• 제목/요약/키워드: translational research

검색결과 527건 처리시간 0.027초

Regulation of HIF-1α stability by lysine methylation

  • Baek, Sung Hee;Kim, Keun Il
    • BMB Reports
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    • 제49권5호
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    • pp.245-246
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    • 2016
  • The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1αKA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1αKA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1αKA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.

Structural Analyses of Zinc Finger Domains for Specific Interactions with DNA

  • Eom, Ki Seong;Cheong, Jin Sung;Lee, Seung Jae
    • Journal of Microbiology and Biotechnology
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    • 제26권12호
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    • pp.2019-2029
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    • 2016
  • Zinc finger proteins are among the most extensively applied metalloproteins in the field of biotechnology owing to their unique structural and functional aspects as transcriptional and translational regulators. The classical zinc fingers are the largest family of zinc proteins and they provide critical roles in physiological systems from prokaryotes to eukaryotes. Two cysteine and two histidine residues ($Cys_2His_2$) coordinate to the zinc ion for the structural functions to generate a ${\beta}{\beta}{\alpha}$ fold, and this secondary structure supports specific interactions with their binding partners, including DNA, RNA, lipids, proteins, and small molecules. In this account, the structural similarity and differences of well-known $Cys_2His_2$-type zinc fingers such as zinc interaction factor 268 (ZIF268), transcription factor IIIA (TFIIIA), GAGA, and Ros will be explained. These proteins perform their specific roles in species from archaea to eukaryotes and they show significant structural similarity; however, their aligned amino acids present low sequence homology. These zinc finger proteins have different numbers of domains for their structural roles to maintain biological progress through transcriptional regulations from exogenous stresses. The superimposed structures of these finger domains provide interesting details when these fingers are applied to specific gene binding and editing. The structural information in this study will aid in the selection of unique types of zinc finger applications in vivo and in vitro approaches, because biophysical backgrounds including complex structures and binding affinities aid in the protein design area.

Spot-GTA 용접자세에 따른 304 스테인리스강 용융지 표면 및 용접부 형상 거동 (Behavior of Weld Pool Shape and Weld Surface Deformation as a Function of Spot-GTA Welding Position for 304 Stainless Steel)

  • 강남현;박영도;조경목
    • Journal of Welding and Joining
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    • 제26권2호
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    • pp.62-68
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    • 2008
  • Effects of gravitational orientation on gas tungsten arc welding (GTAW) for 304 stainless steel were studied to determine the critical factors for weld pool formation, such as weld surface deformation and weld pool shape. This study was accomplished through an analytical study of weld pool stability as a function of primary welding parameters (arc current and arc holding time), material properties (surface tension and density), and melting efficiency (cross-sectional area). The stability of weld pool shape and weld surface deformation was confirmed experimentally by changing the welding position. The arc current and translational velocity were the major factors in determining the weld pool stability as a function of the gravitational orientation. A 200A spot GTAW showed a significant variation of the weld pool formation as the arc held longer than 3 seconds, however the weld pool shape and surface morphology for a 165A spot GTAW were 'stable', i.e., constant regardless of the gravitational orientation. The cross-sectional area of the weld (CSA) was one of the critical factors in determining the weld pool stability. The measured CSA ($13.5mm^2$) for the 200A spot GTAW showed a good agreement with the calculated CSA ($14.9mm^2$).

The Use of Electrostatic Repulsion-Hydrophilic Interaction Chromatography (ERLIC) for Proteomics Research

  • Ng, Justin Tze-Yang;Hao, Piliang;Sze, Siu Kwan
    • Mass Spectrometry Letters
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    • 제5권4호
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    • pp.95-103
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    • 2014
  • Characterization and studies of proteome are challenging because biological samples are complex, with a wide dynamic range of abundance. At present the proteins are identified by digestion into peptides, with subsequent identification of the peptides by mass spectrometry (MS). MS is a powerful technique for the purpose, but it cannot identify every peptide in such complex mixtures simultaneously. For accurate analysis and quantification it is important to separate the peptides first by chromatography into fractions of a size that MS can handle. With these less complex fractions, the probability is increased of identifying peptides of low abundance that would otherwise experience ion suppression effects due to the presence of peptides of high abundance. Enrichment for peptides with certain post-translational modifications helps to increase their detection rates as well. Electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) is a mixed-mode chromatographic technique which combines the use of electrostatic repulsion and hydrophilic interaction. This review provides an overview of ERLIC and its various proteomics applications. ERLIC has been demonstrated to have good orthogonality to reverse phase liquid chromatography (RPLC), making it useful as a first dimension in multidimensional liquid chromatography (MDLC) and fractionation of digests in general. Peptides elute in order of their isoelectric points and polarity. ERLIC has also been successfully utilized for the enrichment for phosphopeptides and glycopeptides, facilitating their identification. In addition, it is promising for the study of peptide deamidation. ERLIC performs comparably well or better than established methods for these various applications, and serves as a viable and efficient workflow alternative.

