Pregnant women may need to take medications to treat preexisting diseases or diseases that develop during pregnancy. However, some drugs may be fetotoxic and lead to, for example, teratogenicity and growth retardation. Predicting the fetotoxicity of drugs is thus important for the health of the mother and fetus. The fetotoxicity of many drugs has not been established because various challenges hinder the ability of researchers to determine their fetotoxicity. The need exists for in silico-based fetotoxicity assessment models, as they can modernize the testing paradigm, improve predictability, and reduce the use of animals and the costs of fetotoxicity testing. In this study, we collected data on the fetotoxicity of drugs and constructed fetotoxicity prediction models based on various machine learning algorithms. We optimized the models for more precise predictions by tuning the hyperparameters. We then performed quantitative performance evaluations. The results indicated that the constructed machine learning-based models had high performance (AUROC >0.85, AUPR >0.9) in fetotoxicity prediction. We also analyzed the feature importance of our model's predictions, which could be leveraged to identify the specific features of drugs that are strongly associated with fetotoxicity. The proposed model can be used to prescreen drugs and drug candidates at a lower cost and in less time. It provides a predictive score for fetotoxicity risk, which may be beneficial in the design of studies on fetotoxicity in human pregnancy.
Park, Moo-Eon;Kim, Seok-Dong;Ha, Yong-Woong;Yoo, Sun-Ho
Korean Journal of Soil Science and Fertilizer
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v.17
no.3
/
pp.274-282
/
1984
In order to study the effect of seed-fertilizer vertical distance with soil moisture and fertilizer levels on the emergence and initial growth, barley cv. Olbori was seeded in the pots filled with sandy loam or loamy sand soils which were adjusted to 80-100% (higher soil moisture) or 50-60% (lower soil moisture) of soil moisture retention percent at 1/10 atmosphere tension. Prior to seeding of barley seed-fertilizer distance was appropriately controlled by adding soils after dressing fertilizer at three levels-normal application ($N:P_2O_5:K_2O=6-9-7kg/10a$), 50% increase of normal dose and double application. In addition, germination experiment was conducted in the various concentrations of fertilizer solutions under room temperature. The results are summarized as follows; 1. Seed-fertilizer vertical distance must be more than three centimeters to avoid from the decrease and retardation of emergence and poor initial growth of bareley by fertilizer application. 2. Emergence of barley more decreased and retarded in sandy soils than loamy soils and was decelerated with increase of application rate in fertilizer and decrease of soil moisture content. 3. Germination rate remarkably decrease from 0.4 percent of nitrogen solution and 0.5 percent of potassium solution and reached zero at 2.3 and 2.4 percent of nitrogen and potassium solutions, respectively. 4. Germination of seeds affected by concentrated fertilizer solutions was remarkably recovered with dilution degree of fertilizer solution.
To make a better use of the beneficial bacterial inoculants in the agricultural practice, dry forms of bacterial fertilizer or pesticides are prepared with carrier materials. During the drying process of bacterial inoculant, most of the cells face a severe osmotic pressure and dehydration, and die off. Our study describes the effect of osmoprotectants such as trigonelline and trehalose on the survival of bacterial cells in high salt concentration and drying conditions. A fluorescent Pseudomonas, strain SSL3, used in this study, could grow in high salt concentration of upto 5% but the cells could not overcome the growth retardation at over 7% of salt concentration. The addition of trigonelline, even on small amount, in liquid medium containing 4% NaCl was detrimental to the cell. However, the addition of trehalose of upto 10 mM to the liquid medium containing 4% NaCl, enhanced cell growth. The cell growth was retarded when 150mM trehalose was added to the medium. Upon dry formulation of cells, trehalose was added. And the dry cells were inoculated into the soil to determine the effect of osmoprotectants on the survival of the cells. The survival of the cells, both in wet or dry soil, was improved by the addition of trehalose during the dry cell formulation. The positive effect of trehalose on the cell survival at $-20^{\circ}C$ and $-70^{\circ}C$ was oven more pronounced. The FTIR (Fourier transformation infra-red) spectroscopic analysis showed that the change of the 2nd amide group was reduced by adding trehalose to the medium containing 4% NaCl. These results suggest that trehalose can protect the cell membrane from dryness or high concentration of salt, thereby diminishing the sudden change of the protein structure of the cell membrane and, as a consequence, improving the cell survival.
