Esophageal squamous cell carcinoma (ESCC) is a world-wide prevalent cancer, which is particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified novel significantly mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to previously discovered ones (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Moreover, our approaches uncovered many novel druggable candidates, and XPO1 was further explored as a therapeutic target because of its mutation and protein overexpression. Together, our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
Arbuscular mycorrhizal (AM) fungi facilitate plant uptake of mineral nutrients and draw organic nutrients from the plant. Organic nutrients are thought to be supplied primarily in the form of sugars. Here we show that the AM fungus is a fatty acid auxotroph and that fatty acids synthesized in the host plants are transferred to the fungus to sustain mycorrhizal colonization. The transfer is dependent on RAM2 (REQUIRED FOR ARBUSCULAR MYCORRHIZATION 2) and the ATP binding cassette transporter-mediated plant lipid export pathway. We further show that plant fatty acids can be transferred to the pathogenic fungus and are required for colonization by pathogens. We suggest that the mutualistic mycorrhizal and pathogenic fungi similarly recruit the fatty acid biosynthesis program to facilitate host invasion.
We experimentally investigate an optical clock based on ;{171}Yb (I = 1/2) atoms confined in an optical lattice. We have evaluated all known frequency shifts to the clock transition, including a density-dependent collision shift, with a fractional uncertainty of 3.4 x 10;{-16}, limited principally by uncertainty in the blackbody radiation Stark shift. We measured the absolute clock transition frequency relative to the NIST-F1 Cs fountain clock and find the frequency to be 518 295 836 590 865.2(0.7) Hz.
Most land plants form symbiotic associations with arbuscular mycorrhizal (AM) fungi. These are the most common and widespread terrestrial plant symbioses, which have a global impact on plant mineral nutrition. The establishment of AM symbiosis involves recognition of the two partners and bidirectional transport of different mineral and carbon nutrients through the symbiotic interfaces within the host root cells. Intriguingly, recent discoveries have highlighted that lipids are transferred from the plant host to AM fungus as a major carbon source. In this review, we discuss the transporter-mediated transfer of carbon, nitrogen, phosphate, potassium and sulfate, and present hypotheses pertaining to the potential regulatory mechanisms of nutrient exchange in AM symbiosis. Current challenges and future perspectives on AM symbiosis research are also discussed.
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