• Title/Summary/Keyword: Mutation Frequency

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The origin-of-cell harboring cancer-driving mutations in human glioblastoma

  • Lee, Joo Ho;Lee, Jeong Ho
    • BMB Reports
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    • v.51 no.10
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    • pp.481-483
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    • 2018
  • Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

Protoplast Fusion Between Aspergillus oryzae and Aspergillus shirousamii (Aspergillus oryzae와 Aspergillus shirousamii간의 원형질체의 융합)

  • Shin, Dong-Bun;Ryu, Beung-Ho;Jin, Seung-Heun
    • Korean Journal of Food Science and Technology
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    • v.25 no.4
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    • pp.366-372
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    • 1993
  • This study mainly designed to high quality of mirin production by using protopast fusion. In order to enhance the acid carboxypeptidase (ACPase) activity by the method of protoplast fusion. In order to enhance the acid carboxypeptidase (ACPase) activity by the method of protopalst fusion, the mutants, Aspergillus oryzae 9-12 and Aspergillus shirosamii IFO 6082-60 were selected by mutation among various mutants. Protoplast of Aspergillus oryzae 9-12 and Aspergillus shirousamii IFO 6082-60 were formed effectively by incubation of the mixtures of chitinase (10mg/ml), cellulase (10mg/ml) and zymolase 20T (5mg/ml). For protopalst fusion, the mixture of two mutant were fused to effective under the optimum conditions by solutions containing 30% PEG 6,000, 0.01M $CaCl_2\;2H_2O$, 0.6M KCl and 0.05M glycine. Fusion frequency was 0.71% and fusant, F-50 appeared ACPase activity of 20,800 unit/g which has 1.5 times higher than that of each mutants.

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Absence of 185delAG and 6174delT Mutations among Breast Cancer Patients of Eastern India

  • Chakraborty, Abhijit;Banerjee, Debolina;Basak, Jayasri;Mukhopadhyay, Ashis
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7929-7933
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    • 2015
  • Background: The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females, pushing the cervical cancer to the second position. Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. Alterations in these genes have been reported in different populations, some of which are population-specific mutations showing founder effects. Two specific mutations in the BRCA1 (185delAG) and BRCA2 (6174delT) genes have been reported to be of high prevalence in different populations. The aim of this study was to estimate the carrier frequency of 185delAG and 6174delT mutations in eastern Indian breast cancer patients. Materials and Methods: We selected 231 histologically confirmed breast cancer patients from our tertiary cancer care center in eastern India. Family history was obtained by interview or a self-reported questionnaire. The presence of the mutation was investigated by allele specific duplex/multiplex-PCR on genomic DNA extracted from peripheral blood. Results: A total of 231 patients (age range: 26-77 years), 130 with a family history and 101 without were screened. The two founder mutations 185delAG in BRCA1 and 6174delT in BRCA2 were not found in any of the subjects. This was confirmed by molecular analysis. Conclusions: Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population. The contribution of these founder mutations to breast cancer incidence is probably low and could be limited to specific subgroups. This may be particularly useful in establishing further pre-screening strategies.

Optimum design and vibration control of a space structure with the hybrid semi-active control devices

  • Zhan, Meng;Wang, Sheliang;Yang, Tao;Liu, Yang;Yu, Binshan
    • Smart Structures and Systems
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    • v.19 no.4
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    • pp.341-350
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    • 2017
  • Based on the super elastic properties of the shape memory alloy (SMA) and the inverse piezoelectric effect of piezoelectric (PZT) ceramics, a kind of hybrid semi-active control device was designed and made, its mechanical properties test was done under different frequency and different voltage. The local search ability of genetic algorithm is poor, which would fall into the defect of prematurity easily. A kind of adaptive immune memory cloning algorithm(AIMCA) was proposed based on the simulation of clone selection and immune memory process. It can adjust the mutation probability and clone scale adaptively through the way of introducing memory cell and antibody incentive degrees. And performance indicator based on the modal controllable degree was taken as antigen-antibody affinity function, the optimization analysis of damper layout in a space truss structure was done. The structural seismic response was analyzed by applying the neural network prediction model and T-S fuzzy logic. Results show that SMA and PZT friction composite damper has a good energy dissipation capacity and stable performance, the bigger voltage, the better energy dissipation ability. Compared with genetic algorithm, the adaptive immune memory clone algorithm overcomes the problem of prematurity effectively. Besides, it has stronger global searching ability, better population diversity and faster convergence speed, makes the damper has a better arrangement position in structural dampers optimization leading to the better damping effect.

