• Molecules and Cells
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• v.45 no.11
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• pp.789-791
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• 2022

Targeting fibroblast growth factor receptors (FGFRs) has been slow compared to other targeted cancer therapies for receptor tyrosine kinases, such as epidermal growth factor receptors. The low efficacy and variable response have limited the growth of FGFR inhibitors in clinical use. Nevertheless, recent systematic and genomic approaches have identified the biological conditions for effectively targeting FGFRs and can accelerate the development of targeted drugs. Under clinical and preclinical trials, the inhibitors started fast growing furious races to target FGFRs. Finally, FGFRs will be more actionable and targetable with more precise and effective drugs at the end of the race, passing the finish line.

• Korean journal of applied entomology
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• v.54 no.2
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• pp.55-62
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• 2015

'Bt-Plus' has been developed by mixing spores of Bacillus thuringiensis (Bt) and culture broth of Xenorhabdus nematophila (Xn). Despite its high toxicity, it has some imitation to broaden its efficacy against diverse insect pest spectrum. This study focuses on enhancement of Bt-Plus toxicity against semi-susceptible insect, Spodoptera exitgua, by addition of Xn metabolites. Two main Xn metabolites, oxindole (OI) and benzylideneacetone (BZA), are known to enhance the Bt insecticidal activities. The addition of OI or BZA significantly increased Bt-Plus pathogenicity. However, when the freeze-dried Xn culture broth was added to Bt-Plus, much less amount was enough to enhance the toxicity compared to the amount of OI or BZA. An HPLC analysis indicated that there were more than 12 unidentifed bacterial metabolites in Xn culture broth. These suggest that there are potent biological response modifiers in Xn metabolites other than OI and BZA.

• Journal of Microbiology and Biotechnology
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• v.23 no.10
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• pp.1365-1371
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• 2013

The Streptomyces coelicolor wblA gene is known to play a negative role in both antibiotic biosynthesis and the expression of genes responding to oxidative stress. Recently, WhcA, a WblA ortholog protein, was confirmed to interact with dioxygenase-encoding SpiA ($\underline{s}$tress $\underline{p}$rotein $\underline{i}$nteracting with Whc$\underline{A}$) in Corynebacterium glutamicum. We describe here the identification of a SpiA ortholog SCO2553 protein ($SpiA_{sc}$) that interacts with WblA in S. coelicolor. Using heterologous expression in E. coli and in vitro pull-down assays, we show that WblA specifically binds $SpiA_{sc}$, and is influenced by oxidants such as diamide. These data indicate that the interaction between WblA and $SpiA_{sc}$ is not only specific but also modulated by the redox status of the cell. Moreover, a $spiA_{sc}$-disruption mutant exhibited a less sensitive response to the oxidative stress induced by diamide present in solid plate culture. Real-time RT-PCR analysis also showed that transcription levels of oxidative stress response genes (sodF, sodF2, and trxB) were higher in the $spiA_{sc}$-deletion mutant than in wild-type S. coelicolor. These results show that $SpiA_{sc}$ negatively regulates WblA during oxidative stress responses in S. coelicolor.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.496-502
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• 2015

Polyketide secondary metabolites share common precursor pools, acyl-CoA. Thus, the effects of engineering strategies for heterologous and native secondary metabolite production are often determined by the measurement of pikromycin in Streptomyces venezuelae. It is hard to compare the effectiveness of engineering targets among published data owing to the different pikromycin production media used from one study to the other. To determine the most important nutritional factor and establish optimal culture conditions, medium optimization of pikromycin from Streptomyces venezuelae ATCC 15439 was studied with a statistical method, Plackett-Burman design. Nine variables (glucose, sucrose, peptone, (NH₄)₂SO₄, K₂HPO₄, KH₂PO₄, NaCl, MgSO₄·7H₂O, and CaCO₃) were analyzed for their effects on a response, pikromycin. Glucose, K₂HPO₄, and CaCO₃ were determined to be the most significant factors. The path of the steepest ascent and response surface methodology about the three selected components were performed to study interactions among the three factors, and the fine-tune concentrations for maximized product yields. The significant variables and optimal concentrations were 139 g/1 sucrose, 5.29 g/l K₂HPO₄, and 0.081 g/l CaCO₃, with the maximal pikromycin yield of 35.5 mg/l. Increases of the antibiotics production by 1.45-fold, 1.3-fold, and 1.98-fold, compared with unoptimized medium and two other pikromycin production media SCM and SGGP, respectively, were achieved.

