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      • SCOPUSKCI등재

        Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway

        Park, Yoon Hee,Oh, Eun Yi,Han, Heejae,Yang, Misuk,Park, Hye Jung,Park, Kyung Hee,Lee, Jae-Hyun,Park, Jung-Won Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.5

        <▼1><P>Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)−4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.</P></▼1><▼2><P><B>Obesity: A trigger for asthma onset</B></P><P>Insulin resistance may be an important causative factor underlying the increased risk of asthma and other respiratory issues in obese individuals. Obesity doubles the likelihood of developing asthma, with symptoms that are more difficult to control than in non-obese patients. The connection between these conditions is poorly understood, but researchers led by Jung-Won Park, Yonsei University College of Medicine, Seoul, South Korea, have identified a potential mechanism. They demonstrated that a signaling molecule called TGF-β1 contributes to airway sensitivity and tissue scarring in a mouse model of diet-induced obesity. Subsequent experiments showed that treatment with insulin also gives rise to increased TGF-β1 production in the mouse lung. Since insulin resistance is a common feature of obesity, resulting in abnormally high levels of circulating insulin, this could also account for the increased risk of respiratory problems.</P></▼2>

      • 피로를 유발하는 등속성 수축시와 회복기 혈중젖산 및 외측광근의 EMG Power Specturm 변화

        정정진,조현철,김기진,윤성원,오수일,홍관이,손태열 龍仁大學校 體育科學硏究所 1991 體育科學硏究論叢 Vol.1 No.1

        To examine the change of blood lactate concentration, EMG power spectrum, and Torque during fatiguing isokinetic contraction and recovery phrase, 6 sprinters performed maximal isokinetic knee extension at angular velocity of 3.14 rad.sec??(180°sec??) to 75% decreasing point (25%PT) using CybexⅡ system. In exercise phase, there was significant correlation between the decrement of peak EMG and median frequency and that of torque, and decrement of torque was greater than that of EMG . In recovery phase, EMG was restituded as normal value rapidly in a minute, but torque was restituded more slowly, and blood lactate concentration increased gradually from 50%PT to 3 minute after recovery. As a result of this study, it is suggested that muscle fatique due to decreasing of metabolic substrate and accumulation of metabolic products in peripheral site of muscle, and that inhibitory factors act neuromuscular junction in the end of exercise from rapid restitution of EMG in recovery phase.

      • 카이로프랙틱 경추 교정이 주의집중력에 미치는 영향에 대한 연구

        Yoon Beom Kook,Joo Hyun Ham,Jin Ok Choi,Jung Soo Yi1 한서대학교 보완대체의학연구소 2016 Research Journal of Complementary and Alternative Vol.- No.7

        This study is about the effect chiropractic correction has on the changes in attention cathexis. A total of 20 who are currently students at Hanseo University were selected. The study measured changes in the score for the attention cathexis ability and the changes in delta wave, theta wave, alpha wave, SMR, BetaL wave, and BetaH wave of the prefrontal lobe. The changes in brainwaves of the prefrontal lobe and the score of the attention cathexis ability for the false procedure before and after the treatment did not show much difference statistically(p>.05). The chiropractic correction group showed statistically meaningful results of the decrease of delta wave, theta wave, and BetaH, and the increase of alpha wave, SMR, and BetaL on the left side(p<.05). The decrease of delta wave, theta wave, and BetaH, and the increase of alpha wave, SMR, and BetaL on the right were statistically meaningful as well(p<.05). The increase in the score of the attention cathexis ability was significant statistically as well(p<.05). The chiropractic correction affected the increase of the attention cathexis ability.

