Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations

Xu Zhiyang,Zhou Kaixiang,Wang Zhenni,Liu Yang,Wang Xingguo,Gao Tian,Xie Fanfan,Yuan Qing,Gu Xiwen,Liu Shujuan,Xing Jinliang 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the improvement of treatment in OC patients. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth mtDNA sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients. Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.

Variations of Available Nitrogen along the Upland Meadow in Wugong Mountain

Zhiyang Yuan,Zhi Li,Dekui Niu,Wenyuan Zhang,Xiaomin Guo,Xu Chen,Xiao Cheng 한국토양비료학회 2014 한국토양비료학회 학술발표회 초록집 Vol.2014 No.6

Candidate Pruning-Based Differentially Private Frequent Itemsets Mining

Yangyang Xu,Zhaobin Liu,Zhonglian Hu,Zhiyang Li 보안공학연구지원센터 2016 International Journal of Database Theory and Appli Vol.9 No.7

Frequent Itemsets Mining(FIM) is a typical data mining task and has gained much attention. Due to the consideration of individual privacy, various studies have been focusing on privacy-preserving FIM problems. Differential privacy has emerged as a promising scheme for protecting individual privacy in data mining against adversaries with arbitrary background knowledge. In this paper, we present an approach to exploring frequent itemsets under rigorous differential privacy model, a recently introduced definition which provides rigorous privacy guarantees in the presence of arbitrary external information. The main idea of differentially privacy FIM is perturbing the support of item which can hide changes caused by absence of any single item. The key observation is that pruning the number of unpromising candidate items can effectively reduce noise added in differential privacy mechanism, which can bring about a better tradeoff between utility and privacy of the result. In order to effectively remove the unpromising items from each candidate set, we use a progressive sampling method to get a super set of frequent items, which is usually much smaller than the original item database. Then the sampled set will be used to shrink candidate set. Extensive experiments on real data sets illustrate that our algorithm can greatly reduce the noise scale injected and output frequent itemsets with high accuracy while satisfying differential privacy.

Differential Privacy via Weighted Sampling Set Cover

Zhonglian Hu,Zhaobin Liu,Yangyang Xu,Zhiyang Li 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.4

Differential privacy is a security guarantee model which widely used in privacy preserving data publishing, but the query result can’t be used in data research directly, especially in high-dimensional datasets. To address this problem, we propose a dimensionality reduction method. The core idea of this method is using a series of low-dimensional datasets to reconstruct a high-dimensional dataset, it improves data availability eventually. The main issue of this method is the reconstruction integrity, so a special sampling via set cover model is proposed in this article, which builds a multidimensional composite marginal tables set as a new middleware in differential privacy model. As a result, any form of disjunctive queries can be answered, and the accuracy of data query is improved. The experiment results also show the effectiveness of our method in practice.

Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer’s Disease

Xinhua Zhou,Liang Wang,Wei Xiao,Zhiyang Su,Chengyou Zheng,Zaijun Zhang,Yu Qiang Wang,Benhong Xu,Xifei Yang,Maggie Pui Man Hoi 한국뇌신경과학회 2019 Experimental Neurobiology Vol.28 No.3

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer’s disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.

Genome-wide analyses of the NAC transcription factor family to reveal the potential candidate genes responding to powdery mildew in balsam pear

Ning Yu,Liu Jing,Song Bo,Xu Hai,Liu Zhiyang,Chen Longzheng 한국식물생명공학회 2023 Plant biotechnology reports Vol.17 No.6