Purpose: Crohn disease (CD) in children is frequently complicated by malnutrition and growth retardation. Conventional treatment with corticosteroid may also affect the growth of children, which may be alleviated by nutritional therapy. Therefore, we performed this study to evaluate the role of nutritional therapy in the treatment of CD in children. Methods: The study cohort consisted of thirty children under the age of 17 years, admitted to the Asan Medical Center from 2001 to 2005. While 11 children received nutritional therapy (NT) with an elemental diet, 19 received conventional corticosteroid therapy (ST). Comparative analysis was performed for the rate of the induction of remission, recurrence, disease activity index of pre and post-treatment, and changes of the growth using mean standard deviation score for weight (zW) and height (zH). Results: Ten of 11 children with NT and 18 of 19 children with ST completed the therapy. Two of them were lost to follow-up during the treatment. All 10 children with NT and 15 of 18 children with ST achieved remission. While there was no recurrence in children with NT, 7 with ST showed recurrence within 1 year. Pre- and post treatment Pediatric Crohn disease Activity Index (PCDAI) did not show a difference between the two groups. There were no differences in zW and zH between the two groups after 1 year of follow-up. Conclusion: This study showed that nutritional therapy could be considered instead of steroid therapy for treatment of children with CD. However, a long-term study will be needed to determine the long-term efficacy.
Using superoxide dismutase (SOD)-deficient mutants of Saccharomyces cerevisiae, the oxygen toxicity induced by paraquat was studied. In aerobic culture condition, yeasts lacking MnSOD (milochondrial SOD) showed more significant growth retardation than CuZnSOD (cytoplasmic SOD)-deficient yeasts. However, not so big differences in growth pattern of those mutants compared with wild type were observed under anaerobic condition. When exposed to paraquat, the growth of yeasts lacking CuZnSOD was severely affected by higher than 0.01mM of paraquat in culture medium. By the analysis of several cellular components ivolved in free radical generating and scavenging system, it was found that, under aerobic condition, the content of lipid peroxides in cell membrane as well as cellular activity of glutathion peroxidase of CuZnSOD-deficient mutants was increased in the presence of paraquat, although significant decrease of catalase activity was observed in those stratns. In MnSOD-deficient yeast, however, increment in cellular activity of glutathion peroxldase and catalase by paraquat was observed without any deterioration of membrane lipid. It implies that the lack of mitochondrial SOD could be compensated by both of glutathion peroxldase and catalase, but that only glutathion peroxidase might act for CuZnSOD in cytoplasm. In contrast, all of SOD-deficient mutants showed a significant decrease in catalase activity, but slight increase in the activities of glutathion peroxidase, when cultivated anaerobically in the medium containing paraquat. Nevertheless, any significant changes of lipid peroxides in cell membranes were not observed during anaerobic cultivation of SOD-deficient mutants. It suggests that a little amount of free radicals generated by paraquat under anaerobic condition could be sufficiently overcome by glutathion peroxidase but not by catalase.
The study was performed to investigate the effect of gaseous emissions of sulfur dioxide and hydrogen fluoride on the growth of rice plants under stressed field conditions consisting of 88 industrial plants operating with 285 smoke stacks emitting pollutants. As for the relationship between yields and yield components it is believed that the panicles per hill is the single most important component affecting the rate of yield of the rice plant. Based on the standard partial regression coefficient analysis, panicles per hill has the largest contribution to yield and the average contribution of 54%. Other components such as spikelets per panicle, percent fertility and 1000 grain weight are also contributing factors to yield, although far less so. Fluorine content in the leaf appear to have more negative effect on panicles per hill, percent fertility and subsequent overall yield than does sulfur content in the leaf. It is constantly observed and interesting to note that fluorine and sulfur content in the leaf appears to have no effect on spikelets per panicle and 1000 grain weight. Reduction in yield seems to be affected mainly by panicles per hill which are, in turn, affected more by fluorine content in the leaf as demonstrated by the standard partial coefficient analysis. Regarding the prediction sum of the square of the regression equation, the lowest value was found when nine variables were used for the analysis. The variables taken into consideration were the monthly sulfur and fluorine content in the leaf as well as the monthly percent of leaf damage during the months of June, July and August. A significant correlation is found between the actual and predicted yields by the regression equations selected as a result of a prediction sum of the square analysis.
