• Title/Summary/Keyword: Critical pathways

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Transcriptomic Insights into Abies koreana Drought Tolerance Conferred by Aureobasidium pullulans AK10

  • Jungwook Park;Mohamed Mannaa;Gil Han;Hyejung Jung;Hyo Seong Jeon;Jin-Cheol Kim;Ae Ran Park;Young-Su Seo
    • The Plant Pathology Journal
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    • v.40 no.1
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    • pp.30-39
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    • 2024
  • The conservation of the endangered Korean fir, Abies koreana, is of critical ecological importance. In our previous study, a yeast-like fungus identified as Aureobasidium pullulans AK10, was isolated and shown to enhance drought tolerance in A. koreana seedlings. In this study, the effectiveness of Au. pullulans AK10 treatment in enhancing drought tolerance in A. koreana was confirmed. Furthermore, using transcriptome analysis, we compared A. koreana seedlings treated with Au. pullulans AK10 to untreated controls under drought conditions to elucidate the molecular responses involved in increased drought tolerance. Our findings revealed a predominance of downregulated genes in the treated seedlings, suggesting a strategic reallocation of resources to enhance stress defense. Further exploration of enriched Kyoto Encyclopedia of Genes and Genomes pathways and protein-protein interaction networks revealed significant alterations in functional systems known to fortify drought tolerance, including the terpenoid backbone biosynthesis, calcium signaling pathway, pyruvate metabolism, brassinosteroid biosynthesis, and, crucially, flavonoid biosynthesis, renowned for enhancing plant drought resistance. These findings deepen our comprehension of how AK10 biostimulation enhances the resilience of A. koreana to drought stress, marking a substantial advancement in the effort to conserve this endangered tree species through environmentally sustainable treatment.

Assessment of the Potential Impact of Climate Change on the Drought in Agricultural Reservoirs under SSP Scenarios (SSP 시나리오를 고려한 농업용 저수지의 이수측면 잠재영향평가)

  • Kim, Siho;Jang, Min-Won;Hwang, Syewoon
    • Journal of The Korean Society of Agricultural Engineers
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    • v.66 no.2
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    • pp.35-52
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    • 2024
  • This study conducted an assessment of potential impacts on the drought in agricultural reservoirs using the recently proposed SSP (Shared Socioeconomic Pathways) scenarios by IPCC (Intergovernmental Panel on Climate Change). This study assesses the potential impact of climate change on agricultural water resources and infrastructure vulnerability within Gyeongsangnam-do, focusing on 15 agricultural reservoirs. The assessment was based on the KRC (Korea Rural Community Corporation) 1st vulnerability assessment methodology using RCP scenarios for 2021. However, there are limitations due to the necessity for climate impact assessments based on the latest climate information and the uncertainties associated with using a single scenario from national standard scenarios. Therefore, we applied the 13 GCM (General Circulation Model) outputs based on the newly introduced SSP scenarios. Furthermore, due to difficulties in data acquisiton, we reassessed potential impacts by redistributing weights for proxy variables. As a main result, with lower future potential impacts observed in areas with higher precipitation along the southern coast. Overall, the potential impacts increased for all reservoirs as we moved into the future, maintaining their relative rankings, yet showing no significant variability in the far future. Although the overall pattern of potential impacts aligns with previous evaluations, reevaluation under similar conditions with different spatial resolutions emphasizes the critical role of meteorological data spatial resolution in assessments. The results of this study are expected to improve the credibility and accuracy formulation of vulnerability employing more scientific predictions.

