Biology subjects

Manivasagam, S.

Publications and source records attributed to Manivasagam, S..

5 recordsLinked to original sources

bioRxiv2025

Distinct neural routes for evaluative and informational social influence

Humans routinely revise their judgments based on input from others, yet how the brain mechanisms distinguish evaluative from informational social influence remains unclear. Using preregistered electroencephalography (EEG, N = 87) and the Judge-Advisor System, we identified distinct neurocognitive routes by which feedback and advice shape judgment revision. Participants made numerical estimates, received either feedback ("good"/"bad") or advice (alternative estimates) of varying proximity to their own judgment, and then revised their response. Feedback engaged rapid evaluative monitoring: a feedback-related negativity (FRN, 200-300ms) that decreased with confidence, indicating reflexive performance assessment. Advice triggered delayed deliberate processing: late positive complex (LPC) onset latencies that slowed when confident individuals encountered discrepant advice, indicating effortful integration of external information. Both routes converged on the P300 (250-250ms),whose amplitudes increased with proximity, consistent with the reward value of social validation. These findings reveal a dual-route architecture: feedback determines whether to revise through rapid evaluative signals, while advice specifies how much to revise through sustained integrative processes. Confidence calibrates both routes, protecting against misleading feedback while intensifying deliberation over discrepant advice. This temporal dissociation clarifies how metacognitive and social processes coordinate adaptive judgment revision.

neuroscience↗

bioRxiv2025

Social learning of emotion and its implication for memory: An ERP Study

Social learning of emotional salience from surrounding social cues is especially advantageous under conditions of uncertainty. Yet, the neural mechanisms underlying this process and its consolidation into long-term memory remain poorly understood. In this two-day EEG study, we examined whether emotional salience from social cues (facial expressions) transfers to perceptually uncertain target images, and whether such learned salience is preserved in memory even after the social cues are removed. On Day 1 (learning session), we found no evidence for automatic emotional salience transfer across trials. Instead, ERP results indicated that social cue use was modulated by participants metacognitive state of subjective uncertainty, as reflected in the P1 amplitudes. On Day 2 (test session), recognition memory revealed evidence of additive emotional salience: EPN amplitudes were enhanced for accurately classified positive target images previously paired with social cues. In contrast, LPC amplitudes were reduced for negative target images in the social condition, regardless of classification accuracy. Together, these findings suggest that the influence of social cues is contingent on subjective uncertainty. Social cues enhanced emotional salience when internal valence judgments were strong (as for positive images), but led to increased reliance on the cue--and therefore dampened memory encoding--when internal valence judgments were weaker (as for negative images).

neuroscience↗

bioRxiv2022

Avian and Human Influenza Viruses Exhibit Distinct Glycoconjugate Receptor Specificities in Human Lung Cells

IAV utilize sialic acid (Sia) containing cell surface glycoconjugates for host cell infection, and IAV strains from different host species show preferences for structurally distinct Sia at the termini of glycoconjugates. Various types of cell surface glycoconjugates (N-glycans, O-glycans, glycolipids) display significant diversity in both structure and carbohydrate composition. To define the types of glycoconjugates that facilitate IAV infection, we utilized the CRISPR/Cas9 technique to truncate different types of glycoconjugates, either individually or in combination, by targeting glycosyltransferases essential to glycan biosynthesis in a human lung epithelial cell line. Our studies show that both human and avian IAV strains do not display strict preferences for a specific type of glycoconjugate. Interestingly, truncation of all three types of glycoconjugates significantly decreased the replication of human IAV strains, yet did not impact the replication of avian IAV strains. Taken together, our studies demonstrate that avian IAV strains utilize a broader repertoire of glycoconjugates for host cell infection as compared to human IAV strains. Author SummaryIt is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These glycoconjugates can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugates for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. Our studies indicate that avian IAV strains can utilize a wide variety of glycoconjugates for infection, whereas human IAV strains display restrictions in glycoconjugate type usage. These novel studies show distinct differences in host glycoconjugate preferences between human and avian IAV strains.

microbiology↗

bioRxiv2021

Targeting interferon-{lambda} signaling promotes recovery from central nervous system autoimmunity

Type III interferons (IFNLs) are newly discovered cytokines, acting at epithelial and other barriers, that exert immunomodulatory functions in addition to their primary roles in antiviral defense. Here we define a role for IFNLs in maintaining autoreactive T cell effector function and limiting recovery in a murine model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Genetic or antibody-based neutralization of the IFNL receptor (IFNLR) resulted in lack of disease maintenance during EAE, with loss of CNS Th1 effector responses and limited axonal injury. Phenotypic effects of IFNLR signaling were traced to increased antigen presenting cell (APC) function, with associated increase in T cell production of IFN{gamma} and GM-CSF. Consistent with this, IFNL levels within lesions of CNS tissues derived from MS patients were elevated compared to MS normal appearing white matter (NAWM). Furthermore, expression of IFNLR was selectively elevated in MS active lesions compared to inactive lesions or NAWM. These findings suggest IFNL signaling as a potential therapeutic target to prevent chronic autoimmune neuroinflammation.

immunology↗

bioRxiv2021

Host Factor Rab11a is Critical for Efficient Assembly of Influenza A Virus Genomic Segments

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.

microbiology↗