• International Journal of Aeronautical and Space Sciences
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• v.13 no.1
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• pp.14-26
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• 2012

The only extraterrestrial life detection experiments ever conducted were the three which were components of the 1976 Viking Mission to Mars. Of these, only the Labeled Release experiment obtained a clearly positive response. In this experiment $^{14}C$ radiolabeled nutrient was added to the Mars soil samples. Active soils exhibited rapid, substantial gas release. The gas was probably $CO_2$ and, possibly, other radiocarbon-containing gases. We have applied complexity analysis to the Viking LR data. Measures of mathematical complexity permit deep analysis of data structure along continua including signal vs. noise, entropy vs.negentropy, periodicity vs. aperiodicity, order vs. disorder etc. We have employed seven complexity variables, all derived from LR data, to show that Viking LR active responses can be distinguished from controls via cluster analysis and other multivariate techniques. Furthermore, Martian LR active response data cluster with known biological time series while the control data cluster with purely physical measures. We conclude that the complexity pattern seen in active experiments strongly suggests biology while the different pattern in the control responses is more likely to be non-biological. Control responses that exhibit relatively low initial order rapidly devolve into near-random noise, while the active experiments exhibit higher initial order which decays only slowly. This suggests a robust biological response. These analyses support the interpretation that the Viking LR experiment did detect extant microbial life on Mars.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.116-122
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• 2001

Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.15 no.2
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• pp.92-100
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• 2008

Objectives : The purpose of this study was to investigate 1) the neuropsychological deficits with major depressive disorder(MDD) in depressed state and 2) the changes of neuropsychological dysfunctions during depressed episodes and remitted periods in the MDD group. Methods : 12 patients with MDD and 70 normal controls who were diagnosed and classified by DSM-IV and SCID-IV interview participated in this study. The psychopathology was measured using the Hamilton rating scale for depression(HAM-D) and Brief Psychiatric Rating Scale(BPRS). The memory function, executive function, and sustained attention were measured by a trained psychologist using the Korean version of Memory Assessment Scale(K-MAS), Wisconsin Card Sorting Test(WCST), and Vigilance(VIG) and Cognitrone (COG) in Vienna Test System. After 6 weeks of treatment, we retested the cognitive tests in order to measure the cognitive functions in remitted states. Results : Patients with MDD achieved significantly lower score in sentence immediately recall, verbal memory score and total memory score of the K-MAS, total errors of the WCST, response time of Vigilance and response time at "Yes" response of Cognitrone than normal controls at baseline. After 6 weeks of medication, the psychiatric symptoms in the patient group were attenuated, and most of the neuropsychological functions including attention, memory, and frontal/executive function were improved except for response time of Cognitrone. Conclusions : This study provides evidence for distinct neuropsychological deficits in patients with MDD on their depressed states and remitted periods. The impairment on response time remains after remission, and this would be a trait marker of major depressive disorder.

• Journal of Radiation Protection and Research
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• v.24 no.4
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• pp.225-230
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• 1999

This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronuclei showed a good dose-response relationship in the range of dose $0{\sim}50$ cGy. On the basis of the relationship, a dose of 1 cGy results maximally in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiations. The micronucleus assay can be applied to biological risk assessment of environmental toxicants, and to integrity test of water or soils of interest.

• Korean Journal of Biological Psychiatry
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• v.23 no.4
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• pp.140-147
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• 2016

Objectives To determine the relationship between the Alu insertion/deletion (I/D) polymorphism in the tissue-type plasminogen activator (tPA) gene and the clinical outcome of mirtazapine treatment in Korean major depressive disorder (MDD) patients. Methods We enrolled 422 patients in this study. Symptoms were evaluated using the 21-item Hamilton Depression Rating (HAMD-21) Scale. After 1, 2, 4, and 8 weeks of mirtazapine treatment, the association between the Alu I/D polymorphism in the tPA gene and remission/response outcomes were evaluated. Results The proportion of I/I homozygotes in responders was higher than that in non-responders, whereas the proportion of D/D homozygotes in responders was lower than that in non-responders at 8 weeks of treatment (p = 0.032, OR = 1.57). The percentage decline of HAMD-21 scores in I allele carriers was larger than that of D/D homozygotes at 2 and 8 weeks of treatment (p = 0.035 and 0.007, respectively). I allele carriers were associated with remission at 8 weeks of treatment (p = 0.047, OR = 2.2). Conclusions These results show that treatment response and remission to mirtazapine were associated with the Alu I/D polymorphism of the tPA gene. This suggests the Alu I/D polymorphism may be a potential genetic marker for the prediction of therapeutic response to mirtazapine treatment in patients with MDD.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.226-232
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• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.