• Title/Summary/Keyword: Translational control

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Polyadenylation-Dependent Translational Control of New Protein Synthesis at Activated Synapse

  • Shin Chan-Young;Yang Sung-Il;Kim Kyun-Hwan;Ko Kwang-Ho
    • Biomolecules & Therapeutics
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    • v.14 no.2
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    • pp.75-82
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    • 2006
  • Synaptic plasticity, which is a long lasting change in synaptic efficacy, underlies many neural processes like learning and memory. It has long been acknowledged that new protein synthesis is essential for both the expression of synaptic plasticity and memory formation and storage. Most of the research interests in this field have focused on the events regulating transcriptional activation of gene expression from the cell body and nucleus. Considering extremely differentiated structural feature of a neuron in CNS, a neuron should meet a formidable task to overcome spatial and temporal restraints to deliver newly synthesized proteins to specific activated synapses among thousands of others, which are sometimes several millimeters away from the cell body. Recent advances in synaptic neurobiology has found that almost all the machinery required for the new protein translation are localized inside or at least in the vicinity of postsynaptic compartments. These findings led to the hypothesis that dormant mRNAs are translationally activated locally at the activated synapse, which may enable rapid and delicate control of new protein synthesis at activated synapses. In this review, we will describe the mechanism of local translational control at activated synapses focusing on the role of cytoplasmic polyadenylation of dormant mRNAs.

Compliance Analysis for Effective handling of Peg-In/Out-Hole Tasks Using Robot Hands (로봇 손을 이용한 팩의 조립 및 분해 작업을 효율적으로 수행하기 위한 컴플라이언스 해석)

  • Kim, Byoung-Ho;Yi, Byung-Ju;Suh, Il-Hong;Oh, Sang-Rok
    • Journal of Institute of Control, Robotics and Systems
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    • v.6 no.9
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    • pp.777-785
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    • 2000
  • This paper provides a guideline for the determination of compliance characteristics and the proper location of the compliance center in typical peg-in-hole and peg-out-hole tasks using hands. We first observe the fact that some of coupling stiffness elements cannot be planned arbitrarily. The given peg-in/out-hole tasks are classified into two contact styles. Then, we analyze concluded of the operational siffness matrix, which achieve the give peg-in/out-hole tasks effectively for each case. It is concluded that the location of the compliance center on the peg and the coupling stiffness element existing between the translational and the rotational direction play ompliance on the peg and the coupling siffness element existing between the translational and the rotational direction play important roles for successful peg-in/out-hole tasks. The analytic results verified through simulations.

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Analysis on Kinematic Characteristics of the Revolute-joint-based Translational 3-DOF Parallel Mechanisms (회전관절만을 활용하는 병진 3자유도 병렬 메커니즘의 기구학 특성 분석)

  • Park, Jae-Hyun;Kim, Sung Mok;Kim, WheeKuk
    • The Journal of Korea Robotics Society
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    • v.10 no.2
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    • pp.119-132
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    • 2015
  • Two novel parallel mechanisms (PMs) employing two or three PaPaRR subchains are suggested. Each of those two PMs has translational 3-DOF motion and employs only revolute joints such that they could be adequate for haptic devices requiring minimal frictions. The position analyses of those two PMs are conducted. The mobility analysis, the kinematic modeling, and singularity analysis of each of two PMs are performed employing the screw theory. Then through optimal kinematic design, each of two PMs has excellent kinematic characteristics as well as useful workspace size adequate for haptic applications. In particular, by applying an additional redundantly actuated joint to the 2-PaPaRR type PM which has a closed-form position solution, it is shown that all of its parallel singularities within reachable workspace are completely removed and that its kinematic characteristics are improved.

The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology

  • Park, Jumin;Park, Jongmin;Lee, Jongbin;Lim, Chunghun
    • BMB Reports
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    • v.54 no.9
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    • pp.439-450
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    • 2021
  • Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities.

Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines

  • Xing Wei;Chin Wen Png;Madhushanee Weerasooriya;Heng Li;Chenchen Zhu;Guiping Chen;Chuan Xu;Yongliang Zhang;Xiaohong Xu
    • IMMUNE NETWORK
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    • v.23 no.4
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    • pp.34.1-34.15
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    • 2023
  • Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice

  • Park, Ji-Yeun;Lee, Jiyoung;Jeong, Minsu;Min, Seorim;Kim, Song-Yi;Lee, Hyejung;Lim, Yunsook;Park, Hi-Joon
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.404-409
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    • 2014
  • BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

Efficacy of Korean Red Ginseng Supplementation on Eradication Rate and Gastric Volatile Sulfur Compound Levels after Helicobacter pylori Eradication Therapy

  • Lee, So-Jung;Park, Ji-Young;Choi, Ki-Seok;Ock, Chan-Young;Hong, Kyung-Sook;Kim, Yoon-Jae;Chung, Jun-Won;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • v.34 no.2
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    • pp.122-131
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    • 2010
  • This clinical study was performed to evaluate whether supplementation of proton pump inhibitor (PPI)-based triple therapy with Korean red ginseng can enhance Helicobacter pylori (H. pylori) eradication and reduce levels of halitosis-associated volatile sulfur compounds (VSCs) in the stomach. Seventy-six patients were randomized into an eradication regimen-only group (n=45) or an eradication regimen plus 10 weeks of Korean red ginseng supplementation group (n=31). The eradication regimen consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d.. for seven days. Korean red ginseng supplementation commenced on the last day of the eradication regimen. $^{13}C$-urea breath test and halimeter measurements were performed prior to protocol repetition. By intention-to-treat analysis, the H. pylori eradication rate in the Korean red ginseng group (77.4%, 24 of 31) was higher than that in the control group (45.0%, 26 of 45). However, by per protocol analysis, the eradication rate in the Korean red ginseng group was significantly higher than that in the control group (92.3%, 24/26 vs. 69.4%, 26/38; p<0.05). H. pylori infection was significantly associated with increased VSC levels. However, VSC levels decreased significantly in the Korean red ginseng group (p<0.05). In conclusion, supplementation of triple therapy with Korean red ginseng increased the H. pylori eradication rate and led to significant reductions in VSC levels, suggesting the usefulness of this substance in combating H. pylori infection.

Effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Immune Functions in Healthy Adults in a Randomized Controlled Trial

  • Hwang, Hee-Jin;Sohn, Ki-Young;Han, Yong-Hae;Chong, Saeho;Yoon, Sun Young;Kim, Young-Jun;Jeong, Jinseoun;Kim, Sang-Hwan;Kim, Jae Wha
    • IMMUNE NETWORK
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    • v.15 no.3
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    • pp.150-160
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    • 2015
  • We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-$\gamma$ by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement.

Vitamin D Deficiency and Comorbidities as Risk Factors of COVID-19 Infection: A Systematic Review and Meta-analysis

  • Mishra, Pinki;Parveen, Rizwana;Bajpai, Ram;Agarwal, Nidhi
    • Journal of Preventive Medicine and Public Health
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    • v.55 no.4
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    • pp.321-333
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    • 2022
  • Objectives: Extensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection. Methods: We searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: Significantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; p=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; p<0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; p=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally nonsignificant, associations with COVID-19 infection. Conclusions: Low serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.

Moving Object Following Control for Differential Drive Robot Based on Two Distance Sensors (두 개의 거리 센서를 이용한 차륜형 로봇의 이동물체 추종제어)

  • Seo, Dong-Jin;Noh, Sung-Woo;Ko, Nak-Yong
    • The Journal of the Korea institute of electronic communication sciences
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    • v.6 no.5
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    • pp.765-773
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    • 2011
  • This paper proposes a control method for a differential robot to track and follow a moving object based on ultrasonic sensor. To track a target object, the method uses a transmitter and two receivers to get distances from the object. The method derives translational and rotational error by the distances and then it uses the errors to calculate control values based on PID control method. The control values are used to control the robot to follow moving object. The authors do some experimentations to analyze some characteristics such as influence of PID gain, influence of translational and rotational gain. This method not only can be applied for following moving object problem but also can be done group unit control problems.