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    ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์—์„œ ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ ์ง„๋‹จ์„ ์œ„ํ•œ ์ธ๊ณต์ง€๋Šฅ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ(๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต๋Œ€ํ•™์› : ์น˜๊ณผ๋Œ€ํ•™ ์น˜์˜๊ณผํ•™๊ณผ, 2021.8. ๋ฐ•ํฌ๊ฒฝ.Orthopantomogram (OPG) is important for primary diagnosis of temporomandibular joint osteoarthritis (TMJ OA), because of cost and the radiation associated with computed tomograms (CT). The aims of this study were to develop an artificial intelligence (AI) model and compare its TMJ OA diagnostic performance from OPGs with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karasโ€™ ResNet model and trained to classify images into three categories: normal, indeterminate OA, and definite OA. This study included 1,189 OPG images confirmed by cone-beam CT (CBCT) and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI was developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJ OA in a similar manner to an expert and was in most accord with CBCT when the indeterminate OA category was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJ OA from OPGs in most general practice clinics where OMFR experts or CT are not available.ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์€ ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ์˜ ์ผ์ฐจ ์ง„๋‹จ์—์„œ ์ผ๋ฐ˜์ ์œผ๋กœ ์‚ฌ์šฉ๋œ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€ ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์„ ์ด์šฉํ•˜์—ฌ ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ์„ ์ง„๋‹จํ•˜๋Š” ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ์„ ๊ฐœ๋ฐœํ•˜๊ณ , ๊ทธ ์ง„๋‹จ ์„ฑ๋Šฅ์„ ์˜์ƒ์น˜์˜ํ•™ ์ „๋ฌธ๊ฐ€์™€ ๋น„๊ตํ•˜๋Š” ๊ฒƒ์ด๋‹ค. Karasโ€™ResNet ๋ชจ๋ธ์„ ์‚ฌ์šฉํ•˜์—ฌ ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ์„ ๊ฐœ๋ฐœํ•˜์˜€๋‹ค. ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์„ no osteoarthritis, indeterminate osteoarthritis ๋ฐ definite osteoarthritis์˜ ์„ธ ๊ฐ€์ง€ ๋ฒ”์ฃผ๋กœ ๋ถ„๋ฅ˜ํ•˜๋„๋ก ํ›ˆ๋ จํ–ˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” cone beam CT๋กœ ํ™•์ธ๋œ 1,189๊ฐœ์˜ ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์„ ํฌํ•จํ•˜๊ณ  ์žˆ์œผ๋ฉฐ, ๋ชจ๋ธ ์„ฑ๋Šฅ(์ •ํ™•๋„, ์ •๋ฐ€๋„, ์žฌํ˜„์œจ ๋ฐ F1 score) ๋ฐ ์ง„๋‹จ ์„ฑ๋Šฅ(์ •ํ™•๋„, ๋ฏผ๊ฐ๋„ ๋ฐ ํŠน์ด๋„)์„ ํ‰๊ฐ€ํ–ˆ๋‹ค. ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ์ด ์„ธ ๊ฐ€์ง€ ๋ฒ”์ฃผ๋ฅผ ๊ฐ€์ง€๊ณ  ๊ฐœ๋ฐœ๋˜์—ˆ์„ ๋•Œ, ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ ์ง„๋‹จ ๋ชจ๋ธ์˜ ์ •ํ™•๋„, ์ •๋ฐ€๋„, ์žฌํ˜„์œจ, F1 score๋Š” ๊ฐ๊ฐ 0.51, 0.55, 0.51, 0.53์˜ ๊ฒฐ๊ณผ๊ฐ’์„ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ๋”ฐ๋ผ์„œ Indeterminate for osteoarthritis ์˜์ƒ์„ no osteoarthritis(Trial 1), osteoarthritis(Trial 2) ๋ฐ ์ƒ๋žต(Trial 3)์œผ๋กœ ์žฌ๋ถ„๋ฅ˜ํ•˜์—ฌ ํ‰๊ฐ€ํ•˜์˜€๋‹ค. Trial 3์˜ ๊ฒฝ์šฐ ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ์˜ ์ •ํ™•๋„, ๋ฏผ๊ฐ๋„, ํŠน์ด๋„๋Š” ๊ฐ๊ฐ 0.78, 0.73, 0.82 ์˜€์œผ๋ฉฐ, ์˜์ƒ์น˜์˜ํ•™ ์ „๋ฌธ๊ฐ€๋Š” ๊ฐ๊ฐ 0.85, 0.72, 0.97์ด์—ˆ๋‹ค. ๋˜ํ•œ McNemar's test๋ฅผ ์ด์šฉํ•˜์—ฌ ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ๊ณผ CBCT ๊ฒฐ๊ณผ๋ฅผ ๋น„๊ตํ•œ ๊ฒฐ๊ณผ ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜ํ•œ ์ฐจ์ด๋ฅผ ๋ณด์ด์ง€ ์•Š์•˜๋‹ค(p value = 0.366). ๋ณธ ์—ฐ๊ตฌ์˜ ์ธ๊ณต์ง€๋Šฅ ๋ชจ๋ธ์€ ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ ์ง„๋‹จ์— ์žˆ์–ด์„œ ์ „๋ฌธ๊ฐ€์— ์ƒ์‘ํ•˜๋Š” ๋ฏผ๊ฐ๋„์™€ ํŠน์ด๋„๋ฅผ ๋ณด์ธ๋‹ค. ์ด๋Š” ์˜์ƒ ์น˜์˜ํ•™์ „๋ฌธ์˜๊ฐ€ ๋ถ€์žฌํ•˜๊ฑฐ๋‚˜ CT ์ดฌ์˜์ด ๋ถˆ๊ฐ€๋Šฅํ•œ ์ƒํ™ฉ์—์„œ ํŒŒ๋…ธ๋ผ๋งˆ ์˜์ƒ์„ ๊ธฐ๋ฐ˜์œผ๋กœ ์ธก๋‘ํ•˜์•…๊ด€์ ˆ ๊ณจ๊ด€์ ˆ์—ผ์˜ ์ผ์ฐจ ์ง„๋‹จ์ด ์ด๋ค„์งˆ ๋•Œ, ์ธ๊ณต์ง€๋Šฅ์ด ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•  ์ˆ˜ ์žˆ๋‹ค๋Š” ๊ฒƒ์„ ๋ณด์—ฌ์ค€๋‹ค.I. INTRODUCTION 4 II. REVIEW OF LITERATURE 6 III. MATERIALS AND METHODS 14 IV. RESULTS 20 V. DISCUSSION 22 VI. CONCLUSIONS 30 REFERENCES 31 TABLES 41 FIGURES 47 KOREAN ABSTRACT 52๋ฐ•

    ์‹œ๊ณต๊ฐ„์„ ์ดˆ์›”ํ•˜๋Š” ๋ฐ”๋‹ค๋กœ ๋‚˜์•„๊ฐ€๋‹ค: ์…ฐ์ต์Šคํ”ผ์–ด์˜ <ํŽ˜๋ฆฌํด๋ ˆ์Šค> ๊ณต์—ฐํ‰

