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Functional genomics

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https://www.readbyqxmd.com/read/28749466/knockout-of-march2-inhibits-the-growth-of-hct116-colon-cancer-cells-by-inducing-endoplasmic-reticulum-stress
#1
Dan Xia, Wanli Ji, Chentong Xu, Xin Lin, Xiaokun Wang, Yan Xia, Ping Lv, Quansheng Song, Dalong Ma, Yingyu Chen
Membrane-associated RING-CH protein 2 (MARCH2), a member of the MARCH family, functions in vesicle trafficking and autophagy regulation. In this study, we established MARCH2 knockout HCT116 cell lines using CRISPR/Cas9-mediated genome editing to evaluate the role of MARCH2 in colon cancer in vitro and in vivo. Knockout of MARCH2 suppressed cell proliferation, and promoted autophagy, apoptosis and G2/M phase cell cycle arrest. These effects were associated with activation of endoplasmic reticulum (ER) stress...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749461/dnmt1-maintained-hypermethylation-of-kr%C3%A3-ppel-like-factor-5-involves-in-the-progression-of-clear-cell-renal-cell-carcinoma
#2
Rong-Jie Fu, Wei He, Xiao-Bo Wang, Lei Li, Huan-Bin Zhao, Xiao-Ye Liu, Zhi Pang, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It is a challenge to explore effective therapeutic targets and drugs for this kind of cancer. Transcription factor Krüppel-like factor 5 (KLF5) exerts diverse functions in various tumor types. By analyzing cohorts of the Cancer Genome Atlas (TCGA) data sets, we find that KLF5 expression is suppressed in ccRCC patients and higher level of KLF5 expression is associated with better prognostic outcome...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749367/genome-wide-association-study-of-susceptibility-to-particulate-matter-associated-qt-prolongation
#3
Rahul Gondalia, Christy L Avery, Melanie D Napier, Raúl Méndez-Giráldez, James D Stewart, Colleen M Sitlani, Yun Li, Kirk C Wilhelmsen, Qing Duan, Jeffrey Roach, Kari E North, Alexander P Reiner, Zhu-Ming Zhang, Lesley F Tinker, Jeff D Yanosky, Duanping Liao, Eric A Whitsel
BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986-2004), longitudinal data on in diameter (), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis...
June 8, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28749324/investigation-of-the-fim1-putative-pilus-locus-of-streptococcus-equi-subspecies-equi
#4
Karen Frances Steward, Carl Robinson, Duncan J Maskell, Chiara Nenci, Andrew Stephen Waller
The Gram-positive bacterium Streptococcus equi subspecies equi (S. equi) is the causative agent of strangles, among the most frequently diagnosed infectious diseases of horses worldwide. Genome analysis of S. equi strain 4047 (Se4047) identified a putative operon, Fim1, with similarity to the pilus loci of other Gram-positive bacteria. The Fim1 locus was present in all strains of S. equi and its close relative S. equi subspecies zooepidemicus (S. zooepidemicus) that have been studied to date. In this study we provide evidence that the putative structural pilus proteins, SEQ_0936 and CNE, are produced on the cell surface during in vitro growth and in vivo infection...
July 28, 2017: Microbiology
https://www.readbyqxmd.com/read/28749196/double-stranded-telomeric-dna-binding-proteins-diversity-matters
#5
Filip Červenák, Katarína Juríková, Regina Sepšiová, Martina Neboháčová, Jozef Nosek, Ľubomír Tomáška
Telomeric sequences constitute only a small fraction of the whole genome yet they are crucial for ensuring genomic stability. This function is in large part mediated by protein complexes recruited to telomeric sequences by specific telomere-binding proteins (TBPs). Although the principal tasks of nuclear telomeres are the same in all eukaryotes, TBPs in various taxa exhibit a surprising diversity indicating their distinct evolutionary origin. This diversity is especially pronounced in ascomycetous yeasts where they must have co-evolved with rapidly diversifying sequences of telomeric repeats...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28748856/the-short-isoform-of-nuclear-mitotic-apparatus-protein-1-functions-as-a-putative-tumor-suppressor
#6
Wang-Sen Qin, Jin Wu, Yang Chen, Fa-Cai Cui, Fu-Ming Zhang, Guan-Ting Lyu, Hong-Mei Zhang
BACKGROUND: Nuclear mitotic apparatus protein 1 (NuMA1) had been reported to produce three groups of isoforms categorized as long, middle, and short groups, of which short NuMA displayed distinct localization patterns compared to long and middle isoforms. However, the function of short NuMA was not clear in the progress of cancer formation. This study aimed to unveil the role of short NuMA in cancer pathogenesis. METHODS: The expression levels of short isoforms were explored in paired gastric carcinoma (GC) samples and different cell lines...
