• Title/Summary/Keyword: damage accumulation

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Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

  • Hyunji Choi;Moonkyung Kang;Kee-Ho Lee;Yeon-Soo Kim
    • BMB Reports
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    • v.56 no.11
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    • pp.612-617
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    • 2023
  • Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

TEM investigation of helium bubble evolution in tungsten and ZrC-strengthened tungsten at 800 and 1000℃ under 40keV He+ irradiation

  • I. Ipatova;G. Greaves;D. Terentyev;M.R. Gilbert;Y.-L. Chiu
    • Nuclear Engineering and Technology
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    • v.56 no.4
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    • pp.1490-1500
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    • 2024
  • Helium-induced defect nucleation and accumulation in polycrystalline W and W0.5 wt%ZrC (W0.5ZrC) were studied in-situ using the transmission electron microscopy (TEM) combined with 40 keV He+ irradiation at 800 and 1000℃ at the maximum damage level of 1 dpa. Radiation-induced dislocation loops were not observed in the current study. W0.5ZrC was found to be less susceptible to irradiation damage in terms of helium bubble formation and growth, especially at lower temperature (800 ℃) when vacancies were less mobile. The ZrC particles present in the W matrix pin the forming helium bubbles via interaction between C atom and neighbouring W atom at vacancies. This reduces the capability of helium to trap a vacancy which is required to form the bubble core and, as a consequence, delays, the bubble nucleation. At 1000 ℃, significant bubble growth occurred in both materials and all the present bubbles transitioned from spherical to faceted shape, whereas at 800 ℃, the faceted helium bubble population was dominated in W.

An Experimental Study on the Determination of Damage Thresholds in Rock at Different Stress Levels (응력수준에 따른 암석의 손상기준 결정에 관한 실험적 연구)

  • Chang Soo-Ho;Lee Chung-In
    • Explosives and Blasting
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    • v.23 no.4
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    • pp.31-44
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    • 2005
  • In highly stressed conditions, the excavation damage zone induced by stress redistribution and disturbance must be evaluated after tunnel excavation. Therefore, the investigation of stress-induced deformation and fracture in rock is indispensable. In this study, fracture and damage mechanisms of rock induced by the accumulation of microcracks were investigated by the moving point regression technique as well as acoustic emission measured during uniaxial compression tests. Especially, the modified procedures to determine damage thresholds more systematically were newly proposed, and successfully applied to rock. From experiments, crack initiation and track damage stress levels were estimated to be $33{\~}36\%$ and $84{\~}89\%$ of uniaxial compressive strength respectively, for both of Hwangdeung granite and Yeosan marble. However, the normalized crack closure stress level for Yeosan marble was much higher than for Hwangdeung granite. In addition, the largest proportion of total axial strain in Hwangdeung granite was attributable to elastic deformation and initial microcracking. However, the greatest part of axial deformation in Yeosan marble arose from initial crack closure and unstable cracking. Finally, it was seen that unstable cracking after the crack damage stress level played a key part in the lateral deformation in rocks under uniaxial compression.

Transcriptional Regulation of a DNA Repair Gene in Saccharomyces cerevisiae

  • Jang, Yeon-Kyu;Sancar, Gwen-B.;Park, Sang-Dai
    • Proceedings of the Zoological Society Korea Conference
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    • 1998.10b
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    • pp.113-113
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    • 1998
  • In Saccharomyces cerevisiae UV irradiation and a variety of chemical DNA -damaging agents induce the transcription of specific genes, including several involved in DNA repair. One of the best characterized of DNA -damage inducible genes is PHRI, which encodes the apoenzyme for DNA photolyase. Basal-level and damage-induced expression of PHRI require an upstream activation sequence, UASPHRI. Here we report the identification of the UlvIE6 gene of S. cerevisiae as a regulator of UASPHRl activity. Surprisingly, the effect of deletion of UME6 is growth phase dependent. In wild-type cells PHRI is induced in late exponential phase, concomitant with the initiation of glycogen accumulation that precedes the diauxic shift. Deletion of UNIE6 abolishes this induction, decreases the steady-state concentration of photolyase molecules and PHRI mRNA, and increases the UV sensitivity of a rad2 mutant. The results suggest that UM E6 contributes to the regulated expression of a subset of damage-responsive genes in yeast. Furthermore, the upstream repression sequence, URSPHRI, is required for repression and damage-induced expression of PHRl. Here we show identification of YER169W and YDR096W as putative regulators acting through $URS_{PHRI}$. These open reading frames were designated as RPHI (YERl69W) and RPH2 (YDR096W) indicating regulator of PHRI. Simultaneous disruption of both genes showed a synergistic effect, producing a four-fold increase in basal level expression and a similar decrease m the induction ratio following treatment of methyl methanesulfonate(MMS). Mutation of the sequence ($AG_4$) bound by Rphlp rendered the promoter of PHRI insensitive to changes in RPHI or RPH2 status. The data suggest that RPHI and RPH2 act as damage-responsive negative regulators of PHRI. Surprisingly, the sequence bound by Rphlp in vitro is found to be $AG_4$ which is identical to the consensus binding site for the regulators Msn2p and Msn4p involved in stress-induced expression. Deletion of MSN2 and MSN4 has little effect on the induction$.$ ratio following DNA damage. However, all deletions led to a significant decrease in basal-level and induced expression of PHRI. These results imply that MSN2 and MSN4 are positive regulators of P HRI but are not required for DNA damage repression. [Supported by grant from NIH]om NIH]