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    ์œŒ๋ฆฌ์—„ ์…ฐ์ต์Šคํ”ผ์–ด์˜ 1607๋…„์ž‘ ใ€ŽํŽ˜๋ฆฌํด๋ ˆ์Šคใ€(Pericles)์˜ ์ดˆ๊ธฐ ๊ณต์—ฐ์‚ฌ ๊ธฐ๋ก์€ ๋‹น๋Œ€์— ์ด ๊ทน์ด ๊ฐ€์กŒ๋˜ ํญ๋ฐœ์ ์ธ ๋Œ€์ค‘์„ฑ์„ ์ž…์ฆํ•œ๋‹ค.1) ๋น„๋ก ์˜ค๋Š˜๋‚  ์…ฐ์ต์Šคํ”ผ์–ด์˜ 4๋Œ€ ๋กœ๋งจ์Šค๋ฅผ ์ด๋ฃจ๋Š” ๋‹ค๋ฅธ ์ž‘ํ’ˆ๋“ค[ใ€Žํƒœํ’ใ€(The Tempest), ใ€Ž๊ฒจ์šธ์ด์•ผ๊ธฐใ€(The Winters Tale), ใ€Ž์‹ฌ๋ฒŒ๋ฆฐใ€ (Cymbeline)]์— ๋น„ํ•ด ๋น„๊ต์  ๋œ ์•Œ๋ ค์ ธ ์žˆ๊ธฐ๋Š” ํ•˜๋‚˜, ใ€ŽํŽ˜๋ฆฌํด๋ ˆ์Šคใ€๋Š” ์—˜๋ฆฌ์ž๋ฒ ์Šค-์ œ์ž„์Šค ์กฐ ์‹œ๋Œ€์— ใ€Ž๋ฆฌ์ฒ˜๋“œ 3์„ธใ€, ใ€Ž๋กœ๋ฏธ์˜ค์™€ ์ค„๋ฆฌ์—ฃใ€, ใ€Žํ–„๋ฆฟใ€ ๋“ฑ๊ณผ ํ•จ๊ป˜ ๊ฐ€์žฅ ์ธ๊ธฐ ์žˆ๋Š” ์…ฐ์ต์Šคํ”ผ ์–ด ๋ ˆํผํ† ๋ฆฌ(Dunton-Downer 403)์— ํฌํ•จ๋˜์—ˆ์—ˆ๋‹ค. ๋˜ํ•œ ์ด๋Š” ํฌ๋กฌ์›ฐ์˜ ์ฒญ๊ต๋„ ์ •๊ถŒ ํ•˜์—์„œ ํ์‡„๋๋˜ ๊ทน์žฅ์ด 20๋…„ ๋’ค ์™•์ •๋ณต๊ณ ๊ธฐ์— ์žฌ ๊ฐœ์žฅ๋˜์—ˆ์„ ๋•Œ, ๊ฐ€์žฅ ๋จผ์ € ๊ณต์—ฐ๋œ ์…ฐ ์ต์Šคํ”ผ์–ด ๊ทน ์ž‘ํ’ˆ ์ค‘์˜ ํ•˜๋‚˜(Tompkins 315)์˜€์œผ๋‚˜ 18~20์„ธ๊ธฐ ๋™์•ˆ ๊ธด ๊ณต๋ฐฑ๊ธฐ๋ฅผ ๊ฐ€์ง€ ๊ณ  ์ตœ๊ทผ์—์•ผ ์žฌ์กฐ๋ช…์„ ๋ฐ›์€ ๋น„์šด์˜ ๊ทน์ด๊ธฐ๋„ ํ•˜๋‹ค. ใ€ŽํŽ˜๋ฆฌํด๋ ˆ์Šคใ€๋Š” ์ตœ๊ทผ์—์•ผ ๋น„๋กœ์†Œ ํ•œ ๊ตญ ์ดˆ์—ฐ์˜ ๋น›์„ ๋ณด๊ฒŒ ๋˜์—ˆ๋Š”๋ฐ, ๋ฐ”๋กœ ๊ทผ 20๋…„ ๋™์•ˆ ์…ฐ์ต์Šคํ”ผ์–ด ๊ทน์„ ์ „๋ฌธ์œผ๋กœ ํ•ด์˜จ ๊ทน ๋‹จ ํ™”๋™ ์—ฐ์šฐํšŒ๊ฐ€ 2010๋…„ 12์›” 4์ผ์—์„œ 12์›” 12์ผ๊นŒ์ง€ ์ด๋ฅผ ๊ณต์—ฐํ•˜์˜€๋‹ค. ์ด์ธ์ˆ˜ยท๋ฐ•์ค€ ๊ทผ ๊ฐ์ƒ‰, ๊น€๊ด‘๋ฆผ ์—ฐ์ถœ์˜ ๋Š” ๋กœ๋งจ์Šค์  ํŒํƒ€์ง€์™€ ์‚ฌํšŒ๋น„ํŒ์  ์‚ฌ์‹ค์ฃผ์˜์˜ ๊ฒฐ ํ•ฉ์ด๋ผ๋Š” ์ด์ค‘์  ๊ตฌ์กฐ๋ฅผ ๋ณด์—ฌ์ฃผ์—ˆ์œผ๋ฉฐ, ํ•œ๊ตญ์˜ ์ „ํ†ต๊ทน์  ์š”์†Œ์™€ ์…ฐ์ต์Šคํ”ผ์–ด์  ๊ณต์—ฐ ๋ฌธ ๋ฒ•์˜ ์œตํ•ฉ์„ ํ†ตํ•ด ํ˜„๋Œ€์ธ์—๊ฒŒ ์‚ฌ๋ž‘๊ณผ ์žฌํšŒ, ๊ทธ๋ฆฌ๊ณ  ์žฌ์ƒ์˜ ์ฃผ์ œ๋ฅผ ํ‘œํ˜„ํ•˜๊ณ ์ž ์‹œ๋„ํ•˜์˜€ ๋‹ค. ๊ณต์—ฐ ๋Š” ๋Œ€ํ•™๋กœ ์˜ˆ์ˆ ๊ทน์žฅ ๋Œ€๊ทน์žฅ์˜ ๋ฌด๋Œ€ ๊ทœ๋ชจ๋ฅผ ์ž˜ ํ™œ์šฉํ•˜์˜€๋‹ค. ๋ฌด๋Œ€์˜ ๋†’์ด๋Š” ์•ž ์ขŒ์„ ๊ด€๊ฐ์˜ ๋ˆˆ๋†’์ด์— ๋งž์ถ”์–ด ๋‚ฎ์€ ํŽธ์ด์—ˆ์œผ๋‚˜, ๋ฌด๋Œ€ ์•ˆ์ชฝ์€ ์—ฌ๋Ÿฌ ๊ฐœ์˜ ๊นŠ์€ ์ธต์œผ๋กœ ์ด๋ฃจ์–ด์ ธ ๊ฐ ์บ๋ฆญํ„ฐ์˜ ๋“ฑ์žฅ/ํ‡ด์žฅ ์žฅ๋ฉด์—์„œ ์œ ์šฉํ•œ ๊ณต๊ฐ„ ํ™œ์šฉ์„ ์œ ๋„ํ•˜์˜€๋‹ค. ๋ฌด ๋Œ€๋Š” ์•ก์ž ํ‹€์„ ์—ฐ์ƒ์‹œํ‚ค๋Š” ์‹ฌํ”Œํ•œ ๋ฐฐ๊ฒฝ์„ ๊ธฐ๋ณธ์œผ๋กœ ํ•˜์˜€์ง€๋งŒ ํ›„๋ฐ˜์œผ๋กœ ๊ฐˆ์ˆ˜๋ก ์„ฌ,๊ทธ ๋ฆฌ๊ณ  ๋ฐ”๋‹ค์˜ ๋ฐฐ๊ฒฝ์— ์•Œ๋งž๊ฒŒ ์ž…์ฒด์ ์œผ๋กœ ํ™œ์šฉ๋˜์–ด, ๋ฌด๋Œ€์˜ ๋‹ค๊ฐ์ ์ธ ๋ณ€์‹ ์„ ๋ณผ ์ˆ˜ ์žˆ๊ฒŒ ๋” ํ•ด์ฃผ์—ˆ๋‹ค. ๋ฌด๋Œ€ ์œ„์—๋Š” ์ปคํŠผ ๋Œ€์‹  ์›์ž‘์˜ ์˜๋ฌธ๋ช… Pericles, Prince