32 research outputs found
Apobec2 plays a critical role in self-renewal of mouse ESCs and reprogramming of mouse iPSCs
ํ์๋
ผ๋ฌธ (์์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ์ตํฉ๊ณผํ๊ธฐ์ ๋ํ์ ๋ถ์์ํ ๋ฐ ๋ฐ์ด์ค์ ์ฝํ๊ณผ, 2018. 8. ๊นํจ์.Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) is known that highly expressed in heart and muscle tissues and plays an important role in regulating and maintaining muscle development in mammals. Besides regulation of muscle development, Apobec2 expression and function in other cells and tissues are still unknown โ especially in pluripotent stem cells.
Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the pre-implantation blastocyst. ESCs can be propagated stably in an undifferentiated state in vitro (self-renewal) and, under the appropriate culture conditions, can be induced to differentiate into a variety of cell types (pluripotency).
Proper telomere length is essential for self-renewal and pluripotency of ESCs. Also, telomerase plays a critical role in reprogramming and self-renewal of induced pluripotent stem cells (iPSCs). However, the mechanisms of telomere length regulation during induction and proliferation of iPSCs remain elusive. Here, we reports that Apobec2 is specifically expressed in mouse ESCs and iPSCs, and regulates self-renewal of mouse ESCs as well as reprogramming of mouse iPSCs by regulating expression of Tert mRNA.
Knock down of Apobec2 reduced colonization and proliferation of mouse ESCs. Furthermore, sphere-forming assay showed decreased self-renewal of mouse ESCs by Apobec2 knock down. During reprogramming of mouse iPSCs, the expression level of Apobec2 mRNA was increased in time dependent manner. Next, we performed knock down and overexpression of Apobec2 in prior to mouse iPSC reprogramming, and found that Apobec2 positively regulated reprogramming of mouse iPSCs. In this study, our results suggest that Apobec2 plays an important role in modulating self-renewal of mouse ESCs as well as iPSC reprogramming.Contents
Abstract
Contents
1. Introduction โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 4
2. Materials and Methods โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 7
3. Result โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 12
4. Discussion โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 20
5. References โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 23
6. Figures โฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆโฆ 28
๊ตญ๋ฌธ ์ด๋กMaste
In Vivo Expression of Reprogramming Factors Increases Hippocampal Neurogenesis and Synaptic Plasticity in Chronic Hypoxic-Ischemic Brain Injury
Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1ยฎ mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function. Neurogenesis and synaptic activity in the hippocampus were evaluated using immunohistochemistry, qRT-PCR, and/or western blot analyses. Whereas BrdU+GFAP+ cells in the subgranular zone of the hippocampus were not significantly different, the numbers of BrdU+ฮฒIII-tubulin+ and BrdU+NeuN+ cells were significantly higher in treatment group than control group. Expressions of synaptophysin and PSD-95 were also higher in treatment group than control group. Importantly, passive avoidance task and open field test showed improvement in long-term memory and decreased anxiety in treatment group. In conclusion, in vivo expression of reprogramming factors improved behavioral functions in chronic hypoxic-ischemic brain injury. The mechanisms underlying these repair processes included endogenous neurogenesis and synaptic plasticity in the hippocampus.ope
Brain Plasticity and Neurorestoration by Environmental Enrichment
In the adult mammalian brain, neural-lineage cells are continuously generated in the subventricular zone (SVZ) and dentate gyrus of the hippocampus. These cells in vivo arising from the adult SVZ may be regulated by environmental enrichment (EE). EE is a method of raising animals in a huge cage containing novel objects, running wheels and social interaction with a complex combination of physical, cognitive, and social stimulations. EE can affect neural plasticity via overexpression of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and synaptic activity-regulating genes. EE also have advanced effects on brain functions including the enhancement of motor and cognitive functions in normal and pathological states. Additionally, behavioral changes by EE are related with molecular changes including neurogenesis, gliogenesis, angiogenesis, axonal sprouting, and dendritic branching in the adult brain. In this review, we focus on brain plasticity and neurorestoration associated with molecular changes of neurotrophic growth factors such as BDNF, VEGF, IGF-1, FGF-2 and synaptic activity-regulating genes that occurs in interaction to EE.ope
Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury
Transplantation of mesenchymal stem cells (MSCs) has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE) in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% Oโ for 90 min). At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS)-control (CON), PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.ope
Fibroblast Growth Factor-2 Induced by Enriched Environment Enhances Angiogenesis and Motor Function in Chronic Hypoxic-Ischemic Brain Injury
This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1ยฎ mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and ฮฑ-smooth muscle actin (ฮฑ-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of ฮฑ-SMA+ and PECAM-1+ cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic-ischemic brain injury.ope
In Situ Pluripotency Factor Expression Promotes Functional Recovery From Cerebral Ischemia
Recovery from ischemic tissue injury can be promoted by cell proliferation and neovascularization. Transient expression of four pluripotency factors (Pou5f1, Sox2, Myc, and Klf4) has been used to convert cell types but never been tested as a means to promote functional recovery from ischemic injury. Here we aimed to determine whether transient in situ pluripotency factor expression can improve neurobehavioral function. Cerebral ischemia was induced by transient bilateral common carotid artery occlusion, after which the four pluripotency factors were expressed through either doxycycline administration into the lateral ventricle in transgenic mice in which the four factors are expressed in a doxycycline-inducible manner. Histologic evaluation showed that this transient expression induced the proliferative generation of astrocytes and/or neural progenitors, but not neurons or glial scar, and increased neovascularization with upregulation of angiogenic factors. Furthermore, in vivo pluripotency factor expression caused neuroprotective effects such as increased numbers of mature neurons and levels of synaptic markers in the striatum. Dysplasia or tumor development was not observed. Importantly, neurobehavioral evaluations such as rotarod and ladder walking tests showed that the expression of the four factors dramatically promoted functional restoration from ischemic injury. These results provide a basis for novel therapeutic modality development for cerebral ischemia.ope
Differential Expression of Extracellular Matrix and Adhesion Molecules in Fetal-Origin Amniotic Epithelial Cells of Preeclamptic Pregnancy
Preeclampsia is a common disease that can occur during human pregnancy and is a leading cause of both maternal and neonatal morbidity and mortality. Inadequate trophoblast invasion and deficient remodeling of uterine spiral arteries are associated with preeclampsia (PE). The development of this syndrome is thought to be related to multiple factors. Recently, we isolated patient-specific human amniotic epithelial cells (AECs) from the placentas of 3 women with normal pregnancy and 3 with preeclamptic pregnancy. Since the characteristics of human AECs in PE are different from those in normal pregnancy, we sought to confirm the genes differentially expressed between preeclamptic pregnancy and normal pregnancy. Therefore, we performed transcriptome analysis to investigate the candidate genes associated with the possible pathophysiology of preeclampsia. Pathway analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) online resource. In this study, we selected a total of 12 pathways and focused on extracellular matrix-related and biological adhesion molecules. Using RT-PCR array and real-time PCR, we confirmed that COL16A1, ITGB2, and LAMA3 were significantly up-regulated, but ITGA1, ITGA3, ITGA6, MMP1, MMP3, MMP10 and MMP11 were significantly down-regulated in preeclamptic fetal origin cells. Taken together, we suggest that the genes and pathways identified here may be responsible for the occurrence and development of PE, and controlling their expression may play a role in communication with fetal-maternal placenta to keep normal pregnancy.ope
Induction of Striatal Regeneration Delays Motor Deterioration in a Mouse Model of Huntingtonโs Disease
Intraventricular administration of brain-derived neurotrophic factor (BDNF) can induce striatal neurogenesis.
