• Title/Summary/Keyword: Systems Biology

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Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm

  • Choi, Yoon Young;Jang, Eunji;Seo, Won Jun;Son, Taeil;Kim, Hyoung-Il;Kim, Hyeseon;Hyung, Woo Jin;Huh, Yong-Min;Noh, Sung Hoon;Cheong, Jae-Ho
    • Journal of Gastric Cancer
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    • v.18 no.2
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    • pp.142-151
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    • 2018
  • Purpose: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. Materials and Methods: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. Results: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41-2.72; P<0.001) and 2.54 (95% CI, 1.84-3.50; P<0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P<0.001). Conclusions: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

Selection of transgenic sweetpotato plants expressing 2-Cys peroxiredoxin with enhanced tolerance to oxidative stress (Peroxiredoxin 유전자 발현 산화스트레스 내성 형질전환 고구마의 선발)

  • Kim, Myoung-Duck;Yang, Kyoung-Sil;Kwon, Suk-Yoon;Lee, Sang-Yeol;Kwak, Sang-Soo;Lee, Haeng-Soon
    • Journal of Plant Biotechnology
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    • v.36 no.1
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    • pp.75-80
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    • 2009
  • In order to develop transgenic sweetpotato plants [Ipomoea batatas (L.) Lam. cv. Yulmi] with enhanced tolerance to oxidative stress, we constructed transformation vectors expressing 2-Cys peroxiredoxin (Prx) gene under the control of the stress-inducible SWPA2 or enhanced 35S promoter (named as SP or EP). Transgenic sweetpotato plants were attempted to generate from embryogenic calli using an Agrobacterium-mediated transformation system. Embryogenic calli gave rise to somatic embryos and then converted into plantlets on MS medium containing 100 mg/L kanamycin. Transgenic plants were regenerated in the same medium. Southern blot analysis confirmed that the Prx gene was inserted into the genome of the plants. To further study we selected the transgenic plant lines with enhanced tolerance against methyl viologen (MV). When sweetpotato leaf discs were subjected to methyl MV at $20{\mu}M$, transgenic plants showed about 40% higher tolerance than non-transgenic or empty vector-transformed plants.

Control and Incidence of Leaf Blight on Lily with Different Cultural Systems (재배 형태별 백합 잎마름병의 발생 양상 및 몇가지 경종적 처리의 방제 효과)

  • Hahm, Soo-Sang;Lee, Ki-Hwan;Lee, Jong-Won;Lee, Hee-Duck;Yu, Seung-Hun
    • Research in Plant Disease
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    • v.13 no.3
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    • pp.152-156
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    • 2007
  • Incidences of leaf blight of lily cultivars Raizan and Casa Blanca in the open field cultivation were 50% and 45.4%, respectively, while those in the green house cultivation were significantly reduced to 1.5% and 1.9%, respectively, In the green house, the incidences of the disease in sprinkler watering cultivation were $14.5{\sim}16.5%$, while those in drip watering cultivation were only $1.5{\sim}2%$. Incidence of the disease was severe in the field where the lily was cultivated successively for 2 to 3 years. Isolation frequencies of B. elliptica from overwintered plant debrises such as leaves, stems, capsules, and bulbs were 43.3%, 46.7%, 60% and 0%, respectively, while those of B. cinerea were 10.3%, 0%, 3.3% and 0%, respectively, Incidence of leaf blight in the field where diseased plant debris was cleaned was 7.3%, while that in the field where diseased plant debris was not cleaned was 56.5%. Incidences of the disease in the field where coverages of soil surface with black vinyl, bark or rice straw were used were 6.6%, 8.2% and 11.3%, respectively, while that in the field where the coverage was not used was 21.3%.

Comparative Studies of Protein Modification Mediated by Fenton-like Reactions of Iron, Hematin, and Hemoglobin: Generation of Different Reactive Oxidizing Species

