| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
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| 4. |
- Liang, Lin, et al.
(author)
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Non-Interpenetrated Single-Crystal Covalent Organic Frameworks
- 2020
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:41, s. 17991-17995
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Journal article (peer-reviewed)abstract
- Growth of covalent organic frameworks (COFs) as single crystals is extremely challenging. Inaccessibility of open-structured single-crystal COFs prevents the exploration of structure-oriented applications. Herein we report for the first time a non-interpenetrated single-crystal COF, LZU-306, which possesses the open structure constructed exclusively via covalent assembly. With a high void volume of 80 %, LZU-306 was applied to investigate the intrinsic dynamics of reticulated tetraphenylethylene (TPE) as the individual aggregation-induced-emission moiety. Solid-state(2)H NMR investigation has determined that the rotation of benzene rings in TPE, being the freest among the reported cases, is as fast as 1.0x10(4) Hz at 203 K to 1.5x10(7) Hz at 293 K. This research not only explores a new paradigm for single-crystal growth of open frameworks, but also provides a unique matrix-isolation platform to reticulate functional moieties into a well-defined and isolated state.
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| 5. |
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| 6. |
- Wang, Ling, et al.
(author)
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Perfluorooctanesulfonate Induces Hepatomegaly and Lipoatrophy in Mice through Phosphoenolpyruvate Carboxykinase-Mediated Glyceroneogenesis Inhibition
- 2020
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In: Environmental Science and Technology Letters. - : American Chemical Society (ACS). - 2328-8930. ; 7:3, s. 185-190
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Journal article (peer-reviewed)abstract
- Perfluorooctansulfonate (PFOS) is a persistent organic pollutant that has attracted a great deal of attention due to toxic effects such as its lipid metabolism-disrupting potential. Exposure to PFOS can cause hepatomegaly and lipoatrophy in mice, but the underlying mechanisms are still unknown. Considering that glyceroneogenesis is the essential pathway for balancing the triglyceride (TG) cycle between liver and white adipose tissue (WAT), we speculate that PFOS acts via glyceroneogenesis inhibition to alter TG metabolism in the two tissues. Combining gene expression, protein expression, an enzyme activity assay, and molecular docking analysis, we report here that PFOS can interact with cytosolic phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of glyceroneogenesis. Specifically, by repression of PEPCK, PFOS can inhibit the glyceroneogenesis process and thus decrease the glyceroneogenesis-derived glycerol level, leading to a reduced re-esterified TG level and causing atrophy in WAT. Moreover, in PFOS-exposed liver tissue, despite the fact that free glycerol and fatty acids released from WAT were being used for TG synthesis, the export of TG slowed. This eventually resulted in the continuous lipolysis of WAT and accumulation of lipid in the liver. PEPCK can be used as a key biomarker to assess the lipid metabolism disorders induced by other conventional and emerging per- and polyfluoroalkyl substances.
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| 7. |
- Wang, Yu-Cheng, et al.
(author)
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Porous Carbon Membrane-Supported Atomically Dispersed Pyrrole-Type Fe-N-4 as Active Sites for Electrochemical Hydrazine Oxidation Reaction
- 2020
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In: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 16:31
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Journal article (peer-reviewed)abstract
- The rational design of catalytically active sites in porous materials is essential in electrocatalysis. Herein, atomically dispersed Fe-N-x sites supported by hierarchically porous carbon membranes are designed to electrocatalyze the hydrazine oxidation reaction (HzOR), one of the key techniques in electrochemical nitrogen transformation. The high intrinsic catalytic activity of the Fe-N-x single-atom catalyst together with the uniquely mixed micro-/macroporous membrane support positions such an electrode among the best-known heteroatom-based carbon anodes for hydrazine fuel cells. Combined with advanced characterization techniques, electrochemical probe experiments, and density functional theory calculation, the pyrrole-type Fe-N-4 structure is identified as the real catalytic site in HzOR.
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| 8. |
- Wu, ZC, et al.
(author)
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Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake
- 2020
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:5, s. 1693-1708
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Journal article (peer-reviewed)abstract
- Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD–HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD–HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
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| 9. |
- Zhang, Shao-jie, et al.
(author)
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Genomic regions under selection in the feralization of the dingoes
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Dingoes are wild canids living in Australia, originating from domestic dogs. They have lived isolated from both the wild and the domestic ancestor, making them a unique model for studying feralization. Here, we sequence the genomes of 10 dingoes and 2 New Guinea Singing Dogs. Phylogenetic and demographic analyses show that dingoes originate from dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia around 8300 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identifies 50 positively selected genes enriched in digestion and metabolism, indicating a diet change during feralization of dingoes. Thirteen of these genes have shifted allele frequencies compared to dogs but not compared to wolves. Functional assays show that an A-to-G mutation in ARHGEF7 decreases the endogenous expression, suggesting behavioral adaptations related to the transitions in environment. Our results indicate that the feralization of the dingo induced positive selection on genomic regions correlated to neurodevelopment, metabolism and reproduction, in adaptation to a wild environment.
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| 10. |
- Bailey, Matthew H., et al.
(author)
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Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
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