Powdery mildew (PM) is the most serious disease in balsam pear and usually causes severe yield and quality decreases. Although NAC transcription factors involved in the growth, development, and regulation of biotic and abiotic stress responses have been published for many crops, comprehensive data regarding the structure, evolution, and functions of the NAC family in balsam pear are still unavailable. In this study, a comprehensive analysis of the NAC transcription factor family in balsam pear was performed, and 90 NAC genes of balsam pear (McNAC) were identified and divided into 18 subfamilies. Gene structure and protein motif analyses revealed that the functions of McNAC proteins exhibit diversity during evolution and are mainly involved in the response to light, growth, development, and abiotic and biotic stresses. Fifteen McNAC genes (McNAC03, McNAC09, McNAC15, McNAC19, McNAC25, McNAC29, McNAC34, McNAC47, McNAC55, McNAC59, McNAC61, McNAC69, McNAC71, McNAC73, and McNAC78) were differentially expressed after PM pathogen infection. Moreover, the predicted interacting proteins of 7 genes (McNAC09, McNAC15, McNAC25, McNAC29, McNAC34, McNAC73, and McNAC78) were related to the plant hormone signal transduction, betalain biosynthesis, and sphingolipid metabolism pathways by transcriptomic data, implying that the 7 genes participated in PM pathogen infection through these pathways. Metabolome data showed that nine metabolites in the same pathways were changed after PM infection, which suggests that these 7 McNAC genes could regulate these metabolites through the pathways mentioned above to respond to PM infection. The expression levels of McNAC09, McNAC15, McNAC25 and McNAC34 were further confirmed by qPCR to show the reliability of the obtained RNA-seq data. Interestingly, McNAC34 was predicted to be targeted by miRNA164, indicating that McNAC34 might be involved in the response to PM infection by the miRNA-regulated pathway. This study will provide deep insight into NAC gene family evolution and functions, especially in the response to PM pathogen infection in balsam pear.

Iso-migrastatin Titer Improvement in the Engineered Streptomyces lividans SB11002 Strain by Optimization of Fermentation Conditions

Xueyun Wu,Zhengbin Lv,Yaozhou Zhang,Dong Yang,Xiangcheng Zhu,Zhinan Xu,Zhiyang Feng,Ben Shen 한국생물공학회 2010 Biotechnology and Bioprocess Engineering Vol.15 No.4

The heterologous production of iso-migrastatin (iso-MGS) was successfully demonstrated in an engineered S. lividans SB11002 strain, which was derived from S. lividans K4-114, following introduction of pBS11001,which harbored the entire mgs biosynthetic gene cluster. However, under similar fermentation conditions, the iso-MGS titer in the engineered strain was significantly lower than that in the native producer - Streptomyces platensis NRRL 18993. To circumvent the problem of low iso-MGS titers and to expand the utility of this heterologous system for iso-MGS biosynthesis and engineering, systematic optimization of the fermentation medium was carried out. The effects of major components in the cultivation medium,including carbon, organic and inorganic nitrogen sources,were investigated using a single factor optimization method. As a result, sucrose and yeast extract were determined to be the best carbon and organic nitrogen sources, resulting in optimized iso-MGS production. Conversely, all other inorganic nitrogen sources evaluated produced various levels of inhibition of iso-MGS production. The final optimized R2YE production medium produced iso-MGS with a titer of 86.5 mg/L, about 3.6-fold higher than that in the original R2YE medium, and 1.5 fold higher than that found within the native S. platensis NRRL 18993 producer.

Molecular Cloning, Identification and Characteristics of a Novel Isoform of Carbamyl Phosphate Synthetase I in Human Testis

Huo, Ran,Zhu, Hui,Lu, Li,Ying, Lanlan,Xu, Min,Xu, Zhiyang,Li, Jianmin,Zhou, Zuomin,Sha, Jiahao Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.1

A gene coding a novel isoform of carbamyl phosphate synthetase I (CPS1) was cloned from a human testicular library. As shown by cDNA microarray hybridization, this gene was expressed at a higher level in human adult testes than in fetal testes. The full length of its cDNA was 3831 bp, with a 3149 bp open reading frame, encoding a 1050-amino-acid protein. The cDNA sequence was deposited in the GenBank (AY317138). Sequence analysis showed that it was homologous to the human CPS1 gene. The putative protein contained functional domains composing the intact large subunit of carbamoyl phosphate synthetase, thus indicated it has the capability of arginine biosynthesis. A multiple tissue expression profile showed high expression of this gene in human testis, suggesting the novel alternative splicing form of CPS1 may be correlated with human spermatogenesis.