• 제목/요약/키워드: LRR

검색결과 69건 처리시간 0.028초

파킨스병 유전인자인 LRRK2와 상호작용하는 methionyl-tRNA synthetase (Methionyl-tRNA-synthetase is a Novel Interacting Protein of LRRK2)

  • 김혜정;호동환;손일홍;설원기
    • 생명과학회지
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    • 제28권2호
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    • pp.170-175
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    • 2018
  • 파킨슨병은 두번째로 많이 발병하는 퇴행성 신경질환이며 약 5-10%는 유전된다. Leucine-rich repeat kinase 2(LRRK2)는 그 돌연변이의 일부가 파킨슨병을 일으키는 유전자이다. LRRK2에는 인산화효소와 GTPase 기능이 있는 도메인과 함께 단백질 상호작용에 관여하는 Leucine-rich repeat (LRR), WD40 도메인이 존재하여, LRRK2와 상호작용하는 단백질이 파킨슨병 발병에 중요한 역할을 함을 암시한다. 우리는 이러한 LRRK2와 상호작용하는 단백질을 규명하여 그 단백질의 세포내 기능을 통해 역으로 LRRK2의 기능을 밝히고자 하였다. NIH3T3 세포 용해물을 LRRK2 항체와 IgG로 각각 면역침강하여 LRRK2 항체 침강반응에서만 특이적으로 나타나는 단백질 밴드를 질량 분석한 결과, methionyl-tRNA synthetase (MRS)로 나타났다. LRRK2와 MRS의 상호작용은 면역침강반응과 GST-pull down assay를 통해 확인됐다. 병을 유발하는, LRRK2의 돌연변이인 G2019S가 인산화효소 활성을 증가시키므로 LRRK2가 MRS를 인산화하는 지를 조사한 결과, LRRK2재조합단백질은 MRS 단백질을 인산화 하지 않았다. 또한 이들 두 단백질의 각각의 양 증가가 상대 단백질의 양 증가, 즉 안정성에 영향을 미치는 지를 조사하였으나 안정성의 변화를 관찰하지 못하였다. 결론적으로, MRS는 LRRK2와 상호작용을 하지만 LRRK2 인산화효소의 기질은 아니다.

Prognostic analysis of uterine cervical cancer treated with postoperative radiotherapy: importance of positive or close parametrial resection margin

  • Kim, Yi-Jun;Lee, Kyung-Ja;Park, Kyung Ran;Kim, Jiyoung;Jung, Wonguen;Lee, Rena;Kim, Seung Cheol;Moon, Hye Sung;Ju, Woong;Kim, Yun Hwan;Lee, Jihae
    • Radiation Oncology Journal
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    • 제33권2호
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    • pp.109-116
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    • 2015
  • Purpose: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. Materials and Methods: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors. Results: The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS. Conclusion: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.

Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence

  • Sanchez, Cesar;Camus, Mauricio;Medina, Lidia;Oddo, David;Artigas, Rocio;Sepulveda, Alejandra Perez;Domainguez, Francisco;Razmilic, Dravna;Navarro, Maria Elena;Galindo, Hector;Acevedo, Francisco
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권12호
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    • pp.5081-5086
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    • 2016
  • Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without,and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.

낙동강 하구역 울타리 섬의 해안선 변화율 (Rate of Shoreline Changes for Barrier Islands in Nakdong Estuary)

  • 김백운;김부근;이상룡
    • 한국해안해양공학회지
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    • 제19권4호
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    • pp.361-374
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    • 2007
  • 본 연구는 항공사진을 이용하여 낙동강 하구 울타리 섬의 장기간의 지형 변화를 제시한다. 수치사진측량을 이용하여 모자이크 항공사진을 구축하고 이로부터 1975년부터 2001년까지 6회의 해안선 자료를 산출한다. GIS에 근거한 수치해안선분석시스템을 이용하여 EPR(End Point Rate), JKR(Jackknife Rate) 및 LRR(Linear Regression Rate)와 같은 3 종류의 해안선 변화율을 산정한다. 신자도와 도요등에서 매우 현격한 변화가 나타났다. 신자도의 서쪽 부분은 바다 쪽으로 전진한 반면 동쪽 부분은 육지 쪽으로 후퇴하였으며, 이 결과 섬이 반시계 방향으로 회전한 것처럼 보인다. 양쪽 끝 부분에서 해안선 변화율은 20 m/yr에 달한다. 도요등은 1993년에 백합등 전면에 새롭게 출현하였으며 40 m/yr의 해안선 변화율로 전진하였다. 해안선 변화율은 울타리 섬 내에서뿐만 아니라 울타리 섬 간에도 차이가 있으며, 동쪽으로 가면서 증가하는 경향을 보인다. 이러한 해안선 변화율의 공간적인 변동성을 이해하기 위해서는 연안개발이 수리역학과 퇴적작용에 미치는 영향을 상세히 조사할 필요가 있다.

