| 1 | An Earth-mass planet in a time of COVID-19:KMT-2020-BLG-0414Lb显示文摘We report the discovery of KMT-2020-BLG-0414 Lb,with a planet-to-host mass ratio q2=0.9-1.2×10-5=3-4 q⊕at 1σ,which is the lowest mass-ratio microlensing planet to date.Together with two other recent discoveries(4?q/q⊕?6),it fills out the previous empty sector at the bottom of the triangular(log s,log q)diagram,where s is the planet-host separation in units of the angular Einstein radiusθE.Hence,these discoveries call into question the existence,or at least the strength,of the break in the mass-ratio function that was previously suggested to account for the paucity of very low-q planets.Due to the extreme magnification of the event,Amax~1450 for the underlying single-lens event,its light curve revealed a second companion with q3~0.05 and|log s3|~1,i.e.,a factor~10 closer to or farther from the host in projection.The measurements of the microlens parallaxπE and the angular Einstein radiusθE allow estimates of the host,planet and second companion masses,(M1,M2,M3)~(0.3 M⊙,1.0 M⊕,17 MJ),the planet and second companion projected separations,(a⊥,2,a⊥,3)~(1.5,0.15 or 15)au,and system distance DL~1 kpc.The lens could account for most or all of the blended light(I~19.3)and so can be studied immediately with high-resolution photometric and spectroscopic observations that can further clarify the nature of the system.The planet was found as part of a new program of high-cadence follow-up observations of high-magnification events.The detection of this planet,despite the considerable difficulties imposed by COVID-19(two KMT sites and OGLE were shut down),illustrates the potential utility of this program. | Weicheng Zang Cheongho Han Iona Kondo Jennifer C.Yee Chung-Uk Lee Andrew Gould Shude Mao Leandro de Almeida Yossi Shvartzvald Xiangyu Zhang Michael D.Albrow Sun-Ju Chung Kyu-Ha Hwang Youn Kil Jung Yoon-Hyun Ryu In-Gu Shin Sang-Mok Cha Dong-Jin Kim Hyoun-Woo Kim Seung-Lee Kim Dong-Joo Lee Yongseok Lee Byeong-Gon Park Richard W.Pogge John Drummond Thiam-Guan Tan JoséDias do Nascimento Júnior Dan Maoz Matthew T.Penny Wei Zhu Ian A.Bond Fumio Abe Richard Barry David P.Bennett Aparna Bhattacharya Martin Donachie Hirosane Fujii Akihiko Fukui Yuki Hirao Yoshitaka Itow Rintaro Kirikawa Naoki Koshimoto Man Cheung Alex Li Yutaka Matsubara Yasushi Muraki Shota Miyazaki Greg Olmschenk Clément Ranc Nicholas J.Rattenbury Yuki Satoh Hikaru Shoji Stela Ishitani Silva Takahiro Sumi Daisuke Suzuki Yuzuru Tanaka Paul J.Tristram Tsubasa Yamawaki Atsunori Yonehara Andreea Petric Todd Burdullis Pascal Fouqué | 2021 | Research in Astronomy and Astrophysics2021，21，9： | 0 |
| 2 | A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy显示文摘Microphthalmia transcription factor(MITF)regulates melanocyte development and is the“lineage-specific survival”oncogene of melanoma.MITF is essential for melanoma initiation,progression,and relapse and has been considered an important therapeutic target;however,direct inhibition of MITF through small molecules is considered impossible,due to the absence of a ligand-binding pocket for drug design.Here,our structural analyses show that the structure of MITF is hyperdynamic because of its out-of-register leucine zipper with a 3-residue insertion.The dynamic MITF is highly vulnerable to dimer-disrupting mutations,as we observed that MITF loss-of-function mutations in human Waardenburg syndrome type 2 A are frequently located on the dimer interface and disrupt the dimer forming ability accordingly.These observations suggest a unique opportunity to inhibit MITF with small molecules capable of disrupting the MITF dimer.From a high throughput screening against 654,650 compounds,we discovered compound TT-012,which specifically binds to dynamic MITF and destroys the latter’s dimer formation and DNA-binding ability.Using chromatin immunoprecipitation assay and RNA sequencing,we showed that TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells.In addition,TT-012 inhibits the growth of high-MITF melanoma cells,and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models.Together,this study demonstrates a unique hyperdynamic dimer interface in melanoma oncoprotein MITF,and reveals a novel approach to therapeutically suppress MITF activity. | Zaizhou Liu Kaige Chen Jun Dai Peng Xu Wei Sun Wanlin Liu Zhixin Zhao Steven P.Bennett Peifeng Li Tiancheng Ma Yuqi Lin Akinori Kawakami Jing Yu Fei Wang Chunxi Wang Miao Li Peter Chase Peter Hodder Timothy P.Spicer Louis Scampavia Chunyang Cao Lifeng Pan Jiajia Dong Yong Chen Biao Yu Min Guo Pengfei Fang David E.Fisher Jing Wang | 2023 | Cell Research2023，33，1： | 0 |
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