| 1. |
- Adyari, Bob, et al.
(author)
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Strong impact of micropollutants on prokaryotic communities at the horizontal but not vertical scales in a subtropical reservoir, China
- 2020
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 721
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Journal article (peer-reviewed)abstract
- Micropollutants have become of great concern, because of their disrupting effects on the structure and function of microbial communities. However, little is known about the relative importance of trace micropollutants on the aquatic prokaryotic communities as compared to the traditional physico-chemical characteristics, especially at different spatial dimensions. Here, we investigated free-living (FL) and particle-associated (PA) prokaryotic communities in a subtropical water reservoir, China, across seasons at horizontal (surface water) and vertical (depth-profile) scales by using 16S rRNA gene amplicon sequencing. Our results showed that the shared variances of physico-chemicals and micropollutants explained majority of the spatial variations in prokaryotic communities, suggesting a strong joint effect of the two abiotic categories on reservoir prokaryotic communities. Micropollutants appeared to exert strong independent influence on the core sub-communities (i.e., abundant and wide-spread taxa) than on the satellite (i.e., less abundant and narrow-range taxa) counterparts. The pure effect of micropollutants on both core and satellite sub-communities from FL and PA fractions was similar to 1.5 folds greater than that of physico-chemical factors at the horizontal scale, whereas an opposite effect was observed at the vertical scale. Moreover, eight micropollutants including anti-fungal agents, antibiotics, bisphenol analogues, stimulant and UV-filter were identified as the major disrupting compounds with strong associations with core taxa of typical freshwater prokaryotes. Altogether, we concluded that the ecological disrupting effects of micropollutants on prokaryotic communities may vary along horizontal and vertical dimensions in freshwater ecosystems.
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| 3. |
- Zhou, Weihua, et al.
(author)
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Purine metabolism regulates DNA repair and therapy resistance in glioblastoma
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
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