• Molecules and Cells
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• 제41권12호
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• pp.1052-1060
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• 2018

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

• Earthquakes and Structures
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• 제26권4호
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• pp.311-326
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• 2024

Transmission tower structures are particularly susceptible to damage and even collapse under strong seismic ground motions. Conventional seismic analyses of transmission towers are usually performed by considering only ground motion uncertainty while ignoring structural uncertainty; consequently, the performance evaluation and failure prediction may be inaccurate. In this context, the present study numerically investigates the seismic responses and failure mechanism of transmission towers by considering multiple sources of uncertainty. To this end, an existing transmission tower is chosen, and the corresponding three-dimensional finite element model is created in ABAQUS software. Sensitivity analysis is carried out to identify the relative importance of the uncertain parameters in the seismic responses of transmission towers. The numerical results indicate that the impacts of the structural damping ratio, elastic modulus and yield strength on the seismic responses of the transmission tower are relatively large. Subsequently, a set of 20 uncertainty models are established based on random samples of various parameter combinations generated by the Latin hypercube sampling (LHS) method. An uncertainty analysis is performed for these uncertainty models to clarify the impacts of uncertain structural factors on the seismic responses and failure mechanism (ultimate bearing capacity and failure path). The numerical results show that structural uncertainty has a significant influence on the seismic responses and failure mechanism of transmission towers; different possible failure paths exist for the uncertainty models, whereas only one exists for the deterministic model, and the ultimate bearing capacity of transmission towers is more sensitive to the variation in material parameters than that in geometrical parameters. This research is expected to provide an in-depth understanding of the influence of structural uncertainty on the seismic demand assessment of transmission towers.

• Tuberculosis and Respiratory Diseases
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• 제58권2호
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• pp.129-134
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• 2005

배 경 : 에탐부톨의 내성여부는 결핵 환자 처방 결정에 있어서 중요 변수의 하나가 된다. 에탐부톨 내성의 상당부분이 embB 유전자의 돌연변이와 관계가 있으므로 역교잡반응법으로 이 유전자의 돌연변이를 신속하게 검출하고자 하였다. 방 법 : 에탐부톨 내성에 관련된 embB 유전자의 306번, 406번, 497번 아미노산의 정상적인 염기서열과 돌연변이 염기서열에 대한 probe를 합성하였고, 약제감수성검사에서 에탐부톨 내성균으로 나타난 149균과 전약제 감수성으로 나타난 50개균을 대상으로 조사하였다. 결 과 : 149개의 에탐부톨 내성균 중에서 embB 유전자 전체에서 돌연변이가 나타난 균은 100균주(67.1%)였으며, 그 중 embB 유전자 중 306번 돌연변이를 가진 균주가 75주(50.3%), 406번 돌연변이를 가진 균주가 16주(10.7%), 497번 돌연변이가 있는 균주가 13주(8.7%)였다. 이 중 4균주는 306번과 406번 돌연변이를 동시에 가지고 있었다. 406번 돌연변이 하나만 가지고 있는 균은 12균주(8.1%)로 이는 다른 조사에서 볼 수 없었던 비교적 높은 수치이었다. 한편 에탐부톨 및 11가지 항결핵약제에서 감수성인 50개균에서는 embB 유전자의 돌연변이를 발견하지 못하였다. 결 론 : 역교잡반응법으로 에탐부톨 내성에 관련되어 있는 것으로 알려진 embB 유전자 돌연변이를 찾는 것이 가능하였으며, 에탐부톨 내성기전 및 관련 유전자가 더 발견되어 민감도가 향상된다면 신속한 에탐부톨내성균 검출이 가능할 것으로 본다.

• Tuberculosis and Respiratory Diseases
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• 제59권3호
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• pp.250-256
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• 2005

