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      • Depletion of adipocyte Becn1 leads to lipodystrophy and metabolic dysregulation

        Yaechan Song,Young Jin,Yul Ji,Sung Sik Choe,Yong Geun Jeon,Heeju Na,Tae Wook Nam,Hye Jeong Kim,Hahn Nahmgoong,Sung Min Kim,Jae-woo Kim,Ki Taek Nam,Je Kyung Seong,Daehee Hwang,Chan Bae Park,In Hye Lee 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

        Macroautophagy is a catabolic process that delivers damaged and unnecessary cytosolic contents to lysosomes for removal of defective subcellular organelles and proteins. Becn1 is a key regulator of autophagy, forming a complex with class III phosphatidylinositol 3-kinase (PI3K-III) to initiate autophagosome formation. Although Becn1 has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, its function in mature adipocytes remains elusive. In this study, we implemented Adipoq-Cre to generate adipocyte-specific Becn1 KO (BaKO) mice to identify the function of autophagy in adipose tissue homeostasis. BaKO mice naturally developed severe lipodystrophy and metabolic dysregulation, which were exacerbated upon high dietary fat intake. These mice also acquired adipose tissue inflammation, hepatic steatosis, and insulin resistance which advanced to early mortality. Immortalized stromal vascular cells (imSVCs) were established in-vitro to conditionally knock-out Becn1 upon tamoxifen treatment. Ablation of Becn1 in adipocytes led to programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress through activation of protein kinase R-like ER kinase (PERK) – eukaryotic initiation factor 2α (eiF2α) axis. This led to excessive unfolded protein response (UPR) and accelerated cell death through notable induction of C/EBP homologous protein (CHOP) and Bax expression. Taken together, these data suggest that adipocyte-Becn1 would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.

      • <i>Orientia tsutsugamushi</i> Subverts Dendritic Cell Functions by Escaping from Autophagy and Impairing Their Migration

        Choi, Ji-Hye,Cheong, Taek-Chin,Ha, Na-Young,Ko, Youngho,Cho, Chung-Hyun,Jeon, Ju-Hong,So, Insuk,Kim, In-Kyu,Choi, Myung-Sik,Kim, Ik-Sang,Cho, Nam-Hyuk Public Library of Science 2013 PLoS neglected tropical diseases Vol.7 No.1

        <▼1><P><B>Background</B></P><P>Dendritic cells (DCs) are the most potent antigen-presenting cells that link innate and adaptive immune responses, playing a pivotal role in triggering antigen-specific immunity. Antigen uptake by DCs induces maturational changes that include increased surface expression of major histocompatibility complex (MHC) and costimulatory molecules. In addition, DCs actively migrate to regional lymph nodes and activate antigen-specific naive T cells after capturing antigens. We characterize the functional changes of DCs infected with <I>Orientia tsutsugamushi</I>, the causative agent of scrub typhus, since there is limited knowledge of the role played by DCs in <I>O. tsutsugamushi</I> infection.</P><P><B>Methodology/Principal Finding</B></P><P><I>O. tsutsugamushi</I> efficiently infected bone marrow-derived DCs and induced surface expression of MHC II and costimulatory molecules. In addition, <I>O. tsutsugamushi</I> induced autophagy activation, but actively escaped from this innate defense system. Infected DCs also secreted cytokines and chemokines such as IL-6, IL-12, MCP5, MIP-1α, and RANTES. Furthermore, <I>in vitro</I> migration of DCs in the presence of a CCL19 gradient within a 3D collagen matrix was drastically impaired when infected with <I>O. tsutsugamushi</I>. The infected cells migrated much less efficiently into lymphatic vessels of ear dermis <I>ex vivo</I> when compared to LPS-stimulated DCs. <I>In vivo</I> migration of <I>O. tsutsugamushi</I>-infected DCs to regional lymph nodes was significantly impaired and similar to that of immature DCs. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in <I>O. tsutsugamushi</I>-infected DCs.</P><P><B>Conclusion/Significance</B></P><P>These results suggest that <I>O. tsutsugamushi</I> can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.</P></▼1><▼2><P><B>Author Summary</B></P><P>Scrub typhus is an acute febrile illness caused by <I>Orientia tsutsugamushi</I> infection and is one of the main causes of febrile illness in the Asia-Pacific region. If not properly treated with antibiotics, patients often develop severe vasculitis that affects multiple organs, and the mortality rate of untreated patients reaches up to 30%. To understand the pathogenic mechanisms of the infectious disease, we characterized the functional changes of <I>O. tsutsugamushi</I>–infected dendritic cells (DCs), which play a pivotal role in orchestrating innate and adaptive immune responses. The obligate intracellular bacteria efficiently infected bone marrow-derived DCs and activated the cells as measured by induced surface expression of MHC II and costimulatory molecules, secretion of cytokines and chemokines, and autophagy induction. However, the live bacteria actively escaped from host autophagosomes and the migration of infected cells was severely impaired <I>in vitro</I>, <I>ex vivo</I>, and <I>in vivo</I> infection models. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in <I>O. tsutsugamushi</I>-infected DCs. These results suggest that <I>O. tsutsugamushi</I> can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.</P></▼2>