August 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28748849/a-novel-missense-mutation-in-peripheral-myelin-protein-22-causes-charcot-marie-tooth-disease
#7
Li-Xi Li, Hai-Lin Dong, Bao-Guo Xiao, Zhi-Ying Wu
BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. A great number of causative genes have been described in CMT, and among them, the heterozygous duplication of peripheral myelin protein-22 (PMP22) is the major cause. Although the missense mutation in PMP22 is rarely reported, it has been demonstrated to be associated with CMT. This study described a novel missense mutation of PMP22 in a Chinese family with CMT phenotype. METHODS: Targeted next-generation sequencing (NGS) was used to screen the causative genes in a family featured with an autosomal dominant demyelinating form of CMT...
August 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28748670/whole-genome-detection-of-signature-of-positive-selection-in-african-cattle-reveals-selection-for-thermotolerance
#8
Mengistie Taye, Wonseok Lee, Kelsey Caetano-Anolles, Tadelle Dessie, Olivier Hanotte, Okeyo Ally Mwai, Stephen Kemp, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods...
July 27, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28748551/identification-of-a-dimeric-kdg-aldolase-from-agrobacterium-tumefaciens
#9
Tatiana P Soares da Costa, Madhvi Patel, Sebastien Desbois, Ruchi Gupta, Pierre Faou, Matthew A Perugini
Agrobacterium tumefaciens is a Gram-negative bacterium and causative agent of Crown Gall disease that infects a variety of economically-important plants. The annotated A. tumefaciens genome contains 10 putative dapA genes, which code for dihydrodipicolinate synthase (DHDPS). However, we have recently demonstrated that only one of these genes (dapA7) encodes a functional DHDPS. The function of the other nine putative dapA genes is yet to be determined. Here, we demonstrate using bioinformatics that the product of the dapA5 gene (DapA5) possesses all the catalytic residues canonical to 2-keto-3-deoxygluconate (KDG) aldolase, which is a class I aldolase involved in glucose metabolism...
July 27, 2017: Proteins
https://www.readbyqxmd.com/read/28748527/the-prevalence-of-dicer1-pathogenic-variation-in-population-databases
#10
Jung Kim, Amanda Field, Kris Ann P Schultz, D Ashley Hill, Douglas R Stewart
The DICER1 syndrome is associated with a variety of rare benign and malignant tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and Sertoli-Leydig cell tumor (SLCT). The prevalence and penetrance of pathogenic DICER1 variation in the general population is unknown. We examined three publicly-available germline whole exome sequence datasets: Exome Aggregation Consortium (ExAC), 1000 Genomes (1000G), and the Exome Sequencing Project (ESP). To avoid over-estimation of pathogenic DICER1 variation from cancer-associated exomes, we excluded The Cancer Genome Atlas (TCGA) variants from ExAC...
July 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#11
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28748134/genomic-characterization-reconfirms-the-taxonomic-status-of-lactobacillus-parakefiri
#12
Yasuhiro Tanizawa, Hisami Kobayashi, Eli Kaminuma, Mitsuo Sakamoto, Moriya Ohkuma, Yasukazu Nakamura, Masanori Arita, Masanori Tohno
Whole-genome sequencing was performed for Lactobacillus parakefiri JCM 8573(T) to confirm its hitherto controversial taxonomic position. Here, we report its first reliable reference genome. Genome-wide metrics, such as average nucleotide identity and digital DNA-DNA hybridization, and phylogenomic analysis based on multiple genes supported its taxonomic status as a distinct species in the genus Lactobacillus. The availability of a reliable genome sequence will aid future investigations on the industrial applications of L...
