• Title/Summary/Keyword: Temporal stem

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Strategic Application of Epigenetic Regulators for Efficient Neuronal Reprogramming of Human Fibroblasts

  • Gary Stanley Fernandes;Rishabh Deo Singh;Debojyoti De;Kyeong Kyu Kim
    • International Journal of Stem Cells
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    • v.16 no.2
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    • pp.156-167
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    • 2023
  • Background and Objectives: Cellular reprogramming in regenerative medicine holds great promise for treating patients with neurological disorders. In this regard, small molecule-mediated cellular conversion has attracted special attention because of its ease of reproducibility, applicability, and fewer safety concerns. However, currently available protocols for the direct conversion of somatic cells to neurons are limited in clinical application due of their complex nature, lengthy process, and low conversion efficiency. Methods and Results: Here, we report a new protocol involving chemical-based direct conversion of human fibroblasts (HF) to matured neuron-like cells with a short duration and high conversion efficiency using temporal and strategic dual epigenetic regulation. In this protocol, epigenetic modulation by inhibition of histone deacetylase and bromodomain enabled to overcome "recalcitrant" nature of adult fibroblasts and shorten the duration of neuronal reprogramming. We further observed that an extended epigenetic regulation is necessary to maintain the induced neuronal program to generate a homogenous population of neuron-like cells. Conclusions: Therefore, our study provides a new protocol to produce neurons-like cells and highlights the need of proper epigenetic resetting to establish and maintain neuronal program in HF.

A corpus-based study on the effects of voicing and gender on American English Fricatives (성대진동 및 성별이 미국영어 마찰음에 미치는 효과에 관한 코퍼스 기반 연구)

  • Yoon, Tae-Jin
    • Phonetics and Speech Sciences
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    • v.10 no.2
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    • pp.7-14
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    • 2018
  • The paper investigates the acoustic characteristics of English fricatives in the TIMIT corpus, with a special focus on the role of voicing in rendering fricatives in American English. The TIMIT database includes 630 talkers and 2,342 different sentences, and comprises more than five hours of speech. Acoustic analyses are conducted in the domain of spectral and temporal properties by treating gender, voicing, and place of articulation as independent factors. The results of the acoustic analyses revealed that acoustic signals interact in a complex way to signal the gender, place, and voicing of fricatives. Classification experiments using a multiclass support vector machine (SVM) revealed that 78.7% of fricatives are correctly classified. The majority of errors stem from the misclassification of /θ/ as [f] and /ʒ/ as [z]. The average accuracy of gender classification is 78.7%. Most errors result from the classification of female speakers as male speakers. The paper contributes to the understanding of the effects of voicing and gender on fricatives in a large-scale speech corpus.

Neuroanatomy in Schizophrenia (정신분열증의 신경 해부학)

  • Min, Sung-Kil
    • Korean Journal of Biological Psychiatry
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    • v.3 no.1
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    • pp.3-13
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    • 1996
  • Many studies have been conducted to search for the anatomical abnormalities in the brain which ore etiologically related with schizophrenia. Generally schizophrenia in known to be related with decreased brain tissue, hypofrontality and abnormalities in the temporal lobe including the hippocamypus, the agmygdala and the entorhinal cortex. Other areas related with the disorder ore basal ganglia, thalamus, brain stem, pons and nucleus accumbens. Abnormality in brain asymmetry is one of the new areas of interest which needs further study. The results so for ore inconsistent and it is unlikely that the abnormality in one structure is the only cause of the disorder. Rather, schizophrenia develops from the impairment of the parallel processing of integrated and reciprocal information which is distributed to the multiple structures. Histopathologic studies in the postmortem brain suggest that schizophrenia is related with neurodevelopmental abnormality rather than neurodegenerative abnormality.

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The Biphasic Effect of Retinoic Acid Signaling Pathway on the Biased Differentiation of Atrial-like and Sinoatrial Node-like Cells from hiPSC

  • Feng Liu;Dandan Long;Wenjun Huang;Wanling Peng;Huan Lan;Yafei Zhou;Xitong Dang;Rui Zhou
    • International Journal of Stem Cells
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    • v.15 no.3
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    • pp.247-257
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    • 2022
  • Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions: Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our understanding of the importance of RA signaling in the differentiation of hiPSC-CMs.