      • KCI등재

        Public and Clinician Perspectives on Ventilator Withdrawal in Vegetative State Following Severe Acute Brain Injury: A Vignette Survey

        Yoo Shin Hye,Lee Jung,Song In Gyu,Jeon So Yeon,Kim Min Sun,Park Hye Yoon 대한의학회 2024 Journal of Korean medical science Vol.39 No.35

        Background: The vegetative state (VS) after severe acute brain injury (SABI) is associated with significant prognostic uncertainty and poor long-term functional outcomes. However, it is generally distinguished from imminent death and is exempt from the Life-Sustaining Treatment (LST) Decisions Act in Korea. Here, we aimed to examine the perspectives of the general population (GP) and clinicians regarding decisions on mechanical ventilator withdrawal in patients in a VS after SABI. Methods: A cross-sectional survey was undertaken, utilizing a self-reported online questionnaire based on a case vignette. Nationally selected by quota sampling, the GP comprised 500 individuals aged 20 to 69 years. There were 200 doctors from a tertiary university hospital in the clinician sample. Participants were asked what they thought about mechanical ventilator withdrawal in patients in VS 2 months and 3 years after SABI. Results: Two months after SABI in the case, 79% of the GP and 83.5% of clinicians had positive attitudes toward mechanical ventilator withdrawal. In the GP, attitudes were associated with spirituality, household income, religion, the number of household members. On the other hand, clinicians’ attitudes were related to their experience of completing advance directives (AD) and making decisions about LST. In this case, 3 years after SABI, 92% of the GP and 94% of clinicians were more accepting of ventilator withdrawal compared to previous responses, based on the assumption that the patient had written AD. However, it appeared that the proportion of positive responses to ventilator withdrawal decreased when the patients had only verbal expressions (82% of the GP; 75.5% of clinicians) or had not previously expressed an opinion regarding LST (58% of the GP; 39.5% of clinicians). Conclusion: More than three quarters of both the GP and clinicians had positive opinions regarding ventilator withdrawal in patients in a VS after SABI, which was reinforced with time and the presence of AD. Legislative adjustments are needed to ensure that previous wishes for those patients are more respected and reflected in treatment decisions.

      • KCI등재후보

        Seasonal Fluctuation of Chlorophyll a Concentration in the Size Fractionation of Phytoplankton in Daechung Reservoir

        Mun, Jong-Jeon,Lee, Sang-Wook,Hwang, Soon-Jin,Oh, In-Hye 한국육수학회 2001 생태와 환경 Vol.34 No.4