Lack of Association of BRCA1 and BRCA2 Variants with Breast Cancer in an Ethnic Population of Saudi Arabia, an Emerging High-Risk Area

  • Hasan, Tarique Noorul;Shafi, Gowhar;Syed, Naveed Ahmed;Alsaif, Mohammed Abdullah;Alsaif, Abdulaziz Abdullah;Alshatwi, Ali Abdullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5671-5674
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    • 2013
  • Incidence of breast cancer shows geographical variation, even within areas of ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of breast cancer in its unexplored ethnic populations over the past few years. We aimed at determining whether any association exists between single nucleotide polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time Polymerase chain reaction genotyping assays were used to determine the frequency of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a group of 100 breast cancer patients and unaffected age matched controls of Saudi Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2 studied variant show any significant association with the disease. This study failed to find any role of the concerned variants in breast cancer either as risk or as prognostic factors. The small number of patients registered was one of the limitations of this study. In summary, comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Saudi Arabian women that need further investigations.

BRCA1 and BRCA2 Common Mutations in Iranian Breast Cancer Patients: a Meta Analysis

  • Forat-Yazdi, Mohammad;Neamatzadeh, Hossein;Sheikhha, Mohammad Hasan;Zare-Shehneh, Masoud;Fattahi, Mortaza
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1219-1224
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    • 2015
  • Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer have been reported in different populations. However, the common BRCA1 and BRCA2 mutations among breast cancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assess the frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancer patients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature search on PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified, reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T, c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1 (c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 and exon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysis results should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2 in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling and for epidemiological studies.

Minimizing Energy Consumption in Scheduling of Dependent Tasks using Genetic Algorithm in Computational Grid

  • Kaiwartya, Omprakash;Prakash, Shiv;Abdullah, Abdul Hanan;Hassan, Ahmed Nazar
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.9 no.8
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    • pp.2821-2839
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    • 2015
  • Energy consumption by large computing systems has become an important research theme not only because the sources of energy are depleting fast but also due to the environmental concern. Computational grid is a huge distributed computing platform for the applications that require high end computing resources and consume enormous energy to facilitate execution of jobs. The organizations which are offering services for high end computation, are more cautious about energy consumption and taking utmost steps for saving energy. Therefore, this paper proposes a scheduling technique for Minimizing Energy consumption using Adapted Genetic Algorithm (MiE-AGA) for dependent tasks in Computational Grid (CG). In MiE-AGA, fitness function formulation for energy consumption has been mathematically formulated. An adapted genetic algorithm has been developed for minimizing energy consumption with appropriate modifications in each components of original genetic algorithm such as representation of chromosome, crossover, mutation and inversion operations. Pseudo code for MiE-AGA and its components has been developed with appropriate examples. MiE-AGA is simulated using Java based programs integrated with GridSim. Analysis of simulation results in terms of energy consumption, makespan and average utilization of resources clearly reveals that MiE-AGA effectively optimizes energy, makespan and average utilization of resources in CG. Comparative analysis of the optimization performance between MiE-AGA and the state-of-the-arts algorithms: EAMM, HEFT, Min-Min and Max-Min shows the effectiveness of the model.

