CRISPR-Cas9システムを用いた味覚受容体発現調節物質のスクリーニング系の開発

Taste recognition mediated by taste receptors is critical for the survival of animals in nature and is an important determinant of nutritional status and quality of life in humans. However, many factors including aging, diabetes, zinc deficiency, infection with influenza or cold viruses, and chemotherapy can trigger dysgeusia, for which a standard treatment has not been established. We here established an engineered strain of medaka (Oryzias latipes) that expresses green fluorescent protein (GFP) from the endogenous taste 1 receptor 3 (T1R3) gene locus with the use of the CRISPR-Cas9 system. This T1R3-GFP knock-in (KI) strain allows direct visualization of expression from this locus by monitoring of GFP fluorescence. The pattern of GFP expression in the T1R3-GFP KI fish thus mimicked that of endogenous T1R3 gene expression. Furthermore, exposure of T1R3-GFP KI medaka to water containing monosodium glutamate or the anticancer agent 5-fluorouracil resulted in an increase or decrease, respectively, in GFP fluorescence intensity, effects that also recapitulated those on T1R3 mRNA abundance. Finally, screening for agents that affect GFP fluorescence intensity in T1R3-GFP KI medaka identified tryptophan as an amino acid that increases T1R3 gene expression. The establishment of this screening system for taste receptor expression in medaka provides a new tool for the development of potential therapeutic agents for dysgeusia

Performance Analysis of CRC Codes for Systematic and Nonsystematic Polar Codes with List Decoding

Successive cancellation list (SCL) decoding of polar codes is an effective approach that can significantly outperform the original successive cancellation (SC) decoding, provided that proper cyclic redundancy-check (CRC) codes are employed at the stage of candidate selection. Previous studies on CRC-assisted polar codes mostly focus on improvement of the decoding algorithms as well as their implementation, and little attention has been paid to the CRC code structure itself. For the CRC-concatenated polar codes with CRC code as their outer code, the use of longer CRC code leads to reduction of information rate, whereas the use of shorter CRC code may reduce the error detection probability, thus degrading the frame error rate (FER) performance. Therefore, CRC codes of proper length should be employed in order to optimize the FER performance for a given signal-to-noise ratio (SNR) per information bit. In this paper, we investigate the effect of CRC codes on the FER performance of polar codes with list decoding in terms of the CRC code length as well as its generator polynomials. Both the original nonsystematic and systematic polar codes are considered, and we also demonstrate that different behaviors of CRC codes should be observed depending on whether the inner polar code is systematic or not

Enhanced gene activation by Notch and BMP signaling cross-talk

The signaling systems of Notch and bone morphogenetic protein (BMP) are highly conserved from flies to mammals and have been shown to be important in the development of multiple organs. For instance, in the fate determination of mouse neuroepithelial cells, Notch signaling plays a role in keeping the progenitors from differentiating into neurons. BMP is also known to inhibit neuronal differentiation. In this paper, we show that BMP2 enhances Notch-induced transcriptional activation of Hes-5 and Hesr-1 in mouse neuroepithelial cells. BMP2 stimulation, in addition to the introduction of the intracellular domain of Notch (NIC), resulted in enhanced activation of the Hes-5 gene promoter. RBP-Jκ binding to its target sequence is important not only for Notch signaling, but also for BMP2 signaling, to activate the Hes-5 gene promoter. Smad1, a Smad species that is activated by BMP2, barely interacted with NIC, but did form a complex with NIC in the simultaneous presence of the coactivators P/CAF and p300. Recruitment of p300 to the NIC-containing complex was facilitated by activated Smad1, which is suggested to contribute to BMP2-mediated enhancement of Notch-induced Hes-5 expression. These data suggest a novel functional cooperation between Notch signaling and BMP signaling