Moreover, about 70% of colorectal cancers with a KRAS mutation also have an excess of small chemical marks on other genes, some of which are known to suppress the growth of tumors. Mutations that change the gene encoding a protein called KRAS are found in many different types of cancer. Like these other cancers, this disease is caused by mutations to genes that allow cells to multiply in an out of control manner. Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.Ĭolorectal cancer, which affects the large intestine, is a leading cause of cancer deaths worldwide, ranking fourth after cancers of the lung, stomach, and liver. KRAS promotes silencing through upregulation of ZNF304, which drives DNA binding. Promoter-bound ZNF304 recruits a corepressor complex that includes the DNA methyltransferase DNMT1, resulting in DNA hypermethylation and transcriptional silencing. In KRAS-positive human CRC cell lines and tumors, ZNF304 is bound at the promoters of INK4-ARF and other CIMP genes. In this study, we perform an RNA interference screen and identify ZNF304, a zinc-finger DNA-binding protein, as the pivotal factor required for INK4-ARF silencing and CIMP in CRCs containing activated KRAS. Among the CIMP genes are the tumor suppressors p14 ARF, p15 INK4B, and p16 INK4A, encoded by the INK4-ARF locus. The factors involved in, and the mechanistic basis of, CIMP is not understood. Di Renzo, F.Approximately 70% of KRAS-positive colorectal cancers (CRCs) have a CpG island methylator phenotype (CIMP) characterized by aberrant DNA hypermethylation and transcriptional silencing of many genes.
LIGO (Observatory : Massachusetts Institute of Technology)Ībbott, B. MIT Kavli Institute for Astrophysics and Space Research “Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A.” The Astrophysical Journal 848, 2 (October 2017): L13 © 2017 The American Astronomical Society Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817AĪbbott, B.
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Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1-1.4 per year during the 2018-2019 observing run and 0.3-1.7 per year at design sensitivity.Ĭreative Commons Attribution 3.0 Unported license A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays.
We use the observed time delay of (+1.74☐.05)between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between -3 × 10 -15 and +7 × 10 -16 times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is 5.0 × 10 -8. On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory.
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