      • KCI등재

        정신분열병 환자에서 가족력, 산과적 합병증 및 신체미세기형의 관련성에 관한 연구

        안용민,김용식,정희연,신지용,윤세창,배안,이중서,주은정,이창인 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.2

        연구목적 : 저자들은 태생기 동안에 받는 유전외적 요인, 즉 환경적 요인이 산발성 정신분열병 환자들의 발병에 크게 관여할 것이라고 가정하였다. 이를 검증하기 위하여 형제 중 1인 이상이 발병하여 가족력을 분명히 알 수 있는 정신분열병 환자군(이하 형제 환자군)과 가족력이 없는 산발성 정신분열병 환자군(이하 산발성 환자군) 및 정상대조군을 대상으로 산과적 합병증, 신체미세기형 및 정신분열병의 임상 양상을 비교하였다. 방 법 : 연구 대상은 형제 환자군 43명(남 22명, 여 21명), 산발성 환자군 43명(남 23명, 여 20명), 정상대조군 43명(남 20명, 여 23명)이었다. 산과적 합병증은 Lewis 척도를 이용하여 평가하였고 신체미세기형은 Waldrop 척도를 이용하여 측정하였다. 임상 양상으로서 발병 연령, 병전 기능 수준, 정신병리, 약물에 대한 반응, 회복시의 전반적 기능 수준, 지연성 운동장애의 유무를 평가하였다. 결 과 : 정상대조군과 정신분열병 환자군 전체를 비교하였을 때 산과적 합병증과 신체미세기형의 총점과 각 소항목의 점수에 차이가 없었다. 산발성 환자군과 형제 환자군을 비교하였을 때 산과적 합병증의 전체 점수에서는 유의한 차이가 없었으나, 출생 당시에 태아가 받은 스트레스 항목의 점수가 산발성 환자군에서 유의하게 높았다. 신체미세기형에서는 전체 점수 및 입의 미세기형 점수가 산발성 환자군에서 유의하게 높았다. 신체미세기형의 전체 점수가 4점 이상인 환자수도 산발성 환자군에서 높은 경향성을 보였다. 산과적 합병증과 신체미세기형 사이의 상호 연관성은 찾을 수 없었다. 정신분열병의 임상 양상 중에서는 Krawiecka 척도의 총점 및 양성 증상 점수와 회복시의 전반적 기능 수준만이 형제 환자군에 비해 산발성 환자군에서 유의하게 높았다. 성별에 따라서는 형제 환자군에서 남자 환자의 산과적 합병증이 유의하게 높았다. 결 론 : 본 연구를 통해 산과적 합병증 및 신체미세기형 연구가 정신분열병의 원인을 규명하기 위한 유용한 방법임이 시사되었지만, 가족력, 산과적 합병증 및 신체미세기형의 관련성에 대해서는 분명한 결론을 내리지 못하였다. The authors hypothesized that sporadic schizophrenic patients had more chances of receiving environmental insults during the fetal neural development compared with familial schizophrenics. We tested our hypothesis by comparing obstetric complications(OCs), minor physical anomalies(MPAs) and other clinical features, and examining the correlation between OCs and MPAs in schizophrenic patients who had one or more sibling with schizophrenia(sibling group) and sporadic schizophrenics(sporadic group) and normal controls. OCs were evaluated by the scale of Lewis, and MPAs were measured by the Waldrop scale. There were no significant difference in OCs and MPAs between schizophrenic and control groups. Sporadic group had significantly higher fetal distress, total Waldrop score and Waldrop score for mouth than sibling group. And there was a tendency that the number of subjects having the Waldrop score over 4 points was greater in the sporadic group. No significant correlation was observed between CCs and MPAs. The scores of initial psychopathology and post-treatment functioning were much higher in the sporadic group, but the other clinical feature showed no difference. Although male patients had more OCs than female patients in sibling group, no sex difference were observed as a whole. Our results suggest that, if the methodological weakness were complemented, OCs and MPAs would be useful tools in the search for the cause of schizophrenia.