Biosynthesis of a Biological Active Single Chain Equine Chorionic Gonado-tropin

  • Min, Kwan-Sik
    • Journal of Life Science
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    • 제11권2호
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    • pp.103-107
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    • 2001
  • The equine chorionic gonadotropin (eCG) subunits $\alpha$ and ${\beta}$ are transcribed from different genes and associate noncovalently to form the bioactive eCG heterodimer. Dimerization is rate limiting for eCG secretion, and dissociation leads to hormone inactivation. The correct conformation of the heterodimer is alto important for efficient secretion, hormone-specific post-translational modifications, receptor binding and signal transduction. To determine whether ${\alpha}$ and ${\beta}$ subunits can be synthesized as a single polypeptide chain (tethered-eCG) and also display biological activity, the tethered-eCG molecule by fusing the carboxyl terminus of the eCG ${\beta}$-subunit to the amino terminus of the af-subunit was construe-ted and transfected into chinese hamster ovary (CHO-Kl) cells. LH- and FSH-like activities were assayed in terms of testosterone production and aromatase activity in primary cultured rat Leydig cells and granulosa cells, respectively. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG ${\alpha}$/${\beta}$ and native eCG. FSH-like activity of the tethered-eCG was also shown similarly in comparison with the native and wild type eCG ${\alpha}$/${\beta}$. Our data for the first time suggest that the tethered-eCG can be expressed efficiently and the produced product by the CHO-K1 cells is fully LH- and FSH-like activities in rat in vitro bioassay system. Our results also suggest that this molecular can imply particular models of FSH-like activity not LH-like activity in the eCG. Taken together, these data indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion.

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Leiomyosarcoma of the jaw: case series

  • Choi, Yong-Suk;Almansoori, Akram Abdo;Jung, Tae-Young;Lee, Jae-Il;Kim, Soung Min;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제46권4호
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    • pp.275-281
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    • 2020
  • Objectives: Leiomyosarcoma is a malignant neoplasm that affects smooth muscle tissue and it is very rare in the field of oral and maxillofcial surgery. The purpose of this study was to obtain information on diagnosis of and treatment methods for leiomyosarcoma by retrospectively reviewing of the cases. Patients and Methods: The study included nine patients who were diagnosed with leiomyosarcoma in the Department of Oral and Maxillofacial Surgery at Seoul National University Dental Hospital. The subjects were analyzed with respect to sex, age, clinical features, primary site of disease, treatment method, recurrence, and metastasis. Results: Particular clinical features included pain, edema, mouth-opening limitations, dysesthesia, and enlarged lymph nodes. All cases except one were surgically treated, and recurrence was found in two cases. Four of nine patients were followed up without recurrence and one patient underwent additional surgery due to recurrence. Conclusion: In our case series, notable symptoms included pain, edema, mouth-opening limitations, and dysesthesia; however, it was difficult to label these as specific symptoms of leiomyosarcoma. Considering the aggressive characteristics of the disease and poor prognosis, surgical treatment is necessary with careful consideration of postoperative radiotherapy and chemotherapy.

입체영상의 양안 깊이 변화에 따른 시청 피로도 분석 (Visual Discomfort Analysis of Binocular Depth Change on 3D Stereoscopic Imaging)