배 검은별무늬병 감염과 저항성 방어반응 연관 전사체 프로파일 (Transcriptomic Profile in Pear Leave with Resistance Against Venturia nashicola Infection)

  • 신일섭;천재안;김세희;조강희;원경호;정해원;김금선
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2022년도 추계학술대회
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    • pp.36-36
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    • 2022
  • The molecular understanding of resistance and susceptibility of host plants to scab, a most threatful disease to pome fruit production worldwide, is very limited. Comparing resistant line '93-3-98' to susceptible one 'Sweet Skin' at seven time points of 0, 0.5, 1, 2, 3, 4, 8 days post inoculation, RNA-sequencing data derived from infected and mock-inoculated young leaves were analyzed to evaluate the tolerant response and to mine candidate genes of pear to the scab pathogen Venturia nashicola. Analysis of the mapped reads showed that the infection of V. nashicola led to significant differential expression of 17,827 transcripts with more than 3-fold change in the seven pairs of libraries, of which 9,672 (54%) are up- and 8,155(46%) are down-regulated. These included mainly receptor (NB-ARC domains-containing, CC-NBS-LRR, TIR-NBS-LRR, seven transmembrane MLO family protein) and transcription factor (ethylene responsive element binding, WRKY DNA-binding protein) related gene. An arsenal of defense response of highly resistant pear accessions derived from European pear was probably supposed no sooner had V. nashicola infected its host than host genes related to disease suppression like Polyketide cyclase/dehydrase and lipid transport protein, WRKY family transcription factor, lectin protein kinase, cystein-rich RLK, calcium-dependent phospholipid-binding copine protein were greatly boosted and eradicated cascade reaction induced by pathogen within 24 hours. To identify transcripts specifically expressed in response to V. nashicola, RT-PCRs were conducted and compare to the expression patterns of seven cultivars with a range of highly resistant to highly susceptible symptom. A DEG belonging to the PR protein family genes that were higher expressed in response to V. nashicola suggesting extraordinary role in the resistance response were led to the identification. This study provides the first transcriptional profile by RNA-seq of the host plant during scab disease and insights into the response of tolerant pear plants to V. nashicola.

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자율주행을 위한 레이더 기반 인지 알고리즘의 정량적 분석 (Quantitative Analysis of Automotive Radar-based Perception Algorithm for Autonomous Driving)

  • 이호준;채흥석;서호태;이경수
    • 자동차안전학회지
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    • 제10권2호
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    • pp.29-35
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    • 2018
  • This paper presents a quantitative evaluation method and result of moving vehicle perception using automotive radar. It is also important to analyze the accuracy of the perception algorithm quantitatively as well as to accurately percept nearby moving vehicles for safe and efficient autonomous driving. In this study, accuracy of the automotive radar-based perception algorithm which is developed based on interacting multiple model (IMM) has been verified via vehicle tests on real roads. In order to obtain experimental data for quantitative evaluation, Long Range Radar (LRR) has been mounted on the front of the ego vehicle and Short Range Radar (SRR) has been mounted on the rear side of both sides. RT-range has been installed on the ego vehicle and the target vehicle to simultaneously collect reference data on the states of the two vehicles. The experimental data is acquired in various relative positions and velocity, and the accuracy of the algorithm has been analyzed according to relative position and velocity. Quantitative analysis is conducted on relative position, relative heading angle, absolute velocity, and yaw rate of each vehicle.

Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease

  • Seol, Won-Gi
    • BMB Reports
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    • 제43권4호
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    • pp.233-244
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    • 2010
  • Parkinson's disease (PD) is the second most common neurodegenerative disease, and 5-10% of the PD cases are genetically inherited as familial PD (FPD). LRRK2 (leucine-rich repeat kinase 2) was first reported in 2004 as a gene corresponding to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein interaction motifs such as LRR (leucine-rich repeat) and WD40. Most pathogenic LRRK2 mutations are located in either the GTPase or kinase domain, implying important roles for the enzymatic activities in PD pathogenic mechanisms. In comparison to other PD causative genes such as parkin and PINK1, LRRK2 exhibits two important features. One is that LRRK2's mutations (especially the G2019S mutation) were observed in sporadic as well as familial PD patients. Another is that, among the various PD-causing genes, pathological characteristics observed in patients carrying LRRK2 mutations are the most similar to patients with sporadic PD. Because of these two observations, LRRK2 has been intensively investigated for its pathogenic mechanism (s) and as a target gene for PD therapeutics. In this review, the general biochemical and molecular features of LRRK2, the recent results of LRRK2 studies and LRRK2's therapeutic potential as a PD target gene will be discussed.