      • 정신분열병 및 정신분열형 장애에 대한 올란자핀의 효과와 안전성

        안용민,강대엽,권준수,김창윤,김철응,반건호,신영민,이기철,이동우,이중서,조현상,채정호,김용식 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

        연구목적 : 본 다기관 공동임상연구는 국내 환자를 대상으로 새로운 항정신병약물인 올라자핀의 치료 효과와 안전성을 확인하고자 시행되었다. 방 법 : 1999년 7월부터 2000년 3월까지 국내 10개 병원에 방문한 정신분열병 및 정신분열형 장애 105명을 대상으로 비대조 개방 임상연구를 시행하였다. 중등도 이상의 정신병 증상을 지니거나, 부작용으로 약물교체가 필요한 경우 또는 기분장애 증상의 치료가 필요한 환자를 대상으로 하였다. 2∼7일간의 약물 배설기간 후에 1일 10mg의 올란자핀을 투여하였고, 이후로 3∼7일 간격으로 용량을 조절하여 총 8주간 투여하였다. 치료 효과는 PANSS(Positive and Negative Syndrome Scale), BPRS(Brief Psychiatric Rating Scale), CGI(Clinical Global Impression-Severity), MADRS(Montgomery-Asberg Depression Rating Scale), HAM-A(Hamilton Rating Scale for Anxiety)로 판정하였다. 안전성 평가는 자발적인 이상반응 보고, 활력징후와 혈액 검사 및 SAS(Simpson-Angus Scale), BARS(Barnes Akathisia Rating Scale), AIMS(Abnormal Involuntary Movement Scale)척도를 이용하였다. 결 과 : 105명중에서 85.7%인 90명이 8주간의 치료를 완료하였다. 평균 최빈 용량은 일일 16.1(±4.7)mg이었고, 종료시점에서의 BPRS전체 점수가 기저 상태에 비해 40%이상 감소된 반응군은 69.5%이었다. PANSS의 양성 증후군과 일반정신병리 뿐만 아니라 음성 증후군 소척도에서도 유의한 감소를 보였으며, 이 감소들은 치료 초기부터 나타나서 8주간 지속되었다. 43.8%의 피험자가 중등도 이상의 우울증상을 같이 지니고 있었으며, 올란자핀에 의해 MADRS와 HAM-A가 유의하게 감소하였다. 치료 기간 동안에 활력징후에는 뚜렷한 변화가 없었으나 체중은 8주간 지속적으로 증가하였다. SAS와 AIMS는 감소하였으며, 정좌불능증을 제외한 나머지 추체외로 증상의 발생비율도 낮았다. 임상적인 증상이나 징후를 동반하지 않는 ALT/SGPT의 상승을 보였지만 프로락틴을 포함하는 대부분의 혈액 검사상 뚜렷한 이상 변화는 없었다. 결 론 ; 비록 본 임상연구가 비대조 개방 임상연구로서 많은 제한점을 가지고 있지만, 올란자핀이 기존 약물에 내약성을 보이거나 기분증상을 동반하는 정신병에 치료 효과가 있었다. 그리고 기존 항정신병약물 치료시에 문제가 되었던 추체외로 증상과 고프르로락틴 혈증을 포함하는 대부분의 부작용면에서 안전성을 보여 주었다. Objective : This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzpine for the treatment of Korean patients. Mothod : 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. Results : 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(±4.7%)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale)and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-Asberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms)and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed to significant changes during the trial. Conclusions : Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder.In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.

      • 한국인 제2형 당뇨병 환자의 골격근에서 인슐린 신호전달체계의 결함

        최준혁,이관우,김효정,이동훈,이종우,김정은,엄현채,김경미,최성이,정윤석,김현만 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

