Biology subjects

Parvin, S.

Publications and source records attributed to Parvin, S..

5 recordsLinked to original sources

bioRxiv2026

Adaptive Bayesian localization of motor representation areas

Transcranial magnetic stimulation (TMS) enables non-invasive localization of cortical motor representations, with important clinical applications in presurgical planning. Existing methods either disregard spatial information about the TMS-induced electric field (E-field) or use acquisition schemes that do not leverage previously elicited motor responses to guide subsequent stimulation. We present an adaptive Bayesian localization method that combines real-time E-field optimization with per-trial probabilistic inference. The cortical origin of the motor responses is represented as a spatial probability distribution that is updated after each stimulus. Subsequent stimuli are then optimized to maximize the expected localization improvement given previous responses. We validated the method experimentally, using multi-locus TMS for adaptive localization and single-coil TMS as a non-adaptive reference with randomized coil placements. Across eight subjects, the adaptive protocol at least halved the number of stimuli required for stable localization compared to the randomized protocol, converging in 60 stimuli on average, with 95% highest-density regions often below 10 mm2 by 150 stimuli.

neuroscience↗

bioRxiv2026

Coupled intracellular redox and extracellular respiration sensing for quantitative oxidative stress profiling

Quantitative assessment of cellular oxidative stress requires simultaneous measurement of intracellular redox state and extracellular respiratory activity, yet integrated sensing approaches remain limited. Here, we present a dual-fluorescent sensing platform combining a genetically encoded redox biosensor (roGFP2{square}Tsa2{Delta}CR) with an optical oxygen sensor embedded in microwell plates for parallel, non-invasive quantification of intracellular reactive oxygen species (ROS) and oxygen consumption rates (OCR) in industrial yeast systems. The roGFP2-based sensor was stably expressed in Saccharomyces cerevisiae (S. cerevisiae) and Yarrowia lipolytica (Y. lipolytica), enabling dynamic monitoring of oxidative stress at population, single-cell, and subcellular levels, while oxygen-sensitive films provided real-time respiration measurements. Using this platform, we identified distinct redox-respiration phenotypes between the two yeasts. Crabtree-positive S. cerevisiae exhibited low OCR and mitochondrial ROS during glucose cultivation, whereas growth on glycerol increased OCR and mitochondrial ROS by ~2.5-fold and 12%, respectively. In contrast, the obligate respiratory yeast Y. lipolytica displayed 3-fold higher OCR and 16% lower mitochondrial ROS than respiring S. cerevisiae, indicating differences in respiratory oxidative burden. Antimycin A treatment reduced OCR by 60% in respiring S. cerevisiae while increasing mitochondrial ROS by 35%, whereas Y. lipolytica showed greater resistance to respiratory and oxidative perturbations. By integrating intracellular redox sensing with extracellular oxygen measurements, this platform enables quantitative coupling of redox state and respiration in living cells. The approach provides a scalable framework for evaluating cellular fitness, stress tolerance, and metabolic state in biomanufacturing and synthetic biology.

bioengineering↗

bioRxiv2025

A novel bioinformatics approach reveals key transcription factors regulating type 1 diabetes-associated transcriptomes

We developed a novel bioinformatics pipeline that reveals key transcription factors (TFs) regulating type 1 diabetes transcriptomes by combining automated Python workflows, DESeq2-based differential expression analysis, motif enrichment, and genome-wide TF abundance profiling, a rare but powerful strategy that deepens our understanding of disease mechanisms. This approach not only uncovers TFs driving pathology but also quantifies TF abundance across multiple genomic loci, enabling rapid and precise monitoring of their occupancy. Analyzing 21 RNA sequencing datasets, including 13 from early-stage T1D patients and 8 matched controls, we identified nearly 6 000 differentially expressed genes; 1 900 met strict significance and fold-change criteria and 211 are previously uncharacterized transcripts that distinguish T1D from healthy samples. Pathway analysis highlighted disruptions in beta-cell signaling, ALK-linked drug responses, neurodegenerative processes, and cytoskeletal organization. Upstream motif analysis revealed enrichment of Myc/Max, AP-1, SP-1, TATA-box, and NF-{kappa}B binding sites in upregulated genes, confirming their central role in the T1D transcriptome. By placing TFs at the core of our discovery platform, this work uncovers novel molecular drivers of T1D and identifies actionable biomarkers and therapeutic targets for personalized treatment.

