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Biology subjects

Vashistha, H.

Publications and source records attributed to Vashistha, H..

6 recordsLinked to original sources

A neural circuit for olfactory motion detection

Movement is a defining feature of dynamic environments and a key variable encoded by sensory systems. In vision, neural mechanisms that extract motion direction have been studied extensively across species, revealing circuits that compare signals across space and time. Odor plumes likewise carry motion information in their spatiotemporal structure, which walking fruit flies detect and exploit to improve navigation (Brudner et al., 2025; Kadakia et al., 2022), independent of wind sensing. However, how olfactory circuits compute odor motion remains unknown. Here we identify circuitry in the Drosophila antennal lobe that transforms bilateral odor inputs into direction-selective signals that are propagated to higher brain regions. These direction-selective signals were widespread across most measured olfactory channels, spanning pheromones, food odors, and aversive cues. Directional responses were elicited by odor traces with naturalistic temporal statistics and tuned to inter-antennal delays of {approx}40 ms. Connectomic, physiological, and behav-ioral analyses identified one GABAergic inhibitory neuron in the antennal lobe as a key mediator of direction selectivity. Measurements of dynamics in direction-selective neurons revealed ipsilateral excitation and delayed contralateral inhibition. In a minimal data-driven model, this mechanism was sufficient to generate the observed direction-selective responses. These results establish motion detection as a circuit-level olfactory computation and reveal how an early sensory circuit transforms spatiotemporal chemical signals into a neural representation of odor motion to guide navigation.

neuroscience↗

Dynamic trajectory cues drive sequenced integration in approach detectors

Detecting approaching objects is essential for survival, and studies across animals have identified neurons and circuits selective for objects that grow in size over time, a hallmark of visual approach. However, approach as a physical process generates a rich ensemble of correlated cues governed by geometry and physics, of which size expansion is just one, and how the brain incorporates this broader cue structure to detect approach remains unknown. Here, we show that a visual stimulus without size expansion but with modulated luminance, a cue intrinsic to approach, elicits compelling percepts of approach and retreat in both humans and the fruit fly Drosophila, revealing an unsuspected, cross-species percept of approach based on luminance alone. Using targeted genetic silencing and two-photon calcium imaging in flies, we identify neurons that mediate evasive responses to both expansion-based and luminance-based approach, establishing them as general approach detectors. Guided by the geometry of approach, we show that luminance cues should precede detectable expansion signals during naturalistic approach. Consistent with this, these neurons combine luminance and expansion cues synergistically, but only when luminance changes precede expansion, matching their natural temporal order, thus performing sequenced cue integration. Together, these findings anchor a cross-species perceptual phenomenon to a defined circuit computation and reveal how neural circuits are tuned to the dynamic cue structure of natural events.

neuroscience↗

Metabolomic rearrangement controls the intrinsic microbial response to temperature changes

Temperature is one of the key determinants of microbial behavior and survival, whose impact is typically studied under heat- or cold-shock conditions that elicit specific regulation to combat lethal stress. At intermediate temperatures, cellular growth rate varies according to the Arrhenius law of thermodynamics without stress responses, a behavior whose origins have not yet been elucidated. Using single-cell microscopy during temperature perturbations, we show that bacteria exhibit a highly conserved, gradual response to temperature upshifts with a time scale of [~]1.5 doublings at the higher temperature, regardless of initial/final temperature or nutrient source. We find that this behavior is coupled to a temperature memory, which we rule out as being neither transcriptional, translational, nor membrane dependent. Instead, we demonstrate that an autocatalytic enzyme network incorporating temperature-sensitive Michaelis-Menten kinetics recapitulates all temperature-shift dynamics through metabolome rearrangement, which encodes a temperature memory and successfully predicts alterations in the upshift response observed under simple-sugar, low-nutrient conditions, and in fungi. This model also provides a mechanistic framework for both Arrhenius-dependent growth and the classical Monod Equation through temperature-dependent metabolite flux.

cell biology↗

Multiple timescales in bacterial growth homeostasis

In balanced exponential growth, bacterial cells maintain the stability of multiple properties simultaneously: cell size, growth rate, cycle time and more. These are not independent but strongly coupled variables; it is not a-priori clear which are under direct regulation and which are stabilized as a by-product of interactions. Here, we address this problem by separating different timescales in bacterial single-cell dynamics. Disentangling homeostatic set-points from fluctuations around them, we find that some properties have flexible set-points that highly sensitive to environment - defining "sloppy" variables, while other set-points are buffered and held tightly controlled - "stiff" variables. These control variables are combinations of sloppy ones that compensate one another over long times, creating a hierarchical buffering that protects them from environmental perturbations. This is manifested geometrically as a control manifold in the space of growth and division variables, whose in-plane directions span sloppy variables, while out-of-plane deviations are highly constrained. Cell size is found to be a sloppy variable, which is coupled to growth and division only on the short, single-cycle timescale. Our results show that cellular homeostasis involves multi-level regulation operating on multiple timescales. More generally, our work offers a data-driven approach for identifying control variables in a multi-dimensional system that can be applicable also in other contexts.

biophysics↗

Integrated genomic view of SARS-CoV-2 in India

India first detected SARS-CoV-2, causal agent of COVID-19 in late January-2020, imported from Wuhan, China. March-2020 onwards; importation of cases from rest of the countries followed by seeding of local transmission triggered further outbreaks in India. We used ARTIC protocol based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT from Oxford Nanopore Technology to understand introduction and local transmission. The analyses revealed multiple introductions of SARS-CoV-2 from Europe and Asia following local transmission. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, here, proposed as A4-clade based on its divergence within A-cluster. The viral haplotypes may link their persistence to geo-climatic conditions and host response. Despite the effectiveness of non-therapeutic interventions in India, multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.

microbiology↗

Apolipoprotein L1 Dynamics in Human Parietal Epithelial Cell Molecular Phenotype Kinetics

Human Parietal Epithelial cells (PECs) are considered as a source of progenitor cells to sustain podocyte (PD) homeostasis. We hypothesized that the absence of apolipoprotein (APO) L1 favors the PEC phenotype and that induction of APOL1 transitions to PD renewal. During PECs transition, APOL1 expression coincided with the expression of PD markers (PEC transition) along with down regulation of miR193a. The induction of APOL1 down regulated miR193a and induced PD markers in PECs/HEKs; whereas, the APOL1-silencing in transited (Tr)-PECs/HepG2s up regulated miR193a expression suggesting a reciprocally linked feedback loop relationship between APOL1 and miR193a. HIV, IFN-y, and vitamin D receptor agonist (VDA) induced APOL1 expression and PEC transition markers but down regulated miR193a in PECs/HEKs. Glomeruli in HIV patients and HIV: APOL1 transgenic mice displayed foci of PECs expressing synaptopodin, a PEC transition marker. Since APOL1 silencing in PECs partially attenuated HIV-, VDA-, and IFN-y-induced PECs transition, this would suggest that APOL1 is an important functional constituent of APOL1-miR193a axis.

molecular biology↗