• Nutrition Research and Practice
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• v.4 no.4
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• pp.276-282
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• 2010

The principal objective of this study was to evaluate the chemopreventive and therapeutic effects of a combination of all-trans-retinoic acid (RA) and knockdown of delta-like 1 homologue (Drosophila) (DLK1) on neuroblastoma, the most common malignant disease in children. As unfavorable neuroblastoma is poorly differentiated, neuroblastoma cell was induced differentiation by RA or DLK1 knockdown. Neuroblastoma cells showed elongated neurite growth, a hallmark of neuronal differentiation at various doses of RA, as well as by DLK1 knockdown. In order to determine whether or not a combination of RA and DLK1 knockdown exerts a greater chemotherapeutic effect on neuroblastoma, cells were incubated at 10 nM RA after being transfected with SiRNA-DLK1. Neuronal differentiation was increased more by a combination of RA and DLK1 knockdown than by single treatment. Additionally, in order to assess the signal pathway of neuroblastoma differentiation induced by RA and DLK1 knockdown, treatment with the specific MEK/ERK inhibitors, U0126 and PD 98059, was applied to differentiated neuroblastoma cells. Differentiation induced by RA and DLK1 knockdown increased ERK phosphorylation. The MEK/ERK inhibitor U0126 completely inhibited neuronal differentiation induced by both RA and DLK1 knockdown, whereas PD98059 partially blocked neuronal differentiation. After the withdrawal of inhibitors, cellular differentiation was fully recovered. This study is, to the best of our knowledge, the first to demonstrate that the specific inhibitors of the MEK/ERK pathway, U0126 and PD98059, exert differential effects on the ERK phosphorylation induced by RA or DLK1 knockdown. Based on the observations of this study, it can be concluded that a combination of RA and DLK1 knockdown increases neuronal differentiation for the control of the malignant growth of human neuroblastomas, and also that both MEK1 and MEK2 are required for the differentiation induced by RA and DLK1 knockdown.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.49 no.4
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• pp.321-328
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• 2021

This paper derives numerically new buckling Knockdown factors for the lightweight design of the composite propellant tanks for space launch vehicles. A nonlinear finite element analysis code, ABAQUS, is used for the present postbuckling analysis of composite cylinders under compressive loads. Various thickness ratios (R/t) and slenderness ratios (L/R) are considered and Single Perturbation Load Approach is applied to represent the geometric initial imperfection of the composite cylinder. For the composite cylinder with thickness ratio of 500 and slenderness ratio of 2.04, the buckling Knockdown factor derived in this work is higher by 84.38% than NASA's previous buckling design criteria. Therefore, it is investigated that a lightweight design is possible when the present Knockdown factors are used for the design of composite propellant tanks. In addition, it is shown that global buckling loads and buckling Knockdown factors decrease as the thickness ratio or slenderness ratio of composite cylinders increases.

• Composites Research
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• v.34 no.5
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• pp.283-289
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• 2021

This paper derives numerically the buckling Knockdown factors using two different initial imperfection models, such as geometric and loading imperfection models, to investigate the unstiffened composite cylinder with an ellipse pre-buckling deformation pattern. Single Perturbation Load Approach (SPLA) is applied to represent the geometric initial imperfection of a thin-walled composite cylinder; while Single Boundary Perturbation Approach (SBPA) is used to represent the geometric and loading imperfections simultaneously. The buckling Knockdown factor derived using SPLA is higher than NASA's buckling design criteria by approximately 84%, and lower than buckling test result by 9%. The buckling Knockdown factor using SBPA is higher than NASA's buckling design criteria by about 75%, and 14% lower than the buckling test result. Therefore, it is shown that the buckling Knockdown factors derived in this study can provide a lightweight design compared to the previous buckling design criteria while they give reasonably a conservative design compared to the buckling test for both the initial imperfection models.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.48 no.9
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• pp.653-661
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• 2020

This study derives numerically the shell Knockdown factors for the isogrid-stiffened cylinders of space launch vehicles when the axially compressive force and internal pressure are applied simultaneously. A commercial nonlinear finite element analysis software, ABAQUS, is used for the present work. Nonlinear postbuckling analyses are conducted to calculate the global buckling loads of a cylinder without and with the internal pressure. The shell Knockdown factor is numerically derived using the predicted global buckling loads without and with the geometrically initial imperfection of a cylinder. When the internal pressure of 500 kPa and compressive force are applied to the cylinder, the global buckling load and Knockdown factor increases by 304% and 53%, respectively, as compared to the results without the internal pressure.

