Biology subjects

Das, R. K.

Publications and source records attributed to Das, R. K..

7 recordsLinked to original sources

bioRxiv2026

Language-associated brain representations covary with disruption of selfhood under psilocybin

Language helps organise experience into an idiosyncratic, temporally extended sense of self. We therefore used fMRI to investigate whether greater similarity between participants in the activity of language-associated brain regions accompanied psilocybin-induced loss of selfhood. Participants heard music and viewed moving clouds at baseline and after 19 mg psilocybin. At each brain location and time point, we tested whether similarity increased with each pair's summed rank on the Ego Dissolution Inventory (EDI; N=43). We grouped independent components of these associations by time course and decoded each group's map with Neurosynth. Elementary visual imagery (SI; N=49) and baseline activity served as comparators. Under psilocybin, one group formed a distributed, left-lateralised frontotemporal network matching the Neurosynth language map (r=.382, spatial-null p<.001, q=.003), nearly twice the largest comparator estimate (SI: r=.208, p=.004, q=.028; baseline: r<.12). In exploratory analyses, resting-state connectivity of this network decreased with posterior visual cortex and increased with thalamic and frontal regions. Participants with higher EDI scores showed larger changes (Spearman's rho=.455, Bonferroni-adjusted p=.048; SI: rho=.008), most strongly for items describing loss of ego or identity (rho=.43 to .51). We propose that language-associated systems incorporate each person's semantic and autobiographical context into experience, and that disrupting them contributes to loss of ego and identity.

neuroscience↗

bioRxiv2026

A PSMA-Targeted Up-conversion Nanoplatform for Deep-Tissue dual activation Photodynamic and Sonodynamic Therapy of Castration Resistant Prostate Cancer.

Photodynamic therapy (PDT) for prostate cancer is limited by the shallow penetration of visible light into deep-seated tumors. In contrast, sonodynamic therapy (SDT) enables noninvasive deep-tissue activation using ultrasound, while near-infrared photodynamic therapy (NIR-PDT) enhances tissue penetration through up-conversion-mediated activation. Based on these advantages, we developed a prostate-specific membrane antigen (PSMA)-targeted nanotheranostic platform (UCNPs@mSiO2/HPPH@TCS) to compare NIR-PDT and SDT in vitro for penetration-enhanced and targeted prostate cancer therapy. The nanoformulation consists of NaYF4:Yb3+, Er3+ up-conversion nanoparticles coated with mesoporous silica for high loading of HPPH (Photochlor), which functions as both photosensitizer and sonosensitizer, and a PSMA-targeted chitosan shell for selective tumor targeting. Physicochemical characterization confirms a uniform core-shell structure ([~]63 nm). Tissue-mimicking depth studies demonstrate that SDT and NIR-PDT achieve greater penetration than conventional 665 nm PDT in thicker tissue layers. Intracellular reactive oxygen species (ROS) analysis shows that SDT generates higher total ROS levels, whereas NIR-PDT produces greater singlet oxygen generation. Three-dimensional spheroid models further validate efficacy, demonstrating rapid spheroid collapse via apoptosis, with SDT inducing earlier apoptosis and more uniform penetration than PDT. Collectively, the results suggest SDT provides superior overall therapeutic efficacy compared with NIR-PDT, highlighting the potential of this nanoplatform for precision prostate cancer therapy.

cancer biology↗

bioRxiv2025

Oxidative Stress, Hypoxia and Cellular Metabolism: Unraveling the Effects of Fentanyl on Lung Cancer Cells

Fentanyl, a widely used opioid analgesic for cancer pain management, is effective but requires cautious administration due to its potential for respiratory depression. Beyond its analgesic properties, fentanyls broader impact on cancer biology and biochemical alterations in lung carcinoma cells remains underexplored. This study investigates fentanyls influence on oxidative stress, mitochondrial function, hypoxia-inducing factors, apoptosis, and cytokine production in A549 lung cancer cells. Our findings reveal that fentanyl increases reactive oxygen species (ROS) generation, disrupts cellular homeostasis, induces DNA damage, and alters key signaling pathways, potentially affecting tumor metabolism and progression. Our "Ramanomics" data further highlight fentanyl-driven changes in key ions (inorganic phosphate, calcium) and biomolecules (glycogen, phospholipids, proteins, nucleic acids, and enzymes) at subcellular mitochondrial levels. These insights contribute to understanding fentanyls mechanistic impact on lung cancer progression and may inform optimized therapeutic strategies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/665412v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1fb7aaaorg.highwire.dtl.DTLVardef@13255deorg.highwire.dtl.DTLVardef@1a398cdorg.highwire.dtl.DTLVardef@184d63e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Where the present gets remembered: Sensory regions communicate with the brain over the longest timescales.

