Biology subjects

Bhowmik, R.

Publications and source records attributed to Bhowmik, R..

2 recordsLinked to original sources

bioRxiv2022

Uncertainty revealed by delayed responses during olfactory matching

Matching of olfactory stimuli involves both sensory and higher cognitive functioning. Different decision processes such as detection and discrimination, along with holding the perceived information are involved during the matching process. Accuracy and decision times, the interdependent readouts, can define the uncertainty involved in matching of sensory stimuli. To probe sensory and cognitive functions involving olfactory system in human subjects, we have developed a novel olfactory matching paradigm using an automated custom-built olfactory-action meter. With precise and consistent odor delivery and real-time data analysis, our system automates the entire process without any intervention by the experimenter, making it suitable as a diagnostic tool for quantifying olfactory and neurocognitive fitness. In around 400 healthy human subjects, with mean detection accuracy of 90%, we observed significantly better olfactory matching performance for simple monomolecular odors, in comparison to complex binary odor mixtures. Odor matching accuracy declined significantly with the increase in odor complexity. Olfactory matching was more rapid when subjects made correct versus incorrect decisions, indicating perceptual certainty. Subjects also took longer matching time for complex odors compared to simple odor stimuli. Thus, olfactory matching that provides a combined readout of sensory and cognitive fitness, establishes a direct link between the performance accuracy and the certainty of decisions.

neuroscience↗

bioRxiv2022

Structure and Neutralization Mechanism of a Human Antibody Targeting a Complex Epitope on Zika Virus

We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency.

microbiology↗