• Title/Summary/Keyword: USP

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Precise control of mitophagy through ubiquitin proteasome system and deubiquitin proteases and their dysfunction in Parkinson's disease

  • Park, Ga Hyun;Park, Joon Hyung;Chung, Kwang Chul
    • BMB Reports
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    • v.54 no.12
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    • pp.592-600
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    • 2021
  • Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly population and is caused by the loss of dopaminergic neurons. PD has been predominantly attributed to mitochondrial dysfunction. The structural alteration of α-synuclein triggers toxic oligomer formation in the neurons, which greatly contributes to PD. In this article, we discuss the role of several familial PD-related proteins, such as α-synuclein, DJ-1, LRRK2, PINK1, and parkin in mitophagy, which entails a selective degradation of mitochondria via autophagy. Defective changes in mitochondrial dynamics and their biochemical and functional interaction induce the formation of toxic α-synuclein-containing protein aggregates in PD. In addition, these gene products play an essential role in ubiquitin proteasome system (UPS)-mediated proteolysis as well as mitophagy. Interestingly, a few deubiquitinating enzymes (DUBs) additionally modulate these two pathways negatively or positively. Based on these findings, we summarize the close relationship between several DUBs and the precise modulation of mitophagy. For example, the USP8, USP10, and USP15, among many DUBs are reported to specifically regulate the K48- or K63-linked de-ubiquitination reactions of several target proteins associated with the mitophagic process, in turn upregulating the mitophagy and protecting neuronal cells from α-synuclein-derived toxicity. In contrast, USP30 inhibits mitophagy by opposing parkin-mediated ubiquitination of target proteins. Furthermore, the association between these changes and PD pathogenesis will be discussed. Taken together, although the functional roles of several PD-related genes have yet to be fully understood, they are substantially associated with mitochondrial quality control as well as UPS. Therefore, a better understanding of their relationship provides valuable therapeutic clues for appropriate management strategies.

Genetic diversity and population structure of Mongolian regional horses with 14 microsatellite markers

  • Yun, Jihye;Oyungerel, Baatartsogt;Kong, Hong Sik
    • Animal Bioscience
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    • v.35 no.8
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    • pp.1121-1128
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    • 2022
  • Objective: This study aimed to identify the genetic diversity and population structure of Mongolian horse populations according to the province of residence (Khentii, KTP; Uvs, USP; Omnogovi and Dundgovi, GOP; Khovsgol, KGP) using 14 microsatellite (MS) markers. Methods: A total of 269 whole blood samples were obtained from the four populations (KTP, USP, GOP, KGP) geographically distinct provinces. Multiplex polymerase chain reaction (PCR) was conducted using 14 MS markers (AHT4, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, and VHL20), as recommended by the International Society for Animal Genetics. Capillary electrophoresis was conducted using the amplified PCR products, alleles were determined. Alleles were used for statistical analysis of genetic variability, Nei's DA genetic distance, principal coordinate analysis (PCoA), factorial corresponding analysis (FCA), and population structure. Results: On average, the number of alleles, expected heterozygosity (HExp), observed heterozygosity (HObs), and polymorphic information content among all populations were 11.43, 0.772, 0.757, and 0.737, respectively. In the PCoA and FCA, GOP, and KGP were genetically distinct from other populations, and the KTP and USP showed a close relationship. The two clusters identified using Nei's DA genetic distance analysis and population structure highlighted the presence of structurally clear genetic separation. Conclusion: Overall, the results of this study suggest that genetic diversity between KTP and USP was low, and that between GOP and KGP was high. It is thought that these results will help in the effective preservation and improvement of Mongolian horses through genetic diversity analysis and phylogenetic relationships.

CircCOL1A2 Sponges MiR-1286 to Promote Cell Invasion and Migration of Gastric Cancer by Elevating Expression of USP10 to Downregulate RFC2 Ubiquitination Level

  • Li, Hang;Chai, Lixin;Ding, Zujun;He, Huabo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.7
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    • pp.938-948
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    • 2022
  • Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.

Phytase Production by Rhizopus microsporus var. microsporus Biofilm: Characterization of Enzymatic Activity After Spray Drying in Presence of Carbohydrates and Nonconventional Adjuvants

  • Sato, Vanessa Sayuri;Jorge, Joao Atilio;Oliveira, Wanderley Pereira;Souza, Claudia Regina Fernandes;Guimaraes, Luis Henrique Souza
    • Journal of Microbiology and Biotechnology
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    • v.24 no.2
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    • pp.177-187
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    • 2014
  • Microbial phytases are enzymes with biotechnological interest for the feed industry. In this article, the effect of spray-drying conditions on the stability and activity of extracellular phytase produced by R. microsporus var. microsporus biofilm is described. The phytase was spray-dried in the presence of starch, corn meal (> $150{\mu}m$), soy bean meal (SB), corn meal (< $150{\mu}m$) (CM), and maltodextrin as drying adjuvants. The residual enzyme activity after drying ranged from 10.7% to 60.4%, with SB and CM standing out as stabilizing agents. Water concentration and residual enzyme activity were determined in obtained powders as a function of the drying condition. When exposed to different pH values, the SB and CM products were stable, with residual activity above 50% in the pH range from 4.5 to 8.5 for 60 min. The use of CM as drying adjuvant promoted the best retention of enzymatic activity compared with SB. Spray drying of the R. microsporus var. microsporus phytase using different drying adjuvants showed interesting results, being quite feasible with regards their biotechnological applications, especially for poultry diets.

