Differential Immune Responses to Segniliparus rotundus and Segniliparus rugosus Infection and Analysis of Their Comparative Virulence Profiles

Two closely related bacterial species, Segniliparus rotundus and Segniliparus rugosus, have emerged as important human pathogens, but little is known about the immune responses they elicit or their comparative pathophysiologies. To determine the virulence and immune responses of the two species, we compared their abilities to grow in phagocytic and non-phagocytic cells. Both species maintained non-replicating states within A549 epithelial cells. S. rugosus persisted longer and multiplied more rapidly inside murine bone marrow-derived macrophages (BMDMs), induced more pro-inflammatory cytokines, and induced higher levels of macrophage necrosis. Activation of BMDMs by both species was mediated by toll-like receptor 2 (TLR2), followed by mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) signaling pathways, indicating a critical role for TLR2 in Segniliparus-induced macrophage activation. S. rugosus triggered faster and stronger activation of MAPK signaling and IκB degradation, indicating that S. rugosus induces more pro-inflammatory cytokines than S. rotundus. Multifocal granulomatous inflammations in the liver and lung were observed in mice infected with S. rugosus, but S. rotundus was rapidly cleared from all organs tested within 15 days post-infection. Furthermore, S. rugosus induced faster infiltration of innate immune cells such as neutrophils and macrophages to the lung than S. rotundus. Our results suggest that S. rugosus is more virulent and induces a stronger immune response than S. rotundus.ope

(A) study on the lateral cephalometric tomography of TMJ arthrosis

치의학과/박사[한글] 저자는 악관절증의 진단 및 치료에 다소나마 도움을 주고자 정상군 23명과 환자군 20명을 선정하여 두부축방향 사진분석에 따라서 좌·우측의 측방두부계측 단층방사선사진을 중심교위와 중심교합 상태에서 각각 촬영하여 분석하였으며, 또한 악골내 기능적인 측정 항목들의 상관관계를 비교 분석하여 다음과 같은 결론을 얻었다. 1. 하악과두의 수평경사도의 평균치는 정상군에서 우측부위는 20.348°±6.358°, 좌측부위는 18.870°±7.777°였으며 환자군에서 우측부위는 19.350°±7.576°, 좌측부위는17.750°± 6.146°로서 각각 우측부위의 평균치가 좌측부위의 평균치보다 크게 나타내었 다. 2. 관절와에 대한 하악과두의 위치는 정상TMJ군, 환자증상TMJ군에서 모두 하악이 중심교합에서 중심교위로 이동시 후상방으로 위치하였다. 3. 전방관절공폭에 대한 후방관절공폭의 비율은 중심교위에서 정상TMJ군에서 1.593, 환자무증상TMJ군에서 1.604, 환자증상TMJ군에서는 1.671 이었다. 중심교합에서는 정상TMJ군 에서 1.390, 환자무증상TMJ군에서 1.539, 환자증상TMJ군에서 1.196이었다. 4.중심교위에서의 교합평면선과 구치부폐쇄로가 이루는 각(∠C^^2) 항목에서만이 정상TMJ군, 환자무증상TMJ군, 환자증상TMJ군은 P<0.05수준에서 유의성을 나타내었다. 5. 관절와외 고경 (Fh),중심교합에서의 안이평면과 구치부폐쇄로가 이루는 각 (∠C^^1), 중심교위에서의 교합평면선과 구치부폐쇄로가 이루는 각 (∠C^^2), 항목에서 정상TMJ군과 환자TMJ군은 P<0.05수군에서 유의성을 나타내었다. 6. 모든 계측치들 사이에서의 상관계수(r)는 0.8771≥ r≥ -0.9039에 존재하였으며, 이가운데 최고치는 정상TMJ군에서는 제 1대구치의 교합간 거리 (Fm)대 제 1소구치의 교합간 거리 (Fp) 항목에서 관찰되었고, 환자무증상TMJ군에서는 과두중심정이동거리 (O^^0∼O^^2)대 과두중심절이동각(∠A) 항목에서 관찰되었고, 환자증상TMJ군에서는 안이평면과 구치부폐쇄로가 이루는 각 (∠C^^l ) 대 중심교위에서의 교합평면과 구치부폐쇄로가 이루는 각(∠C^^2) 항목에서 각각 관찰되었다. [영문] The author obtained individualized lateral cephalometric tomograms from 23 young adults(46 of left and right normal TMJ) with normal occlusion and 20 patients (14 of patient asymptomatic TMJ and 26 of patient symptomatic TMJ) with clicking and painful TMJ after the analysis of submental vertex view. Individualized lateral cephlometric tomogram analysis and TMJ space analysis were per-formed after tracing each film. All data from these analysis was recorded and statistically processed with CYBER computer system. The results were obtained as fellows. 1. In submental vertex view, the mean condylar angulation of Rt. side in normal group was 20.348°±6.358°, Lt. side was 18.870°±7.777° and Rt. side in patient group was 19.350°±7.576°, Lt. side was 17.750°±6.146° respectively. The mean condylar angulation of Rt. side was larger than Lt. side in normal and patient group. 2. When the mandible was moved from centric occlusion to centric relation, condylar position relating to the glenoid fossa was placed posteriorly and superiorly in normal TMJ group and patient symptomatic TMJ group. 3. In centric relation position, the proportion of anterior space to posterior space was 1.593 for normal TMJ group, 1.604 for patient asymptomatic TMJ group and 1.671 for patient symptomatic TMJ group. In centric occlusion position, 1.370 for normal TMJ group, 1.539 for patient asymptomatic TMJ group and 1.176 for patient symptomatic group. 4. Normal TMJ group, patient asymptomatic TMS group and patient symptomatic TMJ group and patient symptomatic TMJ group revealed significant difference in ∠C^^2 measurement.(ANOVA-tet, p<0.05) 5. Normal group and patient group revealed significant difference in Fh, ∠C^^1 and ∠C^^2 measurement. (T-test. p<0.05) 6. There were strong positive correlation (0.8771) between Fp and Fm, and strong negative correlation (-0.9039) belween ∠C^^2 and ∠C^^1 from the lateral cephalometric tomogram analysis.restrictio