  • Kim, Young-Myeong;Kim, Sung-Soo;Kang, Gu;Yoo, Yeong-Min;Kim, Ki-Mo;Lee, Mi-Eun;Han, Jeong-A;Hong, Sun-Joo
    • BMB Reports
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    • v.31 no.2
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    • pp.161-169
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    • 1998
  • TThe reactive oxygen species oxidatively modify the biological macromolecules, including proteins, lipids, and nucleic acids. Iron- and heme-mediated Fenton-like reactions produce different pro-oxidants. However, these reactive products have not been clearly characterized. We examined the nature of the oxidizing species from the different iron sources by measuring oxidative protein modification and spectroscopic study. Hemoglobin (Hb) and methemoglobin (metHb) were oxidatively modified in $O{\array-\\\dot{2}}$ and $H_{2}O_{2}$ generating systems. Globin and bovine serum albumin (BSA) were also modified by iron, iron-EDTA, hematin, and Hb in an $O{\array-\\\dot{2}}$ generating system. In a $H_{2}O_{2}$ generating system, the iron- and iron-EDTA-mediated protein modifications were markedly reduced while the Hb-and hematin-mediated modifications were slightly increased. In the $O{\array-\\\dot{2}}$ generating system, the iron- and iron-EDTA-mediated protein modifications were strongly inhibited by superoxide dismutase (SOD) or catalase, but heme- and Hb-mediated protein modifications were inhibited only by catalase and slightly increased by SOD. Mannitol, 5,5-dimethyl-l-pyrroline-N-oxide (DMPO), deoxyribose, and thiourea inhibited the iron-EDTA-mediated protein modification. Mannitol and DMPO, however, did not exhibit significant inhibition in the hematin-mediated modification. Desferrioxamine (DFO) inhibited protein modification mediated by iron, but cyanide and azide did not, while the hematin-mediated protein modification was inhibited by cyanide and azide, but not significantly by DFO. The protein-modified products by iron and heme were different. ESR and UV-visible spectroscopy detected the DMPO spin adduct of the hydroxyl radical and ferryl ion generated from iron-EDTA and metHb, respectively. These results led us to conclude that the main oxidizing species are hydroxyl radical in the iron-EDTA type and the ferry I ion in the hematin type, the latter being more effective for protein modification.

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Sensing the Stress: the Role of the Stress-activated p38/Hog1 MAPK Signalling Pathway in Human Pathogenic Fungus Cryptococcus neoformans

  • Bahn, Yong-Sun;Heitman, Joseph
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2007.05a
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    • pp.120-122
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    • 2007
  • All living organisms use numerous signal-transduction pathways to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we employed Cryptococcus neoformans as a model system to understand how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental stresses, including osmoticshock, UV, high temperature, oxidative stress and toxic drugs/metabolites. The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals, but its regulation is uniquely specialized in a majority of clinical Cryptococcus neoformans serotype A and D strains to control differentiation and virulence factor regulation. C. neoformans Hog1 MAPK is controlled by Pbs2 MAPK kinase (MAPKK). The Pbs2-Hog1 MAPK cascade is controlled by the fungal "two-component" system that is composed of a response regulator, Ssk1, and multiple sensor kinases, including two-component.like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. We also identified and characterized the Ssk2 MAPKKK upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 regulation between the serotype D sibling f1 strains B3501 and B3502 through comparative analysis of their meiotic map with the meiotic segregation of Hog1-dependent sensitivity to the fungicide fludioxonil. Ssk2 is the only polymorphic component in the Hog1 MAPK module, including two coding sequence changes between the SSK2 alleles in B3501 and B3502 strains. To further support this finding, the SSK2 allele exchange completely swapped Hog1-related phenotypes between B3501 and B3502 strains. In the serotype A strain H99, disruption of the SSK2 gene dramatically enhanced capsule biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2, pbs2, and hog1 mutants are all hypersensitive to a variety of stresses and completely resistant to fludioxonil. Taken together, these findings indicate that Ssk2 is the critical interface protein connecting the two-component system and the Pbs2-Hog1 pathway in C. neoformans.

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Effects of Recipient Oocyte and Embryo Culture System on Production of Hanwoo (Korean Native Cattle) Somatic Cell Nuclear Transferred Embryos