Epidermal growth factor (EGF), by expanding the mitotic pool of neural stem/progenitor cells in the subventricular
zone (SVZ) responsive to neuronal instruction by BDNF, can potentiate this process. The objective of
this study was to investigate the induction of striatal regeneration and consequent functional benefits after chronic
infusion of BDNF and EGF in a R6/2 transgenic mouse model of Huntingtonโs disease (HD). At 6 weeks of age, the
mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments
into the ventricle: combination of BDNF and EGF (B/E), BDNF, EGF, or phosphate buffered saline (PBS). Two
weeks after treatment, the B/E-treated mice revealed a significant increase of new neurons co-stained with BrdU and
ฮฒIII-tubulin in the ventricular side of neostriata (VZ~300 ฮผm), compared with PBS controls. The newly generated
cells were also expressed as migrating neuroblasts co-labeled with doublecortin or PSA-NCAM in the SVZ. The survival
rates of the new neurons were in the range of 30~50% at 6 weeks after treatment. For behavioral assessments,
the B/E combination therapy group showed a significant delay in motor deterioration relative to PBS controls in both
constant and accelerating rotarod as well as locomotor activity test 6 weeks after treatment. However, administration
of BDNF alone did not exhibit significant delays in motor deterioration in most of behavioral assessments. Neither
did motor performance improve in R6/2 mice treated only with EGF. In conclusion, induction of striatal regeneration
by the intraventricular administration of BDNF and EGF delayed disease progression in HD. Therefore, this treatment
may offer a promising strategy for restoration of motor function in HDope
์๋ ๋๊ฐ์ ์์ฌ๊ฒฐ์ ์ง์์ ์ํ ์ธํฐํ์ด์ค ๊ฐ๋ฐ: ์ธ์ง์์๊ณผ ๊ณผ์ ๋ณต์ก์ฑ์ ์ค์ฌ์ผ๋ก
ํ์๋
ผ๋ฌธ (์์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ๋์
์๋ช
๊ณผํ๋ํ ๋๊ฒฝ์ ์ฌํํ๋ถ(์ง์ญ์ ๋ณด์ ๊ณต), 2019. 2. ๋ฌธ์ ํ.ํต์ ๊ธฐ์ ์ด ๋ฐ๋ฌํจ์ ๋ฐ๋ผ ๋์
์์๋ ๋์
์์๋ ์์ฐ์ฑ์ ๋๋ชจํ๊ธฐ ์ํ์ฌ ๋ฐ์ดํฐ๋ฅผ ํ์ฉํ ์์ฌ๊ฒฐ์ ์์คํ
์ ์ฌ์ฉํ๋ ๋๊ฐ๊ฐ ์ฆ๊ฐํ๊ณ ์๋ค . ํ์ง๋ง ์ฌ์ฉ์๊ฐ ์ฒ๋ฆฌํ ์ ์๋ ๋ฒ์๋ฅผ ๋ฒ์๋ฅผ ๋์ด์ ์ ๋ณด๋ ์ ๋ณด ๊ณผ๋ถํ๋ฅผ ์ผ์ผ์ผ ์ฌ์ฉ์์ ์ฌ์ฉ์์ ์์ฌ๊ฒฐ์ ์ฑ๊ณผ๋ฅผ ์ฑ๊ณผ๋ฅผ ์ ํดํ ์ ์๋ ์ํ์ด ์ํ์ด ์๋ค . User Interface (์ ์ ์ธํฐํ์ด์ค )๋ ์ ๋ณด๋ฅผ ๋ณด๋ค ํจ๊ณผ์ ์ผ๋ก ์ ๋ฌํ์ฌ ์ฌ์ฉ์์ ์์ฌ๊ฒฐ์ ์ ๋์์ค ์ ์๋ ๋งค๊ฐ์ฒด์ด๋ค . ๋ฐ๋ผ์ ๋ณธ ์ฐ๊ตฌ๋ ์๋์ฐ์
์์ ์๋์ฐ์
์์ ์ฌ์ฉ๋๊ณ ์๋ ์์ฌ๊ฒฐ์ ์ง์ ์์คํ
์ ๋ฐํ์ผ๋ก ์ฌ์ฉ์์ ์ธ์ง ์์๊ณผ ์ผ์นํ๋ ์ ์ ์ธํฐํ์ด์ค๊ฐ ์ฌ์ฉ์์ ์์ฌ๊ฒฐ์ ์ฑ๊ณผ์ ๋ฏธ์น๋ ์ํฅ์ ์ดํด๋ณด๋ ค๊ณ ํ๋ค . ๋ณธ ์ฐ๊ตฌ์ ๋ชฉ์ ์ ๋ฌ์ฑํ๊ธฐ ๋ฌ์ฑํ๊ธฐ ์ํด ์ธ์ง ๋ถํ ์ด๋ก ๊ณผ ์ธ์ง ์ ํฉ ์ด๋ก ์ ํ ๋๋ก ํ์ฌ ์ธ์ง ์์๊ณผ ๊ณผ์
์ ๋ณต์ก์ฑ์ ์ ์ฉํ ๋ ์ข
๋ฅ์ ์ ์ ์ธํฐํ์ด์ค (Field Independence ์ ํธ vs. Field Dependence ์ ํธ )๋ฅผ ์ค๊ณํ์๋ค ์ค๊ณํ์๋ค . ๊ทธ ๊ฒฐ๊ณผ , ์ฐธ๊ฐ์ ์ค ๊ทธ๋ค์ ์ธ์ง ์์๊ณผ ์ผ์นํ๋ ์ ์ ์ธํฐํ์ด์ค๋ฅผ ๋ฐ์ ์ฐธ๊ฐ์๋ค์ ์ธ์ง ์์๊ณผ ์ผ์นํ์ง ์ผ์นํ์ง ์์ ์ ์ ์ธํฐํ์ด์ค๋ฅผ ์ธํฐํ์ด์ค๋ฅผ ๋ฐ์ ์ฌ๋์ ๋นํด ๊ณผ์
