• Title/Summary/Keyword: Activators

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Circadian Clock Genes, PER1 and PER2, as Tumor Suppressors (체내 시계 유전자 PER1과 PER2의 종양억제자 기능)

  • Son, Beomseok;Do, Hyunhee;Kim, EunGi;Youn, BuHyun;Kim, Wanyeon
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1225-1231
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    • 2017
  • Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

Activation Property of Blast furnace Slag by Alkaline Activator (알칼리 자극제에 의한 고로수쇄슬래그의 활성화 특성)

  • Ahn, Ji-Whan;Cho, Jin-Sang;Kim, Hyung-Seok;Han, Gi-Chun;Han, Ki-Suk;Kim, Hwan
    • Journal of the Korean Ceramic Society
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    • v.40 no.10
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    • pp.1005-1014
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    • 2003
  • This paper examines the hydration and physical properties of alkali-blast furnace slag cement activated by Na$_2$SiO$_3$, Na$_2$CO$_3$, NaOH, Na$_2$SO$_4$. Four levels of Na$_2$O content in mixtures, 1, 3, 5, and 7 wt%, were investigated, and a W/S ratio 0.5 was used to prepare paste and mortar specimens. Compressive strength measurement of mortars was carried out adding alkali activated slag 30 wt% to OPC. The main hydration products with alkali activator kinds were C-S-H,C$_4$AH$\_$13/, AFt and Al(OH)$_3$ etc. For using Na$_2$CO$_3$ activated slag, hydration ratio of slag was higher than that of different activators, and Na$_2$SO$_4$ activated slag mortar appeared the highest compressive strength values at 28 days with activator content of 5 and 7 wt%.

Studies on Inhibition of Self-Incompatibility with Micronutrients in Apple (미량요소 첨가가 자가불화합성 억제에 미치는 영향)

  • Chung, Il-Kyung;Son, Tae-Kwon;Kim, Min-Ji
    • Korean Journal of Plant Resources
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    • v.25 no.2
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    • pp.285-292
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    • 2012
  • Self-incompatibility (SI) system is a genetic barrier that prevents self-fertilization and promotes cross-pollination among different S genotypes. In many of these species, SI is controlled by a single genetic locus known as S locus, which prevents the fertilization by pollen with same locus. S RNases are the products of the S-locus expressed in the stylar tissue of Fuji Apple with gametophytic self-incompatibility system. This study investigated the various types of chemicals in order to select more effective inhibitors and activators. The effect on the inhibition of S RNase of Fuji apples was investigated $in$ $vitro$. The result showed that the enzyme activity was reduced 24.3% by Iron(II) Sulfate, significantly. $In$ $vitro$ studies of pollen growth tube showed that pollen tube growth had a higher germination rate (90%) in 10% Sucrose than in 2% sucrose extension medium. Data on the fruit set of apples treated with inhibitor and activator. Double application of $A^+$(Apple Plus, ISTECH Co. Ltd.,)+Vitamin B6 had the highest central fruit set as 86.1%(Andong). One time application of $A^{++}$Vitamin B1 in Yeongju obtained the highest central fruit set (91.9%).