The Synthesis of Lithium Lanthanum Titanium Oxide for Solid Electrolyte via Ultrasonic Spray Pyrolysis (초음파 분무 열분해법을 이용한 고체전해질용 Lithium Lanthanum Titanium Oxide 제조)

  • Jaeseok, Roh;MinHo, Yang;Kun-Jae, Lee
    • Journal of Powder Materials
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    • v.29 no.6
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    • pp.485-491
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    • 2022
  • Lithium lanthanum titanium oxide (LLTO) is a promising ceramic electrolyte because of its high ionic conductivity at room temperature, low electrical conductivity, and outstanding physical properties. Several routes for the synthesis of bulk LLTO are known, in particular, solid-state synthesis and sol-gel method. However, the extremely low ionic conductivity of LLTO at grain boundaries is one of the major problems for practical applications. To diminish the grain boundary effect, the structure of LLTO is tuned to nanoscale morphology with structures of different dimensionalities (0D spheres, and 1D tubes and wires); this strategy has great potential to enhance the ion conduction by intensifying Li diffusion and minimizing the grain boundary resistance. Therefore, in this work, 0D spherical LLTO is synthesized using ultrasonic spray pyrolysis (USP). The USP method primarily yields spherical particles from the droplets generated by ultrasonic waves passed through several heating zones. LLTO is synthesized using USP, and the effects of each precursor and their mechanisms as well as synthesis parameters are analyzed and discussed to optimize the synthesis. The phase structure of the obtained materials is analyzed using X-ray diffraction, and their morphology and particle size are analyzed using field-emission scanning electron microscopy.

No Association Between the USP7 Gene Polymorphisms and Colorectal Cancer in the Chinese Han Population

  • Li, Xin;Wang, Yang;Li, Xing-Wang;Liu, Bao-Cheng;Zhao, Qing-Zhu;Li, Wei-Dong;Chen, Shi-Qing;Huang, Xiao-Ye;Yang, Feng-Ping;Wang, Quan;Wang, Jin-Fen;Xiao, Yan-Zeng;Xu, Yi-Feng;Feng, Guo-Yin;Peng, Zhi-Hai;He, Lin;He, Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1749-1752
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    • 2012
  • Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

Studies on the Adiministration of Botanical Products's Quality in USA (미국에서의 Botanical Products(한약) 품질관리에 관한 연구)

  • Seong, Hyun-Jea;Choi, Sun-Mi;Yoon, Yoo-Sik
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.13 no.2
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    • pp.182-187
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    • 2000
  • Current status and quality administration of botanical products in America which has one of the biggest market need to be analyzed for the internationalization of oriental medicine. In this study, current status of botanical products as dietary supplements was analyzed and quality adminstration by United States Pharmacopoeia and National Formulary(USP-NF) was compared with The Korea Pharmacopoeia and botanical drug standard collection(KP), Even though the number of botanical products in USP-NF is small, it is rapidly increasing and more detailed compared with KP. Especially, reference standard compound should be determined for each botanical drugs, and more detailed standard for other items should be established in KP considering international trends. Though the history of botanical drugs in America is short, its annual market is about 3.2 billion dollar, so American administration system should be examined carefully for the internationalization of oriental medicine and related industry.

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Regulation and Function of the Peg3 Imprinted Domain

  • He, Hongzhi;Kim, Joomyeong
    • Genomics & Informatics
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    • v.12 no.3
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    • pp.105-113
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    • 2014
  • A subset of mammalian genes differ functionally between two alleles due to genomic imprinting, and seven such genes (Peg3, Usp29, APeg3, Zfp264, Zim1, Zim2, Zim3) are localized within the 500-kb genomic interval of the human and mouse genomes, constituting the Peg3 imprinted domain. This Peg3 domain shares several features with the other imprinted domains, including an evolutionarily conserved domain structure, along with transcriptional co-regulation through shared cis regulatory elements, as well as functional roles in controlling fetal growth rates and maternal-caring behaviors. The Peg3 domain also displays some unique features, including YY1-mediated regulation of transcription and imprinting; conversion and adaptation of several protein-coding members as ncRNA genes during evolution; and its close connection to human cancers through the potential tumor suppressor functions of Peg3 and Usp29. In this review, we summarize and discuss these features of the Peg3 domain.

Regression models generated by gamma random variables with long-term survivors

  • Ortega, Edwin M.M.;Cordeiro, Gauss M.;Hashimoto, Elizabeth M.;Suzuki, Adriano K.
    • Communications for Statistical Applications and Methods
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    • v.24 no.1
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    • pp.43-65
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    • 2017
  • We propose a flexible cure rate survival model by assuming that the number of competing causes of the event of interest has the Poisson distribution and the time for the event follows the gamma-G family of distributions. The extended family of gamma-G failure-time models with long-term survivors is flexible enough to include many commonly used failure-time distributions as special cases. We consider a frequentist analysis for parameter estimation and derive appropriate matrices to assess local influence on the parameters. Further, various simulations are performed for different parameter settings, sample sizes and censoring percentages. We illustrate the performance of the proposed regression model by means of a data set from the medical area (gastric cancer).