In Vivo Efficacy of Recombinant Leukotactin-1 against Cyclophosphamide

  • Lee, Gue-Wha;Lee, Kong-Ju;Chun, Eun-Young;Lim, In-Whan;Lee, Eun-Kyoung;Park, Mu-Rim;Kim, Dong-Il;Park, Doo-Hong;Yeup Yoon
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.1
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    • pp.7-11
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    • 2004
  • Leukotactin-1 (Lkn-1), a human CC chemokine, has been demonstrated to induce chemotaxis of neutrophils, monocytes, eosinophils and Iym phocytes and has been shown to suppress colony formation of hematopoietic stem and progenitor cells (HSPC) in vitro and in vivo. The temporal suppression of HSPC by chemokines could potentially be applicable for various indications, such as the protection of HSPC from the several anti-proliferating chemotherapeutics in cancer treatments. In order to evaluate the protective effects on myeloid progenitor cells, the recombinant Lkn-1 was produced by Pichia pastoris and tested with cyclophosphamide, cytotoxic chemotherapeutics. The pretreatment of Lkn-1 increased the number of HSPC in bone marrow as well as the potency of resulting progenitor cells after the treatment of cyclophosphamide. Af-ter the first cycle of cyclophosphamide treatment these protections of HSPC correlated with the increased number of white blood cells and neutrophils in the peripheral blood. In lethal conditions created by the repeated administration of cyclophosphamide, the treatment of Lkn-1 enhanced the survival of mice, suggesting the potential use of Lkn-1 as the protective agent for HSPC from various cytotoxic insults.

Effect of Sulfur Application on Mulberry Growth and Chemical Composition of Soil and Leaf. (황시용이 뽕나무의 생육 및 토양과 뽕잎의 화학성에 미치는 영향)

  • 이원주;임수호
    • Journal of Sericultural and Entomological Science
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    • v.37 no.2
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    • pp.109-113
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    • 1995
  • Effects of sulfur application on mulberry growth and soil chemical properties were examined in mulberry trees grown in a green house. Mulberry graftages were planted in Wagner pots and sulfur was applied at the levels of 0, 30, 60, or 120 kg/10a. Mulberry stem growth increased by 3.2 cm at 30 kg/ha than at 0 kg/ha sulfur application. Stem growth, however, decreased by 3.7 cm with the application of sulfur higher than at 60 kg/10a. Soil pH changed by the application of sulfur. With the application of sulfur at 120 kg/10a, soil pH decreased by 3.0. Temporal changes in the effective from sulfur content in soil indicated that sulfur dissolved between 4 to 10 days after application in the soil. Content of moisture and chemical components in mulberry leaves was also affected by the application levels of sulfur. Moisture, total-N, No3-N, K, and S content decreased, but F and Ca content increased with the application of sulfur lower than at 60 kg/10a. With the application of sulfur higher than at 60 kg/10a, P, S, and K content increased.

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Current Progress in Generation of Genetically Modified Mice (유전자 조작 마우스 개발의 최신 연구 동향)

  • Song, Ki-Duk;Cho, Byung-Wook
    • Journal of Life Science
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    • v.17 no.4 s.84
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    • pp.587-592
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    • 2007
  • Manipulation of the mouse genome by activating or inactivating the gene has contributed to the understanding of the function of the gene in the subset of cells during embryonic development or postnatal period of life. Most of all, gene targeting, which largely depends on the availability of mouse embryonic stem (ES) cells, is the milestone of development of animal models for human disease. Recombinase-mediated genome modification (Cre-LoxP and Flp-Frt etc) and the ligand-dependent regulation system, more accurate and elaborate manipulation tools, have been successfully developed and applied to dissect the mechanisms governing complex biological processes and to understand the role of protein in temporal-and spatial aspects of development. As technologies concerning refined manipulation of mouse genome are developed, they are expected to open new opportunities to better understand the diverse in vivo functions of genes.