of Tyre(ํ‹ฐ๋ ˆ์˜ ์™•์ž ํŽ˜๋ฆฌํด๋ ˆ์Šค)์„ ๊ธฐ์ž…ํ•œ ์ปค๋‹ค๋ž€ ์ง€๋„๊ฐ€ ๋ง‰-์žฅ์„ ๋‚˜๋ˆ„๋Š” ์—ญํ• ์„ ํ•  ๋ฟ ์•„๋‹ˆ๋ผ ์—ฌ๋Ÿฌ ํ˜•์ƒ ์˜ ์œค๊ณฝ๋งŒ์„ ์ด์šฉํ•œ ์ด๋ฅธ๋ฐ” ์‹ค๋ฃจ์—ฃ ์• ๋‹ˆ๋ฉ”์ด์…˜(Silhouette Animation) ์ด ํˆฌ์‚ฌ๋˜๋Š” ์Šคํฌ๋ฆฐ์˜ ์—ญํ• ๋„ ๋ณ‘ํ–‰ํ•˜์˜€๋‹ค. ์‹œ์‹œ๊ฐ๊ฐ ๋ณ€ํ•˜๋Š” ์—ฌ๋Ÿฌ ๋ฐฐ๊ฒฝ๋“ค์— ์•ž์„œ ๋ฏธ๋ฆฌ ํ•ด๋‹น ์„ฌ์ด๋‚˜ ๋„ ์‹œ์— ํ•€ ์กฐ๋ช…์„ ๋น„์ถ”์–ด ๊ด€๊ฐ์„ ๋ฐฐ๋ คํ•œ ๊ฒƒ๋„ ์ฐธ์‹ ํ•œ ์Šคํฌ๋ฆฐ ํ™œ์šฉ๋ฒ•์— ์†ํ•˜์˜€๋‹ค. ๊ฐ์ข… ์‹œ ๋„๋“ค๋กœ ์ธํ•ด ์ด ์ปคํŠผ์€ ๊ทน์˜ ๋ณด์กฐ ์†Œํ’ˆ์— ๋จธ๋ฌผ์ง€ ์•Š๊ณ  ์—ญ์‚ฌ์ ์ธ ์š”์†Œ์™€ ์ง€๋ฆฌ์ ์ธ ์š”์†Œ ๋ฅผ ๊ฒฐํ•ฉ์‹œ์ผœ ์—ฐ๊ทน์˜ ๋ฌ˜๋ฏธ๋ฅผ ๋”์šฑ ์‚ด๋ ค์ฃผ์—ˆ์œผ๋ฉฐ, ๋“œ๋„“์€ ์‹œ๊ณต๊ฐ„์„ ์•„์šฐ๋ฅด๋Š” ์žฅ๋ฉด๋“ค์˜ ํ‹ˆ ๋“ค์„ ๋ฉ”๊พธ์–ด ๊ธด ๊ทน์˜ ํ๋ฆ„์ด ์ง€๋ฃจํ•˜์ง€ ์•Š๋„๋ก ํ•ด์ฃผ์—ˆ๋‹ค

    ๊ตฌ๊ฐ• ๋‚ด ๋ถˆํŽธ๊ฐ์„ ๊ฐ€์ง„ ํ™˜์ž์—์„œ ์บ”๋””๋‹ค ๊ฐ์—ผ์— ๋Œ€ํ•œ ํ›„ํ–ฅ์  ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์น˜์˜๊ณผํ•™๊ณผ, 2015. 8. ๋ฐ•ํฌ๊ฒฝ.The aims of the study were to evaluate the value of Dentocultโ“‡ CA compared to Sabouraud dextrose agar (SDA) culture, to compare the candida culture positive rate, symptom improved rate after antifungal therapy among the patients with oral discomfort retrospectively, and to provide a clinical guideline for diagnosis and treatment in oral candidal infection. The 328 dental records of patients who complained various oral discomforts at Seoul National University Dental Hospital from January 2012 to September 2013 were reviewed. Candida culture data were obtained from both DentocultยฎCA and SDA and analyzed with McNemer test. Based on initial clinical diagnosis, patients records were categorized as group 1 (glossodynia without objective sign, 58 patients), group 2 (oral mucosal lesion, 101 patients), group 3 (hyposalivation, 31 patients) and group 4 (oral candidiasis, 38 patients). 