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Article ; Online: Cutaneous Leukocytoclastic Vasculitis Associated with Pulmonary Tuberculosis and an Anti-tuberculosis Drug.

Tanaka, Yuya / Kobayashi, Takehiko / Shimizu, Shigeki / Kurahara, Yu

2024

Language	English
Publishing date	2024-02-19
Publishing country	Japan
Document type	Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.3144-23
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Zs.A 240: Show issues

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Article ; Online: Replication fork blocking deficiency leads to a reduction of rDNA copy number in budding yeast.

Murai, Taichi / Yanagi, Shuichi / Hori, Yutaro / Kobayashi, Takehiko

iScience

2024 Volume 27, Issue 3, Page(s) 109120

Abstract: The ribosomal RNA genes are encoded as hundreds of tandem repeats, known as the rDNA, in eukaryotes. Maintaining these copies seems to be necessary, but copy number changes in an active manner have been reported in only frogs, flies, ...

Abstract	The ribosomal RNA genes are encoded as hundreds of tandem repeats, known as the rDNA, in eukaryotes. Maintaining these copies seems to be necessary, but copy number changes in an active manner have been reported in only frogs, flies,
Language	English
Publishing date	2024-02-06
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109120
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Article ; Online: Efficacy of an oscillating positive expiratory pressure device in patients with Mycobacterium avium complex pulmonary disease.

Kurahara, Yu / Tanaka, Yuya / Kobayashi, Takehiko / Yoshida, Shiomi / Tsuyuguchi, Kazunari

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2024

Abstract: Patients with Mycobacterium avium complex pulmonary disease (MAC-PD) often suffer from chronic symptoms such as sputum production, which reduces quality of life. Oscillatory positive expiratory pressure (OPEP) devices are used in physiotherapy to promote ...

Abstract	Patients with Mycobacterium avium complex pulmonary disease (MAC-PD) often suffer from chronic symptoms such as sputum production, which reduces quality of life. Oscillatory positive expiratory pressure (OPEP) devices are used in physiotherapy to promote the clearance of respiratory secretions. We report two cases of improved lung function and improved scores on the Leicester Cough Questionnaire (LCQ) and the Breathlessness, Cough and Sputum Scale (BCSS) after the use of OPEP in patients with MAC-PD where treatment with guideline-based therapy, including amikacin liposome inhalation suspension, had proved ineffective for symptoms. Use of OPEP might maximize the efficacy of therapy and thereby improves outcomes in patients with MAC-PD. It is important to use both guideline-based therapy and OPEP, especially in patients whose health-related quality of life is affected by sputum symptoms. Further prospective studies are warranted to assess the benefit of adding OPEP to guidelines concerning therapy for patients with MAC-PD and sputum symptoms.
Language	English
Publishing date	2024-01-03
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2024.01.001
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Zs.A 5236: Show issues

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Article ; Online: Regulatory processes that maintain or alter ribosomal DNA stability during the repair of programmed DNA double-strand breaks.

Sasaki, Mariko / Kobayashi, Takehiko

Genes & genetic systems

2022 Volume 98, Issue 3, Page(s) 103–119

Abstract: Organisms have evolved elaborate mechanisms that maintain genome stability. Deficiencies in these mechanisms result in changes to the nucleotide sequence as well as copy number and structural variations in the genome. Genome instability has been ... ...

