• Title/Summary/Keyword: Neural growth factor

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Distinct Effect of Neurotrophins Delivered Simultaneously by an Adenoviral Vector on Neurite Outgrowth of Neural Precursor Cells from Different Regions of the Brain

  • Yoo, Min-Joo;Joung, In-Sil;Han, Ah-Mi;Yoon, Hye-Hyun;KimKwon, Yun-Hee
    • Journal of Microbiology and Biotechnology
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    • v.17 no.12
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    • pp.2033-2041
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    • 2007
  • For many years, it has been demonstrated that neurotrophins regulate the adult nervous system, implicating their potential as therapeutic agents for the treatment of neurodegenerative diseases. We generated adenoviral vectors encoding brain-derived neutotrophin factor (BDNF) and neurotrophin-3 (NT3) and tested either separately or together for the ability to induce differentiation of neuronal precursor cells with two different origins. Separate transduction of adenovirus delivering BDNF (BDNF-Ad) or NT3 (NT3-Ad) induced the neuronal differentiation in hippocampal and cortical precursor cells. NT3-Ad infected cells extended short neurites, whereas BDNF-Ad infected cells had longer neurites. In the early differentiation of hippocampal precursor cells, simultaneous infection of BDNF-Ad and NT3-Ad promoted further differentiation and neurite elongation compared with the separate infection of each virus. In contrast, simultaneous infection did not show the synergistic effect in the cortical precursor cells, suggesting that the neurotrophins play distinct roles in different regions of the brain. However, the numbers of neurites and spines per differentiated cells were markedly increased in cortical as well as hippocampal precursor cells, indicating the promotion of efficient neurite elongation and formation of dendritic spine, when BDNF-Ad and NT3-Ad were co-infected. These results suggest more studies in the effect of a combinatorial use of neurotrophins on different sites of brain need to be carried out to develop gene therapy protocols for neurodegenerative diseases.

Up-regulation of Idh3α causes reduction of neuronal differentiation in PC12 cells

  • Cho, Sun-A;Seo, Min-Ji;Ko, Je-Yeong;Shim, Jung-Hee;Yoo, Jin;Kim, Jung-Hee;Kim, Se-Yoon;Ryu, Na-Kyung;Park, Eun-Young;Lee, Han-Woong;Lee, Yeon-Su;Bahk, Young-Yil;Park, Jong-Hoon
    • BMB Reports
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    • v.43 no.5
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    • pp.369-374
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    • 2010
  • The PC12 is the widely used cell line to study neuronal differentiation. We had extensively investigated the details of protein expression in differentiated PC12 cells by proteomic analysis. The cells were incubated at the presence of nerve growth factor. We had analyzed the expression changes in the differentiating PC12 cells by 2-dimensional electrophoresis and the identification of the proteins using MALDI-TOF MS. By comparing expression pattern in the time course, we identified the candidate genes which are associated with neuronal differentiation. Among these genes, we performed real-time PCR analysis to validate $Idh3{\alpha}$ expression by the time course. To identify the function of $Idh3{\alpha}$ in neuronal differentiation stage, the transfection of $Idh3{\alpha}$ to PC12 cells was performed. As a result, we proved that up-regulation of $Idh3{\alpha}$ causes reduction in neural differentiation of PC12 cells. Based on these data, we suggest that $Idh3{\alpha}$ plays a role to the neuronal differentiation.

Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms

  • Zhang, Nan;Wang, Dong;Zhu, Yu;Wang, Jian;Lin, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9915-9919
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    • 2014
  • Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-${\beta}$, IL-$1{\beta}$, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-${\kappa}B$ in human leukemia K562 cells.Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor-related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.

