• Title/Summary/Keyword: Target degradation

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Mechanisms for Hfq-Independent Activation of rpoS by DsrA, a Small RNA, in Escherichia coli

  • Kim, Wonkyong;Choi, Jee Soo;Kim, Daun;Shin, Doohang;Suk, Shinae;Lee, Younghoon
    • Molecules and Cells
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    • v.42 no.5
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    • pp.426-439
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    • 2019
  • Many small RNAs (sRNAs) regulate gene expression by base pairing to their target messenger RNAs (mRNAs) with the help of Hfq in Escherichia coli. The sRNA DsrA activates translation of the rpoS mRNA in an Hfq-dependent manner, but this activation ability was found to partially bypass Hfq when DsrA is overproduced. The precise mechanism by which DsrA bypasses Hfq is unknown. In this study, we constructed strains lacking all three rpoS-activating sRNAs (i.e., ArcZ, DsrA, and RprA) in $hfq^+$ and $Hfq^-$ backgrounds, and then artificially regulated the cellular DsrA concentration in these strains by controlling its ectopic expression. We then examined how the expression level of rpoS was altered by a change in the concentration of DsrA. We found that the translation and stability of the rpoS mRNA are both enhanced by physiological concentrations of DsrA regardless of Hfq, but that depletion of Hfq causes a rapid degradation of DsrA and thereby decreases rpoS mRNA stability. These results suggest that the observed Hfq dependency of DsrA-mediated rpoS activation mainly results from the destabilization of DsrA in the absence of Hfq, and that DsrA itself contributes to the translational activation and stability of the rpoS mRNA in an Hfq-independent manner.

SUV39H1 is a New Client Protein of Hsp90 Degradated by Chaetocin as a Novel C-Terminal Inhibitor of Hsp90

  • Lian, Bin;Lin, Qian;Tang, Wei;Qi, Xin;Li, Jing
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.73-82
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    • 2021
  • Hsp90 is often overexpressed with activated form in cancer cells, and many key cellular proteins are dependent upon the Hsp90 machinery (these proteins are called "client protein"). Nowadays, more client proteins and more inhibitors of Hsp90 are being discovered. Chaetocin has been identified as an inhibitor of histone methyl transferase SUV39H1. Herein, we find that Chaetocin is an inhibitor of Hsp90 which binds to the C-terminal of Hsp90α. Chaetocin inhibited a variety of Hsp90 client proteins including AMl1-ETO and BCL-ABL, the mutant fusion-protein in the K562 and HL-60 cells. SUV39H1 mediates epigenetic events in the pathophysiology of hematopoietic disorders. We found that inhibition of Hsp90 by Chaetocin and 17-AAG had ability to induce degradation of SUV39H1 through proteasome pathway. In addition, SUV39H1 interacted with Hsp90 through co-chaperone HOP. These results suggest that SUV39H1 belongs to a client protein of Hsp90. Moreover, Chaetocin was able to induce cell differentiation in the two cells in the concentration range of Hsp90 inhibition. Altogether, our results demonstrate that SUV39H1 is a new client protein of Hsp90 degradated by Chaetocin as a novel C-terminal inhibitor of Hsp90. The study establishes a new relationship of Chaetocin and SUV39H1, and paves an avenue for exploring a new strategy to target SUV39H1 by inhibition of Hsp90 in leukemia.

Wheat phytase can alleviate the cellular toxic and inflammatory effects of lipopolysaccharide

  • An, Jeongmin;Cho, Jaiesoon
    • Journal of Animal Science and Technology
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    • v.63 no.1
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    • pp.114-124
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    • 2021
  • The objective of this study was to characterize the enzymatic hydrolysis of lipopolysaccharide (LPS) by wheat phytase and to investigate the effects of wheat phytase-treated LPS on in vitro toxicity, cell viability and release of a pro-inflammatory cytokine, interleukin (IL)-8 by target cells compared with the intact LPS. The phosphatase activity of wheat phytase towards LPS was investigated in the presence or absence of inhibitors such as L-phenylalanine and L-homoarginine. In vitro toxicity of LPS hydrolyzed with wheat phytase in comparison to intact LPS was assessed. Cell viability in human aortic endothelial (HAE) cells exposed to LPS treated with wheat phytase in comparison to intact LPS was measured. The release of IL-8 in human intestinal epithelial cell line, HT-29 cells applied to LPS treated with wheat phytase in comparison to intact LPS was assayed. Wheat phytase hydrolyzed LPS, resulting in a significant release of inorganic phosphate for 1 h (p < 0.05). Furthermore, the degradation of LPS by wheat phytase was nearly unaffected by the addition of L-phenylalanine, the inhibitor of tissue-specific alkaline phosphatase or L-homoarginine, the inhibitor of tissue-non-specific alkaline phosphatase. Wheat phytase effectively reduced the in vitro toxicity of LPS, resulting in a retention of 63% and 54% of its initial toxicity after 1-3 h of the enzyme reaction, respectively (p < 0.05). Intact LPS decreased the cell viability of HAE cells. However, LPS dephosphorylated by wheat phytase counteracted the inhibitory effect on cell viability. LPS treated with wheat phytase decreased IL-8 secretion from intestinal epithelial cell line, HT-29 cell to 14% (p < 0.05) when compared with intact LPS. In conclusion, wheat phytase is a potential therapeutic candidate and prophylactic agent for control of infections induced by pathogenic Gram-negative bacteria and associated LPS-mediated inflammatory diseases in animal husbandry.