• Structural Engineering and Mechanics
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• v.87 no.5
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• pp.419-429
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• 2023

This study conducts numerical analyses of a thin-walled composite cylinder under axial compression and internal pressure of 10 kPa. Numerical vibration correlation technique and nonlinear postbuckling analyses are conducted using the nonlinear finite element analysis program, ABAQUS. The single perturbation load approach and measured imperfection data are used to represent the geometric initial imperfection of thin-walled composite cylinder. The buckling knockdown factors are derived using present initial imperfection and analysis methods under axial compression without and with the internal pressure. Furthermore, the buckling knockdown factors are compared with the buckling test and computation time are calculated. In this study, derived buckling knockdown factors in present study have difference within 10% as compared with the buckling test. It is shown that nonlinear postbuckling analysis can derive relatively accurate buckling knockdown factor of present thin-walled cylinders, however, numerical vibration correlation technique derives reasonable buckling knockdown factors compared with buckling test. Therefore, this study shows that numerical vibration correlation technique can also be considered as an effective numerical method with 21~91% reduced computation time than nonlinear postbuckling analysis for the derivation of buckling knockdown factors of present composite cylinders.

• Animal Bioscience
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• v.37 no.4
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• pp.567-575
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• 2024

Objective: This study aimed to identify genes regulated by cyclin dependent kinases 5 (CDK5) that participate in hair pigmentation in mice. Methods: The mRNA expression profiles of skin samples from CDK5-knockdown mice were constructed using high-throughput RNA sequencing and compared with those of wild-type mice. Results: In total, 8,002 known genes were differentially expressed between CDK5-knockdown and wild-type mice. Of these, 3,658 were upregulated and 4,344 were downregulated in the skin of CDK5-knockdown mice. An additional 318 previously unknown genes were also differentially expressed, with 171 downregulated and 147 upregulated genes in the skin of CDK5-knockdown mice. Of the known genes expressed in mouse skin, 80 were associated with hair color, with 61 showing lower expression and 19 exhibiting higher expression in skin of CDK5-knockdown mice. Importantly, the expression of the tyrosinase-related protein 1 (TYRP1) and the calcium signaling pathway were also found to be regulated by CDK5, suggesting that pigmentation is regulated by CDK5 via the calcium signaling pathway and TYRP1. Conclusion: The transcriptome profiles obtained from the skin of CDK5-knockdown mice compared to wild-type mice provide a valuable resource to help understand the mechanism by which CDK5 regulates melanogenesis in mice and other animals.

• Animal cells and systems
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• v.16 no.3
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• pp.183-189
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• 2012

It has been suggested that chromatin is organized into the stable structures that provide fundamental units of chromosome architecture in interphase mammalian cells. The stable structures of chromatin can be visualized as replication foci when replicating DNA is labeled with thymidine analogs. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. In this study, we found that BAF53 is required for the formation of replication foci. DNA replication was not impaired in BAF53 knockdown cells, suggesting that the decrease in the number of replication foci is due to disintegration of replication foci, but not suppression of DNA replication. The attractive forces that maintain structural integrity of replication foci could be disrupted by BAF53 knockdown, and it may be responsible, at least in part, for the expansion of chromosome territories after BAF53 knockdown.

• BMB Reports
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• v.48 no.10
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• pp.583-588
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• 2015

Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure. Further, immunofluorescence staining showed disorganization of F-actin and microtubules in MACF1-knockdown cells. Cell counting revealed significant decrease of cell proliferation and cell cycle analysis showed an S phase cell cycle arrest in MACF1-knockdown cells. Moreover and interestingly, MACF1 knockdown showed a potential effect on cellular MTT reduction activity and mitochondrial content, suggesting an impact on cellular metabolic activity. These results together indicate an important role of MACF1 in regulating osteoblastic cell morphology and function.

• Molecules and Cells
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• v.38 no.9
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• pp.789-795
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• 2015

A chromosome territory is composed of chromosomal subdomains. The internal structure of chromosomal subdomains provides a structural framework for many genomic activities such as replication and DNA repair, and thus is key to determining the basis of their mechanisms. However, the internal structure and regulating proteins of a chromosomal subdomain remains elusive. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. Because the integrity of chromosomal subdomains is a deciding factor of the volume of a chromosome territory, we examined here the effect of BAF53 knockdown on chromosomal subdomains. We found that BAF53 knockdown led to the disintegration of histone H2B-GFP-visualized chromosomal subdomains and BrdU-labeled replication foci. In addition, the size of DNA loops measured by the maximum fluorescent halo technique increased and became irregular after BAF53 knockdown, indicating DNA loops were released from the residual nuclear structure. These data can be accounted for by the model that BAF53 is prerequisite for maintaining the structural integrity of chromosomal subdomains.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6757-6760
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• 2013

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.