Abstract	Organisms have evolved elaborate mechanisms that maintain genome stability. Deficiencies in these mechanisms result in changes to the nucleotide sequence as well as copy number and structural variations in the genome. Genome instability has been implicated in numerous human diseases. However, genomic alterations can also be beneficial as they are an essential part of the evolutionary process. Organisms sometimes program genomic changes that drive genetic and phenotypic diversity. Therefore, genome alterations can have both positive and negative impacts on cellular growth and functions, which underscores the need to control the processes that restrict or induce such changes to the genome. The ribosomal RNA gene (rDNA) is highly abundant in eukaryotic genomes, forming a cluster where numerous rDNA copies are tandemly arrayed. Budding yeast can alter the stability of its rDNA cluster by changing the rDNA copy number within the cluster or by producing extrachromosomal rDNA circles. Here, we review the mechanisms that regulate the stability of the budding yeast rDNA cluster during repair of DNA double-strand breaks that are formed in response to programmed DNA replication fork arrest.
MeSH term(s)	Humans ; Saccharomyces cerevisiae/genetics ; DNA Breaks, Double-Stranded ; DNA, Ribosomal/genetics ; DNA Replication ; Genomic Instability ; DNA Repair
Chemical Substances	DNA, Ribosomal
Language	English
Publishing date	2022-08-04
Publishing country	Japan
Document type	Review ; Journal Article
ZDB-ID	1323536-9
ISSN	1880-5779 ; 1341-7568
ISSN (online)	1880-5779
ISSN	1341-7568
DOI	10.1266/ggs.22-00046
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Zs.A 3466: Show issues

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Article ; Online: Spt4 promotes cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters.

Yokoyama, Masaaki / Sasaki, Mariko / Kobayashi, Takehiko

Cell reports

2023 Volume 42, Issue 1, Page(s) 111944

Abstract: Genome instability can drive aging in many organisms. The ribosomal RNA gene (rDNA) cluster is one of the most unstable regions in the genome and the stability of this region impacts replicative lifespan in budding yeast. To understand the underlying ... ...

Abstract	Genome instability can drive aging in many organisms. The ribosomal RNA gene (rDNA) cluster is one of the most unstable regions in the genome and the stability of this region impacts replicative lifespan in budding yeast. To understand the underlying mechanism, we search for yeast mutants with stabler rDNA and longer lifespans than wild-type cells. We show that absence of a transcription elongation factor, Spt4, results in increased rDNA stability, reduced levels of non-coding RNA transcripts from the regulatory E-pro promoter in the rDNA, and extended replicative lifespan in a SIR2-dependent manner. Spt4-dependent lifespan restriction is abolished in the absence of non-coding RNA transcription at the E-pro locus. The amount of Spt4 increases and its function becomes more important as cells age. These findings suggest that Spt4 is a promising aging factor that accelerates cellular senescence through rDNA instability driven by non-coding RNA transcription.
MeSH term(s)	Genes, rRNA/genetics ; DNA, Ribosomal/genetics ; Cellular Senescence/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; RNA, Untranslated/genetics ; Transcription, Genetic ; Nuclear Proteins/metabolism ; Transcriptional Elongation Factors/genetics
Chemical Substances	DNA, Ribosomal ; Saccharomyces cerevisiae Proteins ; RNA, Untranslated ; SPT4 protein, S cerevisiae ; Nuclear Proteins ; Transcriptional Elongation Factors
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111944
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Article ; Online: Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes.

Hori, Yutaro / Engel, Christoph / Kobayashi, Takehiko

Nature reviews. Molecular cell biology

2023 Volume 24, Issue 6, Page(s) 414–429

Abstract: One of the first biological machineries to be created seems to have been the ribosome. Since then, organisms have dedicated great efforts to optimize this apparatus. The ribosomal RNA (rRNA) contained within ribosomes is crucial for protein synthesis and ...

Abstract	One of the first biological machineries to be created seems to have been the ribosome. Since then, organisms have dedicated great efforts to optimize this apparatus. The ribosomal RNA (rRNA) contained within ribosomes is crucial for protein synthesis and maintenance of cellular function in all known organisms. In eukaryotic cells, rRNA is produced from ribosomal DNA clusters of tandem rRNA genes, whose organization in the nucleolus, maintenance and transcription are strictly regulated to satisfy the substantial demand for rRNA required for ribosome biogenesis. Recent studies have elucidated mechanisms underlying the integrity of ribosomal DNA and regulation of its transcription, including epigenetic mechanisms and a unique recombination and copy-number control system to stably maintain high rRNA gene copy number. In this Review, we disucss how the crucial maintenance of rRNA gene copy number through control of gene amplification and of rRNA production by RNA polymerase I are orchestrated. We also discuss how liquid-liquid phase separation controls the architecture and function of the nucleolus and the relationship between rRNA production, cell senescence and disease.
MeSH term(s)	RNA, Ribosomal/genetics ; Eukaryota/genetics ; Genes, rRNA/genetics ; DNA Copy Number Variations ; Gene Dosage ; DNA, Ribosomal/genetics
Chemical Substances	RNA, Ribosomal ; DNA, Ribosomal
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/s41580-022-00573-9
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Zs.A 5446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 26: Show issues