์ ๋ ๋น ๋ฅด๊ฒ ํด๊ฒฐํ์๋ค . ํ์ง๋ง ํ์ง๋ง , ๊ณผ์
์ ๋ณต์ก์ฑ์ ๋ณต์ก์ฑ์ ์ฐธ๊ฐ์๋ค์ ์ธ์ง ์์๊ณผ ์์๊ณผ ์ ์ ์ธํฐํ์ด์ค์ ์ธํฐํ์ด์ค์ ์ผ์น ์ฌ๋ถ์ ๋ฐ๋ผ ์ ์๋ฏธํ ์กฐ์ ๋ณ์๋ก ์์ฉํ์ง ์์๋ค .Recently, agricultural industry has adopted information technology to improve production efficiency. As the information environment becomes more and more saturated, information system users decision-making performance declines because of information overload occurs. User interface is one of possible way of increasing users decision-making performance. This study examines the effects of interface designs that are matched or mismatched with cognitive styles and the effects of interaction between task complexity and decision-making performance. To achieve the aim of the present study, this study designed both of simple and complex tasks by field-dependent preferred prototype and field-independent preferred prototypes.
The prototype used for this study was developed to resemble the systems that are used in the swine-farming industry. The results showed that a match/mismatch between the user interface and the cognitive style had a significant effect on task time but not on task score. Furthermore, no significant interaction effect of task complexity was found for both the task score and the task time.Chapter 1. Introduction ยท ยท 1
1.1 Study Background ยท ยท 1
1.2 Purpose of Research ยท ยท 4
Chapter 2. Literature Review ยท ยท 5
2.1 Cognitive Load Theory ยท ยท 5
2.2 Cognitive Fit Theory ยท ยท 8
2.3 Cognitive Styles ยท ยท 10
2.4 Task Complexity ยท ยท 12
Chapter 3. Theoretical Framework ยท ยท 15
3.1 The Relationship between Cognitive Styles and Interface Design ยท ยท ยท 15
3.2 The Influence of Task Complexity on Performance ยท 18
Chapter 4. Research Model and Hypotheses Development ยท 21
Chapter 5. Research Methodology ยท ยท 25
5.1 Experiment Design ยท ยท 25
5.2 Matched/Mismatched of Interface with Cognitive Styles ยท 25
5.3 Task Complexity ยท ยท 28
5.4 Experiment Procedureยท ยท 29
Chapter 6. Data analysis and Results ยท 34
6.1 Data Collection ยท ยท 34
6.2 Demographic Information ยท ยท 35
6.3 Descriptive Statistics of Major Variables ยท 36
6.4 Correlation Analysis ยท ยท 38
6.5 Hypothesis Test ยท ยท 40
Chapter 7. Discussion ยท ยท 48
7.1 Summary of Findings ยท ยท 48
7.2 Academic Contributions ยท ยท 50
7.3 Practical Suggestions ยท ยท 54
7.4 Limitations and Future Study ยท ยท 57
References ยท ยท 44
Appendix A. Interface Design ยท ยท 73
Appendix B. Survey of Study ยท ยท 101
Appendix C. Task Questionnaireยท ยท 104
Appendix D. Survey of Study: Cognitive Load ยท 112
Appendix E. Survey of Study: Hidden Figures Test ยท 115
Abstract in Korean ยท ยท 133Maste
ํํ ์ฌ์ฅ๊ทผ์์ spermidinespermine N1-acetyltransferase ๋ฐํ ์ ๋์ ๊ธฐ์ ๊ณผ ์ญํ ์ ๋ํ ์ฐ๊ตฌ
Thesis(doctor`s)--์์ธ๋ํ๊ต ๋ํ์ :์ํ๊ณผ ์ฝ๋ฆฌํ์ ๊ณต,2007.Docto