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THE IATROGENIC DAMAGES OF THE FIRST MOLARS FOLLOWING THE STAINLESS STEEL CROWN RESTORATION THE SECOND PRIMARY MOLARS (제 2유구치 기성금관 수복에 따른 제 1대구치의 의원성 손상)

  • Bae, Ik-Hyun;Kim, Shin;Jeong, Tae-Sung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.2
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    • pp.153-158
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    • 2004
  • Preformed stainless steel crown is an useful restorative material for the treatment of badly broken down primary teeth. However iatrogenic damage to adjacent teeth might occur during the process of tooth reduction. Such damages might lead to plaque accumulation and increase the risks of caries initiation. Especially the damage can make a problem in the first permanent molar. Purpose of this study was to investigate an iatrogenic damage to the first permanent molar during preparation of second primary molar for preformed stainless steel crown. Twelve children restored with preformed stainless steel crown to second primary molar were selected. Contact areas were separated with separation elastics, and tooth surfaces were cleaned. After taking negative impression using vinylpolysiloxane impression material, the specimens were examined by scanning electron microscope for the detection of iatrogenic damage. The prevalence of iatrogenic damage was 66.7% and variable appearances and So we can suggest that when preparing teeth for preformed stainless steel crown, we should be careful about adjacent teeth not to make an iatrogenic damage.

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Vibration Fatigue Analysis of Spot Welded Component considering Change of Stiffness due to Fatigue Damage (피로손상의 누적에 따른 강성변화를 고려한 점용접부의 진동피로해석)

  • Kang, Ki-Weon
    • Journal of the Korea Convergence Society
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    • v.5 no.1
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    • pp.1-8
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    • 2014
  • The purpose of this paper was to evaluate the fatigue life to apply the vibration fatigue analysis considering the stiffness change of the spot welding due to fatigue damage accumulation. For this, the mechanical and fatigue properties of base and spot welded standard specimens were obtained through the tensile and constant amplitude fatigue test. The transfer function of the spot-welded structure was obtained from the frequency response analysis and fatigue analyisis was performed under the condition of PSD=0.11. A vibration fatigue analysis that considered changes in the frequency response due to the fatigue damage that is, failure of some wleding point was conducted on spot-welded structure. The fatigue life of the spot-welded structure was determined by combining the transfer function, the S-N curve of the tensile-shear spot-welded joint and the input PSD.

A Study on Damage Process Analysis for Steel Pier Subjected to Seismic Excitation (강한 지진 하중하에서 강재 교각의 손상 거동 연구)

  • Park, Yeon Soo;Park, Keun Koo;Park, Sun Joon
    • Journal of Korean Society of Steel Construction
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    • v.12 no.3 s.46
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    • pp.251-258
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    • 2000
  • Based on the numerical investigations using steel bridge pier subjected to strong seismic excitations a new approach to seismic damage assessment for steel structures and their members has been proposed in conjunction with the suggested definition of failure state. The relevant failure form of the steel pier is evaluated. It is revealed that when a seismic load has a short period, the failure of global buckling beyond the allowable displacement is more dominant than that by that of the local buckling caused by the accumulation of plastic strain. When a seismic load is not beyond this certain part, but repeats within the range of where a plastic deformation occurs, the plastic strain is accumulated on the partial element of bottom edge of steel pier and the failure occurs by the local buckling from the accumulated plastic local strain.

