TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells

Heo, S.K.,Noh, E.K.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland 2017 European journal of pharmacology Vol.804 No.-

<P>Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.</P>

Genetic and functional analysis of TBK1 variants in Korean patients with sporadic amyotrophic lateral sclerosis

Kim, Y.E.,Oh, K.W.,Noh, M.Y.,Nahm, M.,Park, J.,Lim, S.M.,Jang, J.H.,Cho, E.H.,Ki, C.S.,Lee, S.,Kim, S.H. Elsevier Science Pub. Co 2017 Neurobiology of aging Vol.50 No.-

The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. One frameshift (c.1414delA) and 3 missense variants of uncertain significance in TBK1 were found in 4 patients each. In vitro functional studies revealed that the c.1414delA (p.Ile472Serfs*8) variant was associated with reduced mRNA expression of TBK1. Moreover, protein expression of this variant in patient-derived fibroblasts disrupted binding to autophagy adapter proteins and inhibited the function of TBK1 in HEK293T cells. In contrast, the 3 other missense variants of uncertain significance showed normal mRNA expression and no abnormalities in protein function. Based on these findings, the frequency of pathogenic TBK1 variants in Korean sALS patients was estimated to be 0.8% (1/129). In conclusion, pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients.

Molecular investigation of tick-borne pathogens in ticks from grazing cattle in Korea

Kang, S.W.,Doan, H.T.T.,Choe, S.E.,Noh, J.H.,Yoo, M.S.,Reddy, K.E.,Kim, Y.H.,Kweon, C.H.,Jung, S.C.,Chang, K.Y. Elsevier 2013 Parasitology international Vol.62 No.3

This study was carried out to identify the tick species that infest grazing cattle and to determine the presence of tick-borne pathogens transmitted by these ticks in Korea. A total of 903 ticks (categorized into 566 tick pools) were collected from five provinces during 2010-2011. The most prevalent tick species was Haemaphysalis longicornis, followed by three Ixodes spp. ticks. The collected ticks were infected with both rickettsial and protozoan pathogens. In all, 469 (82.9%) tick pools tested positive for the Anaplasma/Ehrlichia 16S rRNA gene, whereas 67 (11.8%) were positive for the Babesia/Theileria 18S rRNA gene. Among the rickettsial pathogens, E. canis was detected with the highest rate (22.3%), followed by A. platys (20%), E. chaffeensis (19.4%), E. ewingii (19.3%), Rickettsia sp. (12.4%), A. phagocytophilum (5.5%) and E. muris (0.5%). Among the protozoan pathogens, T. equi was detected with the highest rate (7.2%), followed by T. sergenti/T. buffeli (3.7%) and B. caballi (0.35%). Simultaneous infections with up to seven pathogens were also identified. In particular, ticks infected with rickettsial pathogens were also infected with protozoan pathogens (22 samples). All five provinces investigated infected with tick-borne pathogens.

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells

Heo, S.K.,Noh, E.K.,Yoon, D.J.,Jo, J.C.,Koh, S.,Baek, J.H.,Park, J.H.,Min, Y.J.,Kim, H. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.747 No.-

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b<SUP>+</SUP> and CD14<SUP>+</SUP> cells depended on ERK-NF-κB axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL.

이중밴드 히스테리시스 전류 제어 방식

오원현(W.H Oh),유창훈(C.H. Yoo),신은철(E.C. Shin),박성민(S.M. Park),노학엽(H.Y. Noh),유지윤(J.Y. Yoo) 전력전자학회 2003 전력전자학술대회 논문집 Vol.2003 No.7(2)

Hysteresis controllers are intrinsically robust to system parameters, exhibit very high dynamic response and are suitable for simple implementation But the current control using a conventional hysteresis controller has the disadvantage that high switching frequency may happen due to lack of coordination among individual hysteresis controllers of three phases This will of course increase the switching loss in addition, the current error IS not strictly limited So, In this paper to reduce the switching frequency, a double band hysteresis current contioller is proposed The presented control system was tested with digital simulation in the Borland C++ program and demonstrate the advantage of proposed hysteresis current controller

