Project description:Chromosomal imbalances are implicated in the etiology of developmental delay (DD) and congenital malformation (CM). We therefore conducted high resolution array comparative genomic hybridization (array CGH) of sixty three Saudi patients [11 by Agilent-001850/CGH1x244A and 52 by Agilent-014693/CGH2x400k] for investigating and understanding the genetic heterogeneity underlying DD/CM. A total of 76 disease associated copy number variants (CNVs) were detected in twenty four patients including 1p36, 1q21, 3p23, 6p24, 7q11, 8q24, 9q33, 10p14, 11p15, 11q12, 11q24, 13q21, 15q13, 16p13, 18q23, trisomy 18, 20q11, 21q22, 22q11.21, 47,XXY and 45,X0. The diagnosis rate of array CGH was 2.6 times higher than karyotyping.
Project description:Chromosomal imbalances are implicated in the etiology of developmental delay (DD) and congenital malformation (CM). We therefore conducted high resolution array comparative genomic hybridization (array CGH) of sixty three Saudi patients [11 by Agilent-001850/CGH1x244A and 52 by Agilent-014693/CGH2x400k] for investigating and understanding the genetic heterogeneity underlying DD/CM. A total of 76 disease associated copy number variants (CNVs) were detected in twenty four patients including 1p36, 1q21, 3p23, 6p24, 7q11, 8q24, 9q33, 10p14, 11p15, 11q12, 11q24, 13q21, 15q13, 16p13, 18q23, trisomy 18, 20q11, 21q22, 22q11.21, 47,XXY and 45,X0. The diagnosis rate of array CGH was 2.4 times higher than karyotyping.
Project description:Dynamic modification of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII) regulates transcription-coupled processes in eukaryotes. The CTD in mammals is composed of 52 heptad-repeats with the consensus sequence Y1-S2-P3-T4-S5-P6-S7. Repeats in the distal part of CTD deviate from the consensus sequence and have frequently replaced serine at position 7 by lysine residues (K7). Mass spectrometry analysis revealed modification of K7 residues in heptad-repeats 39, 42, and 47/49 by acetylation and in heptad-repeats 38, 39, 40, 42, and 47/49 by mono-, di-, or trimethylation. Notably, acetylated as well as di- and tri-methylated K7 residues were found exclusively in phosphorylated CTD peptides, while mono-methylated K7 residues occurred also in non-phosphorylated CTD peptides. Methylation of K7 residues was further studied with the monoclonal antibody (mAb) 1F5, which recognizes mono- and di-methylated K7 in CTD. ChIP experiments revealed high levels of K7 methylation at the transcriptional start site of genes. The low levels of K7 methylation in the body of genes results from impairment of epitope recognition in hyper-phosphorylated CTD by mAb 1F5. In agreement with this notion, phosphatase treatment of hyper-phosphorylated CTD or treatment of cells with kinase inhibitor flavopiridol restored the reactivity of mAb 1F5 towards methylated K7 residues in CTD. We conclude that methylation and acetylation of K7 residues further expand the mammalian CTD code and potentially contribute to regulation of gene expression.
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of lncRNA in mouse cells. By obtaining over 47 million bases of sequence, we identified 3,307 lncRNAs based on single-cell RNA sequencing (RNA-Seq) data, discovered 52 lncRNAs that were significantly differentially expressed, and then selected 10 lncRNAs for qRT-PCR validation. Furthermore, we found that 12 lncRNAs with the target gene Tubb4b or Actn4 might be related to the expression of microtubule and microfilament proteins and the binding relationship was confirmed in a dual-luciferase reporter assay. Finally, Gene Ontology (GO) analysis revealed that the target genes of the differentially expressed lncRNAs participated in cellular processes related to protein transport, binding, catalytic activity, membrane-bounded organelles, protein complexes and the cortical cytoskeleton. We believe the paper will be of particular interest to the readers of your journal as lncRNAs regulated the progress of the mouse early embryo development.
Project description:Halobacterium salinarum R1 is an extremely halophilic archaeon capable of adhesion and biofilm formation. We have recently shown that living in biofilms facilitates higher cell survival under heavy metal ion stress in this species, while specific rearrangements of the biofilm architecture were observed upon Ni2+ and Cu2+ exposition, respectively. In this study, quantitative analyses were performed by SWATH-LC-MS/MS to determine the respective proteomes under the influences of Ni2+ and Cu2+ in planktonic and biofilm cells. Quantitative data for 1180 proteins were gained, corresponding to 46% of the predicted proteome. In planktonic cells, 234 proteins showed significant abundance changes after metal ion treatment, of which 47% occurred combined in Cu2+ and Ni2+ treated samples. Regarding biofilms, significant changes were detected for 52 proteins. Only three proteins changed under both conditions, suggesting metal-specific stress responses in biofilms.
Project description:Cisplatin is a common chemotherapeutic drug for hypopharyngeal cancer. But cisplatin-resistance of hypopharyngeal cancer is rarely explored. We cultured hypopharyngeal cancer cell (FaDu) and induced its cisplatin-resistant cell (FaDu/DDP4). The resistance index (RI) of FaDu/DDP4 was 2.828. Then we tested the differentially expressed genes (DEGs) between FaDu and FaDu/DDP4. DEGs contain 2388 lncRNAs, 1932 circRNAs, 745 mRNAs and 202 miRNAs. We used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the DEGs. The differentially expressed 745 mRNAs were classified into 3 domains and 47 secondary GO terms. In KEGG pathway enrichment, “TNF signaling pathway”, “IL-17 signaling pathway” and “JAK-STAT signaling pathway” have greater enrich factors. And we drew the ceRNA networks of DEGs. 52 lncRNAs, 148 circRNAs, 155 mRNAs and 18 miRNAs were selected to draw the network. We noticed several potential targets (as miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1). At last, we chose 8 miRNAs and 6 mRNAs for qRT-PCR to verify our microarray. In them, miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1 might be potential genes inducing resistance.