Adansonia digitata L. Stem Bark Attenuates Epileptic Seizure, Depression, and Neurodegeneration by Mediating GABA and Glutamate in Pentylenetetrazol-Kindled Rats

  • Adamu Muhammad;Luteino Lorna Hamman;Samaila Musa Chiroma;Martha Orendu Oche Attah;Nathan Isaac Dibal
    • Journal of Pharmacopuncture
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    • v.26 no.4
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    • pp.327-337
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    • 2023
  • Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.

Spatio-temporal Fluctuations of Size-structured Phytoplankton over an Annual Cycle in the Youngsan Lake

  • Song, Eun-Sook;Shin, Yong-Sik
    • Korean Journal of Ecology and Environment
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    • v.41 no.4
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    • pp.530-540
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    • 2008
  • The temporal and spatial variations of size-structured phytoplankton dynamics in Youngsan Lake were investigated to explore potential mechanims controlling the dynamics in the Youngsan Lake. Field data were collected monthly from February to October, 2003 at 6 stations along the axis of Youngsan Lake. In this study, phytoplankton (chlorophyll $\alpha$) were categorized into three size classes: micro-size ($>20{\mu}m$), nano-size ($2{\sim}20{\mu}m$) and pico-size ($<20{\mu}m$). Water temperature, light attenuation coefficients, PAR (photosynthetically active radiation) and suspended solids were measured to analyze relationship between physical-chemical properties and size structure of phytoplankton. Phytoplankton blooms developed during March, July and October in the upper region of the main stem whereas small-scaled spring bloom was observed in the lower region. The scales of phytoplankton blooms were higher in the upper regions than the lower region and blooms were predominated by micro-size class in upper region but predominated by nano-size class in lower region. Growth of size-structured phytoplankton appeared to be controlled by rather light availability than temperature-dependant metabolisms in the system. Phytoplankton growth may be also supported by ambient nutrients available in the water column from analyses of chlorophyll $\alpha$ vs. nutrient concentrations including nitrite+nitrate and orthophosphate. Growth of nano-sized phytoplankton alone appeared to be supported by orthophosphate as well as nitrite+nitrate indicating that response of phytoplankton to nutrient inputs may be size-dependent.

The Effect of Enhanced Nitrate Input on the Temporal Variation of the Plankton Community in a Mesocosm (질산염 첨가에 따른 중형폐쇄생태계 내 플랑크톤 군집의 변화)

  • Kang, Jung-Hoon;Kim, Woong-Seo;Shin, Kyoung-Soon;Chang, Man;Hwang, Keun-Choon
    • Ocean and Polar Research
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    • v.27 no.3
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    • pp.341-349
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    • 2005
  • Temporal variation of the natural planktonic community in the Southern Sea of Korea was investigated by using low floating enclosed bags (3.2m deep and 2,500 liter) in order to understand the effect of enriched nitrate on the planktonic community in the spring (March-April) of 2002. Prior to beginning the incubation, the bags were placed in two different concentrations of nitrate, which consisted of control (ambient water) and experimental mesocosms (final concentration of $12{\mu}M$). The nitrate concentration in the experimental mesocosms remained significantly higher than those in control mesocosms throughout the study period (ANOYA, p<0.001). Following the addition of nitrate, abundance and chi-a concentration of phytoplankton peaked on Day 1, when diatoms established the peak in the experimental mesocosms. Diatoms consisted mainly of Thalasxiosira decipiens, Pseudo-nitzschia pungem, Leptocylindrus danicu, Thalassionema nitzschioides, Chaetoceros pseudocrinitus and Actinoptychus senariu. However, the peak did not lead to the difference in abundance and composition of phytoplankton between control and experimental mesocosms during the study period. The dinoflagellates began to increase soon after the diatoms decreased in all mesocosms. Copepods, as a dominant group in the rnosozooplankton community, showed no immediate peak in relation to the nitrate addition, but only their own developmental process from the eggs to adult stage during the study period. The bottom-up control from enriched nitrate via phytoplankton to adult copepods was not distinguished in terms of the abundance of the planktonic community. This might stem from the relatively low nitrate availability of phytoplankton at no N-limited seawater and the weak coupling between rapidly sunken diatoms and copepods through the water column.