bioinformatics↗

bioRxiv2022

C-low threshold mechanoreceptor activation becomes sufficient to trigger affective pain in spinal cord-injured mice in association with increased respiratory rates

The mechanisms of neuropathic pain after spinal cord injury (SCI) are not fully understood. In addition to the plasticity that occurs within the injured spinal cord, peripheral processes, such as hyperactivity of primary nociceptors, are critical to the expression of pain after SCI. In adult rats, truncal stimulation within the tuning range of C-low threshold mechanoreceptors (C-LTMRs) contributes to pain hypersensitivity and elevates respiratory rates (RRs) after SCI. This suggests that C-LTMRs, which normally encode pleasant, affiliative touch, undergo plasticity to transmit pain sensation following injury. Because tyrosine hydroxylase (TH) expression is a specific marker of C-LTMRs, in the periphery, here we used Th-Cre adult mice to investigate more specifically the involvement of C-LTMRs in at-level pain after thoracic contusion SCI. Using a modified light-dark chamber conditioned place aversion (CPA) paradigm, we assessed chamber preferences and transitions between chambers at baseline, and in response to mechanical and optogenetic stimulation of C-LTMRs. In parallel, at baseline and select post-surgical timepoints, mice underwent non-contact RR recordings and von Frey assessment of mechanical hypersensitivity. The results showed that SCI mice avoided the chamber associated with C-LTMR stimulation, an effect that was more pronounced with optical stimulation. They also displayed elevated RRs at rest and during CPA training sessions. Importantly, these changes were restricted to chronic post-surgery timepoints, when hindpaw mechanical hypersensitivity was also evident. Together, these results suggest that C-LTMR afferent plasticity, coexisting with a potentially facilitatory state of sympathetic activation, drives at-level affective pain following SCI in adult mice. Contribution to the field statementPreclinical studies have only recently sought to understand biological mechanisms connecting peripheral afferent neuron hypersensitivity to pain. Using mechanical brush and selective optogenetic activation in transgenic mice, this study investigated the role of an implicated subpopulation of sensory afferents, the C-low threshold mechanoreceptors (C-LTMRs), that may be transformed from pleasurable touch- to pain-encoding neurons after spinal cord injury (SCI). C-LTMR activation after SCI evoked at-level conditioned pain responses associated with sympathetic activation (increased respiratory rates). These studies provide a foundation for research into the peripheral afferent mechanisms of pain that is expected to translate into new options for pain control in humans.

physiology↗

bioRxiv2020

Leukemia cell of origin influences apoptotic priming and sensitivity to LSD1 inhibition

Previous studies have established that the cell of origin of oncogenic transformation is a determinant of therapeutic sensitivity. However, the mechanisms governing cell-of-origin-driven differences in therapeutic response have not been delineated. Leukemias initiating in hematopoietic stem cells (HSC) are less sensitive to cytotoxic chemotherapy and express high levels of the transcription factor Evi1 compared to leukemias derived from myeloid progenitors. Here, we compared drug sensitivity and expression profiles of murine and human leukemias initiated in either HSCs or myeloid progenitors to reveal a novel function for Evi1 in modulating p53 protein stability and activity. HSC-derived leukemias exhibit decreased apoptotic priming, attenuated p53 transcriptional output, and resistance to lysine-specific demethylase 1 inhibitors in addition to classical genotoxic stresses. p53 loss-of-function in Evi1low progenitor-derived leukemias induces resistance to LSD1 inhibition. By contrast, Evi1high leukemias are sensitized to LSD1 inhibition by the BH3 mimetic venetoclax, resulting in enhanced apoptosis and greater reductions in disease burden. Our findings demonstrate a cell-of-origin determined novel role for EVI1 in p53 wild-type cancers in reducing p53 function and provide a strategy to circumvent drug resistance in high-risk, chemoresistant EVI1high AML.

cancer biology↗