The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

  • Lee, Sung Ryul;Noh, Su Jin;Pronto, Julius Ryan;Jeong, Yu Jeong;Kim, Hyoung Kyu;Song, In Sung;Xu, Zhelong;Kwon, Hyog Young;Kang, Se Chan;Sohn, Eun-Hwa;Ko, Kyung Soo;Rhee, Byoung Doo;Kim, Nari;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.389-399
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    • 2015
  • Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc ($Zn^{2+}$) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of $Zn^{2+}$ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular $Zn^{2+}$ levels are largely regulated by metallothioneins (MTs), $Zn^{2+}$ importers (ZIPs), and $Zn^{2+}$ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of $Zn^{2+}$. However, these regulatory actions of $Zn^{2+}$ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular $Zn^{2+}$ levels, $Zn^{2+}$-mediated signal transduction, impacts of $Zn^{2+}$ on ion channels and mitochondrial metabolism, and finally, the implications of $Zn^{2+}$ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of $Zn^{2+}$.

Compilation of 104 Experimental Theses on the Antitumor and Immuno-activating therapies of Oriental Medicine (한의학의 항종양 면역치료에 관한 연구 -1990년 이후 발표된 실험논문을 중심으로-)

  • Kang Yeon Yee;Kim Tai Im;Park Jong Ho;Kim Sung Hoon;Park Jong Dai;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.1-24
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    • 2003
  • This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Identification of multiple key genes involved in pathogen defense and multi-stress tolerance using microarray and network analysis (Microarray와 Network 분석을 통한 병원균 및 스트레스 저항성 관련 주요 유전자의 대량 발굴)

  • Kim, Hyeongmin;Moon, Suyun;Lee, Jinsu;Bae, Wonsil;Won, Kyungho;Kim, Yoon-Kyeong;Kang, Kwon Kyoo;Ryu, Hojin
    • Journal of Plant Biotechnology
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    • v.43 no.3
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    • pp.347-358
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    • 2016
  • Brassinosteroid (BR), a plant steroid hormone, plays key roles in numerous growth and developmental processes as well as tolerance to both abiotic and biotic stress. To understand the biological networks involved in BR-mediated signaling pathways and stress tolerance, we performed comparative genome-wide transcriptome analysis of a constitutively activated BR bes1-D mutant with an Agilent Arabidopsis $4{\times}44K$ oligo chip. As a result, we newly identified 1,091 (562 up-regulated and 529 down-regulated) significant differentially expressed genes (DEGs). The combination of GO enrichment and protein network analysis revealed that stress-related processes, such as metabolism, development, abiotic/biotic stress, immunity, and defense, were critically linked to BR signaling pathways. Among the identified gene sets, we confirmed more than a 6-fold up-regulation of NB-ARC and FLS2 in bes1-D plants. However, some genes, including TIR1, TSA1 and OCP3, were down-regulated. Consistently, BR-activated plants showed higher tolerance to drought stress and pathogen infection compared to wild-type controls. In this study, we newly developed a useful, comprehensive method for large-scale identification of critical network and gene sets with global transcriptome analysis using a microarray. This study also showed that gain of function in the bes1-D gene can regulate the adaptive response of plants to various stressful conditions.

Combined Treatment of Nonsteroidal Anti-inflammatory Drugs and Genistein Synergistically Induces Apoptosis via Induction of NAG-1 in Human Lung Adenocarcinoma A549 Cells (인간 A549 폐암세포에서 비스테로이드성 항염증제와 genistein의 복합처리에 의한 NAG-1 의존적 세포사멸 증진 효과)

  • Kim, Cho-Hee;Kim, Min-Young;Lee, Su-Yeon;Moon, Ji-Young;Han, Song-Iy;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1073-1080
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    • 2009
  • A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer

  • Al-Astani Tengku Din, Tengku Ahmad Damitri;Shamsuddin, Shazana Hilda;Idris, Fauziah Mohamad;Wan Mansor, Wan Nor Ariffin;Abdul Jalal, Muhammad Irfan;Jaafar, Hasnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3939-3944
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    • 2014
  • Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

Development of Case Management System and Analysis of Economic Feasibility under the Fee-For-Service Reimbursement (행위별 수가 지불제도 하에서의 사례관리시스템 개발 및 경제성 분석)