  • Kim, Dong-Hoon;Kim, Se-Woong;Lee, Min-Jung;Bae, Seong-Hoon;Im, Gi-Sun;Lim, Hyun-Joo;Yang, Byoung-Chul;Seong, Hwan-Hoo
    • Reproductive and Developmental Biology
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    • v.32 no.3
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    • pp.175-181
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    • 2008
  • This study was conducted to investigate an effective recipient oocyte and culture system for producing of Hanwoo (Korean native cattle) somatic cell nuclear transfer (SCNT) embryos. Hanwoo ear skin fibroblasts were used as donor cells. In vitro matured Hanwoo or Holstein oocytes were enucleated, and single donor cells were transferred into the perivitelline space of the enucleated oocytes. The couplets were subsequently fused and activated. The reconstructed embryos were cultured in a conventional or sequential culture system. In the former, embryos were cultured in CR2aa medium for eight days; in the latter, embryos were cultured in modified CR2aa-A (mCR2-A) for three days and then further cultured in modified CR2aa-B (mCR2-B) for five days. In the experiment with the recipient oocyte, the rate of embryo development to the blastocyst stage was significantly (p<0.05) higher in Hanwoo recipient oocytes than in Holstein ones (48.8% vs 38.9%). BIastocysts derived from Hanwoo recipient oocytes contained significantly (p<0.05) higher numbers of total cells than those derived from Holstein recipient oocytes ($156.0{\pm}68.2$ vs $134.7{\pm}54.8$). There was no difference in the mean proportion of apoptotic cells in blastocysts between the sources of recipient oocytes. In the experiment with the embryo culture system, the blastocyst rate was somewhat higher in sequential system than in conventional system (50.0% vs 43.5%), though there was no significant difference. The numbers of total ($160.0{\pm}69.0$ vs $156.7{\pm}68.4$) and apoptotic cells ($14.0{\pm}10.4$ vs $11.8{\pm}6.4$) were not different between the culture systems. In conclusion, the present study demonstrated that Hanwoo recipient oocytes and the sequential culture system were more effective in supporting the production of Hanwoo SCNT embryos.

Current Status and Perspective of Weed Management in Herbicide-Resistant Crops (제초제 저항성작물에서 잡초관리기술 동향 및 전망)

  • Pyon, Jong Yeong;Chang, Kyu Seob;Lee, Jeung Joo;Park, Kee Woong
    • Weed & Turfgrass Science
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    • v.2 no.3
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    • pp.221-229
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    • 2013
  • This paper reviews current status of weed control practices in herbicide-resistant crops to examine weed management strategies in cope with cropping herbicide-resistant crops in the near future. Herbicide-resistant crops were rapidly adopted weed management technologies due to broad-spectrum weed control without crop injury. Transgenic glyphosate-resistant cultivars in soybean, corn, canola, and cotton were adopted to manage weeds at lower cost in a simplified weed management system. Dual stack crops with glyphosate and glufosinate resistance were developed to control glyphosate resistant weeds in corn, soybean and cotton. New multiple herbicide-resistant crops with resistance to glyphosate and glufosinate, acetolactate synthase (ALS) inhibitors, synthetic auxin herbicides, 4-hydroxyphenyl pyruvate dioxygenase (HPPD) inhibitors or acetyl Coenzyme A carboxylase (ACCase) inhibitors will expended the utility of existing herbicide technologies to manage the evolution of resistant weeds. However, herbicide resistant crops alone cannot solve weed problems and thus studies on diverse weed managements using an array of alternating herbicides of mode of action, mechanical, and cultural practices are needed for integrated weed management systems in the future.

Association of A/T Rich Microsatellites with Responses to Artificial Selection for Larval Developmental Duration in the Silkworm Bombyx mori

  • Pradeep, Appukuttan Nair Retnabhavan;Awasthi, Arvind Kumar;Urs, Raje Siddaraje
    • Molecules and Cells
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    • v.25 no.4
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    • pp.467-478
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    • 2008
  • Simple sequence repeats (SSRs) and interSSR (ISSR) marker systems were used in this study to reveal genetic changes induced by artificial selection for short/long larval duration in the tropical strain Nistari of the silkworm Bombyx mori. Artificial selection separated longer larval duration (LLD) ($29.428{\pm}0.723days$) and shorter larval duration (SLD) ($22.573{\pm}0.839days$) lines from a base, inbred population of Nistari (larval span of $23.143{\pm}0.35days$). SSR polymorphism was observed between the LLD and SLD lines at one microsatellite locus, Bmsat106 ($CA_7$) and at two loci of 1074 bp and 823 bp generated with the ISSR primer UBC873. Each of these loci was present only in the LLD line. The loci segregated in the third generation of selection and were fixed in opposite directions. In the $F_2$ generation of the $LLD{\times}SLD$ lines, the alleles of Bmsat106 and $UBC873_{1074bp}$ segregated in a 1:1 ratio and the loci were present only in the LLD individuals. $UBC873_{823bp}$ was homozygous. Single factor ANOVA showed a significant association between the segregating loci and longer larval duration. Together, the two alleles contributed to an 18% increase in larval duration. The nucleotide sequences of the $UBC873_{1074bp}$ and $UBC873_{823bp}$ loci had 67% A/T content and consisted of direct, reverse, complementary and palindromic repeats. The repeats appeared to be "nested" (59%) in larger repeats or as clustered elements adjacent to other repeats. Of 203 microsatellites identified, dinucleotides (67.8%) predominated and were rich in A/T and T/A motifs. The sequences of the $UBC873_{1074bp}$ and $UBC873_{823bp}$ loci showed similarity (E = 0.0) to contigs located in Scaffold 010774 and Scaffold 000139, respectively, of the B. mori genome. BLASTN analysis of the $UBC873_{1074bp}$ sequence showed significant homology of (nt.) 45-122 with upstream region of three exons from Bombyx. The complete sequence of this locus showed ~49% nucleotide conservation with transposon 412 of Drosophila melanogaster and the Ikirara insertions of Anopheles gambiae. The A + T richness and lack of coding potential of these small loci, and their absence in the SLD line, reflect the active process of genetic change associated with the switch to short larval duration as an adaptation to the tropics.