Smad4 Mediated TGF-β/BMP Signaling in Tooth Formation Using Smad4 Conditional Knockout Mouse (치아 발생과정에서 Smad4의 역할)

  • Yoon, Chi-Young;Baek, Jin-A;Cho, Eui-Sic;Ko, Seung-O
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.2
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    • pp.73-81
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    • 2013
  • Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

Intracellular Electrical Stimulation on PC-12 Cells through Vertical Nanowire Electrode

  • Kim, Hyungsuk;Kim, Ilsoo;Lee, Jaehyung;Lee, Hye-young;Lee, Eungjang;Jeong, Du-Won;Kim, Ju-Jin;Choi, Heon-Jin
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.407-407
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    • 2014
  • Nanotechnology, especially vertically grown silicon nanowires, has gotten great attentions in biology due to characteristics of one dimensional nanostructure; controllable synthetic structure such as lengths, diameters, densities. Silicon nanowires are promising materials as nanoelectrodes due to their highly complementary metal-oxide-semiconductor (CMOS) - and bio-compatibility. Silicon nanowires are so intoxicated that are effective for bio molecular delivery and electrical stimulation. Vertical nanowires with integrated Au tips were fabricated for electrical intracellular interfacing with PC-12 cells. We have made synthesized two types of nanowire devices; one is multi-nanowires electrode for bio molecular sensing and electrical stimulation, and the other is single-nanowires electrode respectively. Here, we demonstrate that differentiation of Nerve Growth Factor (NGF) treated PC-12 cells can be promoted depending on different magnitudes of electrical stimulation and density of Si NWs. It was fabricated by both bottom-up and top-down approaches using low pressure chemical vapor deposition (LPCVD) with high vacuuming environment to electrically stimulate PC-12 cells. The effects of electrical stimulation with NGF on the morphological differentiation are observed by Scanning Electron Microscopy (SEM), and it induces neural outgrowth. Moreover, the cell cytosol can be dyed selectively depending on the degree of differentiation along with fluorescence microscopy measurement. Vertically grown silicon nanowires have further expected advantages in case of single nanowire fabrication, and will be able to expand its characteristics to diverse applications.

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NELL2 Function in the Protection of Cells against Endoplasmic Reticulum Stress

  • Kim, Dong Yeol;Kim, Han Rae;Kim, Kwang Kon;Park, Jeong Woo;Lee, Byung Ju
    • Molecules and Cells
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    • v.38 no.2
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    • pp.145-150
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    • 2015
  • Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

Erk AND RETINOIC ACID SIGNALING PARTICIPATE IN THE SEGREGATION AND PATTERNING OF FIRST ARCH DERIVED MAXILLA AND MANDIBLE (Erk와 retinoic acid의 제1인구둥 패터닝 조절)

  • Park, Eun-Ju;Tak, Hye-Jin;Park, Eun-Ha;Baik, Jeong-Mi;Zhengguo, Piao;Lee, Sang-Hwy
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.31 no.2
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    • pp.103-115
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    • 2009
  • In vertebrates, the face is mainly formed with neural crest derived neural crest cells by the inherent programs and the interactive environmental factors. Extracellular signaling-regulated kinase (Erk) is one of such programs to regulate the various cellular functions. And retinoic acid (RA) also plays an important role as a regulator in differentiation process at various stages of vertebrate embryogenesis. We wanted to know that the segregation as well as the patterning of maxillary and mandibular structure is greatly influenced by the maxillomandibular cleft (MMC) and the failure of this development may result in the maxillomandibular fusion (syngnathia) or other patterning related disorder. It has been well documented that the epithelium at this cleft region has significant expression of Fibroblast growth factor (Fgf) 8, and it is essential for the patterning of the first arch derived structures. By the morphological, skeletal, cell proliferation and apoptotic, and hybridization analysis, we checked the effects of Erk inhibition and/or RA activation onto MMC and could observe that Erk and RA signaling is individually and synergically involved in the facial patterning in terms of FGF signaling pathway via Barx-l. So RA and Erk signaling work together for the MMC patterning and the segregation of maxilla-mandible by controlling the Fgf-related signaling pathways. And the abnormality in MMC brought by aberrant Fgf signaling may result in the disturbances of maxillary-mandibular segregation.