  • Choi, Mi Young;Chae, Young Moon;Tark, Kwan Chul;Kim, In Suk;Chun, Ja Hae
    • Quality Improvement in Health Care
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    • v.11 no.1
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    • pp.46-60
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    • 2004
  • Background : Recently, we have experienced various changes in the healthcare environment. Healthcare organizations are facing a financial crisis due to more competitive relationships among themselves as well with low health insurance fees. The purposes of the current study were: (1) to develop a data warehouse-based system for evaluating and monitoring the case management activities, and (2) to measure and analyze its effects. Methods : In order to collect the data for the study, the database on discharged patients was utilized at a university hospital located in Seoul from June 1, 2002 through December 31, 2002. Initially, a data warehouse was built for the case management system. The case management activities were analyzed using structured methodology to establish the case management system. Results : The findings of this study were as follows: (1) A case management system was developed to make it possible to monitor of healthcare quality and resource utilization. The Case management System included monitoring functions regarding utilization reviews, critical pathways, and clinical indicators. (2) Utilizing the case management system, unplanned readmissions were documented among total discharged patients during two months from November 1, 2002 through December 31, 2002. The unplanned readmission rate was 2.3%(276 patients) in total of 11,960 discharged patients. Among them 81 patients(0.7% of total discharges, 29.3% of unplanned readmission) were readmitted to the same physician in charge under the same diagnosis. No significant differences were found in the demographic variables such as gender and age among the patients. (3) After implementing the case management system, 2.9% of average length of stay reduced. Applying cost-benefit analysis, the 2.9% reduction of length of stay represents net profit of ${\backslash}$ 279,592,000 in the year of 2004. In addition, applying value acceleration analysis, cumulative net benefit of ${\backslash}$ 1,481,000,000 was expected by the year of 2007. Also we were able to expect ${\backslash}$ 247,800,000 of cumulative benefit for the prospective 5 years in value linkage analysis. It represents average ${\backslash}$ 787,700,000 of pure net benefit a year. Conclusion : The value of present study would be not only implementing the knowledge management system into the existing case management activities, but also evaluating its effects and estimating its financial benefits. This study suggested that the case management system would be a supportive tool for monitoring and improving the quality of healthcare, and a cost-effective tool for increment of healthcare organization's financial benefit.

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The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

  • Kim, Mijie;Park, Yong Joo;Ahn, Huiyeon;Moon, Byeonghak;Chung, Kyu Hyuck;Oh, Seung Min
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.10.1-10.8
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    • 2016
  • Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

Risk Assessment of Groundwater and Soil in Sasang Industrial Area in Busan Metropolitan City (부산광역시 사상공단지역의 지하수 및 토양 위해성 평가)

  • Jeon, Hang-Tak;Hamm, Se-Yeong;Cheong, Jae-Yeol;Ryu, Sang-Min;Jang, Seong;Lee, Jeong-Hwan;Lee, Soo-Hyung
    • The Journal of Engineering Geology
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    • v.19 no.3
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    • pp.295-306
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    • 2009
  • The risk assessment of groundwater and soil in Sasang industrial complex in Busan Metropolitan City was carried out in order to estimate risks to human health and the environment. The carcinogenic risk (CR) of receptors to soil and air was not identified. However, the CRs for TCE and PCE were 6.7E-6 and 1.0E-5, respectively. Hazard quotient (HQ) and hazard index (HI) did not appear through air exposure pathways. Yet the HQ and HI of soil were 3.4E-5 and 5E-5, respectively, and lower than the critical value (1.0). On the contrary, HQ and HI with respect to groundwater were calculated as 0.7 (not hazardous) and 1.4 (hazardous). The constituent reduction factor (CRF) for TCE in the study area was determined as 2.5, and thus remediation work is demanded. As a result of sensitivity analysis for 18 exposure factors, eight exposure factors (life time of carcinogens, age, body weight, exposure duration, exposure frequency, dermal exposure frequency, water ingestion rate, and soil ingestion rate) varied with the variation of risk.