100 patients were excluded because of inconsistency with initial diagnosis (e.g., squamous cell carcinoma, epithelial dysplasia, leukoplakia) and failure to follow-up after initial examination or antifungal therapy. Candida culture positive percents were compared with Chi-square test among group 1, 2, and 3. The correlation between Candida culture positive and systemic diseases was analyzed with Chi-square and Fishers extract test. After antifungal therapy, the mean Candida colony count was compared between symptom-improved and symptom-sustained with Students t-test. The result suggested that the relative validity of DentocultยฎCA approximately equals that of SDA (p=0.066). DentocultยฎCA showed 89.1% sensitivity and 85.3% specificity. Candida culture positive was found in 21 patients (43.1%), 40 patients (39.6%) and 22 patients (72.0%) in three groups, respectively. There was a significant difference among three groups (p=0.003). In addition, gastrointestinal disease (p=0.030) and genitourinary disease (p=0.012) had significant correlations with the Candida culture positive rate. Mean Candida colony count showed no significant differences between symptom-improved and symptom-sustained group. Oral Candida carriage is significantly related to hyposalivation. Antifungal medication can be considered initially or in the process of main symptom treatment, especially in hyposalivation group.I. INTRODUCTION II. MATERIALS AND METHODS III. RESULTS IV. DISCUSSION V. CONCLUSIONS VI. REFERENCES TABLES KOREAN ABSTRACTMaste

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ํ˜‘๋™๊ณผ์ •๋†์ƒ๋ช…์œ ์ „์ฒดํ•™์ „๊ณต, 2017. 2. ์ตœ๋„์ผ.์‹๋ฌผ์˜ Nucleotide-binding site Leucine-rich repeat (NLRs)์€ ๋ณ‘์›๊ท ์˜ ์นจ์ž… ์‹œ ์œ ๋„๋˜๋Š” ๋ฉด์—ญ๋ฐ˜์‘์— ๊ด€์—ฌํ•˜๋Š” ์„ธํฌ์งˆ ๋‚ด ๋‹จ๋ฐฑ์งˆ๋กœ, N-๋ง๋‹จ ๋„๋ฉ”์ธ, NBARC ๋„๋ฉ”์ธ ๊ทธ๋ฆฌ๊ณ  C-๋ง๋‹จ ๋„๋ฉ”์ธ์œผ๋กœ ์ด๋ฃจ์–ด์ ธ ์žˆ๋‹ค. ๋˜ํ•œ NLRs์€ ๊ฐ•๋ ฅํ•œ ๋ฉด์—ญ๋ฐ˜์‘์˜ ํ•˜๋‚˜๋กœ ํ”ํžˆ ๊ตญ์ง€์  ์„ธํฌ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•˜๊ธฐ๋„ ํ•œ๋‹ค. Arabidopsis์˜ RPS4์™€ ๋ฒผ์˜ Orin1๊ณผ ๊ฐ™์ด NLRs์ด ๊ณผ๋ฐœํ˜„ ๋˜์—ˆ์„ ๋•Œ ์ž๊ฐ€ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•œ๋‹ค๋Š” ๋ณด๊ณ ๊ฐ€ ์žˆ๋‹ค. ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ, ์•„๋งˆ์˜ L6์™€ ๋ฐ€์˜ Sr33์ฒ˜๋Ÿผ NLR์˜ N-๋ง๋‹จ ๋„๋ฉ”์ธ์ด ์‹๋ฌผ์ฒด์— ๊ณผ๋ฐœํ˜„ ๋˜์—ˆ์„ ๋•Œ ์ž๊ฐ€ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•œ๋‹ค๋Š” ์„ ํ–‰ ์—ฐ๊ตฌ๊ฐ€ ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ์—์„œ ๊ณ ์ถ”์— ์กด์žฌํ•˜๋Š” NLRs์„ ๊ณผ๋ฐœํ˜„ ์‹œ์ผœ ์„ธํฌ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•˜๋Š”์ง€ ํ™•์ธํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ๊ณ ์ถ” Capsicum annuum CM334์— ์กด์žฌํ•˜๋Š” 755๊ฐœ NLRs ๊ฐ€์šด๋ฐ 415๊ฐœ์˜ NLRs์ด ๋™์ •๋˜์—ˆ๊ณ  Nicotiana benthamiana๋ฅผ ํฌํ•จํ•œ Solanaceae ์‹๋ฌผ ์ข…์—์„œ 15๊ฐœ์˜ NLRs์ด ์ž๊ฐ€ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•˜๋Š” ๊ฒƒ์ด ํ™•์ธ๋˜์—ˆ๋‹ค. ๋˜ํ•œ, 101๊ฐœ NLRs์˜ N-๋ง๋‹จ ๋„๋ฉ”์ธ ์ค‘ 21๊ฐœ๊ฐ€ ๊ณผ๋ฐœํ˜„ ๋˜์—ˆ์„ ๋•Œ ์ž๊ฐ€ ์„ธํฌ ์‚ฌ๋ฉธ์ด ์œ ๋„๋จ์„ ํ™•์ธํ•˜์˜€๋‹ค. ์„ธํฌ์‚ฌ๋ฉธ๊ณผ ๊ด€๋ จ๋œ ์œ ์ „์ž๋“ค์˜ ๋ฐœํ˜„์–‘์ƒ๊ณผ Virus induced gene silencing ์‹คํ—˜์„ ์ˆ˜ํ–‰ํ•œ ๊ฒฐ๊ณผ, ๊ฐ๊ฐ์˜ NLRs์ด ์„œ๋กœ ๋‹ค๋ฅธ ์‹ ํ˜ธ์ „๋‹ฌ ๋‹จ๋ฐฑ์งˆ์„ ๊ฒฝ์œ ํ•˜๊ณ  N-๋ง๋‹จ์— ์˜ํ•œ ์„ธํฌ ์‚ฌ๋ฉธ ์‹ ํ˜ธ ๊ฒฝ๋กœ์— Salicylic acid๊ฐ€ ๊ด€์—ฌ๋˜์–ด ์žˆ์Œ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ, ๊ณ ์ถ”์˜ NLR ๊ณผ N- ๋ง๋‹จ์€ ์‹๋ฌผ์˜ ๋ฉด์—ญ๋ฐ˜์‘์—์„œ ๋‚˜ํƒ€๋‚˜๋Š” ์„ธํฌ์‚ฌ๋ฉธ์˜ ๊ธฐ์ž‘์„ ์ดํ•ดํ•˜๋Š”๋ฐ ๋„์›€์ด ๋  ํ›„๋ณด ์œ ์ „์ž๊ฐ€ ๋  ์ˆ˜ ์žˆ์„ ๊ฒƒ์ด๋‹ค.Nucleotide binding-site Leucine rich Repeat (NLR) is a plant resistance protein that mediates immune response to pathogens. NLR recognize effector secreted from pathogen in plant cytosol and often causes rapid hypersensitive response (HR) cell death. Among known NLRs, Arabidopsis RPS4 and rice Orin1 were reported as induce auto-active cell death as effector-independent manner when they were over-expressed in plant. Auto-active cell death induced by the N-terminal domains of known NLR proteins such as flax L6 and wheat Sr33 have been also reported. To identify whether pepper (Capsicum annnuum CM334) NLRs have potential to induce auto-active cell death, 415 full type pepper NLRs were transiently over-expressed in Nicotiana benthamiana. As a result, over-expressions of 15 pepper NLRs triggered auto-active cell death with different