Biology subjects

Natarajan, N.

Publications and source records attributed to Natarajan, N..

4 recordsLinked to original sources

bioRxiv2026

Feeling the Music: Preceding Vibroacoustic Stimulation Modulates Oscillatory Brain Dynamics During Music Listening

Background: Although typically considered an auditory experience, music listening engages multiple sensory systems, including somatosensory and motor pathways, making it an inherently multisensory phenomenon. However, research has predominantly examined the influence of music on other sensory systems, while the reciprocal question - how the existing state of a sensory system modulates the music listening experience- has received considerably less attention. To address this gap, we examined neural activity during music listening in two somatosensory states: one preceded by vibroacoustic stimulation (VAS) and one preceded by rest alone. Methods: Forty participants completed two MEG sessions in a within-subject crossover design. In one session, they received 20 minutes of 40 Hz VAS before listening to 10 minutes of self-selected relaxing music (VAS_ML); in the other, they lay on the same mattress without stimulation (NoVAS_ML). Oscillatory and aperiodic activity were estimated using DICS beamforming and FOOOF decomposition for the whole music period and for early and late listening segments. Results: Across the full listening period, the VAS condition was associated with reduced alpha power in the posterior temporal lobe and increased low-gamma power in the medial somatosensory and motor cortices compared to the NoVAS condition, suggesting enhanced cortical excitability and stronger auditory-motor engagement. Over time, both music listening conditions showed increases in alpha and beta power, consistent with habituation to the musical stimulus, though the spatial distribution differed qualitatively: changes were widespread across temporal and occipital regions in the NoVAS condition but remained localized to temporal areas after VAS. Additionally, VAS uniquely increased temporal-lobe theta power over time, whereas the NoVAS condition showed a decrease in the aperiodic exponent. Subjectively, participants reported stronger emotional intensity during music listening after VAS. Conclusion: These findings suggest that preceding VAS induces a more engaged neural state and qualitatively alters the temporal dynamics of music processing.

neuroscience↗

bioRxiv2026

Myeloid STING restrains cardiac remodeling by suppressing macrophage amyloid precursor protein

Mitochondrial DNA (mtDNA) released into the cytosol activates innate immune signaling and promotes inflammation, yet its role in macrophages following sterile tissue injury remains poorly understood. Here, we show that cardiac macrophages from both patients and mice with myocardial infarction (MI) exhibit increased mitochondrial biogenesis, mitochondrial content, membrane potential, and expression of mitochondrial nucleases that facilitate mtDNA release. Consistently, macrophage-specific silencing of genes regulating mitochondrial biogenesis or mtDNA processing attenuated adverse cardiac remodeling after MI. Unexpectedly, despite the role of mtDNA in activating the cGAS-STING pathway, myeloid deletion or macrophage-specific silencing of Sting or cGas exacerbated ventricular dilation, fibrosis, and contractile dysfunction following MI. Single-cell transcriptomic and cell communication analyses identified amyloid precursor protein (APP) as a key downstream effector of STING in cardiac macrophages. Macrophage-specific in vivo App silencing rescued the detrimental effects of myeloid Sting deficiency, establishing APP as a critical mediator of adverse remodeling. Mechanistically, STING interacted with the transcriptional repressor MZF1, promoted its nuclear localization, facilitated its binding to the App promoter, and suppressed App transcription to restrain adverse cardiac remodeling. Together, our findings uncover an unexpected cardioprotective function of myeloid STING and identify the STING-MZF1-APP axis as a previously unrecognized mechanism governing cardiac repair after myocardial infarction.

cell biology↗

bioRxiv2019

nkx3.2 mutant zebrafish accommodate the jaw joint loss through a phenocopy of the head shapes of Paleozoic agnathans

The vertebrate jaw is a versatile feeding apparatus that facilitated explosive diversification. To function, it requires a joint between the upper and lower jaws, so jaw joint defects - such as osteoarthritis or even ankylosis - are often highly disruptive and difficult to study. To describe consequences of jaw-joint dysfunction, we engineered two independent null alleles of a single jaw-joint marker gene, nkx3.2, in zebrafish. These mutations caused zebrafish to become functionally jawless via fusion of the upper and lower jaw cartilages (ankylosis). Despite lacking jaw joints, nkx3.2 mutants survive to adulthood and accommodate this defect by: a) remodeling their skulls; and b) altering their behavior from suction feeding to ram feeding. As a result of remodeling, nkx3.2 mutants developed superficial similarities to the skull shapes observed in two lineages of ancient jawless vertebrates (anaspids and furcacaudiid thelodonts), including: a fixed open gape, reduced snout, and enlarged branchial region. However, no homology exists in individual skull elements between these taxa, and most of the modified elements in the mutant zebrafish occur outside known expression domains of nkx3.2. Therefore, we interpret the adult nkx3.2 phenotype not as a reversal to an ancestral state, but as convergence due to similar functional requirement of feeding without moveable jaws. This remarkable convergence strongly suggests that jaw movements themselves dramatically influence the development of jawed vertebrate skulls, which implies that functionally viable skull morphologies are finite, with or without functional jaws. Because nkx3.2 null zebrafish display prominent joint ankylosis, drastically modified skull shape, and altered feeding behaviors, these mutants provide a unique model with which to investigate mechanisms of skeletal remodeling and joint diseases.

evolutionary biology↗

bioRxiv2018

NHA2 promotes cyst development in an in vitro model of polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The molecular pathways linking polycystins to cyst development in ADPKD are still unclear. Intracystic fluid secretion via ion transporters and channels plays a crucial role in cyst expansion in ADPKD. Unexpectedly, we observed significant and selective up-regulation of NHA2, a member of the SLC9B family of Na+/H+ exchangers that correlated with cyst size and disease severity in ADPKD patients. Using three-dimensional cultures of MDCK cells to model cystogenesis in vitro, we show that ectopic expression of NHA2 is causal to increased cyst size. Induction of PC1 in MDCK cells inhibited NHA2 expression with concordant inhibition of Ca2+ influx through store-dependent and independent pathways, whereas reciprocal activation of Ca2+ influx by a dominant negative, membrane-anchored C-terminal tail fragment of PC1 elevated NHA2. We show that NHA2 is a target of Ca2+/NFAT signaling and is transcriptionally induced by methylxanthine drugs such as caffeine and theophylline, which are contraindicated in ADPKD patients. Finally, we observe robust induction of NHA2 by vasopressin, which is physiologically consistent with increased levels of circulating vasopressin and up-regulation of vasopressin V2 receptors in ADPKD. Our findings have mechanistic implications on the emerging use of vasopressin V2 receptor antagonists such as tolvaptan as safe and effective therapy for PKD and reveal a potential new regulator of transepithelial salt and water transport in the kidney.

physiology↗