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Biology subjects

Vasan, G.

Publications and source records attributed to Vasan, G..

4 recordsLinked to original sources

Mapping the Metalloproteome of Deinococcus indicus DR1 through Integrative Structure and Function Annotation

Deinococcus indicus DR1 is a rod-shaped bacterium isolated from the Dadri wetlands (Uttar Pradesh, India) that tolerates ionizing radiation and arsenic. The molecular basis of its wider heavy-metal resilience, particularly among the 1017 out of 4128 proteins still annotated as hypothetical, remains unclear. We performed a proteome-wide structural and functional survey to address this gap. All the 4128 proteins were modeled with AlphaFold2, yielding very-high-confidence structures (pLDDT [≥] 90) for 2145 sequences. CATH/InterPro analysis assigned domains to 2735 proteins. Functions were predicted by combining DeepFRI (graph neural-network), MorphologFinder (Foldseek plus EggNOG-Mapper), and existing GenBank annotations. The integrated workflow suggests that more than 100 previously uncharacterized proteins may bind or transport arsenic, chromium, cobalt, copper, iron, manganese, molybdenum, nickel, or zinc, indicating a metal-handling capacity that extends beyond the known ars operon. Recurrent domain architectures that include P-loop NTPases, Rossmann folds, GNAT acetyl-transferases, and sensor modules (CHASE, PAS, GAF) point to coordinated redox regulation and efflux pathways. Twenty high-confidence metal-binding candidates have been prioritized for experimental validation through expression, mutagenesis, and knockout studies. All structural models, domain assignments, and query tools are available at https://deinococcus.in, providing a resource for future investigations of heavy-metal tolerance in this organism.

bioinformatics↗

Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals

Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell-types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here we describe two complementary TEMPO voltage-sensing technologies that capture neural oscillations up to [~]100 Hz. Fiber-optic TEMPO achieves [~]10-fold greater sensitivity than prior photometry systems, allows hour-long recordings, and monitors two neuron-classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell-classes across a [~]8-mm-wide field-of-view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in the visual cortex, and previously unreported propagation directions for hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.

neuroscience↗

Behavioral discrimination and olfactory bulb encoding of odor plume intermittency

In order to survive, animals often need to navigate a complex odor landscape where odors can exist in airborne plumes. Several odor plume properties change with distance from the odor source, providing potential navigational cues to searching animals. Here we focus on odor intermittency, a temporal odor plume property that measures the fraction of time odor is present at a given point within the plume and decreases with increasing distance from the odor source. We sought to determine if mice are capable of using changes in intermittency to locate an odor source. To do so, we trained mice on an intermittency discrimination task. We establish that mice can discriminate odor plume samples of low and high intermittency and that the neural responses in the olfactory bulb can account for task performance and support intermittency encoding. Modulation of sniffing, a behavioral parameter that is highly dynamic during odor-guided navigation, affects both behavioral outcome on the intermittency discrimination task as well as neural representation of intermittency. Together, this work demonstrates that intermittency is an odor plume property that can inform olfactory search and more broadly supports the notion that mammalian odor-based navigation can be guided by temporal odor plume properties.

neuroscience↗

Dual polarity voltage imaging reveals subthreshold dynamics and concurrent spiking patterns of multiple neuron-types

Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between distinct, targeted cell populations. However, current indicator families lack the requisite sensitivity for in vivo multipopulation imaging. We describe high-performance green and red sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants, pAce and pAceR. Our indicators enable 0.4-1 kHz voltage recordings from >50 neurons per field-of-view in awake mice and [~]30-min continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered behavioral state-dependent interactions between distinct neocortical subclasses, as well as contributions to hippocampal field potentials from non-overlapping projection neuronal ensembles. By combining three mutually compatible indicators, we demonstrate concurrent triple-population voltage imaging. Our approach will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution. One Sentence SummaryA new suite of voltage sensors enables simultaneous cellular-resolution activity imaging from multiple, targeted neuron-types in awake animals.

neuroscience↗