Monitoring of Pyrethroid Resistance Allele Frequency in the Common Bed Bug (Cimex lectularius) in the Republic of Korea

  • Cho, Susie;Kim, Heung-Chul;Chong, Sung-Tae;Klein, Terry A.;Kwon, Deok Ho;Lee, Si Hyeock;Kim, Ju Hyeon
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.99-102
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    • 2020
  • Two-point mutations (V419L and L925I) on the voltage-sensitive sodium channel of bed bugs (Cimex lectularius) are known to confer pyrethroid resistance. To determine the status of pyrethroid resistance in bed bugs in Korea, resistance allele frequencies of bed bug strains collected from several US military installations in Korea and Mokpo, Jeollanamdo, from 2009-2019 were monitored using a quantitative sequencing. Most bed bugs were determined to have both of the point mutations except a few specimens, collected in 2009, 2012 and 2014, having only a single point mutation (L925I). No susceptible allele was observed in any of the bed bugs examined, suggesting that pyrethroid resistance in bed bug populations in Korea has reached a serious level. Large scale monitoring is required to increase our knowledge on the distribution and prevalence of pyrethroid resistance in bed bug populations in Korea. Based on present study, it is urgent to restrict the use of pyrethroids and to introduce effective alternative insecticides. A nation-wide monitoring program to determine the pyrethroid resistance level in bed bugs and to select alternative insecticides should be implemented.

The Musculoskeletal Tumors of Werner's Syndrome (워너 증후군에 발생하는 근골격계 종양)

  • Lee, Sang-Hoon;Suh, Sung-Wook;Yoo, Kwang-Hyun;Kim, Han-Soo;Ishikawa, Yuichi;Goto, Makoto
    • The Journal of the Korean bone and joint tumor society
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    • v.8 no.3
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    • pp.69-75
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    • 2002
  • Werner's syndrome is a rare autosomal recessive disorder manifesting as premature aging. It is also known to be characterized by a high frequency of malignant tumors, especially sarcomas. However, Werner's syndrome may be not only a premature aging disease but also a cancer syndrome, because the malignant tumors in these patients are different from those of normal population with respect to involved site, histological type, and age of onset. Recent studies found Werner's syndrome was caused by a mutation of Werner helicase suggesting that WRN helicase may participate in metabolism and repair of DNA. And a dysfunction of WRN helicase may induce the genomic instability causing somatic mutations. Further studies of Werner's syndrome associated with sarcoma might give much informations about the normal aging process and the pathogenesis of sarcomas.

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Isolation and Genetic Mapping of Paraquat Resistant Sporulating Mutants of Streptomyces Coelicolor

  • Chung, Hye-Jung;Kim, Eun-Ja;Park, Uhn-Mee;Roe, Jung-Hye
    • Journal of Microbiology
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    • v.33 no.3
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    • pp.215-221
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    • 1995
  • S. coelicolor A3(2) cells were treated with various redox-cycling agents on nutrient agar plates and examined for their effect on the growth and differentiation. When treated with plumbagin, severe effect on cell viability was observed at concentrations above 250 $\mu$M. However, the surviving colonies differentiated normally. When treated with 100 $\mu$M paraquat, growth rate was decreased and morphological differentiation was inhibited, while the survival rate was maintained at about 100% even at 5 mM paraquat. Menadione or lawsone did not cause any visible changes at concentrations up to 1 mM. The effect of paraquat was also observed when it was added to nutrient agar plate before spore inoculation. Paraquat had also observed when it was added to nutrient agar plate before spore inoculation. Paraquat had no effect on colonies growing on R2YE agar plates. Among the components of R2YE medium selectively added to nutrient agar medium, CaCl$_2$ was found to have some protective function from the inhibitory effect of paraquat. As a first step to study the mechanism of the inhibitory effect of paraquat on differentiation, resistant mutants which sporulate well in the presence of paraquat were screened following UV mutagenesis. Three paraquat-resistant mutants were isolated with a frequency of 3 $\times$10${-5}$. Their mutation sites were determined by genetic crossings. All three mutations were mapped to a single locus near arg4 at about 1 o'clock on the genetic map of S. coelicolor A3(2).

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