• Molecules and Cells
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• v.42 no.12
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• pp.821-827
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• 2019

Aging is the most important single risk factor for many chronic diseases such as cancer, metabolic syndrome, and neurodegenerative disorders. Targeting aging itself might, therefore, be a better strategy than targeting each chronic disease individually for enhancing human health. Although much should be achieved for completely understanding the biological basis of aging, cellular senescence is now believed to mainly contribute to organismal aging via two independent, yet not mutually exclusive mechanisms: on the one hand, senescence of stem cells leads to exhaustion of stem cells and thus decreases tissue regeneration. On the other hand, senescent cells secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, collectively termed as the senescence-associated secretory phenotype (SASP), which causes chronic inflammation and tissue dysfunction. Much effort has been recently made to therapeutically target detrimental effects of cellular senescence including selectively eliminating senescent cells (senolytics) and modulating a proinflammatory senescent secretome (senostatics). Here, we discuss current progress and limitations in understanding molecular mechanisms of senolytics and senostatics and therapeutic strategies for applying them. Furthermore, we propose how these novel interventions for aging treatment could be improved, based on lessons learned from cancer treatment.

• The Plant Pathology Journal
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• v.21 no.2
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• pp.158-163
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• 2005

Virus-induced gene silencing (VIGS) is a recently developed gene transcript suppression technique for characterizing the function of plant genes. However, efficient VIGS has only been studied in a few plant species. In order to extend the application of VIGS, we examined whether a VIGS vector based on TRV would produce recognizable phenotypes in soybean. Here, we report that VIGS using the Tobacco rattle virus (TRV) viral vector can be used in several soybean cultivars employing various agro-inoculation methods including leaf infiltration, spray inoculation, and agrodrench. cDNA fragments of the soybean phytoene desaturase(PDS) was inserted into TRV RNA-2 vector. By agrodrench, we successfully silenced the expression of PDS encoding gene in soybean. The silenced phenotype of PDS was invariably obvious 3 weeks after inoculation with the TRV-based vector. Real-time RT-PCR analyses showed that the endogenous level of GmPDS transcripts was dramatically reduced in the silenced leaf tissues. These observations confirm that the silenced phenotype is closely correlated with the pattern of tissue expression. The TRV-based VIGS using agrodrench can be applied to functional genomics in a soybean plants to study genes involved in a wide range of biological processes. To our knowledge, this is the first high frequency VIGS method in soybean plants.

• Molecules and Cells
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• v.42 no.4
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• pp.363-375
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• 2019

Fungal sectorization is a complex trait that is still not fully understood. The unique phenotypic changes in sporadic sectorization in mutants of CpBck1, a mitogen-activated protein kinase kinase kinase (MAPKKK) gene, and CpSlt2, a mitogen-activated protein kinase (MAPK) gene, in the cell wall integrity pathway of the chestnut blight fungus Cryphonectria parasitica have been previously studied. Although several environmental and physiological factors cause this sectoring phenotype, genetic variants can also impact this complex morphogenesis. Therefore, RNA sequencing analysis was employed to identify candidate genes associated with sectorization traits and understand the genetic mechanism of this phenotype. Transcriptomic analysis of CpBck1 and CpSlt2 mutants and their sectored progeny strains revealed a number of differentially expressed genes (DEGs) related to various cellular processes. Approximately 70% of DEGs were common between the wild-type and each of CpBck1 and CpSlt2 mutants, indicating that CpBck1 and CpSlt2 are components of the same MAPK pathway, but each component governs specific sets of genes. Functional description of the DEGs between the parental mutants and their sectored progenies revealed several key pathways, including the biosynthesis of secondary metabolites, translation, amino acid metabolism, and carbohydrate metabolism; among these, pathways for secondary metabolism and translation appeared to be the most common pathway. The results of this comparative study provide a better understanding of the genetic regulation of sector formation and suggest that complex several regulatory pathways result in interplays between secondary metabolites and morphogenesis.

• BMB Reports
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• v.42 no.2
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• pp.101-105
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• 2009

The homozygous T-DNA mutant of the AMY1 gene in Arabidopsis was identified and importantly, shown to cause an early flowering phenotype. We found that the disruption of AMY1 enhanced expression of CO and FT. The expression analyses of genes related to starch metabolism revealed that expression of the AGPase small subunit APS1 in the wild type was higher than in the amy1 mutant. However, there were no significant differences in expression levels of the AGPase large subunit genes ApL1, AMY2, or AMY3 between wild type and the amy1 mutant. Expression profiling showed that AMY1 was highly expressed in leaves, stems, and flowers, and expressed less in leafstalks and roots. Furthermore, the level of AMY1 mRNA was highly elevated with age and in senescing leaves. RT-PCR analyses showed that the expression of AMY1 was induced by heat shock, GA, and ABA, while salt stress had no apparent effect on its expression.