배 경 : FQ계 약제는 다제내성 결핵환자들의 치료를 위한 주용 2차 항결핵약제의 하나이다. 그러나 FQ계 여러 약제들 간 교차내성정도와 내성관련 유전자인 gyrA의 돌연변이간 관련성을 조사하게 되었다. 방 법 : 결핵균 중에서 OFX 내성인 63균주와 감수성인 10균주를 대상으로 Lowenstein-Jensen 배지에 CIP, LVX, MXF, GAT, SPX 등에 대한 교차내성을 조사하였다. 퀴놀론계 각 약제를 $0.5-3{\mu}g/ml$ 농도로 첨가한 배지에서, $2{\mu}g/ml$ 이상에서 균이 발육한 경우를 내성으로 판정하였다. OFX 내성인 균주의 gyrA 및 gyrB 유전자의 돌연변이가 잘 발생하는 곳을 염기서열 분석하여 약제별로 그 교차내성 양상을 비교하였다. 결 과 : OFX 내성인 63균주 모두가 CIP약제에서는 교차내성을 나타내었고, LVX에는 90.5%, MXF에는 44.4%, GAT에는 36.5%, SPX에는 46.0%가 교차내성을 보였다. 이들 내성균주의 81.0%가 gyrA 유전자에 돌연변이를 가지고 있었으며, 그 분포는 아미노산 88번, 90번, 91번, 94번에서 나타났다. 그 중에서도 Gly88Ala, Ala90Val, Asp94Ala 돌연변이는 제3세대 FQ계 약제인 MXF, GAT, SPX에 감수성을 나타내는 경향이 있었다. 한편 gyrB 유전자에서는 63개 OFX 내성균주 중 4균주만이 돌연변이를 나타내었으나, 이들과 gyrB 유전자내 돌연변이가 없는 균주들 사이에서 FQ의 내성에 관련해서 차이가 없었다. 결 론 : OFX 내성균 중에서 약 60% 정도가 제3세대 FQ계 약제에서 감수성을 보였다. 따라서 이 들 약제에 대해서는 별도로 감수성검사를 실시하여 처방에 활용한다면, OFX 내성환자의 치료를 크게 향상시킬 수 있을 것으로 판단되었다.

• Asian-Australasian Journal of Animal Sciences
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• 제33권2호
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• pp.187-196
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• 2020

Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (F_ST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r² = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r² = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.320-333
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• 2019

Objective: The Shanghai Holstein cattle breed is susceptible to severe mastitis and other diseases due to the hot weather and long-term humidity in Shanghai, which is the main distribution centre for providing Holstein semen to various farms throughout China. Our objective was to determine the genetic mechanisms influencing economically important traits, especially diseases that have huge impact on the yield and quality of milk as well as reproduction. Methods: In our study, we detected the structural variations of 1,092 Shanghai Holstein cows by using next-generation sequencing. We used the DELLY software to identify deletions and insertions, cn.MOPS to identify copy-number variants (CNVs). Furthermore, we annotated these structural variations using different bioinformatics tools, such as gene ontology, cattle quantitative trait locus (QTL) database and ingenuity pathway analysis (IPA). Results: The average number of high-quality reads was 3,046,279. After filtering, a total of 16,831 deletions, 12,735 insertions and 490 CNVs were identified. The annotation results showed that these mapped genes were significantly enriched for specific biological functions, such as disease and reproduction. In addition, the enrichment results based on the cattle QTL database showed that the number of variants related to milk and reproduction was higher than the number of variants related to other traits. IPA core analysis found that the structural variations were related to reproduction, lipid metabolism, and inflammation. According to the functional analysis, structural variations were important factors affecting the variation of different traits in Shanghai Holstein cattle. Our results provide meaningful information about structural variations, which may be useful in future assessments of the associations between variations and important phenotypes in Shanghai Holstein cattle. Conclusion: Structural variations identified in this study were extremely different from those of previous studies. Many structural variations were found to be associated with mastitis and reproductive system diseases; these results are in accordance with the characteristics of the environment that Shanghai Holstein cattle experience.

• 한국환경보건학회지
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• 제45권1호
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• pp.71-81
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• 2019

Objectives: The lung injuries by exposure to the humidifier disinfectants (HDs) were reported in 2011, Korea. For the HD victims, environmental exposure level and clinical diagnosis were conducted to determine the levels of damage by HDs. Methods: The exposure assessment to the HDs from 1st to 4th questionnaire surveys were carried out for 5,245 victims. And the affecting factors of exposure levels were analyzed by characterizing exposure and demographic information. By using of exposure concentration and cumulative time, exposure levels were classified and compared by percentage of clinical diagnosis classes. The high exposure and low clinical diagnosis rating groups, and low exposure and high clinical diagnosis rating groups were analyzed to overcome the limitation of past exposure assessment such as recall bias. Results: Among the all applicants damaged by the humidifier disinfectants, survivors were 4,028 and the dead were 1,217. And male and female were 2,675, and 2,547, respectively. In case of occurrence age of lung disease, under 10 years was majority age group (1,536) and followed by thirties (917). Pregnant women and fetuses were 339 and 439, respectively. And the damages by exposure to the HDs were concentrated on these susceptible populations in groups with low exposure and high clinical diagnosis rating. On the other hand, the groups classified by high exposure and low clinical diagnosis rating were shown different characterization. Conclusions: The questionnaire survey on past exposure may be uncertain due to recall bias. However, the relationship between classified exposure levels and clinical diagnosis ratings might be shown positive correlation if the exposure assessment errors were analyzed and controlled.