Genetic Control of Asexual Sporulation in Fusarium graminearum

  • Son, Hokyoung;Kim, Myung-Gu;Chae, Suhn-Kee;Lee, Yin-Won
    • 한국균학회소식:학술대회논문집
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    • 2014.10a
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    • pp.15-15
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    • 2014
  • Fusarium graminearum (teleomorph Gibberella zeae) is an important plant pathogen that causes head blight of major cereal crops such as wheat, barley, and rice, as well as causing ear and stalk rot on maize worldwide. Plant diseases caused by this fungus lead to severe yield losses and accumulation of harmful mycotoxins in infected cereals [1]. Fungi utilize spore production as a mean to rapidly avoid unfavorable environmental conditions and to amplify their population. Spores are produced sexually and asexually and their production is precisely controlled. Upstream developmental activators consist of fluffy genes have been known to orchestrate early induction of condiogenesis in a model filamentous fungus Aspergillus nidulans. To understand the molecular mechanisms underlying conidiogenesis in F. graminearum, we characterized functions of the F. graminearum fluffy gene homologs [2]. We found that FlbD is conserved regulatory function for conidiogenesis in both A. nidulans and F. graminearum among five fluffy gene homologs. flbD deletion abolished conidia and perithecia production, suggesting that FlbD have global roles in hyphal differentiation processes in F. graminearum. We further identified and functionally characterized the ortholog of AbaA, which is involved in differentiation from vegetative hyphae to conidia and known to be absent in F. graminearum [3]. Deletion of abaA did not affect vegetative growth, sexual development, or virulence, but conidium production was completely abolished and thin hyphae grew from abnormally shaped phialides in abaA deletion mutants. Overexpression of abaA resulted in pleiotropic defects such as impaired sexual and asexual development, retarded conidium germination, and reduced trichothecene production. AbaA localized to the nuclei of phialides and terminal cells of mature conidia. Successful interspecies complementation using A. nidulans AbaA and the conserved AbaA-WetA pathway demonstrated that the molecular mechanisms responsible for AbaA activity are conserved in F. graminearum as they are in A. nidulans. F. graminearum ortholog of Aspergillus nidulans wetA has been shown to be involved in conidiogenesis and conidium maturation [4]. Deletion of F. graminearum wetA did not alter mycelial growth, sexual development, or virulence, but the wetA deletion mutants produced longer conidia with fewer septa, and the conidia were sensitive to acute stresses, such as oxidative stress and heat stress. Furthermore, the survival rate of aged conidia from the F. graminearum wetA deletion mutants was reduced. The wetA deletion resulted in vigorous generation of single-celled conidia through autophagy-dependent microcycle conidiation, indicating that WetA functions to maintain conidia dormancy by suppressing microcycle conidiation in F. graminearum. In A. nidulans, FlbB physically interacts with FlbD and FlbE, and the resulting FlbB/FlbE and FlbB/FlbD complexes induce the expression of flbD and brlA, respectively. BrlA is an activator of the AbaA-WetA pathway. AbaA and WetA are required for phialide formation and conidia maturation, respectively [5]. In F. graminearum, the AbaA-WetA pathway is similar to that of A. nidulans, except a brlA ortholog does not exist. Amongst the fluffy genes, only fgflbD has a conserved role for regulation of the AbaA-WetA pathway.

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Mechanical Properties and Reaction Products of Activated Slag System Depending on Gypsum Presence and Calcium Carbonate Addition (석고 존재 및 탄산칼슘 첨가에 따른 활성 슬래그의 역학적 성능 및 반응생성물)

  • Jeong, Yeonung;Lim, Gwi Hwan;Park, Su Hyeon;Kim, Joo Hyung;Kim, Tae-Sang
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.24 no.4
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    • pp.55-63
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    • 2020
  • This study investigates the mechanical properties and reaction products of activated slag pastes depending on gypsum presence and calcium carbonate addition in terms of compressive strength tests and synchrotron X-ray diffraction. The chemicals of CaO and NaOH are used as activators with different two dosages. The reaction of CaO-activated slag without gypsum just accelerated by addition of calcium carbonate at early ages, but no improvement was observed at later ages. On the other hand, the mechanical properties of CaO-activated slag pastes with gypsum were improved with calcium carbonate, enhancing the stability of ettringite. The variation of mechanical properties of NaOH-activated slag pastes was negligible depending on calcium carbonate addition in case of no gypsum. The addition of calcium carbonate into NaOH-activated slag pastes with gypsum deteriorated its mechanical properties due to the ion competition between CO32- ions and SO32- ions, decreasing crystallinity of reaction products.

