Biology subjects

Dutta, S.

Publications and source records attributed to Dutta, S..

166 records · Page 10Linked to original sources

bioRxiv2018

Neurodynamic explanation of inter-individual and inter-trial variability in cross-modal perception

A widely used experimental design in multisensory integration is the McGurk paradigm that entail illusory (cross-modal) perception of speech sounds when presented with incongruent audio-visual (AV) stimuli. However, the distribution of responses across trials and individuals is heterogeneous and not necessarily everyone in a given group of individuals perceives the effect. Nonetheless, existing studies in the field primarily focus on addressing the correlation between subjective behavior and cortical activations to reveal the neuronal mechanisms underlying the perception of McGurk effect, typically in the \"frequent perceivers\". Additionally, a solely neuroimaging approach does not provide mechanistic explanation for the observed inter-trial or inter-individual heterogeneity. In the current study we employ high density electroencephalogram (EEG) recordings in a group of 25 human subjects that allow us to distinguish \"frequent perceivers\" from \"rare perceivers\" using behavioral responses as well as from the perspective of large-scale brain functional connectivity (FC). Using global coherence as a measure of large-scale FC, we find that alpha band coherence, a distinctive feature in frequent perceivers is absent in the rare perceivers. Secondly, a decrease in alpha band coherence and increase in gamma band coherence occur during illusory perception trials in both frequent and rare perceivers. Source analysis followed up with source time series reconstructions reveals a large scale network of brain areas involving frontal, temporal and parietal areas that are involved in network level processing of cross-modal perception. Finally, we demonstrate that how a biophysically realistic computational model representing the interaction among key neuronal systems (visual, auditory and multisensory cortical regions) can explain the empirical observations. Each system involves a group of excitatory and inhibitory Hindmarsh Rose neurons that are coupled amongst each other. Large-scale FC between areas is conceptualized using coupling functions and the identity of a specific system, e.g., visual/ auditory/ multisensory is chosen using empirical estimates of the time-scale of information processing in these systems. The model predicts that the disappearance of alpha band coherence observed in rare perceivers stems from a negligible direct A-V (audio-visual) coupling however, an increase in indirect interaction via multisensory node leads to enhanced gamma band and reduced alpha band coherences observed during illusory perception. Overall, we establish the mechanistic basis of large-scale FC patterns underlying cross-modal perception.

neuroscience↗

bioRxiv2018

Green function of correlated genes and themechanical evolution of protein

There has been growing evidence that cooperative interactions and configurational rearrangements underpin protein functions. But in spite of vast genetic and structural data, the information-dense, heterogeneous nature of protein has held back the progress in understanding the underlying principles. Here we outline a general theory of protein that quantitatively links sequence, dynamics and function: The protein is a strongly-coupled amino acid network whose interactions and large-scale motions are captured by the mechanical propagator, also known as the Green function. The propagator relates the gene to the connectivity of the amino acid network and the transmission of forces through the protein. How well the force pattern conforms to the collective modes of the functional protein is measured by the fitness. Mutations introduce localized perturbations to the propagator which scatter the force field. The emergence of function is manifested by a topological transition when a band of such perturbations divides the protein into subdomains. Epistasis quantifies how much the combined effect of multiple mutations departs from additivity. We find that epistasis is the nonlinearity of the Green function, which corresponds to a sum over multiple scattering paths passing through the localized perturbations. We apply this mechanical framework to the simulations of protein evolution, and observe long-range epistasis which facilitates collective functional modes. Our model lays the foundation for understanding the protein as an evolved state of matter and may be a prototype for other strongly-correlated living systems.

biophysics↗

bioRxiv2017

TRIP6 inhibits the Hippo signaling pathway in response to tension at adherens junctions

The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together these findings reveal a novel mechanotransduction cascade that transduces tension signals sensed at adherens junctions to control Hippo pathway signaling.

cell biology↗

bioRxiv2016

Flagellar synchronization is a simple alternative to cell cycle synchronization for ciliary and flagellar studies

The unicellular green alga, Chlamydomonas reinhardtii, is an ideal model organism for studies of ciliary function and assembly. In assays for biological and biochemical effects of various factors on flagellar structure and function, synchronous culture is advantageous for minimizing variability. Here, we have characterized a method in which 100% synchronization is achieved with respect to flagellar length but not with respect to the cell cycle. The method requires inducing flagellar regeneration by amputation of the entire cell population and limiting regeneration time, which results in a maximally homogeneous distribution of flagellar length at three hours post-amputation. We find that time-limiting new protein synthesis during flagellar synchronization limits variability in the unassembled pool of limiting flagellar protein and variability in flagellar length without regulating the cell volume. We also find that long and short flagella mutants that regenerate normally require longer and shorter synchronization times, respectively. By minimizing flagellar length variability using a simple method requiring only hours and no changes in media, flagellar synchronization facilitates the detection of small changes in flagellar length resulting from both chemical and genetic perturbations in Chlamydomonas. This method increases our ability to probe the basic biology of ciliary size regulation and related disease etiologies.

cell biology↗