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Pokharel, P.

Publications and source records attributed to Pokharel, P..

3 recordsLinked to original sources

Speaker-induced suppression in EEG during a naturalistic reading and listening task

Speaking elicits a suppressed neural response when compared to listening to others speech, a phenomenon known as speaker-induced suppression (SIS). Previous research has focused on investigating SIS at constrained levels of linguistic representation, such as the individual phoneme and word level. Here we present scalp EEG data from a dual speech perception and production task where participants read sentences aloud then listened to playback of themselves reading those sentences. Playback was separated into predictable repetition of the previous trial and unpredictable, randomized repetition of a former trial to investigate the role predictive processing plays in SIS. Concurrent EMG was recorded to control for movement artifact during speech production. In line with previous research, event-related potential analyses at the sentence level demonstrated suppression of early auditory components of the EEG for production compared to perception. To evaluate whether specific neural representations contribute to SIS (in contrast with a global gain change), we fit linear encoding models that predicted scalp EEG based on phonological features, EMG activity, and task condition. We found that phonological features were encoded similarly between production and perception. However, this similarity was only observed when controlling for movement by using the EMG response as an additional regressor. Our results suggest SIS is at the representational level a global gain change between perception and production, not the suppression of specific characteristics of the neural response. We also detail some important considerations when analyzing EEG during continuous speech production.

neuroscience↗

Dietary cardenolides enhance growth and change the direction of the fecundity-longevity trade-off in milkweed bugs (Heteroptera: Lygaeinae)

O_LISequestration, i.e., the accumulation of plant toxins into body tissues for defence, is primarily observed in specialised insects. Sequestration was frequently predicted to incur a physiological cost mediated by increased exposure to plant toxins and may require resistance traits different from those of non-sequestering insects. Alternatively, sequestering species could experience a cost in the absence of toxins due to selection on physiological homeostasis under permanent exposure of sequestered toxins in body tissues. C_LIO_LIMilkweed bugs (Heteroptera: Lygaeinae) sequester high amounts of plant-derived cardenolides. Although being potent inhibitors of the ubiquitous animal enzyme Na+/K+-ATPase, milkweed bugs can tolerate cardenolides by means of resistant Na+/K+-ATPases. Both adaptations, resistance and sequestration, are ancestral traits shared by most species of the Lygaeinae. C_LIO_LIUsing four milkweed bug species and the related European firebug (Pyrrhocoris apterus) showing different combinations of the traits cardenolide resistance and cardenolide sequestration, we set out to test how the two traits affect larval growth upon exposure to dietary cardenolides in an artificial diet system. While cardenolides impaired the growth of P. apterus nymphs neither possessing a resistant Na+/K+-ATPase nor sequestering cardenolides, growth was not affected in the non-sequestering milkweed bug Arocatus longiceps, which possesses a resistant Na+/K+-ATPase. Remarkably, cardenolides increased growth in the sequestering dietary specialists Caenocoris nerii and Oncopeltus fasciatus but not in the sequestering dietary generalist Spilostethus pandurus, which all possess a resistant Na+/K+-ATPase. C_LIO_LIWe then assessed the effect of dietary cardenolides on additional life history parameters, including developmental speed, the longevity of adults, and reproductive success in O. fasciatus. Remarkably, nymphs under cardenolide exposure developed substantially faster and lived longer as adults. However, fecundity of adults was reduced when maintained on cardenolide-containing diet for their entire life-time but not when adults were transferred to non-toxic sunflower seeds. C_LIO_LIWe speculate that the resistant Na+/K+-ATPase of milkweed bugs is selected for working optimally in a toxic environment, i.e. when sequestered cardenolides are stored in the body tissues. Contrary to the assumption that toxins sequestered for defence produce a physiological burden, our data suggest that they can even increase fitness in specialised insects. C_LI

ecology↗

Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of reprogramming outcome

Cellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy, as well as for expanding our understanding of the general principles of gene regulation. MYOD-mediated myogenic reprogramming, which converts many cell types into contractile myotubes, remains one of the best characterized model system for direct conversion by defined factors. However, why MYOD can efficiently convert some cell types into myotubes but not others remains poorly understood. Here, we analyze MYOD-mediated reprogramming of human fibroblasts at pseudotemporal resolution using single-cell RNA-Seq. Successfully reprogrammed cells navigate a trajectory with two branches that correspond to two barriers to reprogramming, with cells that select incorrect branches terminating at aberrant or incomplete reprogramming outcomes. Differential analysis of the major branch points alongside alignment of the successful reprogramming path to a primary myoblast trajectory revealed Insulin and BMP signaling as crucial molecular determinants of an individual cells reprogramming outcome, that when appropriately modulated, increased efficiency more than five-fold. Our single-cell analysis reveals that MYOD is sufficient to reprogram cells only when the extracellular milieu is favorable, supporting MYOD with upstream signaling pathways that drive normal myogenesis in development.

genomics↗