Biology subjects

Shashaank, N.

Publications and source records attributed to Shashaank, N..

3 recordsLinked to original sources

bioRxiv2026

Bayesian Factor Analysis for Binary and Ordinal Phenotypes with Missingness

Binary and ordinal phenotypes are common in clinical screening and self-reported questionnaires, but many factor analysis and matrix factorization methods are only applicable for quantitative phenotypes with real-valued and/or continuous data distributions. To address this, we propose FABOr (Factor Analysis of Binary and Ordinal data), a Bayesian framework for matrix factorization in which the low-rank matrices are latent variables with continuous priors while the phenotypes are observed variables modeled with appropriate binary/ordinal likelihoods. We also develop missing not at random (MNAR) extensions of FABOr for analyzing data with structured missingness. In experiments with simulated phenotypes, we found that FABOr performs similarly to the best-performing benchmark methods on binary data at imputation and exceeds the performance of all tested benchmark methods on ordinal data. We then applied FABOr to analyze real-world binary and ordinal phenotypes from the Simons Foundation SPARK dataset on autism spectrum disorder (ASD) and found that it improved imputation accuracy by up to 5% on binary data and up to 23% on ordinal data relative to the benchmark methods.

bioinformatics↗

bioRxiv2025

Safety learning induces postsynaptic potentiation of direct pathway spiny projection neurons in the tail of the striatum

The association of a sensory cue with an outcome is a crucial step in learning to identify safe versus threatening situations. Here we assessed how learned sound-safety association alters neuronal activity in tail of the striatum (TS), where auditory cortical and thalamic inputs converge. Prior to training, foot shock elicited responses by TS direct and indirect pathway spiny projection neurons (SPNs), while sound tones produced no response. However, once the sound association was learned, sound tones strongly activated TS SPNs, even when the animal was under anesthesia. This conditioned auditory response occurred concurrently with alterations of direct pathway SPNs in the TS, including increased responses to cortical and auditory thalamic inputs, increased excitatory response with an enhanced ratio of NMDA to AMPA receptors, decreased responses to inhibitory input, and increased dendritic spines. This convergence of postsynaptic changes provides responses to relevant auditory cues during associative learning. TeaserSound-safety association enhances response to learned sound in striatal neurons via postsynaptic mechanisms

neuroscience↗

bioRxiv2022

Dopamine transporter and synaptic vesicle sorting defects initiate auxilin-linked Parkinson's disease

Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of- function mutations cause early-onset Parkinsons disease (PD). Here, we utilized auxilin-knockout (KO) mice to elucidate the mechanisms through which auxilin deficiency and clathrin-uncoating deficits lead to PD. We demonstrate that auxilin KO mice display the cardinal features of PD, including progressive motor deficits, -synuclein pathology, nigral dopaminergic loss, and neuroinflammation. Through unbiased proteomic and neurochemical analyses, we demonstrate that dopamine homeostasis is disrupted in auxilin KO brains, including via slower dopamine reuptake kinetics in vivo, an effect associated with dopamine transporter misrouting into axonal membrane deformities in the dorsal striatum. We also show that elevated macroautophagy and defective SV protein sorting contribute to ineffective dopamine sequestration and homeostasis, ultimately leading to neurodegeneration. This study advances our knowledge of how presynaptic endocytosis deficits lead to dopaminergic vulnerability and pathogenesis of PD.

neuroscience↗