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Although lithium has long been one of the most widely used pharmacological agents in psychiatry, its mechanisms of action at the cellular and molecular levels remain poorly understood. One of the targets of Li + is the phosphoinositide pathway, but whereas the impact of Li + on inositol lipid metabolism is well documented, information on physiological effects at the cellular level is lacking. We examined in two mammalian cell lines the effect of acute Li + exposure on the mobilization of internal Ca 2+ and phospholipase C (PLC)-dependent membrane conductances. We first corroborated by Western blots and immunofluorescence in HEK293 cells the presence of key signaling elements of a muscarinic PLC pathway (M1AchR, G q , PLC-β1, and IP 3 Rs). Stimulation with carbachol evoked a dose-dependent mobilization of Ca, as determined with fluorescent indicators. This was due to release from internal stores and proved susceptible to the PLC antagonist U73122. Li + exposure reproducibly potentiated the Ca response in a concentration-dependent manner extending to the low millimolar range. To broaden those observations to a neuronal context and probe potential Li modulation of electrical signaling, we next examined the cell line SHsy5y. We replicated the potentiating effects of Li on the mobilization of internal Ca, and, after characterizing the basic properties of the electrical response to cholinergic stimulation, we also demonstrated an equally robust upregulation of muscarinic membrane currents. Finally, by directly stimulating the signaling pathway at different links downstream of the receptor, the site of action of the observed Li effects could be narrowed down to the G protein and its interaction with PLC-β. These observations document a modulation of G q /PLC/IP 3 -mediated signaling by acute exposure to lithium, reflected in distinct physiological changes in cellular responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sánchez Triviño, Landinez, Duran, Gomez and Nasi.)

This study reconsiders the number of effective channels in contemporary cochlear implants. Subjects listened to matrix sentences with a competing talker using their clinical map (up to 22 electrodes) and reduced-channel maps using 12, 8, and 4 electrodes. Spectro-temporal modulation thresholds and reading span were measured to explore intersubject variability. Results show that speech understanding significantly improved with increasing active electrodes up to 22, particularly for subjects with better spectro-temporal resolution. These findings suggest some listeners may be able to utilize the full electrode array and may not be limited to eight channels of information as indicated in previous studies.

The low number of oocytes collected from unstimulated donors by ovum pick-up means that embryos produced from each individual female have to be cultured individually or in very small groups. However, it has been demonstrated that single-embryo culture is less efficient than embryo culture in groups. To overcome this limitation, we developed a direct embryo-tagging system, which allows the collective culture of embryos from different origins whilst preserving their pedigree. Presumptive bovine zygotes were tagged with eight wheat-germ agglutinin biofunctionalised polysilicon barcodes attached to the outer surface of the zona pellucida (ZP). Four different barcodes were used to encode groups of 20-25 embryos, which were then cultured in the same drop. Cleavage, Day-7 and Day-8 blastocysts and barcode retention rates were assessed. In addition, Day-7 blastocysts were vitrified and warmed. Barcode attachment to the ZP of bovine embryos affected neither in vitro embryo development nor post-warming survival of the tagged embryos. All the embryos maintained barcodes attached until Day 8 of culture (3.63±0.37 barcodes per embryo) and could be identified. In conclusion, identification of embryos by barcodes attached to the ZP is feasible and will allow the culture of embryos from different donors in the same drop.

While cochlear implants (CIs) usually provide high levels of speech recognition in quiet, speech recognition in noise remains challenging. To overcome these difficulties, it is important to understand how implanted listeners separate a target signal from interferers. Stream segregation has been studied extensively in both normal and electric hearing, as a function of place of stimulation. However, the effects of pulse rate, independent of place, on the perceptual grouping of sequential sounds in electric hearing have not yet been investigated. A rhythm detection task was used to measure stream segregation. The results of this study suggest that while CI listeners can segregate streams based on differences in pulse rate alone, the amount of stream segregation observed decreases as the base pulse rate increases. Further investigation of the perceptual dimensions encoded by the pulse rate and the effect of sequential presentation of different stimulation rates on perception could be beneficial for the future development of speech processing strategies for CIs.