Biology subjects

Saha, U.

Publications and source records attributed to Saha, U..

4 recordsLinked to original sources

bioRxiv2023

Robust Removal of Slow Artifactual Dynamics Induced by Deep Brain Stimulation in Local Field Potential Recordings using SVD-based Adaptive Filtering

Deep brain stimulation (DBS) is widely used as a treatment option for patients with movement disorders. In addition to its clinical impact, DBS has been utilized in the field of cognitive neuroscience wherein the answers to several fundamental questions underpinning the mechanisms of neuromodulation in decision making rely on how a burst of DBS pulses, usually delivered at clinical frequency, i.e., 130 Hz, perturb participants choices. It was observed that neural activities recorded during DBS were contaminated with stereotype large artifacts, which lasts for a few milliseconds, as well as a low-frequency (slow) signal ([~]1-2 Hz) that can persist for hundreds of milliseconds. While the focus of the most of methods for removing DBS artifact was on the former, the artifact removal of the slow signal has not been addressed. In this work, we propose a new method based on combining singular value decomposition (SVD) and normalized adaptive filtering to remove both large (fast) and slow artifacts in local field potentials recorded during a cognitive task in which bursts of DBS were utilized. Using synthetic data, we show that our proposed algorithm outperforms four commonly used techniques in the literature, namely, (1) Normalized least mean square adaptive filtering, (2) Optimal FIR Wiener filtering, (3) Gaussian model matching, and (4) Moving average. The algorithms capabilities are further demonstrated by its ability to effectively remove DBS artifacts in local field potentials recorded from the subthalamic nucleus during a verbal Stroop task, highlighting its utility in real-world applications.

neuroscience↗

bioRxiv2023

mRNA decay can be uncoupled from deadenylation during stress response

The polyadenosine tail (pA-tail) regulates mRNA nuclear export, stability, and translatability. Based on reporter constructs, the prevailing model suggests that pA-tail removal mediated by Ccr4-NOT or PAN2/3 deadenylases is required for mRNA decapping and degradation. Here, we use direct RNA sequencing to track mRNA deadenylation and decay at steady-state and in stress conditions to show a global correlation between deadenylation and decay. Interestingly, codon optimality, previously postulated to dictate mRNA stability, only strongly affects decay of conserved and abundant transcripts, such as coding for ribosomal protein subunits. Degradation of those mRNAs is also accelerated in response to stress. Still, the in-depth analysis revealed that deadenylation is a factor that contributes to degradation but is not indispensable for decapping. We further demonstrate that deadenylation is the fastest for newly made tails depending on polyA-binding protein Pab1. Unexpectedly, decapping initiates on mRNAs of pA-tails of 20-35 adenosines presumably bound by Pab1.

molecular biology↗

bioRxiv2022

Inferring Cognitive State Underlying Conflict Choices in Verbal Stroop Task Using Heterogeneous Input Discriminative-Generative Decoder Model

The subthalamic nucleus (STN) of the basal ganglia interacts with the medial prefrontal cortex (mPFC) and shapes a control loop, specifically when the brain receives contradictory information from either different sensory systems or conflicting information from sensory inputs and prior knowledge that developed in the brain. Experimental studies demonstrated that significant increases in theta activities (2-8 Hz) in both the STN and mPFC as well as increased phase synchronization between mPFC and STN are prominent features of conflict processing. While these neural features reflect the importance of STN-mPFC circuitry in conflict processing, a low-dimensional representation of the mPFC-STN interaction referred to as a cognitive state, that links neural activities generated by these sub-regions to behavioral signals (e.g., the response time), remains to be identified. Here, we propose a new model, namely, the heterogeneous input discriminative-generative decoder (HI-DGD) model, to infer a cognitive state underlying decision-making based on neural activities (STN and mPFC) and behavioral signals (individuals response time) recorded in 10 Parkinsons disease patients while they performed a Stroop task. PD patients may have conflict processing which is quantitatively (may be qualitative in some) different from healthy population. Using extensive synthetic and experimental data, we showed that the HI-DGD model can diffuse information from neural- and behavioral data simultaneously and estimate cognitive states underlying conflict and nonconflict trials significantly better than traditional methods. Additionally, the HI-DGD model identified which neural features made significant contributions to conflict and non-conflict choices. Interestingly, the estimated features match well with those reported in experimental studies. Finally, we highlight the capability of the HI-DGD model in estimating a cognitive state from a single trial of observation, which makes it appropriate to be utilized in closed-loop neuromodulation systems. HighlightsO_LIResearch highlight 1 C_LIO_LIResearch highlight 2 C_LI

neuroscience↗

bioRxiv2021

The CTEXT complex in Saccharomyces cerevisiae plays a crucial role in degrading distinct sets of aberrant mRNAs by the nuclear exosome

In Saccharomyces cerevisiae, DRN (Decay of RNA in the Nucleus) requiring Cbc1/2p, Tif4631p, and Upf3p promotes the exosomal degradation of aberrantly long 3'-extended-, export-defective transcripts and a small group of normal (special) mRNAs. In this study, using a systematic proteomic analysis we show that each of the known components interacts with one another and they exist as a separate complex, which was dubbed CTEXT (CBC-Tif4631p-dependent EXosome Targeting). We also identified a DEAD-box RNA helicase Dbp2p as an additional novel component of CTEXT during this analysis which was further bolstered by the finding that genomic deletions of Dbp2p led to the stabilization of all the signature nuclear messages. Interestingly, the RRM domain of Tif4631p located at the extreme N-termini of this polypeptide was found to play a vital role in in mediating the interaction of the CTEXT with the core exosome complex. These inferences were substantiated by the finding that deletion of this domain led to the functional impairment of the CTEXT complex. Thus, the CTEXT constitutes an independent complex that assists the nuclear exosome in degrading the select classes of nuclear transcripts in Saccharomyces cerevisiae.

molecular biology↗