Subjects: Pharmaceutical Science >> Structural Biology submitted time 2024-04-27
Heng Zhang
Yuling Yin
Tianwei Zhang
Canrong Wu
Wen Hu
Xinheng He
Benxun Pan
Sanshan Jin
Qingning Yuan
H. Eric Xu
Yi Jiang
Abstract： The norepinephrine transporter (NET) plays a pivotal role in regulating neurotransmitter balance and is critical for normal physiology and neurobiology. Dysfunction of NET has been implicated in numerous neuropsychiatric diseases including depression, anxiety, attention deficit hyperactivity disorder, and Parkinson’s disease. Here we report cryo-EM structures of NET in apo and substrate-bound forms, as well as complexes with six antidepressants. The structures reveal an unexpected NET dimer interface predominantly mediated by cholesterol and lipid molecules. The substrate norepinephrine is found to bind deep within the central binding pocket, with its amine group interacting with a conserved aspartate. The structures also provide insight into antidepressant recognition, including how subtle differences in binding poses confer selectivity over other monoamine transporters. Together these breakthrough findings significantly advance our understanding of NET regulation and inhibition, providing templates for designing improved antidepressants to treat neuropsychiatric disorders.
Subjects: Astronomy >> Astrophysical processes submitted time 2023-02-19
Xunchuan Liu
Tie Liu
Zhiqiang Shen
Sheng-Li Qin
Qiuyi Luo
Yu Cheng
Qilao Gu
Tianwei Zhang
Fengyao Zhu
Sheng-Yuan Liu
Xing Lu
Rongbing Zhao
Weiye Zhong
Yajun Wu
Juan Li
Zhang Zhao
Jinqing Wang
Qinghui Liu
Bo Xia
Bin Li
Abstract： We have conducted a line survey towards Orion KL using the Q-band receiver of Tianma 65 m radio telescope (TMRT), covering 34.8--50 GHz with a velocity resolution between 0.79 km s$^{-1}$ and 0.55 km s$^{-1}$ respectively. The observations reach a sensitivity on the level of 1-8 mK, proving that the TMRT is sensitive for conducting deep line surveys. In total, 597 Gaussian features are extracted. Among them, 177 radio recombination lines (RRLs) are identified, including 126, 40 and 11 RRLs of hydrogen, helium and carbon, with a maximum $\Delta n$ of 16, 7, and 3, respectively. The carbon RRLs are confirmed to originate from photodissociation regions with a $V_{\rm LSR}\sim$9 km s$^{-1}$. In addition, 371 molecular transitions of 53 molecular species are identified. Twenty-one molecular species of this survey were not firmly detected in the Q band by Rizzo et al. (2017), including species such as H$_2$CS, HCOOH, C$_2$H$_5$OH, H$_2^{13}$CO, H$_2$CCO, CH$_3$CHO, CH$_2$OCH$_2$, HCN $v_2=1$, and CH$_3$OCHO $v_t=1$. In particular, the vibrationally excited states of ethyl cyanide (C$_2$H$_5$CN $v$13/$v$21) are for the first time firmly detected in the Q band. NH$_3$ (15,15) and (16,16) are identified, and they are so far the highest transitions of the NH$_3$ inversion lines detected towards Orion KL. All the identified lines can be reproduced by a radiative transfer model.
Peer Review Status:
Awaiting Review
Subjects: Astronomy >> Astrophysical processes submitted time 2023-02-19
Fengwei Xu
Yuefang Wu
Tie Liu
Xunchuan Liu
Chao Zhang
Jarken Esimbek
Sheng-Li Qin
Di Li
Ke Wang
Jinghua Yuan
Fanyi Meng
Tianwei Zhang
David Eden
K. Tatematsu
Neal J. Evans
Paul. F. Goldsmith
Qizhou Zhang
C. Henkel
Hee-Weon Yi
Jeong-Eun Lee
Abstract： Gas at high Galactic latitude is a relatively little-noticed component of the interstellar medium. In an effort to address this, forty-one Planck Galactic Cold Clumps at high Galactic latitude (HGal; $|b|>25^{\circ}$) were observed in $^{12}$CO, $^{13}$CO and C$^{18}$O J=1-0 lines, using the Purple Mountain Observatory 13.7-m telescope. $^{12}$CO (1-0) and $^{13}$CO (1-0) emission was detected in all clumps while C$^{18}$O (1-0) emission was only seen in sixteen clumps. The highest and average latitudes are $71.4^{\circ}$ and $37.8^{\circ}$, respectively. Fifty-one velocity components were obtained and then each was identified as a single clump. Thirty-three clumps were further mapped at 1$^\prime$ resolution and 54 dense cores were extracted. Among dense cores, the average excitation temperature $T_{\mathrm{ex}}$ of $^{12}$CO is 10.3 K. The average line widths of thermal and non-thermal velocity dispersions are $0.19$ km s$^{-1}$ and $0.46$ km s$^{-1}$ respectively, suggesting that these cores are dominated by turbulence. Distances of the HGal clumps given by Gaia dust reddening are about $120-360$ pc. The ratio of $X_{13}$/$X_{18}$ is significantly higher than that in the solar neighbourhood, implying that HGal gas has a different star formation history compared to the gas in the Galactic disk. HGal cores with sizes from $0.01-0.1$ pc show no notable Larson's relation and the turbulence remains supersonic down to a scale of slightly below $0.1$ pc. None of the HGal cores which bear masses from 0.01-1 $M_{\odot}$ are gravitationally bound and all appear to be confined by outer pressure.
Peer Review Status:Awaiting Review
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