| 1. |
- Charitou, Theodosia, et al.
(författare)
-
Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRAS(G13D) mutation
- 2019
-
Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:1, s. 37-50
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFRtargeted therapies. METHODS: To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRAS(G13D) allele (mtKRAS). RESULTS: RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGF alpha stimulation, which was associated with an unexpected downregulation of genes involved in a range of anabolic processes. While TGF alpha treatment strongly activated protein synthesis in wtKRAS cells, protein synthesis was not activated above basal levels in the TGF alpha-treated mtKRAS cells. This was likely due to the defective activation of the mTORC1 and other pathways by TGF alpha in mtKRAS cells, which was associated with impaired activation of PKB signalling and a transient induction of AMPK signalling. CONCLUSIONS: We have found that mtKRAS cells are substantially rewired at the transcriptional, translational and metabolic levels and that this rewiring may reveal new vulnerabilities in oncogenic KRAS CRC cells that could be exploited in future.
|
|
| 2. |
- Kim, Shi Hyeong, et al.
(författare)
-
Harvesting temperature fluctuations as electrical energy using torsional and tensile polymer muscles
- 2015
-
Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 8, s. 3336-3344
-
Tidskriftsartikel (refereegranskat)abstract
- Diverse means have been deployed for harvesting electrical energy from mechanical actuation produced by low-grade waste heat, but cycle rate, energy-per-cycle, device size and weight, or cost have limited applications. We report the electromagnetic harvesting of thermal energy as electrical energy using thermally powered torsional and tensile artificial muscles made from inexpensive polymer fibers used for fishing line and sewing thread. We show that a coiled 27 μm-diameter nylon muscle fiber can be driven by 16.7 °C air temperature fluctuations to spin a magnetic rotor to a peak torsional rotation speed of 70 000 rpm for over 300 000 heating–cooling cycles without performance degradation. By employing resonant fluctuations in air temperature of 19.6 °C, an average output electrical power of 124 W per kg of muscle was realized. Using tensile actuation of polyethylene-based coiled muscles and alternating flows of hot and cold water, up to 1.4 J of electrical energy was produced per cycle. The corresponding per cycle electric energy and peak power output, per muscle weight, were 77 J kg−1 and 28 W kg−1, respectively.
|
|