Transcriptomic Profiling of Resistant and Susceptible Soybean Genotypes Following Inoculation of Phytophthora sojae

  • Hee Jin You;Jeongsun Lee;Sungwoo Lee
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2022년도 추계학술대회
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    • pp.188-188
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    • 2022
  • Our previous study identified a resistance locus to Phytophthora sojae (isolate 2457) in an interval of 3.8-4.7 Mbp on chromosome 3 via genetic mapping using a 'Daepung'×'Daewon' recombinant inbred population. Since differential gene expression between Daepung (susceptible) and Daewon (resistant) after inoculation of P. sojae is unknown, RNA sequencing was carried out to compare transcriptomic changes between the two genotypes following inoculation with P. sojae isolate 2457. The two varieties were inoculated using hypocotyl inoculation at the VC stage and stem tissue of 1 cm above and below of the inoculated site were sampled at 0, 6, 12 hours after inoculation (hai), respectively. Differentially expressed genes (DEGs) under same cultivar in different time point and Daepung vs. Daewon in same time point were investigated. In comparison of Daepung vs. Daewon at 12 hai, a total of 3,513 DEGs were identified, including two nucleotide-binding site-leucine rich repeat (NBS-LRR) genes (Glyma.03g034800 and Glyma.03g034900) that are located in the previously reported resistance locus on chromosome 3. In addition, 14,966 DEGs were detected between 0 vs. 6 hai, containing one of candidate genes (Glyma.03g035300). This gene was upregulated by up to 4-fold in Daewon and Daepung. Additional results will be further discussed in the presentation. This study will provide valuable information for soybean crop improvement.

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Development of scaling approach based on experimental and CFD data for thermal stratification and mixing induced by steam injection through spargers

  • Xicheng Wang;Dmitry Grishchenko;Pavel Kudinov
    • Nuclear Engineering and Technology
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    • 제56권3호
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    • pp.1052-1065
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    • 2024
  • Advanced Pressurized Water Reactors (APWRs) and Boiling Water Reactors (BWRs) employ a suppression pool as a heat sink to prevent containment overpressure. Steam can be discharged into the pool through multi-hole spargers or blowdown pipes in both normal and accident conditions. Direct Contact Condensation (DCC) creates sources of momentum and heat. The competition between these two sources determines the development of thermal stratification or mixing of the pool. Thermal stratification is of safety concern as it reduces the cooling capability compared to a completely mixed pool condition. In this work we develop a scaling approach to prediction of the thermal stratification in a water pool induced by steam injection through spargers. Experimental data obtained from large-scale pool tests conducted in the PPOOLEX and PANDA facilities, as well as simulation results obtained using validated codes are used to develop the scaling. Two injection orientations, namely radial injection through multi-hole Sparger Head (SH) and vertical injection through Load Reduction Ring (LRR), are considered. We show that the erosion rate of the cold layer can be estimated using the Richardson number. In this work, scaling laws are proposed to estimate both the (i) transient erosion velocity and (ii) the stable position of the thermocline. These scaling laws are then implemented into a 1D model to simulate the thermal behavior of the pool during steam injection through the sparger.

Characterization and Utilization of the Clubroot Resistant Genes in Chinese Cabbage (Brassica rapa L.)

  • Hatakeyama, Katsunori
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2015년도 춘계학술대회 및 임시총회
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    • pp.33-33
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    • 2015
  • Clubroot disease is the major threat to the production of Chinese cabbage (Brassica rapa L.) in Japan. Although the breeding of the clubtoot resistant (CR) cultivars is one of the most efficient ways to control this disease, the CR cultivars do not always have effects due to the breakdown of resistance. Therefore, it is necessary to develop the breeding strategy to accumulate multiple CR genes in a single cultivar effectively. We have identified two incomplete dominant CR loci, Crr1 and Crr2, which are originated from the European CR turnip Siloga. To investigate the effectiveness of marker-assisted selection (MAS) for CR breeding, the inbred line with Crr1 and Crr2 was crossed with parental lines of the existing CR $F_1$ cultivar of Chinese cabbage, followed by 5 times of MAS and backcrossing. The $F_1$ derived from a cross between the resulting parental lines improved the clubroot resistance as expected and had the same morphological characters as the original $F_1$ cultivar. We have shown that the Crr1 locus comprised two loci: Crr1a, which by itself conferred resistance to the mild isolate; and Crr1b, which had a minor effect, but was not required for Crr1a-mediated resistance. Further genetic analysis suggested that Crr1b was necessary to acquire resistance to the more virulent isolate in combination with Crr2. Molecular characterization of Crr1a encoding TIR-NB-LRR class of R protein revealed that there were at least 4 alleles in Japanese CR cultivars of Chinese cabbage. PCR analysis with Crr1a-specific markers demonstrated that the functional alleles were predicted to be present in European CR turnips, Debra and 77b besides Siloga, whereas rarely in Japanese CR cultivars, indicating that Crr1a is an useful source to improve the resistance of Chinese cabbage cultivars.

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