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Galazyuk, A.

Publications and source records attributed to Galazyuk, A..

3 recordsLinked to original sources

Responses of inferior colliculus neurons to notched noises in awake mice: putative neural correlates of auditory enhancement and Zwicker tone

Sensory systems are well adapted to constantly changing statistics of the environment and to process specific spectral features of sounds, such as spectral notch (i.e. low energy frequency band) embedded in broadband stimuli. Spectral notches can be added to the stimulus spectrum due to filtering by the outer ear, and can be used as monaural cues related to head or pinna position for localizing sound sources. In addition, broadband sounds with spectral notch are known to produce auditory enhancement, a perceptual phenomenon in which a target within a spectrally notched masker can become salient if preceded by a copy of the masker. Notched noise can also produce an auditory illusion, called Zwicker Tone (ZT), which is perceived immediately after stimulation and whose pitch corresponds to the spectral notch. The present study aimed to further investigate the mechanisms of auditory enhancement, including those of ZT, in the inferior colliculus of awake mice. We show that neural activity can be strongly suppressed during NN stimulation and enhanced immediately after NN stimulation. These effects depend on notch center frequency relative to the best frequency of neurons, stimulus level and notch width. Our results are consistent with the mechanisms described for post-inhibitory rebound in the central auditory system: NN could hyperpolarize the membrane potential, which can then activate several cationic conductances, leading to a rebound of neural activity. We discuss auditory enhancement and ZT as collateral effects of an essential neural mechanism aimed at enhancing the central representation of acoustic spectral contrasts.

neuroscience↗

Limited Cell-Autonomous Anticancer Mechanisms in Long-Lived Bats

Bats are remarkably long-lived for their size with many species living more than 20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigated requirements for malignant transformation in primary bat fibroblasts in four bat species - little brown bat (Myotis lucifugus), big brown bat (Eptesicus fuscus), cave nectar bat (Eonycteris spelaea) and Jamaican fruit bat (Artibeus jamaicensis) - spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence and express active telomerase. Bat cells displayed attenuated stress induced premature senescence with a dampened secretory phenotype. Unexpectedly, we discovered that bat cells could be readily transformed by only two oncogenic perturbations or "hits": inactivation of either p53 or pRb and activation of oncogenic RASV12. This was surprising because other long-lived mammalian species require up to five hits for malignant transformation. Additionally, bat fibroblasts exhibited increased p53 and MDM2 transcript levels, and elevated p53-dependent apoptosis. The little brown bat showed a genomic duplication of the p53 gene. We hypothesize that bats evolved enhanced p53 activity through gene duplications and transcriptional upregulation as an additional anti-cancer strategy, similar to elephants. In summary, active telomerase and the small number of oncogenic hits sufficient to malignantly transform bat cells suggest that in vivo bats rely heavily on non-cell autonomous mechanisms of tumor suppression.

cell biology↗

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Frugivory evolved multiple times in mammals, including bats. However, the cellular and molecular components driving it remain largely unknown. Here, we used integrative single-cell sequencing on insectivorous and frugivorous bat kidneys and pancreases and identified key cell population, gene expression and regulatory element differences associated with frugivorous adaptation that also relate to human disease, particularly diabetes. We found an increase in collecting duct cells and differentially active genes and regulatory elements involved in fluid and electrolyte balance in the frugivore kidney. In the frugivorous pancreas, we observed an increase in endocrine and a decrease in exocrine cells and differences in genes and regulatory elements involved in insulin regulation. Combined, our work provides novel insights into frugivorous adaptation that also could be leveraged for therapeutic purposes.

genomics↗