An Input Transformation with MFCCs and CNN Learning Based Robust Bearing Fault Diagnosis Method for Various Working Conditions (MFCCs를 이용한 입력 변환과 CNN 학습에 기반한 운영 환경 변화에 강건한 베어링 결함 진단 방법)

  • Seo, Yangjin
    • KIPS Transactions on Software and Data Engineering
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    • v.11 no.4
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    • pp.179-188
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    • 2022
  • There have been many successful researches on a bearing fault diagnosis based on Deep Learning, but there is still a critical issue of the data distribution difference between training data and test data from their different working conditions causing performance degradation in applying those methods to the machines in the field. As a solution, a data adaptation method has been proposed and showed a good result, but each and every approach is strictly limited to a specific applying scenario or presupposition, which makes it still difficult to be used as a real-world application. Therefore, in this study, we have proposed a method that, using a data transformation with MFCCs and a simple CNN architecture, can perform a robust diagnosis on a target domain data without an additional learning or tuning on the model generated from a source domain data and conducted an experiment and analysis on the proposed method with the CWRU bearing dataset, which is one of the representative datasests for bearing fault diagnosis. The experimental results showed that our method achieved an equal performance to those of transfer learning based methods and a better performance by at least 15% compared to that of an input transformation based baseline method.

Development and Evaluation of a Thimble-Like Head Bolus Shield for Hemi-Body Electron Beam Irradiation Technique

  • Shin, Wook-Geun;Lee, Sung Young;Jin, Hyeongmin;Kim, Jeongho;Kang, Seonghee;Kim, Jung-in;Jung, Seongmoon
    • Journal of Radiation Protection and Research
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    • v.47 no.3
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    • pp.152-157
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    • 2022
  • Background: The hemi-body electron beam irradiation (HBIe-) technique has been proposed for the treatment of mycosis fungoides. It spares healthy skin using an electron shield. However, shielding electrons is complicated owing to electron scattering effects. In this study, we developed a thimble-like head bolus shield that surrounds the patient's entire head to prevent irradiation of the head during HBIe-. Materials and Methods: The feasibility of a thimble-like head bolus shield was evaluated using a simplified Geant4 Monte Carlo (MC) simulation. Subsequently, the head bolus was manufactured using a three-dimensional (3D) printed mold and Ecoflex 00-30 silicone. The fabricated head bolus was experimentally validated by measuring the dose to the Rando phantom using a metal-oxide-semiconductor field-effect transistor (MOSFET) detector with clinical configuration of HBIe-. Results and Discussion: The thimble-like head bolus reduced the electron fluence by 2% compared with that without a shield in the MC simulations. In addition, an improvement in fluence degradation outside the head shield was observed. In the experimental validation using the inhouse-developed bolus shield, this head bolus reduced the electron dose to approximately 2.5% of the prescribed dose. Conclusion: A thimble-like head bolus shield for the HBIe- technique was developed and validated in this study. This bolus effectively spares healthy skin without underdosage in the region of the target skin in HBIe-.

Effect of Speech Degradation and Listening Effort in Reverberating and Noisy Environments Given N400 Responses

  • Kyong, Jeong-Sug;Kwak, Chanbeom;Han, Woojae;Suh, Myung-Whan;Kim, Jinsook
    • Korean Journal of Audiology
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    • v.24 no.3
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    • pp.119-126
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    • 2020
  • Background and Objectives: In distracting listening conditions, individuals need to pay extra attention to selectively listen to the target sounds. To investigate the amount of listening effort required in reverberating and noisy backgrounds, a semantic mismatch was examined. Subjects and Methods: Electroencephalography was performed in 18 voluntary healthy participants using a 64-channel system to obtain N400 latencies. They were asked to listen to sounds and see letters in 2 reverberated×2 noisy paradigms (i.e., Q-0 ms, Q-2000 ms, 3 dB-0 ms, and 3 dB-2000 ms). With auditory-visual pairings, the participants were required to answer whether the auditory primes and letter targets did or did not match. Results: Q-0 ms revealed the shortest N400 latency, whereas the latency was significantly increased at 3 dB-2000 ms. Further, Q-2000 ms showed approximately a 47 ms delayed latency compared to 3 dB-0 ms. Interestingly, the presence of reverberation significantly increased N400 latencies. Under the distracting conditions, both noise and reverberation involved stronger frontal activation. Conclusions: The current distracting listening conditions could interrupt the semantic mismatch processing in the brain. The presence of reverberation, specifically a 2000 ms delay, necessitates additional mental effort, as evidenced in the delayed N400 latency and the involvement of the frontal sources in this study.

