20 results on '"Jane C. Kim"'
Search Results
2. The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats
- Author
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Samantha T Harris, Kartik A. Shah, Teresa Dinter, Sergei M. Mirkin, and Jane C. Kim
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0301 basic medicine ,Genetics ,Genome instability ,congenital, hereditary, and neonatal diseases and abnormalities ,biology ,Saccharomyces cerevisiae ,RAD52 ,RAD51 ,biology.organism_classification ,Genetic analysis ,MUS81 ,03 medical and health sciences ,030104 developmental biology ,Structural Biology ,Trinucleotide repeat expansion ,Molecular Biology ,Gene - Abstract
A newly developed assay in yeast reveals that large-scale expansions of trinucleotide repeats can occur in a single step, rather than through several small-scale events. Expansions of (CAG)n/(CTG)n trinucleotide repeats are responsible for over a dozen neuromuscular and neurodegenerative disorders. Large-scale expansions are commonly observed in human pedigrees and may be explained by iterative small-scale events such as strand slippage during replication or repair DNA synthesis. Alternatively, a distinct mechanism may lead to a large-scale repeat expansion as a single step. To distinguish between these possibilities, we developed a novel experimental system specifically tuned to analyze large-scale expansions of (CAG)n/(CTG)n repeats in Saccharomyces cerevisiae. The median size of repeat expansions was ∼60 triplets, although we also observed additions of more than 150 triplets. Genetic analysis revealed that Rad51, Rad52, Mre11, Pol32, Pif1, and Mus81 and/or Yen1 proteins are required for large-scale expansions, whereas proteins previously implicated in small-scale expansions are not involved. From these results, we propose a new model for large-scale expansions, which is based on the recovery of replication forks broken at (CAG)n/(CTG)n repeats via break-induced replication.
- Published
- 2016
3. Precarious maintenance of simple DNA repeats in eukaryotes
- Author
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Jane C. Kim, Alexander J. Neil, and Sergei M. Mirkin
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0301 basic medicine ,DNA Replication ,DNA Repair ,Eukaryotic DNA replication ,Biology ,Origin of replication ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Control of chromosome duplication ,Trinucleotide Repeats ,Animals ,Humans ,Genetics ,DNA replication ,Eukaryota ,DNA ,Telomere ,030104 developmental biology ,chemistry ,Prokaryotic Cells ,Origin recognition complex ,Trinucleotide repeat expansion ,Microsatellite Repeats - Abstract
In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in maintaining functional repetitive regions of the genome such as telomeres and centromeres.
- Published
- 2017
4. Phosphate steering by Flap Endonuclease 1 promotes 5′-flap specificity and incision to prevent genome instability
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Steven J. Shaw, Alexander J. Neil, Fahad Rashid, Altaf H. Sarker, Mark J. Thompson, Jane A. Grasby, Mai Zong Her, Victoria J. B. Gotham, Susan E. Tsutakawa, Emma C. Jardine, Andrew S. Arvai, Samir M. Hamdan, John A. Tainer, Sergei M. Mirkin, L. David Finger, Sana I. Algasaier, and Jane C. Kim
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0301 basic medicine ,Genome instability ,DNA Replication ,DNA Repair ,DNA repair ,Flap Endonucleases ,Science ,Flap structure-specific endonuclease 1 ,General Physics and Astronomy ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Genomic Instability ,Phosphates ,Substrate Specificity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Catalytic Domain ,Genetics ,Humans ,Nucleotide ,Amino Acid Sequence ,Flap endonuclease ,Binding site ,Cancer ,chemistry.chemical_classification ,Multidisciplinary ,Binding Sites ,Human Genome ,DNA replication ,General Chemistry ,DNA ,Molecular biology ,030104 developmental biology ,chemistry ,Mutation ,Sequence Alignment ,030217 neurology & neurosurgery - Abstract
DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5′-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5′-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5′polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 5′-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 5′-flap specificity and catalysis, preventing genomic instability., Flap Endonuclease 1 is a DNA replication and repair enzyme indispensable for maintaining genomic stability. Here the authors provide mechanistic details on how FEN1 selects for 5′-flaps and promotes catalysis to avoid large-scale repeat expansion by a process termed ‘phosphate steering’.