In natural contexts, the brain simultaneously processes sensory information over diverse timescales. Here we reveal how this is reflected in the organisation of asynchronous connectivity in the brain. In 86 individuals watching feature-length movies during functional neuroimaging, we calculated the delay at peak connectivity between brain regions. We found the longest delays in received whole-brain functional connectivity within sensory regions (:S 18 seconds). Two complementary dimensionality reduction approaches were used to probe the spatial organisation of connection delays and weights. First, clustering of received delays separated sensory, and transmodal/associative outputting regions, suggesting that putatively localised functions are associated with asynchronous local-to-whole-brain connectivity patterns. Next, we organised delayed connectivity maps by likeness, unveiling five orthogonal gradients of variation, each demonstrating associations between early-sensory and transmodal/associative regions. Together, these findings challenge contemporary conceptualisations of the brains temporal hierarchy by emphasising the role of sensory regions as sites of integration across timescales.

neuroscience↗

bioRxiv2020

Long-term Behavioural Rewriting of Maladaptive Drinking Memories via Reconsolidation-Update Mechanisms

BackgroundAlcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are a key therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. MethodsHazardous/harmful beer-drinking volunteers (N=120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-based counterconditioning of drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels assessed up to 9 months. ResultsGreater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning were noted. Responsiveness to counterconditioning predicted subsequent responses to acute alcohol in RET+PE only, consistent with reconsolidation-update mechanisms. ConclusionsThe longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.

neuroscience↗

bioRxiv2018

Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and ‘sub-clinical’ studies

Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This has been suggested to represent a potentially transformative clinical strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, the ability to modulate naturalistic maladaptive memories may be limited by boundary conditions imposed on reconsolidation by the nature of these memories. As such, the true potential of reconsolidation therapy is currently unknown. Here, we report a meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward and threat memories in (sub)clinical substance use and anxiety/trauma respectively.\n\nOf 4936 publications assessed for eligibility, 7 studies of substance use, and 9 of anxiety (phobia) and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with the majority of effect sizes favouring the Retrieval + Treatment condition. However, the magnitude of effects depended upon the nature of the treatment type, with pharmacological interventions (relative to behavioural strategies) showing a clearer beneficial effect in studies of phobia/trauma and post-retrieval behavioural strategies, a (significantly) larger effect in substance use studies. However, high levels of heterogeneity and small sample sizes limit the strength of conclusions that can be drawn at this stage of inquiry. We hope this review will provide an impetus to address these issues in future research.

neuroscience↗

bioRxiv2017

A deep mutational scan of an acidic activation domain

Transcriptional activation domains are intrinsically disordered peptides with little primary sequence conservation. These properties have made it difficult to identify the sequence features that define activation domains. For example, although acidic activation domains were discovered 30 years ago, we still do not know what role, if any, acidic residues play in these peptides. To address this question we designed a rational mutagenesis scheme to independently test four sequence features theorized to control the strength of activation domains: acidity (negative charge), hydrophobicity, intrinsic disorder, and short linear motifs. To test enough mutants to deconvolve these four features we developed a method to quantify the activities of thousands of activation domain variants in parallel. Our results with Gcn4, a classic acidic activation domain, suggest that acidic residues in particular regions keep two hydrophobic motifs exposed to solvent. We also found that the specific activity of the Gcn4 activation domain increases during amino acid starvation. Our results suggest that Gcn4 may have evolved to have low activity but high inducibility. Our results also demonstrate that high-throughput rational mutation scans will be powerful tools for unraveling the properties that control how intrinsically disordered proteins function.

systems biology↗