        여러 지역의 호소환경에서 picoplankton이 중요한 일차 생산자로 보고되고 있는데 대청호에서 이를 조사하기 위하여 1998년 9월부터 1999년 9월까지 식물 플랑크톤 크기에 따른 엽록소 농도의 계절적 변화를 조사하였다. 200㎛ 이하의 식물플랑크톤은 대전취수탑에서 0.7∼36.9㎍/ℓ, 만입부에서 0.5∼23.5㎍/ℓ 회남대교에서 1.9∼20.1㎍/ℓ, 대청댐에서 0.5∼17.4㎍/ℓ이었는데, 조사지점 4곳에서 모두 9월에 최대치를 나타내었으며 그 이후는 서서히 감소되어 4∼6월에 최소값을 보이는 경향을 나타내었다. 계절에 따른 엽록소 농도의 크기별 조성비율을 보면, 연중 microplankton과 nanoplankton 조성비율은 큰 변이를 보였는데, 회남 대교를 제외한 조사지역 3 곳에서 6∼10월에는 microplankton의 비율이 높았으나 3월에는 조성비율이 매우 낮은 경향을 보였다. 그러나 조사지역 4곳 모두에서 picoplankton은 연중 2.0∼24.3%로 거의 일정하였다. Since a substantial part of the total planktonic primary production is due to the activity of the picoplankton, seasonal change of chlorophyll a in the picoplankton, nanoplankton and microplankton was determined at four locations in Daechung Reservoir from September in 1998 to September in 1999. Chlorophyll a concentration(<200㎛) was 0.7∼36.9㎍/ℓin TAE(Taejeon site), 0.5∼23.5㎍/ℓin MAN(Man site), 1.9∼20.1㎍/ℓ in HOE(Hoenam site), and 0.5∼17.4㎍/ℓin DAM(Dam site). Generally it was observed the the highest concentration of chlorophyll a was in September and the lowest in April to June. The relative contribution of chlorophyll a of each fraction was changed dramatically through the year. Relative contribution of chlorophyll a of microplankton was high from June to October, and low in March in all locations except HOE. However chlorophyll a concentration of picoplankton fraction was 2.0∼24.3% of total chlorophyll a (<200㎛) through the year and did not show any dramatic changes at all locations.

      • KCI등재

        Feasibility and Functional Evaluation of Noninvasive Ventilation Capable Equipment from the Delivery Room to Neonatal Intensive Care Unit: A Bench Study

        ( Hye Jung Cho ),( Eun Jin Kim ),( Dong Woo Son ),( In-sang Jeon ),( Ji Sung Lee ) 대한주산의학회 2019 Perinatology Vol.30 No.2

        Objective: The use of noninvasive ventilation (NIV) for newborns requiring respiratory support in delivery room (DR) is recommended. However, the details related to such use are not well established. A bench investigation on the performance of available NIV equipment was conducted. Methods: Two T-piece resuscitators (TPRs) and three ventilators were tested with a Neonatal Lung Simulator which is capable of recording the pressure, flow, and volume. We measured the pressurization and delivered volume (DV) of nasal continuous positive airway pressure (nCPAP), bubble CPAP (bCPAP)/nasal high-frequency ventilation (nHFV), and synchronized nasal intermittent positive pressure ventilation (SNIPPV) in apneic and breathing models. Temperature and absolute humidity (AH) at the Y-piece were checked for 10 minutes in each setting while the Y-piece on an open bassinet or in a preheated incubator. Results: The pressurization was well achieved with every combination except for TPRs on nCPAP. DV was well provided using bCPAP/nHFV and SNIPPV in the breathing model. With bCPAP, DV decreased significantly in apneic model. On the bassinet, temperature and AH dropped to ambient temperature and approximately 25 mgH2O/L within 4 minutes, respectively. In the incubator, temperature and AH on all pre-humidified machines were maintained above 34°C and 30 mgH2O/L for 5 minutes, respectively. Those without pre-humidification were below 30°C and less than 20 mgH2O/L, respectively. Conclusion: Other combination of device/equipment than TPR tested seemed more feasible for nCPAP. The use of equipment with backup ventilation and heated-humidified gas in preheated incubators would be more appropriate NIV for premature infants in DR and during transport.