- Published
- 2017
5. Corrigendum: Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability
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Susan E. Tsutakawa, Mark J. Thompson, Andrew S. Arvai, Alexander J. Neil, Steven J. Shaw, Sana I. Algasaier, Jane C. Kim, L. David Finger, Emma Jardine, Victoria J. B. Gotham, Altaf H. Sarker, Mai Z. Her, Fahad Rashid, Samir M. Hamdan, Sergei M. Mirkin, Jane A. Grasby, and John A. Tainer
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0303 health sciences ,03 medical and health sciences ,Multidisciplinary ,General Physics and Astronomy ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,0210 nano-technology ,Corrigenda ,General Biochemistry, Genetics and Molecular Biology ,030304 developmental biology - Abstract
Nature Communications 8 Article number: 15855 (2017); Published: 27 June 2017; Updated: 7 August 2017 The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: This research used resources of the Advanced Light Source and the StanfordSynchrotron Radiation Lightsource, which are DOE Office of Science User Facilities under contract no.
- Published
- 2017
6. Genome rearrangements caused by interstitial telomeric sequences in yeast
- Author
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Margaret Dominska, Alexander A. Shishkin, Thomas D. Petes, Anna Y. Aksenova, Jane C. Kim, Patricia W. Greenwell, and Sergei M. Mirkin
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Genome instability ,Genetics ,Multidisciplinary ,biology ,Saccharomyces cerevisiae ,Intron ,Chromosome ,Chromosomal translocation ,Chromosomal rearrangement ,biology.organism_classification ,Genome ,Telomere - Abstract
Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements.
- Published
- 2013
7. The role of break-induced replication in large-scale expansions of (CAG)
- Author
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Jane C, Kim, Samantha T, Harris, Teresa, Dinter, Kartik A, Shah, and Sergei M, Mirkin
- Subjects
DNA Replication ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Repeat Expansion ,Base Sequence ,Chromosome Breakage ,Saccharomyces cerevisiae ,DNA, Fungal ,Article - Abstract
Expansions of (CAG)n•(CTG)n trinucleotide repeats are responsible for over a dozen neuromuscular and neurodegenerative disorders. Large-scale expansions are typical for human pedigrees and may be explained by iterative small-scale events such as strand slippage during replication or repair DNA synthesis. Alternatively, a distinct mechanism could lead to a large-scale repeat expansion at a step. To distinguish between these possibilities, we developed a novel experimental system specifically tuned to analyze large-scale expansions of (CAG)n•(CTG)n repeats in Saccharomyces cerevisiae. The median size of repeat expansions was ~60 triplets, though additions in excess of 150 triplets were also observed. Genetic analysis revealed that Rad51, Rad52, Mre11, Pol32, Pif1, and Mus81 and/or Yen1 proteins are required for large-scale expansions, whereas proteins previously implicated in small-scale expansions are not involved. Based on these results, we propose a new model for large-scale expansions based on recovery of replication forks broken at (CAG)n•(CTG)n repeats via break-induced replication.