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Effect of Nitric Oxide on Paraquat-Tolerance in Lettuce Leaves (상추잎의 Paraquat 내성에 미치는 Nitric oxide의 영향)

  • Lee, Jee-Na;Hong, Jung-Hee
    • Journal of Environmental Science International
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    • v.20 no.12
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    • pp.1509-1519
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    • 2011
  • The protective effect of nitric oxide (NO) on the antioxidant system under paraquat(PQ) stress was investigated in leaves of 8-week-old lettuce (Lactuca sativa L.) plants. PQ stress caused a decrease of leaf growth including leaf length, width and weight. Application of NO donor, sodium nitroprusside (SNP), significantly alleviated PQ stress induced growth suppression. SNP permitted the survival of more green leaf tissue preventing chlorophyll content reduction and of higher quantum yield for photosystem II than in non-treated controls under PQ exposure, suggesting that NO has protective effect on chloroplast membrane in lettuce leaves. Flavonoids and anthocyanin were significantly accumulated in the leaves upon PQ exposure. However, the rapid increase of these compounds was alleviated in the SNP treated leaves. PQ treatment resulted in lipid peroxidation and induced accumulation of hydrogen peroxide ($H_2O_2$) in the leaves, while SNP prevented PQ induced increase in malondialdehyde (MDA) and $H_2O_2$. These results demonstrate that SNP serves as an antioxidant agent able to scavenge $H_2O_2$ to protect plant cells from oxidative damage. The activities of two antioxidant enzymes that scavenge reactive oxygen species, superoxide dismutase (SOD) and catalase (CAT) in lettuce leaves in the presence of NO donor under PQ stress were higher than those under PQ stress alone. Application of 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a specific NO scavenger, to the lettuce leaves arrested SNP mediated protective effect on leaf growth, photosynthetic pigment and antioxidant systems. However, PTIO had little effect on lettuce leaves under PQ stress compared with that of PQ stress alone. The obtained data suggest that the damage caused by PQ stress is in part due to increased generation of active oxygen by maintaining increased antioxidant enzyme activities and SNP protects plants from oxidative stress. From these results it is suggested that NO might act as a signal in activating active oxygen scavenging system that protects plants from oxidative damage induced by PQ stress and thus confer PQ tolerance.

Transgenic Strategy to Improve Stress Resistance of Crop Plants

  • Horvath, Gabor V.;Oberschall, Attila;Deak, Maria;Sass, Laszlo;Vass, Imre;Barna, Balazs;Kiraly, Zoltan;Hideg, Eva;Feher, Attila
    • Journal of Plant Biotechnology
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    • v.1 no.1
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    • pp.61-68
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    • 1999
  • Rapid accumulation of reactive oxygen species (ROS) and their toxic reaction products with lipids and proteins significantly contributes to the damage of crop plants under biotic and abiotic stresses. We have identified several stress activated alfalfa genes, including the gene of the alfalfa ferritin and a novel NADPH-dependent aldose/aldehyde reductase enzyme. Transgenic tobacco plants that synthesize alfalfa ferritin in vegetative tissues-either in its processed form in chloroplast or in the cytoplasmic non-processed form-retained photosynthetic function upon free radical toxicity generated by paraquat treatment and exhibited tolerance to necrotic damage caused by viral and fungal infections. We propose that by sequestering intracellular iron involved in generation of the very reactive hydroxyl radicals through a Fenton reaction, ferritin protects plant cells from oxidative damage. Our preliminary results with the other stress-inducable alfalfa gene (a NADPH-dependent aldo-keto reductase) indicate, that the encoded enzyme may play role in the stress response of the plant cells. These studies reveal new pathways in plants that can contribute to the increased stress resistance with a potential use in crop improvement.

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Relationships between Malignant Melanoma and Chromosome Damage in Human Peripheral Blood Lymphocytes

  • Narin, Abdullah;Tuncay, Orta
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5229-5232
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    • 2012
  • The incidence of malignant melanoma increases with age. One significiant effect of aging processes is an accumulation of oxidative damage in the genetical material. In this study, the relationship between malignant melanoma and damage in chromosomes and proliferative effectiveness of human peripheral lymphocytes were investigated by the micronucleus (MN) technique. A total of 15 malignant melanoma patients and appropriately matching 15 healthy controls were involved in the study. MN frequencies and proliferative indexes (PI) after non toxic levels of hydrogen peroxide treatment were also measured to determine damaging effect of oxidative stress in genome in addition to measuring the spontenous levels of micronuclei and PI. The patient group had a significantly higher rate of spontaneous MN than the control group (p<0.01). After treatment with $H_2O_2$, MN frequencies in the patient group was significantly decreased (p<0.01) although there was no difference between the treated and untreated results of control group (p=0.29). There was also difference (p<0.01) between the MN frequencies of the patient and the control group either in the spontaneous levels or in the $H_2O_2$ treated groups. The same significant difference persisted when the PI values were compared between patient and control groups. Increase in the MN frequency in patients could mean the alterations in the chromosomal structure which may lead to the chromosome instability and therefore genetic susceptibility to cancer. This increased number of micronuclei can also be used for cytological marker in identifying high risk cases for malignant melanoma.