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  • Multisensory Signals Inhibit Pupillary Light Reflex: Evidence from Pupil Oscillation

    分类: 心理学 >> 认知心理学 提交时间: 2021-04-27

    摘要: Multisensory integration, which enhances the stimulus saliency at the early stage of processing hierarchy, is recently shown to produce a larger pupil size than its unisensory constituents. Theoretically, any modulation on pupil size ought to be associated with the sympathetic and parasympathetic pathways that are sensitive to lights. But it remains poorly understood how pupillary light reflex is changed in a multisensory context. The present study evoked an oscillation of pupillary light reflex by periodically changing the luminance of a visual stimulus at 1.25 Hz. It was found that such induced pupil oscillation was substantially attenuated when the bright but not the dark phase of the visual flicker was periodically and synchronously presented with a burst of tones. This inhibition effect persisted when the visual flicker was task-irrelevant and out of attentional focus, but disappeared when the visual flicker was moved from the central field to the periphery. These findings not only offer a comprehensive characterization of the multisensory impact on pupil response to lightness, but also provide valuable clues to the individual contributions of the sympathetic and parasympathetic pathways to multisensory modulation of pupil size.

  • Cryo-EM structures of adenosine receptor A3AR bound to selective agonists

    分类: 药物科学 >> 结构生物学 提交时间: 2024-04-17

    摘要: The adenosine A3 receptor (A3AR) belongs to a subfamily of G protein-coupled receptors and is an important therapeutic target for conditions including inflammation and cancer. The clinical compounds CF101 and CF102 are potent and selective A3AR agonists, but the structural basis of their recognition was unknown. Here we present the cryogenic electron microscopy structures of the full-length human A3AR bound to CF101 and CF102 at 3.3-3.2 Å resolution in complex with heterotrimeric Gi protein. These agonists bind within the orthosteric pocket, with their adenine components engaging in conserved interactions while their substituted 3-iodobenzyl groups exhibit different orientations. Swapping extracellular loop 3 (ECL3) of A3AR onto other adenosine receptor subtypes enabled CF101/CF102 binding and receptor activaton, and mutations in key residues, including His3.37, Ser5.42 and Ser6.52 that form a unique subpocket in A3AR, abolished receptor activation, highlighting these structural elements are critical for ligand selectivity. Compared to inactive A2AAR, the A3AR structures reveal conserved mechanism of receptor activation, including an outward shift of TM6. These structures provide key insights into molecular recognition and signaling mechanisms of A3AR, which should aid rational design of subtype-selective ligands targeting this important class of adenosine receptors. 

  • Identifications of RR Lyrae stars and Quasars from the simulated data of Mephisto-W Survey

    分类: 天文学 >> 天文学 提交时间: 2023-02-19

    摘要: We have investigated the feasibilities and accuracies of the identifications of RR Lyrae stars and quasars from the simulated data of the Multi-channel Photometric Survey Telescope (Mephisto) W Survey. Based on the variable sources light curve libraries from the Sloan Digital Sky Survey (SDSS) Stripe 82 data and the observation history simulation from the Mephisto-W Survey Scheduler, we have simulated the $uvgriz$ multi-band light curves of RR Lyrae stars, quasars and other variable sources for the first year observation of Mephisto-W Survey. We have applied the ensemble machine learning algorithm Random Forest Classifier (RFC) to identify RR Lyrae stars and quasars, respectively. We build training and test samples and extract ~ 150 features from the simulated light curves and train two RFCs respectively for the RR Lyrae star and quasar classification. We find that, our RFCs are able to select the RR Lyrae stars and quasars with remarkably high precision and completeness, with $purity$ = 95.4 per cent and $completeness$ = 96.9 per cent for the RR Lyrae RFC and $purity$ = 91.4 per cent and $completeness$ = 90.2 per cent for the quasar RFC. We have also derived relative importances of the extracted features utilized to classify RR Lyrae stars and quasars.

  • Decoding homodimerization and antidepressant recognition at the norepinephrine transporter

    分类: 药物科学 >> 结构生物学 提交时间: 2024-04-27

    摘要: 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.