- Published
- 2016
8. Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells
- Author
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Chang-Sung Kim, Beomyoung Kim, Gun-Il Im, Kim Binn, Kyoo-Sung Cho, Jung-Chul Park, and Jane C. Kim
- Subjects
Bone sialoprotein ,medicine.medical_specialty ,Stromal cell ,biology ,Chemistry ,Growth factor ,medicine.medical_treatment ,Bone morphogenetic protein ,Cell biology ,Endocrinology ,In vivo ,Adipogenesis ,Internal medicine ,biology.protein ,medicine ,Osteocalcin ,Periodontics ,Alkaline phosphatase - Abstract
Park J-C, Kim J.C, Kim B-K, Cho K-S, Im G-I, Kim B-S, Kim C-S. Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells. J Periodont Res 2012; 47: 645–654. © 2012 John Wiley & Sons A/S Background and Objective: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP-2-induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose- and time-dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro. Material and Methods: hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 (100 μg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8-wk healing period. To further understand the dose-dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d) effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma-2 and lipoprotein lipase, were assessed using quantitative RT-PCR. Results: rhBMP-2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose- and time-dependent manner with minimal deviation in vitro. The expression of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up-regulated by rhBMP-2. Conclusion: The findings of the present study showed that rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose- and time-dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP-2.
- Published
- 2012
9. Acquisition of human alveolar bone-derived stromal cells using minimally irrigated implant osteotomy: in vitro and in vivo evaluations
- Author
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Byung-Soo Kim, Jane C. Kim, Chang-Sung Kim, Jung-Chul Park, Yong Tae Kim, Kyoo-Sung Cho, Gun-Il Im, and Seong-Ho Choi
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Stromal cell ,Cell Transplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Cell Culture Techniques ,Bone Marrow Cells ,Cell Separation ,Bone tissue ,Mice ,Calcification, Physiologic ,Tissue engineering ,Osteogenesis ,Adipocytes ,Alveolar Process ,medicine ,Animals ,Humans ,Dental implant ,Dental alveolus ,Cell Proliferation ,Adipogenesis ,Osteoblasts ,Tissue Engineering ,Chemistry ,Dental Implantation, Endosseous ,Mesenchymal stem cell ,Cell Differentiation ,Anatomy ,Middle Aged ,Mice, Mutant Strains ,Clone Cells ,Osteotomy ,Transplantation ,medicine.anatomical_structure ,Antigens, Surface ,Feasibility Studies ,Periodontics ,Female ,Stromal Cells ,Stem cell - Abstract
Objectives Implant osteotomy yields a substantial amount of bone in the form of bone chips entrapped within drill flutes, and can provide a promising cell source for tissue engineering. The aims of this study were to isolate human alveolar bone-derived stromal cells (hABCs) obtained during implant osteotomy, and to evaluate osteogenic differentiation capacity of hABCs. Material and methods Bone chips were obtained by minimally irrigated implant drilling technique from 10 human donors. Isolated cells were studied with respect to their colony-forming efficiency, surface marker expression by immunofluorescence staining, fluorescence-activated cell sorting analysis and self-renewal potency. To verify the differentiation activity, in vitro osteogenic and adipogenic gene expressions were evaluated by reverse transcription-polymerase chain reaction, and in vitro formation of mineralized nodule and adipocytes was also evaluated. In vivo bone-forming activity was assessed by ectopic transplantation in immunocompromised mice (n = 5). Results Human alveolar bone-derived stromal cells population with characteristics of mesenchymal stem cells was present in the isolated cells. Upon hABC transplantation, significant ectopic bone formation was induced with the characteristics of fully matured bone tissue. Conclusion The data support the feasibility of using hABCs as a source of stem cells for dentoalveolar bone tissue reconstruction. The cell source has an advantage that the hABCs can be easily acquired during implant surgery.