• Horticultural Science & Technology
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• v.31 no.1
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• pp.80-88
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• 2013

Carrot (Daucus carota L. var. sativa) is one of the most extensively used vegetable crops in the world and a significant source of nutrient because of its high content of ${\beta}$-carotene, well known as the precursor of vitamin A carotenoid. However, seed-hairs generated and elongated from the epidermal cell of seeds inhibit absorption and germination by various factors such as carotol and so on. Accordingly, mechanical hair removal process is essential before commercialization of carrot seeds. Because of this process, producers will have additional losses such as time consuming, manpower, capital and so on. Furthermore, physical damage of seeds causes irregular germination rate. To overcome such cumbersome weaknesses, new breeding program for developing hairless-seed carrot cultivar has been needed and studies for molecular markers related to seed-hair characteristic is needed for a new breeding program. Therefore, in this study, cDNA libraries from seeds of short-hair seed phenotype CT-SMR 616 OP 659-1 line, hairy-seed phenotype CT-SMR 616 OP 677-14 line and short-hair seed phenotype CT-ATR 615 OP 666-13 line, hairy-seed phenotype CT-ATR 615 OP 671-9 were constructed, respectively. Furthermore, 1,248 ESTs in each line, total 4,992 ESTs were sequenced. As a result, 19 SNP sites and 14 SNP sites in each of 2 combinations were confirmed by analyzing these EST sequences from short-hair and hairy-seed lines. Then we designed SNP primer sets from EST sequences of SNP sites for high resolution melting (HRM) analysis. Designed HRM primers were analyzed using hairy seed phenotype CT-SMR 616 OP 1040 line and short-hair seed phenotype CT-SMR 616 OP 1024, 1025, 1026 lines. One set of HRM primers showed specific difference between the melting curves of hairy and short-hair seed phenotype lines. Based on this result, allele-specific (AS) PCR primers were designed for easier selection between hairy-seed carrot and hairless seed carrot. These results of HRM and AS-PCR are expected to be useful in breeding of hairless seed carrot cultivar as a molecular marker.

• Journal of Digestive Cancer Reports
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• v.7 no.1
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• pp.8-12
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• 2019

Despite its declining incidence, gastric cancer is globally, still, the third most common cause of cancer-related mortality. Gastric cancer is a heterogeneous disease with diverse pathogenesis and molecular backgrounds. Therefore several systems have been proposed to aid in the classification of gastric adenocarcinoma based on the macroscopic, microscopic and anatomical features of the tumor. However, these classifications did not reflect the pathogenesis of the disease. Recently, genomic analysis has identified several subtypes of gastric adenocarcinoma and a detailed understanding of the molecular biology behind the neoplastic phenotype is possible to develop of more effective therapies. We will describe the existing various classification of gastric cancer and the recently introduced molecular biology and immunological classification.

• Applied Microscopy
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• v.28 no.3
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• pp.391-398
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• 1998

The morphological phenotype on ocellus of Drosophila rdgC mutant was observed with electron microscope. The result showed the particular phenotype that was not found in other retinal degenarative mutants. The most distinct difference was the orientation of photoreceptor cells. The photoreceptor cells did not attached to corneagenous cells but dropped under corneagenous cells and assembled around newly formed space. Enormous multivesicle bodies caused by the degeneration of photoreceptor cells were frequently found. Rhabdomeres were also severely degenerated in consequence of the mutant. Another degeneration was found in a part of photoreceptor cell, but the degeneration of subrhabdomeric cisternae (SRC) was not found. It was a ovious difference of rdgC comparing with other two retinal degenerative mutants, rdgA and rdgB. As a result, rdgC mutant was affected on the attachment between photoreceptor cells and corneageneous cells, and it suggested the defect of cell-cell attachment. In addition, rdgC mutant was accompanied by the defect not only in retina but nerve system. The results were agreed to the reference discussion that the rdgC molecule is exist in the nerve.

• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.59-63
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• 2009

Miyoshi myopathy (MM) is caused by the mutations of dysferlin gene (DYSF), which impairs the function of dysferlin protein causing muscle membrane dysfunction. We report a patient showing the MM phenotype who has a sister with LGMD 2B phenotype, along with the results of the immunohistochemical and molecular analyses of the DYSF gene. Immunohistochemical analysis noted negative immunoreactivity against dysferlin. Direct DNA sequencing of whole exons of DYSF gene revealed heterozygous nonsense mutations (c.610C>T + c.2494C>T). To our knowledge, this is the first reported MM case with this very combination of heterozygous mutations.

• Clinical and Experimental Pediatrics
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• v.53 no.10
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• pp.909-912
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• 2010

Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene $SCN4A$, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.2
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• pp.244-257
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• 2000

Recent progress in molecular biology has made it possible to transfer genes of interest into cells and target tissues of living animals. This enables one to manipulate phenotype of cells and whole animals in selected and intended ways. The consequence of such gene transfer attempts have been the production of various types of "transgenic" animals that cannot be classified by classical nomenclature of exclusively either "transgenic" or "nontransgenic". Emphasis was placed on characterizing two transgenic categories, i.e., "transfectgenic and somatotransgenic" and "genuine transgenic" animals basically from a view point of their use for therapeutic purposes. Current state of art and possible solutions for problems encountered at present are discussed.