다양한 생물학적 하수처리공정에서의 다환방향족탄화수소류(PAHs)의 제거특성

정진희,이지현,노지희,김한석,최호은,박출재,정병길 동아대학교 환경문제연구소 2008 硏究報告 Vol.30 No.1

Polycyclic aromatic hydrocarbons (PAHs) can be formed both natural and anthropogenic processes. Both sources are contributors of hazardous compounds, but anthropogenic sources are considerably more damaging to the environment. The purpose of this research obtains a primary data base to treat PAHs-contaminated sewage sludge effectively and properly by figuring out concentrations and origins of PAHs which load in influent of sewage treatment plant. During the experiment period from April 2007 to June 2007, concentrations of PAHs in influent, effluent and dewatered cake at 5 different sewage treatments at City were analysed by using a gas chromatography/mass spectrometer(GC/MS). The volume of samples from influent and effluent was 2 liters. The weight of sample from the dewatered cake was 500g. Ranges of concentrations of PAHs in influent, effluent and dewatered cake were 72.3-83.9 μg/L, 1.1 -6.8 μg/L and 2,669.6-3,491.5 μg/kg respectively. The most abundant compounds of PAHs were fluorene and phenanthrene for all sewage treatment plants. The ratios have been used extensively to distinguish petrogenic or pyrogenic sources of PAHs in the dewatered cake at 5 different sewage treatment plants. It was not easy to di stinguish between petrogenic and pyrogenic sources of PAHs because the PAHs contained both characteristics. 본 연구에서는 하수처리장으로 유입되는 PAHs 의 배출 원을 파악하여 생물학적 처리에 의해 처분되는 하수 슬러지의 경로별 유입 PAHs 의 배출량 및 농도을 추정한 결과 다음과 같은 결론을 얻을 수 있었다. 1. 하수처리장 유입수, 방류수 및 탈수케잌 의 PAHs 농도는 각각 72.3~83.9 μg/L,1.1~6.8 μg/L, 2,669.6 ~ 3,491.5 μg/kg 의 범위를 나타내 었다. 2. 유입수와 탈수케잌 의 경우 모든 하수처리장에서 PAHs 중 각각 fluorene과 phenanthrene 이 가장 높은 농도를 나타내었으며,공장폐수가 유입되는 하수처리장의 경우 벤젠고리 5 - 6개의 고비점 화합물들이 가정하수가 유입되는 하수처리장 에 비하여 다소 높게 나타났다. 3. 모든 하수처리장에서 PAHs 중 저분자량의 LPAHs 제거효율은 85.0% 이상을 나타내었으며,이는 활성슬러지법을 이용한 미생물에 의한 분해로 판단된다. 그러나 고분자량의 HPAHs 제거효율은 활성슬러지법만으로는 67.3% 정도로 낮아 2차 처리가 필요할 것으로 판단된다.

다양한 생물학적 하수처리공정에서의 다환방향족탄화수소류(PAHs)의 제거특성

정진희,이지현,노지희,김한석,최호은,박출재,정병길 東亞大學校 附設 環境問題硏究所 2008 硏究報告 Vol.29 No.1

Polycyclic aromatic hydrocarbons (PAHs) can be formed both natural and anthropogenic processes. Both sources are contributors of hazardous compounds, but anthropogenic sources are considerably more damaging to the environment. The purpose of this research obtains a primary data base to treat PAHs-contaminated sewage sludge effectively and properly by figuring out concentrations and origins of PAHs which load in influent of sewage treatment plant. During the experiment period from April 2007 to June 2007, concentrations of PAHs in influent, effluent and dewatered cake at 5 different sewage treatments at City were analysed by using a gas chromatography/mass spectrometer(GC/MS). The volume of samples from influent and effluent was 2 liters. The weight of sample from the dewatered cake was 500g. Ranges of concentrations of PAHs in influent, effluent and dewatered cake were 72.3-83.9 μg/L, 1.1 -6.8 μg/L and 2,669.6-3,491.5 μg/kg respectively. The most abundant compounds of PAHs were fluorene and phenanthrene for all sewage treatment plants. The ratios have been used extensively to distinguish petrogenic or pyrogenic sources of PAHs in the dewatered cake at 5 different sewage treatment plants. It was not easy to di stinguish between petrogenic and pyrogenic sources of PAHs because the PAHs contained both characteristics. 본 연구에서는 하수처리장으로 유입되는 PAHs 의 배출 원을 파악하여 생물학적 처리에 의해 처분되는 하수 슬러지의 경로별 유입 PAHs 의 배출량 및 농도을 추정한 결과 다음과 같은 결론을 얻을 수 있었다. 1. 하수처리장 유입수, 방류수 및 탈수케잌 의 PAHs 농도는 각각 72.3~83.9 μg/L,1.1~6.8 μg/L, 2,669.6 ~ 3,491.5 μg/kg 의 범위를 나타내 었다. 2. 유입수와 탈수케잌 의 경우 모든 하수처리장에서 PAHs 중 각각 fluorene과 phenanthrene 이 가장 높은 농도를 나타내었으며,공장폐수가 유입되는 하수처리장의 경우 벤젠고리 5 - 6개의 고비점 화합물들이 가정하수가 유입되는 하수처리장 에 비하여 다소 높게 나타났다. 3. 모든 하수처리장에서 PAHs 중 저분자량의 LPAHs 제거효율은 85.0% 이상을 나타내었으며,이는 활성슬러지법을 이용한 미생물에 의한 분해로 판단된다. 그러나 고분자량의 HPAHs 제거효율은 활성슬러지법만으로는 67.3% 정도로 낮아 2차 처리가 필요할 것으로 판단된다.

Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)‐10 receptor enhances dendritic cell‐based vaccine potency

Kim, J. H.,Kang, T. H.,Noh, K. H.,Bae, H. C.,Ahn, Y‐,H.,Lee, Y‐,H.,Choi, E. Y.,Chun, K‐,H.,Lee, S‐,J.,Kim, T. W. Blackwell Publishing Ltd 2011 Clinical and experimental immunology Vol.165 No.2

<P><B>Summary</B></P><P>Improving dendritic cell (DC) functions is highly promising for therapeutic intervention of diverse diseases, including cancer. Immunosuppressive cytokines such as interleukin (IL)‐10 produced by DCs themselves (autocrine) and other regulatory immune cells (paracrine) down‐regulate functional profiles of DCs through specific cell surface receptors such as IL‐10R. Here, we tried to improve DC functions using small interfering RNA (siRNA) technology to block an IL‐10R‐mediated immunosuppressive axis. DCs modified with siRNA targeting against IL‐10R or IL‐10 (DC/siIL‐10R or DC/siIL‐10) led to up‐regulation of major histocompatibility complex (MHC) class II, CD40 co‐stimulatory molecule, and IL‐12 proinflammatory cytokine after lipopolysacharide (LPS) stimulation compared to DC/siGFP. Notably, the LPS‐induced functional profiles of DC/siIL‐10R were strongly resistant to the addition of recombinant IL‐10, which mimicked paracrine IL‐10. In contrast, those of DC/siIL‐10 were reversed by adding exogenous IL‐10. Consistently, DC/siIL‐10R generated more human papilloma virus (HPV) E7‐specific CD8<SUP>+</SUP> T cells and stronger anti‐tumour effects against E7‐expressing TC‐1 tumour cells in vaccinated mice than DC/siGFP, as well as DC/siIL‐10. Taken together, these results provide the groundwork for future clinical translation of siRNA‐mediated strategy targeting IL‐10R to enhance DC‐based vaccine potency.</P>

EZH2 Generates a Methyl Degron that Is Recognized by the DCAF1/DDB1/CUL4 E3 Ubiquitin Ligase Complex

Lee, J.,Lee, Jason S.,Kim, H.,Kim, K.,Park, H.,Kim, J.Y.,Lee, S.,Kim, I.,Kim, J.,Lee, M.,Chung, C.,Seo, S.B.,Yoon, J.B.,Ko, E.,Noh, D.Y.,Kim, K.,Kim, K.,Baek, S. Cell Press 2012 Molecular cell Vol.48 No.4

Ubiquitination plays a major role in protein degradation. Although phosphorylation-dependent ubiquitination is well known for the regulation of protein stability, methylation-dependent ubiquitination machinery has not been characterized. Here, we provide evidence that methylation-dependent ubiquitination is carried out by damage-specific DNA binding protein 1 (DDB1)/cullin4 (CUL4) E3 ubiquitin ligase complex and a DDB1-CUL4-associated factor 1 (DCAF1) adaptor, which recognizes monomethylated substrates. Molecular modeling and binding affinity studies reveal that the putative chromo domain of DCAF1 directly recognizes monomethylated substrates, whereas critical binding pocket mutations of the DCAF1 chromo domain ablated the binding from the monomethylated substrates. Further, we discovered that enhancer of zeste homolog 2 (EZH2) methyltransferase has distinct substrate specificities for histone H3K27 and nonhistones exemplified by an orphan nuclear receptor, RORα. We propose that EZH2-DCAF1/DDB1/CUL4 represents a previously unrecognized methylation-dependent ubiquitination machinery specifically recognizing ''methyl degron''; through this, nonhistone protein stability can be dynamically regulated in a methylation-dependent manner.