- Published
- 2012
10. Effect of humoral factors from hPDLSCs on the biologic activity of hABCs
- Author
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Chang-Sung Kim, Byung-Soo Kim, Sang-Seob Lee, Gun-Il Im, Jeong-Ho Yun, Kyoo-Sung Cho, Jane C. Kim, and Jung-Chul Park
- Subjects
Stromal cell ,Periodontal ligament stem cells ,Chemistry ,Cell biology ,medicine.anatomical_structure ,Otorhinolaryngology ,Cell culture ,Osteoclast ,Adipogenesis ,Immunology ,medicine ,Periodontal fiber ,Stem cell ,General Dentistry ,Dental alveolus - Abstract
Oral Diseases (2012) 18, 537–547 Objective: The human periodontal ligament stem cells (hPDLSCs) and human alveolar bone–derived stromal cells (hABCs) seem to be closely involved in the maintenance of alveolar bone in an anatomically indirect manner; however, there is little study on this matter. Therefore, the effect of hPDLSCs on the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs was evaluated, focusing on the humoral factors released by hPDLSCs. Materials and methods: Human periodontal ligament stem cells and hABCs were isolated and characterized. hPDLSCs were indirectly cocultured to observe the in vitro effect of humoral factors released from hPDLSCs on the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs. Human gingival fibroblasts (hGFs) were utilized as positive control. Results: Isolated cells demonstrated the presence of stem cells within. Indirect coculture of hPDLSCs greatly inhibited osteoclastogenesis by hABCs. Osteogenesis/adipogenesis of hABCs was also inhibited by indirect coculture with hPDLSC. The magnitude of regulatory effect from hPDLSCs was significantly greater than that of hGFs. Conclusions: Humoral factors released from hPDLSCs seemed to modulate the differentiation of hABCs, and the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs was all inhibited, suggesting the potential role of hPDLSCs in the maintenance of the alveolar bone.
- Published
- 2012
11. Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression
- Author
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David M. MacAlpine, Fang Xie, Helena Kashevsky, Terry L. Orr-Weaver, Jane C. Kim, Thomas Eng, Sharon Li, Jared T. Nordman, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Kim, Jane C., Nordman, Jared T., Xie, Fang, and Orr-Weaver, Terry L.
- Subjects
Genetics ,Gene Amplification ,Origin Recognition Complex ,Acetylation ,Biology ,Amplicon ,Origin of replication ,Protein Structure, Tertiary ,Histones ,Drosophila melanogaster ,Gene Expression Regulation ,Transcription (biology) ,Gene duplication ,Gene expression ,Animals ,Origin recognition complex ,Replicon ,Psychological repression ,Research Paper ,Protein Binding ,Developmental Biology - Abstract
In metazoans, how replication origins are specified and subsequently activated is not well understood. Drosophila amplicons in follicle cells (DAFCs) are genomic regions that undergo rereplication to increase DNA copy number. We identified all DAFCs by comparative genomic hybridization, uncovering two new amplicons in addition to four known previously. The complete identification of all DAFCs enabled us to investigate these in vivo replicons with respect to parameters of transcription, localization of the origin recognition complex (ORC), and histone acetylation, yielding important insights into gene amplification as a metazoan replication model. Significantly, ORC is bound across domains spanning 10 or more kilobases at the DAFC rather than at a specific site. Additionally, ORC is bound at many regions that do not undergo amplification, and, in contrast to cell culture, these regions do not correlate with high gene expression. As a developmental strategy, gene amplification is not the predominant means of achieving high expression levels, even in cells capable of amplification. Intriguingly, we found that, in some strains, a new amplicon, DAFC-22B, does not amplify, a consequence of distant repression of ORC binding and origin activation. This repression is alleviated when a fragment containing the origin is placed in different genomic contexts., Damon Runyon Cancer Research Foundation (Fellowship), G. Harold and Leila Y. Mathers Foundation, National Institutes of Health (U.S.) (modENCODE project Grant 1U01HG004279), National Institutes of Health (U.S.) (Grant GM57960), American Cancer Society (Research Professor Grant)
- Published
- 2011
12. Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations
- Author
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Jeong Min Kim, Kyoo-Sung Cho, Jung-Chul Park, Im Hee Jung, Chang-Sung Kim, Seong-Ho Choi, and Jane C. Kim
- Subjects