        연구배경: 제2형 당뇨병에서 나타나는 인슐린 저항성은 간, 지방, 근육 같은 말초조직에서 인슐린의 작용이 떨어지는 것을 말한다. 제2형 당뇨병의 발생기전에 인슐린 저항성과 인슐린 분비능 저하가 같이 관여함은 잘 알려진 사실이다. 인슐린의 세포내에서의 저항성을 규명하기 위한 인슐린의 세포내 신호전달체계에 대한 연구가 활발히 진행되고 있으며 몇몇 연구에서 인슐린 저항성을 가진 골격근육에서 IRS와 관련된 PI3-kinase의 활성감소와 Akt kinase의 활성감소를 보고하고 있으나 아직까지 명확하게 그 기작이 설명되어지지 않고 있다. 본 연구에서는 정상성인, 제2형 당뇨병 환자를 대상으로 경구당부하검사 및 인슐린 클램프검사를 시행하고 인슐린 클램프 검사시 대상인의 근육을 채취하여 인슐린 신호전달 체계(IR-β, IRS, Akt(PKB, Rac) kinase, GSK-3)를 연구하였다. 방법: 연구대상자는 한국인으로서 경구당부하검사상 정상인 및 당뇨병 환자 각각 11명, 9명을 대상으로 하였으며, 정상인은 건강인으로 과거력상 당대사에 영향을 줄 질환이 없고, 현재 당대사에 영향을 줄 약물 복용 및 다른 소견이 없는 경구당부하검사상 정성 내당능을 보이는 대상자로 하였다. 당뇨병환자는 모두 제2형 당뇨병 환자로 이환기간이 만 5년 이내인 경우로 하고, 인슐린으로 치료하는 대상자는 제외하도록 하였다. 대상자의 연령, 체질량지수, 체지방량, 공복시 총콜레스테롤, 중성지방, 고밀도지단백 콜레스테롤 및 HbA1c, 인슐린, C-peptide를 측정하였고, "HOMA model"을 이용하여 베타세포의 기능와 인슐린저항성 정도를 평가하였다. 정상혈당클램프 검사(euhlycemic hyperinsulinemic clamp test)를 시행하고 인슐린 투입 전과 인슐린 투입 30분후, 두차례에 걸쳐 대퇴부 근육생검을 실시한후 western 법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 측정하였다. 결과: 정상인 11명과 당뇨병 환자 9명을 대상으로 하였으며 대상자의 평균 연령, 평균 체질량지수, 체지방량, 허리/엉덩이 둘레의 비(waist hip ratio; WHR)는 두 군간에 차이가 없었다. 평균 공복혈당은 정상군 98.0±0.3㎎/dL, 당뇨병군 208.1±16.5㎎/dL(p<0.05), HbA1c는 정상군 5.4±0.5%, 당뇨병군 9.2±0.6%(p<0.05)였다. "HOMA model"을 이용한 베타세포의 기능과 인슐린저항성은 정상군 56.4±8.5%, 1.4±0.2, 당뇨병군 72.2±52.3%(p<0.01), 10.2±6.3(p<0.01)였으며 정상혈당클램프 검사상 포도당 이용률은 정상군 8.2±0.6㎎/㎏/min, 당뇨병군 3.7±1.1㎎/㎏/min(p<0.01)로 정상군과 당뇨병군간에 유의한 차이를 나타내었다. Western blot법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 인슐린 투입전과 인슐린 투입 30분후 측정하였을 때 IR-β에서는 정상군이 103.9±2.3에서 241.3±18.6, 당뇨군이 108.9±2.2에서 198.7±6.3으로 증가하였다(p=NS). 이는 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 통계적인 차이가 없었다. IRS에서는 정상군이 111.6±7.3에서 295.6±17.2, 당뇨군이 114.5±6.1에서 222.0±23.2로 증가하였으며(p<0.05), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 24% 감소하였다. Akt kinase에서는 103.4±6.0에서 416.8±29.5로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 43% 감소하였다. GSK-3에서는 정상군이 107.7±6.7에서 595.7±28.1, 당뇨군이 104.3±4.8에서 443.3±12.9로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 25% 감소하였다. 결론: 제2형 당뇨병 환자에서 정상인과 비교하여 인슐린 자극후 IR-β는 인산화량의 증가정도가 큰 차이가 없었으나, IRS, Akt kinase, GSK-3에서는 인산화량의 증가 정도가 감소되는 것으로 보아 상위 인슐린 신호전단체계부터 결함이 있는 것으로 생각된다. Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-β), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes(n=9) and control subjects(n=11). Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphroylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-β), Akt and GSK-3. Result: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA_1c in controls and diabetic patients were 98.0±0.3 and 208.1±16.5ng/dl, and 5.4±0.5 and 9.2±0.6%, and 1.4±0.2 in the control subjects, and 72.2±52.3%(p<0.01) and 10.2±6.3(p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp test were 8.2±0.6㎎/㎏/min and 3.7±1.1ng/㎏/min in the control subjects and in the diabetic patients, respectively(p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively(p<0.05). Conclusion: In Korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus (J Kor Soc Endocrinol 17:685∼697, 2002).

