Zhao,Xiaoguang Li,Timothy Huang,Lu-lin Jiang,Zhenqiu Tan,Muxian Zhang,Irene Han-Juo Cheng,Xin Wang,Guojun Bu,Yun-wu Zhang,Qi Wang,Huaxi Xu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

        Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.

      • KCI등재

        Identification of a Lead small-molecule inhibitor of anthrax Lethal toxin by using fluorescence-based high-throughput screening

        ( Dong Wei ),( Zhao Yun Bu ),( Ai Lian Yu ),( Feng Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.12

        Inhalational anthrax is caused by B. anthracis, a virulent spore- forming bacterium which secretes anthrax toxins consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease and is the main determinant in the pathogenesis of anthrax. Here we report the identification of a lead small-molecule inhibitor of anthrax lethal factor by screening an available synthetic small-molecule inhibitor library using fluorescence-based high-throughput screening (HTS) approach. Seven small molecules were found to have inhibitory effect against LF activity, among which SM157 had the highest inhibitory activity. All theses small molecule inhibitors inhibited LF in a noncompetitive inhibition mode. SM157 and SM167 are from the same family, both having an identical group complex, which is predicted to insert into S1` pocket of LF. More potent small-molecule inhibitors could be developed by modifying SM157 based on this identical group complex. [BMB reports 2011; 44(12): 811-815]

      • KCI등재

        Molecular identification and expression patterns of carboxylesterase genes based on transcriptome analysis of the common cutworm, Spodoptera litura (Lepidoptera: Noctuidae)

        Ya Nan Zhang,Jin-Bu Li,Peng He,Liang Sun,Zhao-Qun Li,Li-Ping Fang,Zhan-Feng Ye,Dao-Gui Deng,Xiu-Yun Zhu 한국응용곤충학회 2016 Journal of Asia-Pacific Entomology Vol.19 No.4

        Carboxylesterases (CXEs) belong to a family of metabolic enzymes that are widely distributed in insects and other organisms and can rapidly degrade the components of sex pheromones and plant volatiles with an acetate functional group. The common cutworm, Spodoptera litura, is an important agricultural pest around the world, causing vast economic losses every year. The female sex pheromones of S. litura comprise four acetates, Z9, E11-14:OAc; Z9, E12-14:OAc; Z9-14:OAc; and E11-14:OAc, but the degradation mechanisms of these components are not well understood. By analysing previously obtained transcriptomic data of the sex pheromone glands,we identified a total of 24 putative CXE genes in S. litura. Gene expression patterns and phylogenetic analysis revealed 5 genes with antennae-specific or biased expression, and clusteredwith genes showed involvement in the degradation of sex pheromones or other detoxification in other insects. SlitCXE10was expressed specifically in the antennae of both sexes, and SlitCXE14, 17, 19, and 21 had high antenna biased expression. Interestingly, RT-PCR and qPCR tests indicated that SlitCXE24 had significantly higher expression in PG than in other tissue, and that it could be a potential candidate gene for sex pheromone degradation in PG. This study is the first to provide solid background information for the further elucidation of sex pheromone degradation, and ultimately provides potential targets for the disruption of sexual communication in S. litura for new pest management.

      • KCI등재

        Molecular identification and sex distribution of two chemosensory receptor families in Athetis lepigone by antennal transcriptome analysis

        Ya-Nan Zhang,Ji-FangMa,Liang Sun,Zhi-PingDong,Zhao-Qun Li,Xiu-Yun Zhu,YiWang,LuWang,Dao-Gui Deng,Jin-Bu Li 한국응용곤충학회 2016 Journal of Asia-Pacific Entomology Vol.19 No.3

        Chemosensory receptors play central roles in insect behavior and can potentially be used as new targets for pest control. Athetis lepigoneMöschler (Lepidoptera: Noctuidae) is a polyphagous insect pest found in many countries in Europe and Asia. However, systemic identification of the chemosensory receptors in the antennae has not been reported. In the present study, we obtained the antennal transcriptome of A. lepigone using Illumina sequencing technology and identified 80 candidate chemosensory receptors, including 61 transcripts encoding for odorant receptors (ORs) and 19 for ionotropic receptors (IRs). This result is similar to that reported for other lepidopteran species, suggesting that our approach successfully identified ORs and IRs of A. lepigone. RT-PCR was used to determine the sex distribution patterns of all OR and IR genes. Some OR and IR genes showed male- or femalespecific/ predominant expression. Our results help understand the functions of chemosensory receptor genes in A. lepigone as well as other insects, and suggest that these genes could be potential targets for developing environment-friendly behavioral antagonists and pesticides against A. lepigone.

      연관 검색어 추천

      이 검색어로 많이 본 자료

      활용도 높은 자료

      해외이동버튼