Pathology ,medicine.medical_specialty ,Periodontal ligament stem cells ,business.industry ,Regeneration (biology) ,Mesenchymal stem cell ,Anatomy ,Transplantation ,medicine.anatomical_structure ,stomatognathic system ,Tissue engineering ,medicine ,Periodontics ,Periodontal fiber ,Cementum ,Stem cell ,business - Abstract
Park J-C, Kim J-M, Jung I-H, Kim JC, Choi S-H, Cho K-S, Kim C-S. Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations. J Clin Periodontol 2011; 38: 721–731. doi: 10.1111/j.1600-051X.2011.01716.x. Abstract Objectives: Mesenchymal stem cells (MSC) could be isolated from healthy periodontal ligaments (PDL). The aims of this study were to isolate and characterize human PDL stem cells (hPDLSCs) from inflamed PDL tissue, and to evaluate their regenerative potential. Materials and Methods: Inflamed hPDLSCs (ihPDLSCs) were isolated from the inflamed PDL tissue obtained from intra-bony defects during flap surgery, and characterized by immunohistochemical staining, colony-forming unit assay, fluorescence-activated cell sorting, and mRNA expression in comparison with healthy hPDLSCs obtained from extracted teeth for orthodontic purpose. The proliferative potential and migratory potential was evaluated, and compared with healthy hPDLSCs. Regenerative potential was assessed by an in vivo ectopic transplantation model. Results: ihPDLSCs were successfully isolated and characterized as MSCs. Both ihPDLSCs and hPDLSCs were successfully differentiated under osteogenic/cementogenic and adipogenic microenvironment. The proliferative potential did not differ between healthy hPDLSCs and ihPDLSCs, while the migratory capacity was significantly increased in ihPDLSCs (p
- Published
- 2011
13. Putting the Brakes on Huntington Disease in a Mouse Experimental Model
- Author
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Sergei M. Mirkin and Jane C. Kim
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,lcsh:QH426-470 ,Neural degeneration ,Disease ,Biology ,Cyclic N-Oxides ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Mutant protein ,mental disorders ,Genetics ,Animals ,Hereditary Neurodegenerative Disorder ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Polyglutamine tract ,lcsh:Genetics ,Huntington Disease ,Female ,Age of onset ,Trinucleotide Repeat Expansion ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery ,Research Article - Abstract
Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible., Author Summary Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. There is no correction for the inherited mutation, but if somatic expansion contributes to disease, then a therapeutic approach is possible. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. Here we describe a mouse model of Huntington’s disease that allows us to separate out the effects of the inherited gene from the expansion that occurs during life. We find that blocking the continued expansion of the gene causes a delay in onset of symptoms. This result opens the doors to future therapeutics designed to shorten the repeat.
- Published
- 2015
14. Regulation of origin activation during Drosophila follicle cell gene amplification
- Author
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Brian L Hua, Terry L. Orr-Weaver, Sharon Li, and Jane C. Kim
- Subjects
Follicle ,medicine.anatomical_structure ,Cell ,Gene duplication ,Genetics ,medicine ,Biology ,Drosophila (subgenus) ,biology.organism_classification ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2013
15. The balancing act of DNA repeat expansions
- Author
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Sergei M. Mirkin and Jane C. Kim
- Subjects
DNA Replication ,DNA Repair ,DNA repair ,ved/biology.organism_classification_rank.species ,Biology ,Genome ,Article ,chemistry.chemical_compound ,Genetics ,Humans ,Model organism ,Recombination, Genetic ,DNA Repeat Expansion ,ved/biology ,Genome, Human ,DNA replication ,Genetic Diseases, Inborn ,DNA ,chemistry ,Evolutionary biology ,Microsatellite ,Human genome ,Developmental Biology - Abstract
Expansions of microsatellite DNA repeats contribute to the inheritance of nearly 30 developmental and neurological disorders. Significant progress has been made in elucidating the molecular mechanisms of repeat expansions using various model organisms and mammalian cell culture, and models implicating nearly all DNA transactions such as replication, repair, recombination, and transcription have been proposed. It is likely that different models of repeat expansions are not mutually exclusive and may explain repeat instability for different developmental stages and tissues. This review focuses on the contributions from studies in budding yeast toward unraveling the mechanisms and genetic control of repeat expansions, highlighting similarities and differences of replication models and describing a balancing act hypothesis to account for apparent discrepancies.
