RESUMO
Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Adulto , Alelos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , PrognósticoRESUMO
The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-ß-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-ß-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 µg/mL.
Assuntos
Azacitidina , Penicillium , Penicillium/química , Estrutura Molecular , Staphylococcus aureus , Espectroscopia de Ressonância Magnética , Epigênese GenéticaRESUMO
A new phthalide derivative named paramlyktone (1) and a new arborinane-type triterpenoid named paramyrpenoid (2), together with ten previously described trichothecenes derivatives (3-12) were isolated and identified from a rhizospheric soil-derived Paramyrothecium sp. KMU22107 associated with Delphinium yunnanense. Their structural elucidation was achieved by the comprehensive analysis of spectroscopic data and comparison with literature values. Notably, paramyrpenoid (2) was the first example of an arborinane-type triterpenoid with a double bond at Δ12(13) and an additional methyl motif at C-8. This was the first report of arborinane-type triterpenoids from a fungus belonging to Paramyrothecium genus. In pharmacological studies, paramyrpenoid (2) demonstrated significant cytotoxic activity against the HL-60, SW480, A-549, MDA-MB-231 and SMMC-7721 cell lines, with IC50 values from 2.0 to 16.1 µM. Compounds 1 and 2 were also evaluated for anti-inflammatory, anti-acetylcholinesterase (AChE), and protein tyrosine phosphatase 1B (PTP1B) inhibitory activities in vitro.
RESUMO
A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3-8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values. Paeciureallin (1) is the first example of hybrid sorbicillinoids possessing a rare sorbicillinoid urea unit and containing a ß-D-ribofuranose functionality. In pharmacological studies, compounds 1 and 2 were evaluated for in vitro anti-inflammatory and cytotoxic activities. Paeciureallin (1) exhibited moderate cytotoxicity against SW480 and A549 cell lines, and the IC50 values were 32.0 ± 0.1 and 34.4 ± 2.0 µM, respectively.
Assuntos
Antineoplásicos , Paecilomyces , Estrutura Molecular , Paecilomyces/química , Antineoplásicos/farmacologia , Anti-InflamatóriosRESUMO
Mutation (substitution, deletion, insertion, etc.) in nucleotide acid causes the maximal sequence lengths of exact match (MALE) between paralogous members from a duplicate event to become shorter during evolution. In this work, MALE changes between members of 26 gene families from four representative species (Arabidopsis thaliana, Oryza sativa, Mus musculus and Homo sapiens) were investigated. Comparative study of paralogous' MALE and amino acid substitution rate (d(A)<0.5) indicated that a close relationship existed between them. The results suggested that MALE could be a sound evolutionary scale for the divergent time for paralogous genes during their early evolution. A reference table between MALE and divergent time for the four species was set up, which would be useful widely, for large-scale genome alignment and comparison. As an example, detection of large-scale duplication events of rice genome based on the table was illustrated.
Assuntos
Arabidopsis/genética , Mapeamento Cromossômico/métodos , Evolução Molecular , Oryza/genética , Proteoma/genética , Alinhamento de Sequência/métodos , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência Conservada/genética , Humanos , Camundongos , Dados de Sequência Molecular , Proteoma/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
An ancient genome duplication (PPP1) that predates divergence of the cereals has recently been recognized. We report here another potentially older large-scale duplication (PPP2) event that predates monocot-dicot divergence in the genome of rice (Oryza sativa L.), as inferred from the age distribution of pairs of duplicate genes based on recent genome data for rice. Our results suggest that paleopolyploidy was widespread and played an important role in the evolution of rice.