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Article ; Online: Establishment of an "in saccharo" experimental system.

Iida, Tetsushi / Kobayashi, Takehiko

Genes & genetic systems

2021 Volume 96, Issue 3, Page(s) 107–118

Abstract: Many proteins form complexes that function in reaction pathways. Therefore, to understand protein function, it is necessary to reconstitute complexes and pathways in vitro. However, it is not straightforward to achieve full activity in reconstituted ... ...

Abstract	Many proteins form complexes that function in reaction pathways. Therefore, to understand protein function, it is necessary to reconstitute complexes and pathways in vitro. However, it is not straightforward to achieve full activity in reconstituted systems. To address this problem, we present a yeast system named "in saccharo" analysis, which uses budding yeast for simultaneous expression and analysis of many kinds of non-host proteins, such as human proteins. For this purpose, vectors that can accommodate many genes are required. Here, we describe the construction of a chromosome vector by insertion of unique barcode sequences (BCs) into the ribosomal RNA gene repeat (rDNA). Each unit of the rDNA has a BC that is used as the target for integration of an external gene. Because rDNA is naturally capable of maintaining many repetitive copies, the vector is expected to retain the numerous external genes that may be required for reconstitution of functional protein complexes and reaction pathways. Consistent with this prediction, we were able to clone three human genes that form the RNA silencing pathway, which has no functional equivalent in budding yeast, and to demonstrate functionality in this in saccharo analysis system.
MeSH term(s)	Chromosomes ; DNA, Ribosomal ; Humans ; Saccharomyces cerevisiae/genetics
Chemical Substances	DNA, Ribosomal
Language	English
Publishing date	2021-06-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1323536-9
ISSN	1880-5779 ; 1341-7568
ISSN (online)	1880-5779
ISSN	1341-7568
DOI	10.1266/ggs.21-00004
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Zs.A 3466: Show issues

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Article ; Online: Cryo-EM structures of RAD51 assembled on nucleosomes containing a DSB site.

Shioi, Takuro / Hatazawa, Suguru / Oya, Eriko / Hosoya, Noriko / Kobayashi, Wataru / Ogasawara, Mitsuo / Kobayashi, Takehiko / Takizawa, Yoshimasa / Kurumizaka, Hitoshi

Nature

2024 Volume 628, Issue 8006, Page(s) 212–220

Abstract: RAD51 is the central eukaryotic recombinase required for meiotic recombination and mitotic repair of double-strand DNA breaks (DSBs) ...

Abstract	RAD51 is the central eukaryotic recombinase required for meiotic recombination and mitotic repair of double-strand DNA breaks (DSBs)
MeSH term(s)	Humans ; Cryoelectron Microscopy ; DNA/chemistry ; DNA/metabolism ; DNA/ultrastructure ; DNA Breaks, Double-Stranded ; DNA Repair/genetics ; Nucleosomes/chemistry ; Nucleosomes/metabolism ; Nucleosomes/ultrastructure ; Protein Subunits/chemistry ; Protein Subunits/metabolism ; Rad51 Recombinase/chemistry ; Rad51 Recombinase/metabolism ; Rad51 Recombinase/ultrastructure ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Mutation ; Protein Domains ; Histones/chemistry ; Histones/metabolism ; Histones/ultrastructure ; Protein Binding
Chemical Substances	DNA (9007-49-2) ; Nucleosomes ; Protein Subunits ; RAD51 protein, human (EC 2.7.7.-) ; RAD51 protein, S cerevisiae (EC 2.7.7.-) ; Rad51 Recombinase (EC 2.7.7.-) ; Saccharomyces cerevisiae Proteins ; Histones
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07196-4
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

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Article: Concomitant Recurrent Pneumothorax and Takotsubo Cardiomyopathy in a Chronic Obstructive Pulmonary Disease Patient.