- Published
- 2013
16. Treatment of FGF-2 on stem cells from inflamed dental pulp tissue from human deciduous teeth
- Author
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Jisoo Lee, Gun-Il Im, Kyoo-Sung Cho, Se Hun Kim, JooSeok Song, Chang-Sung Kim, Eui-Young Choi, Byung-Soo Kim, Jane C. Kim, and Joo-Cheol Park
- Subjects
Pathology ,medicine.medical_specialty ,Biology ,Fibroblast growth factor ,stomatognathic system ,In vivo ,Deciduous teeth ,medicine ,Humans ,Tooth, Deciduous ,General Dentistry ,Cells, Cultured ,Dental Pulp ,Stem cell transplantation for articular cartilage repair ,Mesenchymal stem cell ,Pulpitis ,Cell Differentiation ,Mesenchymal Stem Cells ,Anatomy ,In vitro ,stomatognathic diseases ,medicine.anatomical_structure ,Otorhinolaryngology ,Pulp (tooth) ,Fibroblast Growth Factor 2 ,Stem cell - Abstract
Objective The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic growth factor-2 (FGF-2) on the regenerative potential. Materials and methods We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF-2 (20 ng ml−1) during ex vivo expansion. Isolated stem cells expanded in FGF-2 were characterized using a colony-forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling. Results MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF-2 applied to iSHFD during expansion enhanced the colony-forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF-2 in vivo increased the formation of dentin-like material. Conclusion FGF-2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.
- Published
- 2012
17. Novel application of human periodontal ligament stem cells and water-soluble chitin for collagen tissue regeneration: in vitro and in vivo investigations
- Author
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Seong-Ho Choi, Dong Won Jeon, Jung-Chul Park, Kyoo-Sung Cho, Chang-Sung Kim, Im Hee Jung, Byung Soo Kim, Gun-Il Im, and Jane C. Kim
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Periodontal ligament stem cells ,Adolescent ,Periodontal Ligament ,Transplantation, Heterologous ,Biomedical Engineering ,Bioengineering ,Lysyl oxidase ,Chitin ,Biochemistry ,Biomaterials ,Hydroxyproline ,chemistry.chemical_compound ,Mice ,In vivo ,Hyaluronic acid ,medicine ,Animals ,Humans ,Regeneration ,Child ,Cell Proliferation ,LOXL2 ,Stem Cells ,Cell migration ,Molecular biology ,Antigens, Differentiation ,chemistry ,Adipose Tissue ,Female ,Collagen ,Stem cell ,Stem Cell Transplantation - Abstract
Human periodontal ligament stem cells (hPDLSCs) have been proposed as an alternative to conventional cosmetic fillers because they display an innate ability to synthesize collagen. The aims of this study were to determine the effects of water-soluble chitin (WSC) on the proliferation and migration of hPDLSCs, and to quantify collagen synthesis in vitro and in vivo compared with human adipose-derived stem cell (hADSC)s. hPDLSCs were isolated from healthy extracted teeth, and the cell proliferation and cell migration capacities of untreated hPDLSCs (control group) and WSC-treated hPDLSCs (test group) were compared. Insoluble/soluble collagen synthesis were also assessed, and collagen related markers were evaluated including lysyl oxidase (LOX), lysyl oxidase like (LOXL)1, LOXL2, and hydroxyproline. In vivo collagen formation was examined by transplanting hyaluronic acid as a cell carrier into the subcutaneous pockets of immunocompromised mice in the control and test groups; histology and immunohistochemistry analyses were performed 4 (n=4) and 8 (n=4) weeks later. There was a dose-dependent enhancement of hPDLSCs proliferation in the test group, and a concomitant reduction in cell migration. The amount of insoluble collagen formed was greater in the test group than in the control group (p
- Published
- 2011
18. Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations
- Author
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Jung-Chul, Park, Jeong-Min, Kim, Im-Hee, Jung, Jane C, Kim, Seong-Ho, Choi, Kyoo-Sung, Cho, and Chang-Sung, Kim
- Subjects
Adult ,Adolescent ,Periodontal Ligament ,Alveolar Bone Loss ,Cell Culture Techniques ,Cell Separation ,Mesenchymal Stem Cell Transplantation ,Surgical Flaps ,Colony-Forming Units Assay ,Mice ,Young Adult ,Cell Movement ,Osteogenesis ,Animals ,Humans ,Periodontal Pocket ,Regeneration ,Cementogenesis ,Cell Proliferation ,Adipogenesis ,Cell Differentiation ,Mesenchymal Stem Cells ,Middle Aged ,Flow Cytometry ,Immunohistochemistry ,Antigens, Surface ,Chronic Periodontitis ,Granulation Tissue - Abstract
Mesenchymal stem cells (MSC) could be isolated from healthy periodontal ligaments (PDL). The aims of this study were to isolate and characterize human PDL stem cells (hPDLSCs) from inflamed PDL tissue, and to evaluate their regenerative potential.Inflamed hPDLSCs (ihPDLSCs) were isolated from the inflamed PDL tissue obtained from intra-bony defects during flap surgery, and characterized by immunohistochemical staining, colony-forming unit assay, fluorescence-activated cell sorting, and mRNA expression in comparison with healthy hPDLSCs obtained from extracted teeth for orthodontic purpose. The proliferative potential and migratory potential was evaluated, and compared with healthy hPDLSCs. Regenerative potential was assessed by an in vivo ectopic transplantation model.ihPDLSCs were successfully isolated and characterized as MSCs. Both ihPDLSCs and hPDLSCs were successfully differentiated under osteogenic/cementogenic and adipogenic microenvironment. The proliferative potential did not differ between healthy hPDLSCs and ihPDLSCs, while the migratory capacity was significantly increased in ihPDLSCs (p0.05). Both groups exhibited new cementum-like tissue and related PDL fibre regeneration in an in vivo transplantation model.ihPDLSCs could be successfully isolated from inflamed PDL tissue, and they retained the regenerative potential for cementum and related PDL tissues.
- Published
- 2011
19. Complex partial status epilepticus in paraneoplastic limbic encephalitis
- Author
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Shawn J. Kile, Jane C. Kim, and Masud Seyal
- Subjects
Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Complex partial status epilepticus ,Status epilepticus ,Electroencephalography ,050105 experimental psychology ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Status Epilepticus ,Carcinoma, Non-Small-Cell Lung ,Limbic Encephalitis ,medicine ,Humans ,0501 psychology and cognitive sciences ,Paraneoplastic limbic encephalitis ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Limbic encephalitis ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Tomography x ray computed ,nervous system ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,Differential diagnosis ,business ,Tomography, X-Ray Computed ,030217 neurology & neurosurgery ,Tomography, Emission-Computed - Abstract
Paraneoplastic limbic encephalitis (PLE) results from tumor-related autoimmune mediated inflammation and degeneration of the mesial temporal structures. Cognitive and behavioral changes and seizures occur in PLE. Seizures are an uncommon presenting symptom of PLE occurring in 6 of 50 patients in one series. We present a report of complex partial status epilepticus (CPSE) as the presentation of PLE with anti-neuronal antibodies and improvement in mental status following treatment of seizures.
- Published
- 2007
20. Putting the Brakes on Huntington Disease in a Mouse Experimental Model.
- Author
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Jane C Kim and Sergei M Mirkin
- Subjects
Genetics ,QH426-470 - Published
- 2015
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