      • SCIESCOPUSKCI등재

        Quality of Life and Economic Burden in Recessive Dystrophic Epidermolysis Bullosa

        ( In Kyung Jeon ),( Hye Rang On ),( Soo Chan Kim ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.1

        Background: Patients with recessive dystrophic epidermolysis bullosa (RDEB) exhibit blisters and erosions since birth, causing pain, pruritus and various complications. RDEB affects quality of life (QoL) in physical, emotional and social aspects. Furthermore, interminable dressing changes and supportive therapies impose a significant economic burden on the patient s family. Objective: We assessed the QoL and economic burden in patients with RDEB. Methods:Sixteen patients with RDEB were surveyed to assess the QoL and economic burden. Patients answered questionnaires consisting of a visual analogue scale (VAS) on pain and pruritus, Skindex-29, Quality of Life in EB questionnaire (QOLEB), and the economic burden due to EB. Results:Thirteen patients with RDEB completed the questionnaire. Female patients presented higher VAS, QOLEB and total Skindex-29 scores than male patients. Patients with RDEB showed severe levels of pruritus, which was more intolerable than pain. Mean VAS score on pain in RDEB was higher than in oral lichen planus and post-herpetic neuralgia. VAS score on pruritus was similar to those in chronic urticaria, atopic dermatitis, and prurigo nodularis. Compared with other dermatologic conditions, patients with RDEB were profoundly affected in all three scales of skindex-29. Mean “medical cost” in a month was $257. 54 (USD) (±169. 39) and mean “dressing cost” was $358. 41 (USD) (±312. 55), which was negatively related to patient age. Conclusion: RDEB had a profound impact on QoL and economic burden. Compared with other dermatologic diseases, RDEB showed severe symptoms and QoL was seriously impaired. Most patients sustained economic burdens, especially on preparing dressing materials. Younger patients experienced more economic burdens.

      • SCISCIESCOPUS

        A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses

        Sun, Dawei,Lee, Gina,Lee, Jun Hee,Kim, Hye-Yeon,Rhee, Hyun-Woo,Park, Seung-Yeol,Kim, Kyung-Jin,Kim, Yongsung,Kim, Bo Yeon,Hong, Jong-In,Park, Chankyu,Choy, Hyon E,Kim, Jung Hoe,Jeon, Young Ho,Chung, J Nature Publishing Group, a division of Macmillan P 2010 Nature Structural and Molecular Biology Vol.17 No.10

        In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing cell growth and overcoming stresses. Here we identify functional SpoT orthologs in metazoa (named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila melanogaster) and reveal their structures and functions. Like the bacterial enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a conserved His-Asp??box motif for Mn<SUP>2+</SUP> binding. Consistent with these structural data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3??5??diphosphate (ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria. Notably, deletion of Mesh1 (Q9VAM9) in Drosophila induces retarded body growth and impaired starvation resistance. Microarray analyses reveal that the amino acid??starved Mesh1 null mutant has highly downregulated DNA and protein synthesis??related genes and upregulated stress-responsible genes. These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses.

      • KCI등재

        Concentrations and Distributions of 5 Metals in Groundwater Based on Geological Features in South Korea

        Jeon, Sang-Ho,Park, Sunhwa,Song, Da-Hee,Hwang, Jong-yeon,Kim, Moon-su,Jo, Hun-Je,Kim, Deok-hyun,Lee, Gyeong-Mi,Kim, Ki-In,Kim, Hye-Jin,Kim, Tae-Seung,Chung, Hyen-Mi,Kim, Hyun-Koo 한국토양비료학회 2017 한국토양비료학회지 Vol.50 No.5

