About 8,000 years ago in the Fertile Crescent, a spontaneous hybridization of the wild diploid grass Aegilops tauschii (2n 5 14; DD) with the cultivated tetraploid wheat Triticum turgidum (2n 5 4x 5 28; AABB) resulted in hexaploid wheat (T. aestivum; 2n 5 6x 5 42; AABBDD) 1,2 . Wheat has since become a primary staple crop worldwide as a result of its enhanced adaptability to a wide range of climates and improved grain quality for the production of baker's flour 2 . Here we describe sequencing the Ae. tauschii genome and obtaining a roughly 90-fold depth of short reads from libraries with various insert sizes, to gain a better understanding of this genetically complex plant. The assembled scaffolds represented 83.4% of the genome, of which 65.9% comprised transposable elements. We generated comprehensive RNA-Seq data and used it to identify 43,150 protein-coding genes, of which 30,697 (71.1%) were uniquely anchored to chromosomes with an integrated high-density genetic map. Whole-genome analysis revealed gene family expansion in Ae. tauschii of agronomically relevant gene families that were associated with disease resistance, abiotic stress tolerance and grain quality. This draft genome sequence provides insight into the environmental adaptation of bread wheat and can aid in defining the large and complicated genomes of wheat species.We selected Ae. tauschii accession AL8/78 for genome sequencing because it has been extensively characterized genetically (Supplementary Information). Using a whole genome shotgun strategy, we generated 398 Gb of high-quality reads from 45 libraries with insert sizes ranging from 200 bp to 20 kb (Supplementary Information). A hierarchical, iterative assembly of short reads employing the parallelized sequence assembler SOAPdenovo 3 achieved contigs with an N50 length (minimum length of contigs representing 50% of the assembly) of 4,512 bp (Table 1). Paired-end information combined with an additional 18.4 Gb of Roche/454 long-read sequences was used sequentially to generate 4.23-Gb scaffolds (83.4% were non-gapped contiguous sequences) with an N50 length of 57.6 kb (Supplementary Information). The assembly represented 97% of the 4.36-Gb genome as estimated by K-mer analysis (Supplementary Information). We also obtained 13,185 Ae. tauschii expressed sequence tag (EST) sequences using Sanger sequencing, of which 11,998 (91%) could be mapped to the scaffolds with more than 90% coverage (Supplementary Information).To aid in gene identification, we performed RNA-Seq (53.2 Gb for a 117-Mb transcriptome assembly) on 23 libraries representing eight tissues including pistil, root, seed, spike, stamen, stem, leaf and sheath (Supplementary Information). Using both evidence-based and de novo gene predictions, we identified 34,498 high-confidence protein-coding loci. FGENESH 4 and GeneID models were supported by a 60% overlap with either our ESTs and RNA-Seq reads, or with homologous proteins. More than 76% of the gene models had a significant match (E value # 10
25; alignment length $ 60%) in the ...
CD155 is the fifth member in the nectin‐like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as necl‐5, or PVR. As an immunoglobulin‐like adhesion molecule, CD155 is involved in cell motility, and natural killer and T cell‐mediated immunity. CD155 is barely or weakly expressed in various normal human tissues, but frequently overexpressed in human malignant tumors. CD155 overexpression promotes tumor cell invasion and migration, and is associated with tumor progression and poor prognosis. As the ligand for both costimulatory receptor CD226 and coinhibitory receptor TIGIT and CD96 on natural killer and T cells, CD155 seems to play a dual role in oncoimmunity. However, some recent studies indicate that CD155 overexpression may induce tumor immune escape. Taken together, CD155 may be considered as a target for the treatment of tumors with CD155 overexpression.
The filamentous fungus Fusarium fujikuroi is well-known for its production of natural plant growth hormones: a series of gibberellic acids (GAs). Some GAs, including GA1, GA3, GA4, and GA7, are biologically active and have been widely applied in agriculture. However, the low efficiency of traditional genetic tools limits the further research toward making this fungus more efficient and able to produce tailor-made GAs. Here, we established an efficient CRISPR/Cas9-based genome editing tool for F. fujikuroi. First, we compared three different nuclear localization signals (NLS) and selected an efficient NLS from histone H2B (HTB NLS ) to enable the import of the Cas9 protein into the fungal nucleus. Then, different sgRNA expression strategies, both in vitro and different promoter-based in vivo strategies, were explored. The promoters of the U6 small nuclear RNA and 5S rRNA, which were identified in F. f ujikuroi, had the highest editing efficiency. The 5S rRNA-promoter-driven genome editing efficiency reached up to 79.2%. What's more, multigene editing was also explored and showed good results. Finally, we used the developed genome editing tool to engineer the metabolic pathways responsible for the accumulation of a series GAs in the filamentous fungus F. f ujikuroi, and successfully changed its GA product profile, from GA3 to tailor-made GA4 and GA7 mixtures. Since these mixtures are more efficient for agricultural use, especially for fruit growth, the developed strains will greatly improve industrial GA production.
Increased expression of interleukin 6 (IL-6) is associated with poor prognosis and chemoresistance in many different carcinomas, but its role in head and neck squamous cell carcinoma (HNSCC) is still unsettled. Analyzing tumorous mRNA expression data from 399 HNSCC patients revealed that high IL-6 expression predicted poor prognosis. Similar tendency was observed in platinum treated patients, suggesting an IL-6 associated cisplatin resistance. IL-6 increase was also found in two in-house acquired cisplatin-resistant HNSCC cell lines (both basaloid and conventional squamous cell carcinoma) by using microarray analysis. However, although the in-house acquired cisplatin-resistant cell lines had higher basal and markedly increased cisplatin-induced IL-6 expression, IL-6 did not mediate the cisplatin resistance as neither exogenous IL-6 nor IL-6R/gp130 inhibitors affected cisplatin sensitivity. Moreover, the IL-6/STAT3 pathway was impaired in the resistant cell lines, partly due to decreased IL-6R expression. Thus, high IL-6 expression correlated to poor prognosis and acquired cisplatin resistance, but it did not mediate cisplatin resistance in the HNSCC cell lines.
CD155, one of the nectin‐like molecule family members, is involved in cell adhesion and motility. CD155 is overexpressed in several human cancers, but its role in proliferation and apoptosis of colorectal cancer remains unclear. We found that CD155 was up‐regulated in colorectal cancer tissues. CD155 knockdown via shRNA lentiviruses inhibited colon cancers cell migration and invasion, with a reduction in the expression of FAK, Src and MMP‐2. CD155 down‐regulation also suppressed colon cancer cell proliferation, accompanied by changing expressions of some molecules related to cell cycle. Finally, CD155 knockdown increased the expression ratio between Bax and Bcl‐2, resulting in a significant increase in colon cancer cell apoptosis. Taken together, these results demonstrate that CD155 is involved in not only migration and invasion but also proliferation and survival abilities of colon cancer cells, suggesting that CD155 is one of key molecules promoting the growth and metastasis of colorectal cancer.
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