Development of underwater 3D shape measurement system with improved radiation tolerance

  • Kim, Taewon;Choi, Youngsoo;Ko, Yun-ho
    • Nuclear Engineering and Technology
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    • v.53 no.4
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    • pp.1189-1198
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    • 2021
  • When performing remote tasks using robots in nuclear power plants, a 3D shape measurement system is advantageous in improving the efficiency of remote operations by easily identifying the current state of the target object for example, size, shape, and distance information. Nuclear power plants have high-radiation and underwater environments therefore the electronic parts that comprise 3D shape measurement systems are prone to degradation and thus cannot be used for a long period of time. Also, given the refraction caused by a medium change in the underwater environment, optical design constraints and calibration methods for them are required. The present study proposed a method for developing an underwater 3D shape measurement system with improved radiation tolerance, which is composed of commercial electric parts and a stereo camera while being capable of easily and readily correcting underwater refraction. In an effort to improve its radiation tolerance, the number of parts that are exposed to a radiation environment was minimized to include only necessary components, such as a line beam laser, a motor to rotate the line beam laser, and a stereo camera. Given that a signal processing circuit and control circuit of the camera is susceptible to radiation, an image sensor and lens of the camera were separated from its main body to improve radiation tolerance. The prototype developed in the present study was made of commercial electric parts, and thus it was possible to improve the overall radiation tolerance at a relatively low cost. Also, it was easy to manufacture because there are few constraints for optical design.

Brown preadipocyte transplantation locally ameliorates obesity

  • Takaya, Kento;Matsuda, Naruhito;Asou, Toru;Kishi, Kazuo
    • Archives of Plastic Surgery
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    • v.48 no.4
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    • pp.440-447
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    • 2021
  • Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

Effect of Speech Degradation and Listening Effort in Reverberating and Noisy Environments Given N400 Responses

  • Kyong, Jeong-Sug;Kwak, Chanbeom;Han, Woojae;Suh, Myung-Whan;Kim, Jinsook
    • Journal of Audiology & Otology
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    • v.24 no.3
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    • pp.119-126
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    • 2020
  • Background and Objectives: In distracting listening conditions, individuals need to pay extra attention to selectively listen to the target sounds. To investigate the amount of listening effort required in reverberating and noisy backgrounds, a semantic mismatch was examined. Subjects and Methods: Electroencephalography was performed in 18 voluntary healthy participants using a 64-channel system to obtain N400 latencies. They were asked to listen to sounds and see letters in 2 reverberated×2 noisy paradigms (i.e., Q-0 ms, Q-2000 ms, 3 dB-0 ms, and 3 dB-2000 ms). With auditory-visual pairings, the participants were required to answer whether the auditory primes and letter targets did or did not match. Results: Q-0 ms revealed the shortest N400 latency, whereas the latency was significantly increased at 3 dB-2000 ms. Further, Q-2000 ms showed approximately a 47 ms delayed latency compared to 3 dB-0 ms. Interestingly, the presence of reverberation significantly increased N400 latencies. Under the distracting conditions, both noise and reverberation involved stronger frontal activation. Conclusions: The current distracting listening conditions could interrupt the semantic mismatch processing in the brain. The presence of reverberation, specifically a 2000 ms delay, necessitates additional mental effort, as evidenced in the delayed N400 latency and the involvement of the frontal sources in this study.

Robustness Evaluation of GaN Low-Noise Amplifier in Ka-band (Ka-대역 GaN 저잡음 증폭기의 강건성 평가)

  • Lee, Dongju;An, Se-Hwan;Joo, Ji-Han;Kwon, Jun-Beom;Kim, Younghoon;Lee, Sanghun;Seo, Mihui;Kim, Sosu
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.22 no.6
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    • pp.149-154
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    • 2022
  • Due to high power capabilities and high linearity of GaN devices, GaN Low-Noise Amplifiers (LNAs) without a limiter can be implemented in order to improve noise figure and reduce chip area in radar receivers. In this paper, a GaN LNA is presented for Ka-band radar receivers. The designed LNA was realized in a 150-nm GaN HEMT process and measurement results show that the voltage gain of >23 dB and the noise figure of <6.5 dB including packaging loss in the target frequency range. Under the high-power stress test, measured gain and noise figure of the GaN LNA is degraded after the first stress test, but no more degradation is observed under multiple stress tests. Through post-stress noise and s-parameter measurements, we verified that the GaN LNA is resilient to pulsed input power of ~40 dBm.