Takimoto, Takayuki / Kobayashi, Takehiko / Minomo, Shojiro

Cureus

2022 Volume 14, Issue 10, Page(s) e30850

Abstract: Chest pain is one of the major causes of emergency room visits. Here, we present the case of a patient with chest pain who developed recurrent pneumothorax and Takotsubo cardiomyopathy (TC). An 80-year-old man, receiving supplemental oxygen for chronic ... ...

Abstract	Chest pain is one of the major causes of emergency room visits. Here, we present the case of a patient with chest pain who developed recurrent pneumothorax and Takotsubo cardiomyopathy (TC). An 80-year-old man, receiving supplemental oxygen for chronic obstructive pulmonary disease (COPD), presented to the emergency room with chest pain and dyspnea. On examination, his chest pain was initially assessed to be secondary to recurrent pneumothorax. However, on further evaluation, an electrocardiogram (ECG) showed ST-segment elevation along with elevated troponin levels. Ultimately, he was diagnosed with TC. ECG, if indicated by echocardiography, should be considered to detect concomitant heart disease when dealing with pneumothorax. TC should be recognized as a cardiac disease that can be caused by pneumothorax.
Language	English
Publishing date	2022-10-29
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.30850
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Article ; Online: Changed life course upon defective replication of ribosomal RNA genes.

Hattori, Mei / Horigome, Chihiro / Aspert, Théo / Charvin, Gilles / Kobayashi, Takehiko

Genes & genetic systems

2023 Volume 97, Issue 6, Page(s) 285–295

Abstract: Genome instability is a major cause of aging. In the budding yeast Saccharomyces cerevisiae, instability of the ribosomal RNA gene repeat (rDNA) is known to shorten replicative lifespan. In yeast, rDNA instability in an aging cell is associated with ... ...

Abstract	Genome instability is a major cause of aging. In the budding yeast Saccharomyces cerevisiae, instability of the ribosomal RNA gene repeat (rDNA) is known to shorten replicative lifespan. In yeast, rDNA instability in an aging cell is associated with accumulation of extrachromosomal rDNA circles (ERCs) which titrate factors critical for lifespan maintenance. ERC accumulation is not detected in mammalian cells, where aging is linked to DNA damage. To distinguish effects of DNA damage from those of ERC accumulation on senescence, we re-analyzed a yeast strain with a replication initiation defect in the rDNA, which limits ERC multiplication. In aging cells of this strain (rARS-∆3) rDNA became unstable, as in wild-type cells, whereas significantly fewer ERCs accumulated. Single-cell aging analysis revealed that rARS-∆3 cells follow a linear survival curve and can have a wild-type replicative lifespan, although a fraction of the cells stopped dividing earlier than wild type. The doubling time of rARS-∆3 cells appears to increase in the final cell divisions. Our results suggest that senescence in rARS-∆3 is linked to the accumulation of DNA damage as in mammalian cells, rather than to elevated ERC level. Therefore, this strain should be a good model system to study ERC-independent aging.
MeSH term(s)	Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Genes, rRNA ; Cellular Senescence/genetics ; DNA, Ribosomal/genetics ; Saccharomyces cerevisiae Proteins/genetics ; DNA Replication/genetics
Chemical Substances	DNA, Ribosomal ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2023-03-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1323536-9
ISSN	1880-5779 ; 1341-7568
ISSN (online)	1880-5779
ISSN	1341-7568
DOI	10.1266/ggs.22-00100
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