2017: Bioscience of Microbiota, Food and Health
https://www.readbyqxmd.com/read/28747909/the-physiological-functions-and-structural-determinants-of-catalytic-bias-in-the-fefe-hydrogenases-cpi-and-cpii-of-clostridium-pasteurianum-strain-w5
#13
Jesse B Therien, Jacob H Artz, Saroj Poudel, Trinity L Hamilton, Zhenfeng Liu, Seth M Noone, Michael W W Adams, Paul W King, Donald A Bryant, Eric S Boyd, John W Peters
The first generation of biochemical studies of complex, iron-sulfur-cluster-containing [FeFe]-hydrogenases and Mo-nitrogenase were carried out on enzymes purified from Clostridium pasteurianum (strain W5). Previous studies suggested that two distinct [FeFe]-hydrogenases are expressed differentially under nitrogen-fixing and non-nitrogen-fixing conditions. As a result, the first characterized [FeFe]-hydrogenase (CpI) is presumed to have a primary role in central metabolism, recycling reduced electron carriers that accumulate during fermentation via proton reduction...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28747816/prediction-with-dimension-reduction-of-multiple-molecular-data-sources-for-patient-survival
#14
Adam Kaplan, Eric F Lock
Predictive modeling from high-dimensional genomic data is often preceded by a dimension reduction step, such as principal component analysis (PCA). However, the application of PCA is not straightforward for multisource data, wherein multiple sources of 'omics data measure different but related biological components. In this article, we use recent advances in the dimension reduction of multisource data for predictive modeling. In particular, we apply exploratory results from Joint and Individual Variation Explained (JIVE), an extension of PCA for multisource data, for prediction of differing response types...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28747736/association-of-ubash3a-gene-polymorphism-and-atopic-dermatitis-in-the-chinese-han-population
#15
Y Li, H Cheng, F-L Xiao, B Liang, F-S Zhou, P Li, X-D Zheng, L-D Sun, S Yang, X-J Zhang
Genome-wide association studies have revealed a large number of genetic-risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases share susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A single-nucleotide polymorphisms (SNPs) and atopic dermatitis (AD) in a Chinese Han population...
July 27, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28747711/a-systems-approach-to-a-spatio-temporal-understanding-of-the-drought-stress-response-in-maize
#16
Zhenyan Miao, Zhaoxue Han, Ting Zhang, Siyuan Chen, Chuang Ma
Crops are often subjected to periods of drought stress during their life cycle. However, how stress response mechanisms contribute to the crosstalk between stress signaling pathways and developmental signaling pathways is still unknown. We built a gene co-expression network from a spatio-temporal transcriptomic map of the drought stress response in maize (Zea mays), profiled from three tissues and four developmental stages and characterized hub genes associated with duplication events, selection, and regulatory networks...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747548/long-non-coding-rna-miat-promotes-breast-cancer-progression-and-functions-as-cerna-to-regulate-dusp7-expression-by-sponging-mir-155-5p
#17
Tian Luan, Ximei Zhang, Shuyuan Wang, Yan Song, Shunheng Zhou, Jing Lin, Weiwei An, Weiguang Yuan, Yue Yang, Huilong Cai, Qingyuan Zhang, Lihong Wang
Long non-coding RNAs (lncRNA) have been reported as key regulators in the progression and metastasis of breast cancer. In this study, we found that the lncRNA myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets. We validated that MIAT was higher in breast cancer cell lines and advanced breast tumors than in normal controls. And MIAT overexpression associated with TNM stage and lymphnode metastasis. Knockdown MIAT inhibited breast cancer cell proliferation and promoted apoptosis...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747543/mutation-profile-based-methods-for-understanding-selection-forces-in-cancer-somatic-mutations-a-comparative-analysis
#18
Zhan Zhou, Yangyun Zou, Gangbiao Liu, Jingqi Zhou, Jingcheng Wu, Shimin Zhao, Zhixi Su, Xun Gu
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes (CN/CS) and normal populations (pN/pS). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747509/a-domain-of-herpes-simplex-virus-pul33-required-to-release-monomeric-viral-genomes-from-cleaved-concatameric-dna
#19
Kui Yang, Xiaoqun Dang, Joel D Baines
Monomeric herpesvirus DNA is cleaved from concatamers and inserted into preformed capsids through the actions of the viral terminase. The terminase of herpes simplex virus (HSV) is composed of three subunits encoded by UL15, UL28, and UL33. The UL33 encoded protein (pUL33) interacts with pUL28 but its precise role in the DNA cleavage and packaging reaction is unclear. To investigate the function of pUL33 we generated a panel of recombinant viruses with either deletions or substitutions in the most conserved regions of UL33 using a bacterial artificial chromosome system...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747502/permissivity-of-dpp4-orthologs-to-mers-coronavirus-is-governed-by-glycosylation-and-other-complex-determinants
#20
Kayla M Peck, Trevor Scobey, Jesica Swanstrom, Kara L Jensen, Christina L Burch, Ralph S Baric, Mark T Heise
Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several DPP4 orthologs, including mouse, ferret, hamster, and guinea pig, do not. Previous work revealed that glycosylation of mouse DPP4 plays a role in blocking MERS-CoV infection. Here, we test whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig DPP4. We find that while glycosylation plays an important role in these orthologs, additional sequence and structural determinants impact their ability to act as functional receptors for MERS-CoV...
July 26, 2017: Journal of Virology
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