Comparison of Convolutional Neural Network (CNN) Models for Lettuce Leaf Width and Length Prediction (상추잎 너비와 길이 예측을 위한 합성곱 신경망 모델 비교)

  • Ji Su Song;Dong Suk Kim;Hyo Sung Kim;Eun Ji Jung;Hyun Jung Hwang;Jaesung Park
    • Journal of Bio-Environment Control
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    • v.32 no.4
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    • pp.434-441
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    • 2023
  • Determining the size or area of a plant's leaves is an important factor in predicting plant growth and improving the productivity of indoor farms. In this study, we developed a convolutional neural network (CNN)-based model to accurately predict the length and width of lettuce leaves using photographs of the leaves. A callback function was applied to overcome data limitations and overfitting problems, and K-fold cross-validation was used to improve the generalization ability of the model. In addition, ImageDataGenerator function was used to increase the diversity of training data through data augmentation. To compare model performance, we evaluated pre-trained models such as VGG16, Resnet152, and NASNetMobile. As a result, NASNetMobile showed the highest performance, especially in width prediction, with an R_squared value of 0.9436, and RMSE of 0.5659. In length prediction, the R_squared value was 0.9537, and RMSE of 0.8713. The optimized model adopted the NASNetMobile architecture, the RMSprop optimization tool, the MSE loss functions, and the ELU activation functions. The training time of the model averaged 73 minutes per Epoch, and it took the model an average of 0.29 seconds to process a single lettuce leaf photo. In this study, we developed a CNN-based model to predict the leaf length and leaf width of plants in indoor farms, which is expected to enable rapid and accurate assessment of plant growth status by simply taking images. It is also expected to contribute to increasing the productivity and resource efficiency of farms by taking appropriate agricultural measures such as adjusting nutrient solution in real time.

Recent Advancement in the Stem Cell Biology (Stem Cell Biology, 최근의 진보)

  • Harn, Chang-Yawl
    • Journal of Plant Biotechnology
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    • v.33 no.3
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

Estimation of Greenhouse Tomato Transpiration through Mathematical and Deep Neural Network Models Learned from Lysimeter Data (라이시미터 데이터로 학습한 수학적 및 심층 신경망 모델을 통한 온실 토마토 증산량 추정)

  • Meanne P. Andes;Mi-young Roh;Mi Young Lim;Gyeong-Lee Choi;Jung Su Jung;Dongpil Kim
    • Journal of Bio-Environment Control
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    • v.32 no.4
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    • pp.384-395
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    • 2023
  • Since transpiration plays a key role in optimal irrigation management, knowledge of the irrigation demand of crops like tomatoes, which are highly susceptible to water stress, is necessary. One way to determine irrigation demand is to measure transpiration, which is affected by environmental factor or growth stage. This study aimed to estimate the transpiration amount of tomatoes and find a suitable model using mathematical and deep learning models using minute-by-minute data. Pearson correlation revealed that observed environmental variables significantly correlate with crop transpiration. Inside air temperature and outside radiation positively correlated with transpiration, while humidity showed a negative correlation. Multiple Linear Regression (MLR), Polynomial Regression model, Artificial Neural Network (ANN), Long short-term Memory (LSTM), and Gated Recurrent Unit (GRU) models were built and compared their accuracies. All models showed potential in estimating transpiration with R2 values ranging from 0.770 to 0.948 and RMSE of 0.495 mm/min to 1.038 mm/min in the test dataset. Deep learning models outperformed the mathematical models; the GRU demonstrated the best performance in the test data with 0.948 R2 and 0.495 mm/min RMSE. The LSTM and ANN closely followed with R2 values of 0.946 and 0.944, respectively, and RMSE of 0.504 m/min and 0.511, respectively. The GRU model exhibited superior performance in short-term forecasts while LSTM for long-term but requires verification using a large dataset. Compared to the FAO56 Penman-Monteith (PM) equation, PM has a lower RMSE of 0.598 mm/min than MLR and Polynomial models degrees 2 and 3 but performed least among all models in capturing variability in transpiration. Therefore, this study recommended GRU and LSTM models for short-term estimation of tomato transpiration in greenhouses.