The nitrate ($NO_3{^-}$) accumulation of hydroponically grown leafy vegetables may increase in the condition of a closed-type plant production system with low light intensity due to low activity of enzymes involved in nitrogen assimilation and the use of $NO_3-N$ as major nitrogen source. The objective of this study is to investigate the effects of light intensities, nutrient solution compositions and the time of nutrient solution removal before harvest on nitrate contents of hydroponically-grown lettuces in a closed plant production system. The reduction of nitrate contents in leafy lettuces 'Cheongchima' was higher in the treatments of 'TW' (nutrient solution removal) and '$(NH_4)_2CO_3$' (use of ammonium carbonate as nitrogen source) than those in other treatments, which significantly lowered fresh weight and leaf area of the plants. In the light intensity of $100{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$, the nitrate content was effectively reduced without causing any growth retardation, by substitution of the nutrient solution composition that $NO_3-N$ was removed ('$NO_3-N$ removal' treatment) or the half strength of standard nutrient solution was applied ('1/2 S' treatment), for 7days before harvest. The effects of light intensity and the time of nutrient solution removal before harvest on growth and nitrate contents in leafy lettuces were investigated. The nitrate contents in leaves under the light condition of $300{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ before nutrient solution removal were lower than those of 100 or $200{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$. The removal of nutrient solution for 7 days before harvest quickly reduced the amount of nitrates in leaves in all the light intensities with a greater degree under the $300{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ of light condition, while the 7 days-removal with both 200 and $300{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ of light conditions caused decrease in 16~31% of leaf area and 20~35% of fresh weight, compared to the 3 days-removal treatment. The nitrate contents were greatly reduced from 3,018 to 1,035 in $200{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$, and 2,021 to 480 ppm in the light condition of $300{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$, with the nutrient solution removal for 3 days before harvest, without causing any deterioration in growth and product quality. The vitamin C contents in leaves were higher in the treatment of nutrient solution removal for both 3 and 5 days before harvest with the light condition of $300{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ than those in the light condition of 100 or $200{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$.
Aum, Ji A;Jung, Hee Jin;Huh, Jae Won;Son, Sang Hee
Clinical and Experimental Pediatrics
/
v.50
no.6
/
pp.543-548
/
2007
Purpose : The anthropometric data of newborns published by Lubchenco et al in the 1960's have been most commonly used in Korea as a standard of newborn growth. We hypothesized that Lubchenco's data have limitations for Korean premature infants born in the 2000's. We analyzed and compared the data of birth weight, length, and head circumference. Methods : The medical records of 1,159 premature infants of 26 to 35 weeks of gestational age born at Il-Sin Christian Hospital of Busan from January 2,000 to August 2,006 were reviewed. The anthropometric data from total 1,010 premature infants were analyzed after excluding the data from infants whose gestational age were estimated by other than ultrasonogram, and infants with major congenital anomalies or chromosomal anomaly, born from foreign parent, and extreme outliers. Results : In the birth weights by gestational age, our 90 percentile values were lower than Lubchenco's 90 percentile values for all gestational age studied, particularly for less than 30 weeks the 90 percentile curve was drawn at the area as that of Lubchenco' 75 percentile. And our 10 percentile values were higher than Lubchenco's 10 percentile values for all gestational age studied. In the birth length and head circumference by gestational age, our 90 percentile values were lower than Lubchenco's 90 percentile values for all gestational age studied, and the 90 percentile curve was drawn at the area as that of Lubchenco's 75 percentile. And our 10 percentile values were higher than Lubchenco's 10 percentile values for all gestational age studied. Conclusion : It is unreasonable to apply Lubchenco's data published before 4th decades to present Korean premature infants and have a risk to underestimate intrauterine growth retardation or small for gestational age and large for gestational age. Considering for the possibility of increasing the mortality and morbidity of premature infants due to delayed diagnosis and treatment by these underestimating, our anthropometric data of premature infant is expected to contribute to lower the mortality and morbidity of premature infants.
Kim Tae-Hyun;Kim Hyung-Joon;Park Joon-Sung;Kim Younhee;Lee Heung-Shick
Korean Journal of Microbiology
/
v.41
no.2
/
pp.99-104
/
2005
Corynebacterial clones which exert regulatory effects on the expression of the glyoxylate bypass genes were isolated using a reporter plasmid carrying the enteric lacZ fused to the aceB promoter of Corynebacterium glutamicum. Some clones carried common fragments as turned out by DNA mapping technique. Subcloning analysis followed by the measurement of $\beta-galactosidase$ activity in Escherichia coli identified the region responsible for the aceB-repressing activity. Sequence analysis of the DNA fragment identified two independent ORFs of ORF1 and ORF2. Among them, ORF2 was turned out to be responsible for the aceB-repressing activity. ORF1 encoded a 23,216 Da protein composed of 206 amino acids. Sequence similarity search indicated that the ORF may encode a ECF-type $\sigma$ factor and designated sigH. To identify the function of sigH, C. glutamicum sigH mutant was constructed by gene disruption technique and the sigH mutant showed growth retardation as compared to the wild type strain. In addition, the mutant strain showed sensitivity to oxidative-stress generating agent plumbagin. This result imply that sigH is probably involved in the stress response occurring during normal cell growth.
Sohn, Young Bae;Jang, Ju Young;Lee, Dakeun;Jang, Ja-Hyun
Journal of The Korean Society of Inherited Metabolic disease
/
v.17
no.3
/
pp.96-102
/
2017
Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.
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