A Study on the surface segregation and oxidation of Fe-36wt%Ni invar alloys

학위논문(박사)--서울대학교 대학원 :금속공학과,1995.Docto

실크 피브로인 섬유와 수용액의 항산화 특성

학위논문(석사)--서울대학교 대학원 :천연섬유학과,2000.Maste

Amyloidβ-Induced mTORC1 Activation Up-Regulates cyclinD1/CDK4 and cyclinE/CDK2 Levels Leading to Neuronal Apoptosis

학위논문 (석사)-- 서울대학교 대학원 : 수의학과, 2016. 8. 한호재.Alzheimer's disease (AD) is a neurodegenerative disorder induced by Amyloid β (Aβ) resulting in tau hyper-phosphorylation which is associated with neuronal apoptosis. Because no therapeutic targets for AD have been identified yet, I investigated relationship of cyclin-dependent kinases (CDKs) with tau phosphorylation in Aβ-induced neuronal apoptosis. In the present study, Aβ induced apoptosis in a time-dependent manner. Aβ increased the calcium influx which was dependent on the L-type calcium channel. I showed that the Aβ increased ROS (Reactive oxygen species) generation was blocked by EGTA (extracellular calcium chelator) but not by BAPTA-AM (intracellular calcium chelator) indicating that Aβ-induced calcium influx up-regulates ROS. The Aβ-induced ROS increased the HIF-1α expression which was blocked by N-acetyl-L-cysteine (NAC, ROS scavenger). Through HIF-1α siRNA transfection, I determined that Aβ stimulates mTORC1 phosphorylation through PI3K/AKT signaling. Moreover, my results show that Aβ-induced mTOR activation inhibits autophagy, while Aβ-activated mTOR increases cyclinD1/CDK4 and cyclinE/CDK2 expression. Interestingly, Aβ-inhibited autophagy up-regulated cyclinD1/CDK4 and cyclinE/CDK2 which were blocked by Trehalose (an autophagy inducer). These results suggest that Aβ-induced mTOR activation up-regulates the expression of cyclins and CDKs while the accumulation of cyclins and CDKs is attributed to Aβ-inhibited autophagy. CDKs were directly bound to tau, and leaded to phosphorylating tau which was blocked by Flavopiridol (CDK inhibitor). Phosphorylation of tau induced detachment from microtubule leading microtubule destabilization-mediated neuronal apoptosis which was blocked by Paclitaxel (microtubule stabilizer). In conclusion, Aβ-induced mTOR activation through HIF1α up-regulated the cyclinD1/CDK4 and cyclinE/CDK2 levels which were essential for tau hyper-phosphorylation leading to neuronal apoptosis.INTRODUCTION 1 MATERIALS AND METHODS 5 RESULTS 17 DISCUSSION 41 CONCLUSION 48 REFERENCES 51 ABSTRACT IN KOREAN (국문 초록) 62Maste