Derivation of Neural Precursor Cells from Human Embryonic Stem Cells

  • Kim Sehee;Hong Ji Young;Joo So Yeon;Kim Jae Hwan;Moon Shin Yong;Yoon Hyun Soo;Kim Doo Han;Chung Hyung Min;Choi Seong-Jun
    • Reproductive and Developmental Biology
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    • v.28 no.4
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    • pp.247-252
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    • 2004
  • Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo. Human ES cells have the capacity to differentiate into various types of cells in the body. Human ES cells are indefinite source of cells for cell therapy in various degenerative disorders including neuronal disorders. Directed differentiation of human ES cells is a prerequisite for their clinical application. The objective of this study is to develop the culture condition for the derivation of neural precursor cells from human ES cells. Neural precursor cells were derived from human ES cells in a stepwise culture condition. Neural precursor cells in the form of neural rosette structures developed into neurospheres when cultured in suspension. Suspension culture of neurospheres has been maintained over 4 months. Expressions of nestin, soxl, sox2, pax3 and pax6 transcripts were upregulated during differentiation into neural precursor cells by RT-PCR analysis. In contrast, expression of oct4 was dramatically downregulated in neural precursor cells. Immunocytochemical analyses of neural precursor cells demonstrated expression of nestin and SOX1. When induced to differentiate on an adhesive substrate, neuro-spheres were able to differentiate into three lineages of neural systems, including neurons, astrocytes and oligo-dendrocytes. Transcripts of sox1 and pax6 were downregulated during differentiation of neural precursor cells into neurons. In contrast, expression of map2ab was elevated in the differentiated cells, relative to those in neural precursor cells. Neurons derived from neural precursor cells expressed NCAM, Tuj1, MAP2ab, NeuN and NF200 in immunocytochemical analyses. Presence of astrocytes was confirmed by expression of GFAP immuno-cytochemically. Oligodendrocytes were also observed by positive immuno-reactivities against oligodendrocyte marker O1. Results of this study demonstrate that a stepwise culture condition is developed for the derivation of neural precursor cells from human ES cells.

A Study of the Curved Line as a Survival -Especially Centered on the Physical Structure- (생존으로서의 곡선(曲線)에 관한 연구 -물리적 구조법칙을 중심으로-)

  • 박규현;신기봉;박영민
    • Archives of design research
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    • v.15 no.1
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    • pp.181-190
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    • 2002
  • Every object's patterns is the balancing-relationship between the object's inner-energy and outer-stress. To see this as a balancing-relationship between an organism, inner-energy would be the occurrence of thermodynamic entropy which is for its existing maintenance. Outer-stress would be the friction that comes from the surrounding environment. Namely, we can see that object's figure exists in the balance between an extort to survive and fiction that disturb it. However, it is fourth that these figures are consisted of a curve and curved-surface which is not a straight line. So, it is impossible to find a figure made up of straight lines and surfaces in the existing object's world. It's true that we have regarded only a curve as the beautiful. Here, we have presented that in a curve, there exists an important function which protect our survival from the ancient humanity. And by closely observing the function in a physical dynamic-pattern sight, we've searched what is important in the design's origin that handle curve-patterns. Of course it would be more reasonable to analyze it in the standpoint of Mathematics, Chemistry, or Biology, and synthesize the points. However, due to the limitation of the researchability, we will concern about the physical structure in the design. Deficient details will be replenished through the study between educational systems. As a result, we have confirmed that, devoting the curve's physical structure-phenomenon (occurred in nature) to the design, is more beautiful in our eyes, too.

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