Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.
Most estuaries and inland waters are significant source for atmospheric CO2 because of input of terrestrial inorganic carbon and mineralization of terrestrially supplied organic carbon. In contrast to most coastal waters, some estuaries with small freshwater discharge are weak source or sometimes sink for CO2. Extensive surveys of pCO2 in Tokyo Bay showed that the overall bay acts as a strong net sink for atmospheric CO2. Although small area was a consistent source for CO2, active photosynthesis driven by nutrient loading from the land overwhelmed the CO2 budget in the bay. Here we show a comprehensive scheme with a border where air-sea CO2 flux was ±0 between nearshore waters emitting CO2 and offshore waters absorbing CO2. The border in Tokyo Bay was extremely shifted toward the land-side. The shift is characteristic of highly urbanized coastal waters with an extensive sewage treatment system in the catchment area. Because highly urbanized coastal areas worldwide are expected to quadruple by 2050, coastal waters such as Tokyo Bay are expected to increase as well. Through extrapolation of Tokyo Bay data, CO2 emission from global estuaries would be expected to decrease roughly from the current 0.074 PgC year−1 to 0.014 PgC year−1 in 2050.
Fungus-growing termites efficiently decompose plant litter through their symbiotic relationship with basidiomycete fungi of the genus Termitomyces. Here, we investigated phenol-oxidizing enzymes in symbiotic fungi and fungus combs (a substrate used to cultivate symbiotic fungi) from termites belonging to the genera Macrotermes, Odontotermes, and Microtermes in Thailand, because these enzymes are potentially involved in the degradation of phenolic compounds during fungus comb aging. Laccase activity was detected in all the fungus combs examined as well as in the culture supernatants of isolated symbiotic fungi. Conversely, no peroxidase activity was detected in any of the fungus combs or the symbiotic fungal cultures. The laccase cDNA fragments were amplified directly from RNA extracted from fungus combs of five termite species and a fungal isolate using degenerate primers targeting conserved copper binding domains of basidiomycete laccases, resulting in a total of 13 putative laccase cDNA sequences being identified. The full-length sequences of the laccase cDNA and the corresponding gene, lcc1-2, were identified from the fungus comb of Macrotermes gilvus and a Termitomyces strain isolated from the same fungus comb, respectively. Partial purification of laccase from the fungus comb showed that the lcc1-2 gene product was a dominant laccase in the fungus comb. These findings indicate that the symbiotic fungus secretes laccase to the fungus comb. In addition to laccase, we report novel genes that showed a significant similarity with fungal laccases, but the gene product lacked laccase activity. Interestingly, these genes were highly expressed in symbiotic fungi of all the termite hosts examined.
Background
Glioblastoma-initiating cells (GICs) comprise a tumorigenic subpopulation of cells that are resistant to radio- and chemotherapies and are responsible for cancer recurrence. The aim of this study was to identify novel compounds that specifically eradicate GICs using a high throughput drug screening approach.
Methods
We performed a cell proliferation/death-based drug screening using 10 560 independent compounds. We identified dihydroorotate dehydrogenase (DHODH) as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays.
Results
Among the effective compounds, we identified 10580, which induced cell cycle arrest, decreased the expression of stem cell factors in GICs, and prevented tumorigenesis upon oral administration without any visible side effects. Mechanistic studies revealed that 10580 decreased pyrimidine nucleotide levels and enhanced sex determining region Y–box 2 nuclear export by antagonizing the enzyme activity of DHODH, an essential enzyme for the de novo pyrimidine synthesis.
Conclusion
In this study, we identified 10580 as a promising new drug against GICs. Given that normal tissue cells, in particular brain cells, tend to use the alternative salvage pathway for pyrimidine synthesis, our findings suggest that 10580 can be used for glioblastoma therapy without side effects.
Key Points
1. Chemical screening identified 10580 as a novel GIC-eliminating drug that targets DHODH, an essential enzyme for the de novo pyrimidine synthesis pathway.
2. Compound 10580 induced cell cycle arrest, apoptosis, and differentiation in GICs.
Termitomyces-related symbiotic basidiomycetes in the nests of fungus-growing termites (Macrotermitinae) of several genera in Thailand were cultivated and analyzed phylogenetically based on the DNA sequence of nuclear ribosomal RNA genes. The relationships of the symbiotic fungi with host termites and their locality were apparently complex, supporting intricate mechanisms for the termites to acquire the symbionts.
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