(A)Study on the youth discourse in Korea during Japanese colonial rule

학위논문(박사)--서울대학교 대학원 :국사학과,2005.Docto

녹농균(pseudomonas aeruginosa)의 단일종과 복수종의 세균막 형성에 영향을 주는 유전학적 및 분자생물학적 요인

Dept. of Medical Science/박사Pseudomonas aeruginosa is an opportunistic pathogen, and it became one of the greatest threats to human health worldwide due to their adaptation ability for various environments and resistance against multiple classes of antibiotics. These characteristics of the bacterium contributed to them to become a major causative agent of healthcare-associated infections (HAIs). They are, also, known to develop robust biofilms. Biofilm is a community of microbes that inhabits on various surfaces and typically surrounded by extracellular matrices (ECM). Chapter I is a literature review that includes brief history of biofilms, background information of P. aeruginosa and its biofilm, biofilm infections and multi-species biofilms. In chapter II, the investigation was initiated to identify genes that affect the enhancement of the P. aeruginosa biofilm by the sub-minimal inhibitory concentrations (MICs) treatment of antibiotics. We screened a transposon (Tn) mutant library of PAO1, a prototype P. aeruginosa strain. Among ~5,000 mutants, a fiuA gene mutant was verified to form very defective biofilms in the presence of sub-MIC carbenicillin. The fiuA gene encodes ferrichrome receptor A, involved in the iron acquisition process. Of note, biofilm formation was not decreased in the ΔpchΔpvd mutant defective in the production of pyochelin and pyoverdine, two well-characterized P. aeruginosa siderophore molecules. Moreover, the ΔfiuA, a non-polar fiuA deletion mutant, produced a significantly decreased level of elastase, a major virulence determinant. Mouse airway infection experiments revealed that the mutant expressed significantly less pathogenicity. In chapter III, we investigate pathogenic factors of the Pseudomonas aeruginosa polymicrobial biofilm. Since the introduction of biofilm infection model in medical field, it has discovered that biofilms are responsible for majority of chronic infections. However, the treatments of the chronic biofilm infections are still very limited to surgical removal of the infected sites. Most of the chronic biofilm infections are known to be polymicrobial infections. Pseudomonas aeruginosa and Enterococcus faecalis are two of the most spotted bacterial species in biofilm infections but the study of the interactions between these bacteria was very limited. In this investigation, we observed phenotypic changes in the dual-species biofilm of P. aeruginosa and E. faecalis, such as dramatic enhancement in elasticity of the biofilm, and distinct spatial distribution of each bacterial species in the biofilm. We have found that these phenotypic characteristics were associated with exopolysaccharides (EPS), especially Pel and Psl. Together, our results suggest that fiuA gene has pleiotropic functions that affect P. aeruginosa biofilm development and virulence. The targeting of FiuA could enable the attenuation of P. aeruginosa virulence and may be suitable for the development of a drug that specifically controls the virulence of this important pathogen. Also, Psl is more associated to the bacteria-surface adhesion and the interaction between P. aeruginosa cells to form a structured biofilm, and Pel is more related to interspecies interaction in the polymicrobial biofilm. Therefore, these two EPS can be targets for polymicrobial biofilm infection eradication. 녹농균는 기회감염균으로서 다양한 환경에 대한 높은 적응력과 여러 항생제에 대한 저항성으로 인해 인류의 건강에 큰 위협으로 급부상하고 있다. 이러한 균의 특성들은 이 균이 원내감염을 일으키는 주요 원인이 되는데 큰 역할을 하였다. 또한 이 균은 바이오필름을 매우 잘 형성하는 균으로 알려져 있다. 바이오필름은 미생물들의 공동체 집단으로서 다양한 물질의 표면에 존재하며 일반적으로 세포외기질 등에 의해 둘러싸여 있다. Chapter I 은 바이오필름에 대한 간단한 역사와 녹농균과 녹농균의 바이오필름에 대한 기본 정보, 바이오필름 감염과 multi-species 바이오필름에 대한 literature review로 구성되어 있다. Chapter II에서는 녹농균 바이오필름의 형성이 최소생장억제농도 이하의 항생제 처리 시, 오히려 더 증가하는 현상의 원인이 되는 유전자를 찾기 위해 연구가 시작되었다. 녹농균의 protoptye인 PAO1균주의 transposon (Tn) mutant library의 돌연변이를 약 5,000개 정도 검사한 결과, fiuA 유전자에 transposon이 삽입된 균주에서 carbenecillin이 최소생장억제농도 이하로 처리되었을 경우, 바이오필름의 형성이 결여됨이 확인되었다. fiuA 유전자는 녹농균의 철 이온 획득에 관여하는 ferrich...ope

멘터(mentor)-프로터제이(protege)간 관계 다양성(diversity)과 멘터링 효과에 관한 연구

학위논문(석사)--서울대학교 대학원 :경영학과 경영학전공,2002.Maste

명령어 분포와 시멘틱 분석을 통한 다형성 웜의 탐지 기법

Maste