  • 김남규
    • 디지털콘텐츠학회 논문지
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    • 제16권1호
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    • pp.127-135
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    • 2015
  • 입체영상 디스플레이 제조 및 콘텐츠 저작 소프트웨어 기술의 발달은 3차원 입체영상의 응용 분야를 특수한 가상시뮬레이션의 응용 분야에서 주변에서 흔히 접할 수 있는 영화, 게임, 광고, 전시 등 다양한 분야로 확장시키고 있다. 하지만, 현존하는 양안시차 원리 기반의 입체영상은 시청자에게 피로감을 유발시킨다. 양안시차에 의한 깊이 인지와 피로감 사이의 관계를 도출하기 위해 시청자 실험 기반의 연구가 활발히 진행되고 있으며, 현재 3차원 입체영상 제작 및 시청 가이드라인의 결과물들이 제시되고 있다. 또한, 입체영상 기술은 과다 깊이 제공을 통한 몰입도 증대의 제작자 측면과 허용 범위 내의 최소 피로 추구의 시청자 측면의 상반되는 목적성을 갖고 있다. 본 연구는 3D입체영상 제작 및 가이드라인에 기초가 되는 깊이 변화도 중심의 분석 데이터를 제공한다. 입체영상 제작자 측면에서 활용 가능한 안정적 깊이 변화 구간과 장면 간 깊이 변화의 속도 기준을 도출하였으며, 시청자 측면에서는 뇌파 장치를 활용하여 깊이 변화 적응 시간에 대한 기준 값을 제시하였다.

X-linked Gene Expression Profiles by RNAi-Mediated BRCA1 Knockdown in MCF7 Cells

  • Song, Min-Ae;Park, Jung-Hoon;Ahn, Hee-Jeong;Ko, Jung-Jae;Lee, Su-Man
    • Genomics & Informatics
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    • 제3권4호
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    • pp.154-158
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    • 2005
  • Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF7 breast cancer cell line. The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF7 cells after BRCA1 knockdown. The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1 %) and 12 down-regulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells.

일반화된 부분강절을 갖는 뼈대구조물의 안정성 및 P-Δ 해석 (Stability and P-Δ Analysis of Generalized Frames with Movable Semi-Rigid Joints)

  • 민병철
    • 대한토목학회논문집
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    • 제33권2호
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    • pp.409-422
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    • 2013
  • 부재간의 연결조건에 따른 다양하고 복잡한 강구조물의 P-${\Delta}$ 해석 및 좌굴 거동특성을 파악하기 위하여, 본 연구에서는 부재의 연결이 회전 및 이동스프링으로 구성된 부분강절(semi-rigid) 뼈대요소의 일반화된 접선강도 행렬을 유도하였고 이로부터 다시 Taylor 전개를 적용하여 탄성강도 행렬과 기하학적 강도행렬을 일반화된 형태로 제시하였다. 이를 위하여, 보-기둥부재의 좌굴조건을 만족시키는 처짐함수로부터 안정함수(stability function)를 유도하였고, 횡변위(sway)를 고려한 힘-변위관계와 적합조건을 고려하여 엄밀한 부분강절 뼈대요소의 접선강도행렬을 제시하였다. 다양한 수치해석 예제에 대해 타 연구자의 해석 결과 및 본 연구의 선형 및 비선형 해석이론을 통한 좌굴해석 결과를 비교하여 본 연구의 타당성과 부분강절 뼈대구조물의 좌굴거동 특성을 제시하였다.

Quinetides: diverse posttranslational modified peptides of ribonuclease-like storage protein from Panax quinquefolius as markers for differentiating ginseng species

  • Zhao, Qiang;Bai, Yunpeng;Liu, Dan;Zhao, Nan;Gao, Huiyuan;Zhang, Xiaozhe
    • Journal of Ginseng Research
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    • 제44권5호
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    • pp.680-689
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    • 2020
  • Background: Peptides have diverse and important physiological roles in plants and are ideal markers for species identification. It is unclear whether there are specific peptides in Panax quinquefolius L. (PQ). The aims of this study were to identify Quinetides, a series of diverse posttranslational modified native peptides of the ribonuclease-like storage protein (ginseng major protein), from PQ to explore novel peptide markers and develop a new method to distinguish PQ from Panax ginseng. Methods: We used different fragmentation modes in the LTQ Orbitrap analysis to identify the enriched Quinetide targets of PQ, and we discovered Quinetide markers of PQ and P. ginseng using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. These "peptide markers" were validated by simultaneously monitoring Rf and F11 as standard ginsenosides. Results: We discovered 100 Quinetides of PQ with various post-translational modifications (PTMs), including a series of glycopeptides, all of which originated from the protein ginseng major protein. We effectively distinguished PQ from P. ginseng using new "peptide markers." Four unique peptides (Quinetides TP6 and TP7 as markers of PQ and Quinetides TP8 and TP9 as markers of P. ginseng) and their associated glycosylation products were discovered in PQ and P. ginseng. Conclusion: We provide specific information on PQ peptides and propose the clinical application of peptide markers to distinguish PQ from P. ginseng.