Pharmacophore Mapping and Virtual Screening for SIRT1 Activators

  • Sakkiah, Sugunadevi;Krishnamoorthy, Navaneethakrishnan;Gajendrarao, Poornima;Thangapandian, Sundarapandian;Lee, Yun-O;Kim, Song-Mi;Suh, Jung-Keun;Kim, Hyong-Ha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.5
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    • pp.1152-1156
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    • 2009
  • Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

Carbonation Characteristics of Alkali Activated Blast-Furnace Slag Mortar (알칼리활성 고로슬래그 모르타르의 탄산화 특성)

  • Song, Keum-Il;Yang, Keun-Hyeok;Lee, Bang-Yeon;Song, Jin-Kyu
    • Journal of the Korea Concrete Institute
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    • v.24 no.3
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    • pp.315-322
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    • 2012
  • Alkali-activated slag (AAS) is the most obvious alternative materials that can replace OPC. But, AAS industrial usage as a structural material should be evaluated for its durability. Carbonation resistance is one of the most important factors in durability evaluation. Test results for 18 slag-based mortars activated by sodium silicate and 6 OPC mortars were obtained in this study to verify the carbonation property. Main variables considered in the study were flow, compressive strength before and after carbonation, and carbonation depth. Mineralogical and micro-structural analysis of OPC and AAS specimens prior to and after carbonation was conducted using XRD, TGA, FTIR FE-SEM. Test results showed that CHS was major hydration products of AAS and, unlike OPC, no other hydration products were found. After carbonation, CSH of hydration product in AAS turned into an amorphous silica gel, and alumina compounds was not detected. From the analysis of the results, it was estimated that the micro-structures of CSH in AAS easily collapsed during carbonation. Also, the results showed that this collapse of chemical chain of CSH lowered the compressive strength of concrete after carbonation. By increasing the dosage of activators, carbonation resistance and compressive strength were effectively improved.

Comparison of Immunohistochemical Expression of CBP(cAMP-responsive Element Binding Protein) Transcriptional Co-activator between Premalignant Lesions and Squamous Cell Carcinomas in the Lungs (전암성 폐병변 및 편평상피세포폐암 조직에서 CBP(cAMP-responsive Ele-ment Binding Protein) 전사 공동 활성인자의 면역조직화학적 발현양상의 비교)

  • Shin, Jong Wook;Kim, Jin Soo;Kim, Mi Kyung
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.2
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    • pp.165-172
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    • 2007
  • Background: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. Materials and Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. Results: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). Conclusion: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

Actinomycin D Induces Phosphorylation of STAT3 through Down-Regulation of SOCS3 in Renal Cancer Cells (신장암 세포주에서 actinomycin D에 의한 SOCS3 발현 감소를 통한 STAT3 활성화)

  • Woo, Seon-Min;Park, Eun-Jung;Kwon, Taeg-Kyu
    • Journal of Life Science
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    • v.21 no.1
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    • pp.141-145
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    • 2011
  • Actinomycin D is a natural antibiotic that is used in anti-cancer chemotherapy and is known as a transcription inhibitor. Interestingly, actinomycin D induces phosphorylation of signal transducers and activators of transcription 3 (STAT3) in renal cancer Caki cells. In this study, we examined the molecular mechanism of actinomycin D-induced STAT3 phosphorylation. Treatment with actinomycin D induced phosphorylation of STAT3 (Tyr705) in a dose- and time-dependent manner. However, actinomycin D did not induce phosphorylation of STAT3 (Ser727), STAT1 (Tyr701) and STAT1 (Ser727). Moreover, actinomycin D-induced STAT3 phosphorylation was caused by decreased protein and mRNA levels of SOCS3, but not by JAK2 and SHP-1. In addition, other transcription inhibitor (5,6-dichloro-1-b-D-ribofuranosyl benzimidazole; DRB) also induced phosphorylation of STAT3 (Tyr705). Taken together, the present study demonstrates that transcriptional inhibitors (actinomycin D and DRB) induce phosphorylation of STAT3 (Tyr705) in Caki cells by down-regulation of SOCS3.

Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction in Tetanus-Toxin Treated Mice

  • Yun, Jaesuk;Gu, Sun Mi;Lee, Tac-hyung;Song, Yun Jeong;Seong, Seonhwa;Kim, Young-Hoon;Cha, Hye Jin;Han, Kyoung Moon;Shin, Jisoon;Oh, Hokyung;Jung, Kikyung;Ahn, Chiyoung;Park, Hye-Kyung;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.266-271
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    • 2017
  • Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.