        To establish new metal groundwater standard, 5 metals such as aluminum, chromium, iron, manganese, and selenium were evaluated by Chemical Ranking Of groundWater pollutaNts (CROWN) including possibility of exposure, toxicity, interest factor, connection standard for other media, and data reliability. 430 groundwater samples in 2013 and 2014 were collected semiannually from 110 groundwater wells and they were analyzed for selenium, manganese, iron, chromium, and aluminum. For this study, 430 groundwater samples were categorized into 3 geological distribution features, such as igneous, metamorphic, and sedimentary rock region and geological background levels were divided by pre-selection methods. For the results, the average concentrations of aluminum, chromium, iron, manganese, and selenium in 430 groundwater samples were $0.0008mg\;L^{-1}$, $0.0001mg\;L^{-1}$, $0.174mg\;L^{-1}$, $0.083mg\;L^{-1}$, and $0.0004mg\;L^{-1}$, respectively. In addition, among various geologies, average concentration of selenium was the highest in igneous rock region, average concentrations of chromium, manganese and aluminum were the greatest in sedimentary rock region, and average concentration of iron was the most high in metamorphic rock region. As a result of the geological background concentration with pre-selection method, background concentrations of selenium and aluminum in groundwater samples were the highest from sedimentary rock as $0.0010mg\;L^{-1}$ and $0.0029mg\;L^{-1}$ and background concentrations of manganese and iron in groundwater samples were the greatest from metamorphic rock as $0.460mg\;L^{-1}$ and $1.574mg\;L^{-1}$, and no chromium background concentration in groundwater samples was found from all geology.

      • KCI등재

        Evaluation on Four Volatile Organic Compounds (VOCs) Contents in the Groundwater and Their Human Risk Level

        Song, Dahee,Park, Sunhwa,Jeon, Sang-Ho,Hwang, Jong Yeon,Kim, Moonsu,Jo, Hun-Je,Kim, Deok-Hyun,Lee, Gyeong-Mi,Kim, Ki-In,Kim, Hye-Jin,Kim, Tae-Seung,Chung, Hyen Mi,Kim, Hyun-Koo 한국토양비료학회 2017 한국토양비료학회지 Vol.50 No.4

        In this study, we monitored 4 volatile organic compounds (VOCs) such as chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane in groundwater samples to determine the detection frequency and their concentrations and evaluated the health risk level considering ingestion, inhalation, and skin contact. 75 groundwater wells were selected. 24 wells were from monitoring background groundwater quality level and 51 wells were from monitoring groundwater quality level in industrial or contamination source area. In the results, the detection frequency for chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane was 42.3%, 8.1%, 6.0%, and 3.4%, respectively. The average concentrations of VOCs were high in the order of chloroform ($1.7{\mu}g\;L^{-1}$), dichloromethane ($0.08{\mu}g\;L^{-1}$), tetrachloromethane ($0.05{\mu}g\;L^{-1}$), and 1,2-dichloroethane ($0.05{\mu}g\;L^{-1}$). Chloroform had the highest detection frequency and average detection concentration. In the contaminated groundwater, the detection frequency of VOCs was high in the order of chloroform, dichloromethane, 1,2-dchloroethane, and tetrachloromethane. The average concentrations for chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane were $2.23{\mu}g\;L^{-1}$, $0.08{\mu}g\;L^{-1}$, $0.07{\mu}g\;L^{-1}$, and $0.06{\mu}g\;L^{-1}$, respectively. All the 4 compounds were detected at industrial complex and storage tank area. The maximum concentration of chloroform, dichloromethane, and 1,2-dichloroethane was detected at industrial complex area. Especially, the maximum concentration of chloroform and dichloromethane was detected at a chemical factory area. In the uncontaminated groundwater, the detection frequency of VOCs was high in the order of chloroform, dichloromethane, and 1,2-dchloroethane and tetrachloromethane was not detected. The average concentrations for chloroform, dichloromethane, and 1,2-dichloroethane were $0.57{\mu}g\;L^{-1}$, $0.07{\mu}g\;L^{-1}$, and $0.03{\mu}g\;L^{-1}$, respectively. Although chloroform in the uncontaminated groundwater was detected the most, the concentration of chloroform was not exceeding water quality standards. By land use, the maximum detection frequency of 1,2-dichloroethane was found near a traffic area. For human risk assessment, the cancer risk for the 4 VOCs was $10^{-6}{\sim}10^{-9}$, while the non-cancer risk (HQ value) for the 4 VOCs is $10^{-2}{\sim}10^{-3}$.

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