strength in N. benthamiana. To verify over-expression of N-terminal domain fragments of pepper NLRs induce auto-active cell death, we first justified the N-terminal domain using COILS and SMART program and selected 101 N-terminal domain fragments of pepper NLRs. Over-expression of 21 N-terminal domain fragments induced auto-active cell death in N. benthamiana. Among them, pepper NLRs including 16 N-terminal domain fragments belong to specific group, CNL-G10. In addition, to investigate signaling component related to auto-cell death we performed qRT-PCR and virus induces gene silencing (VIGS) known components including ICS1, SGT1, EDS1. Taken together, our results suggest that pepper NLRs probably have auto-activity leading to cell death and pepper NLRs of certain group (CNL-G10) may have specific functions in plant immunity. Consequently, pepper NLRs and N-terminal domain fragments of pepper NLRs will provide important tool for understanding the cell death mechanism in plant immunity.INTRODUCTION 1 LITERATURE REVIEWS 5 NLRs in plant 5 Auto-active cell death induced by plant NLRs 7 Signaling components related to NLRs in cell death responses 8 MATERIAL AND METHODS 11 Plant materials 11 DNA and RNA isolation 21 Cloning of N-terminal domain fragments of pepepr NLRs by ligase-independent cloning 12 In planta expression assay 13 Virus-induced gene silencing (VIGS) in N. benthamiana 14 Semi-quantitative RT-PCR analysis 16 Ion conductivity measurement 18 RESULTS 19 Over-expression of pepper NLR genes induces auto-active cell death in Nicotiana benthamiana. 19 Over-expression of the N-terminal domain fragments of the pepper NLRs induces auto-active cell death in N. benthamiana. 27 Over-expression of N-terminal domain fragments of the pepper NLRs induces auto-active cell death in other Nicotiana species and C. annuum ECW-30R. 35 Various signaling components are involved in auto-active cell death. 39 DISCUSSION 46 REFERENCES 50 ABSTRACT IN KOREAN 55Maste
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