      • SCIESCOPUSKCI등재

        Improved Cryopreservation Using Droplet-vitrification and Histological Changes Associated with Cryopreservation of Madder (Rubia akane Nakai)

        Jung-Yoon Yi,Isabelle Sylvestre,Myriam Colin,Mohammad Salma,Sok-Young Lee,Haeng-Hoon Kim,Hong-Jae Park,Florent Engelmann 한국원예학회 2012 원예과학기술지 Vol.30 No.1

        An efficient protocol for cryopreservation of madder hairy root cultures has been developed using droplet-vitrification. In previous study, combining loading solution C4 (35% PVS3) and vitrification solution B5 (80% PVS3) was the most effective method. In this study, we tried three types of vitrification solution, B5, A3 (90% PVS2, on ice), and A5 (70% PVS2, on ice). Combining loading solution C4 and vitrification solution A5 (on ice) showed the best regeneration rate in this study. Histological changes of the cells within the hairy root of madder were also observed in different steps. The cells from the hairy roots of the control treatment were full and intact with different size of vacuoles and obvious cell nucleus having a dark nucleolus. After the stage of preparing for cryopreservation (after preculturing, loading, followed by dehydration solution A5 or B5), intercellular spaces had become distinct, and within cells, the cytoplasms had become denser and week plasmolyses had appeared. The cell plasmolyses were much more apparent and we measured the degree of plasmolysis by calculating, the area of cell/the area of cytoplasm. The value of plasmolysis degree was the highest in the combination of preculture, loading solution C4, and dehydration solution A5, 1.97. Because the highest regeneration rates appeared in the treatment of A5 for 20 min, we could assume that the optimal degree of plasmolysis for cryopreservation might be around 1.97. The changes in cell structure during cryopreservation might be a useful basis for the development of a proper long-term preservation method for madder germplasms.

      • KCI등재

        Agronomic Characteristics and Field Resistance to Bacterial Soft Rot of Transgenic Potatoes with Shiva-1 Gene

        Jung Yoon Yi,Hyo Won Seo,Young Eun Park,Ji Hong Cho,Hyun Mook Cho 한국육종학회 2007 한국육종학회지 Vol.39 No.2

        We performed field trials to assess levels of changes in intrinsic properties and resistance against soft rot of the potato cultivar ‘Irish Cobbler’ upon the introduction of the Shiva-1 gene. Each five lines, transformed with Shiva-1 gene controlled by the PAL5 promoter (P) and by the CaMV 35S promoter (E) were evaluated in the field. In based on evaluation of 10 defined morphological characteristics, all the transgenic clones of both lines proved to be true to type. When five agronomic characteristics were taken into account as well, all the transgenic lines except E8 were considered to be true to type. According to the result of northern blot analysis, seven (P1, P3, P4, P6, E10, E12, and E16) transgenic clones could be distinguished clearly from corresponding untransformed clones. But in three lines (P8, E5, and E8), no hybridization signal was detected. There seems to be positive correlation between the levels of resistance to soft rot and the transgenic expression at mRNA levels in P lines. But in the case of E lines, however, there doesn’t seem to be any correlation between the levels of disease resistance and mRNA expression

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