Biology subjects

Jayakumar, S.

Publications and source records attributed to Jayakumar, S..

8 recordsLinked to original sources

bioRxiv2026

Ebola virus exploits host lncRNA LINC01740 to enhance ATF3 and suppress antiviral immune responses

Ebola virus (EBOV) infection causes severe hemorrhagic fever marked by dysregulated cytokine production, impaired antiviral defenses, and multi-organ failure. Macrophages are primary targets of EBOV, and viral replication profoundly alters macrophage transcriptional programs, driving hyperinflammation. Although long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of immunity and viral pathogenesis, their roles in EBOV infection remain poorly understood. We performed comprehensive transcriptomic profiling of primary human monocyte-derived macrophages infected with the highly pathogenic EBOV Mayinga variant. Infection triggered extensive remodeling of both coding and non-coding transcriptomes, including hundreds of differentially expressed lncRNAs. Functional analysis of neighboring protein-coding genes of EBOV-induced lncRNAs (EVILs) revealed enrichment of pathways linked to cytokine signaling, transcriptional regulation, and cell signaling, all of which are central to Ebola virus disease (EVD) pathogenesis. Among the most strongly induced EVILs, LINC01740 and its neighboring protein-coding gene, Activating Transcription Factor 3 (ATF3), were significantly upregulated. Antisense oligonucleotide-mediated inhibition of LINC01740 reduced ATF3 mRNA and protein levels. CRISPR/Cas13d-mediated knockdown of ATF3 restored type I interferon (IFN-I) signaling and antiviral gene expression in EBOV-infected macrophages. Mechanistically, ATF3 functions as a negative regulator of IFN-I and type I interferon-stimulated gene expression, thereby suppressing antiviral immune responses in EBOV-infected macrophages. Together, these findings identify a previously unrecognized LINC01740-ATF3-IFN-I regulatory axis that EBOV exploits to promote immune suppression and viral replication.

immunology↗

bioRxiv2026

Oxytocin Modulation of Spinal Circuits Drives Therapeutic Benefits of Massage

Across social species, social touch enhances well-being and reduces pain -- two seemingly distinct benefits that enhance survival. Yet where and how the nervous system integrates these functions, and whether a single mechanism could serve both, remains unknown. Here we show that massage triggers oxytocin release, which shapes both pain and touch reward at the earliest stage of central processing -- the spinal cord -- through a single, state-dependent circuit mechanism. We report that in humans, massage enhances well-being, effects that correlate with endogenous oxytocin release. In mice, gentle touch activates hypothalamic oxytocin neurons that project directly to the spinal dorsal horn. Genetic manipulation of spinal oxytocin circuits alters behavioral responses to both gentle touch and noxious stimuli. Spinal calcium imaging and slice electrophysiology reveal that oxytocin acts on both excitatory and inhibitory spinal neurons to sculpt the relative activity of spinal ascending systems that convey both social touch and pain to the brain. Extending these findings to humans, we show that oxytocin receptors are also expressed on spinal excitatory and inhibitory neurons, and that endogenous oxytocin during massage correlates with altered spinal touch processing. Thus, spinal oxytocin signaling provides an evolutionarily conserved mechanism for the therapeutic benefits of massage.

neuroscience↗

bioRxiv2025

Mice navigate scent trails using predictive policies

Many terrestrial animals accurately follow odor trails, but their navigation strategies remain unclear. We presented mice with dynamic, non-repeating odor trails using a paper treadmill, and found that they rapidly learned to track trails effectively. Odor detections by one or both nostrils during inhalation evoked rapid, stereotyped motor responses. Blocking one nostril led to biased tracking, while disconnecting interhemispheric neural communication disrupted tracking almost entirely. We found that trail tracking is more than a reflex, with mice adapting their movements according to a memory of recently encountered trail geometry. A Bayesian model captures these behaviors, suggesting mice combine bilateral olfactory input with short-term memory to guide navigation actively. Functional perturbations and neural recordings from behaving animals implicate an early olfactory cortical region in trail tracking. These results lay the groundwork to uncover the computational architecture of sensorimotor integration in naturalistic tasks.

neuroscience↗

bioRxiv2025

Perception and neural representation of intermittent odor stimuli in mice

Odor cues in nature are sparse and highly fluctuating due to turbulent transport. To investigate how animals perceive these intermittent cues, we developed a behavioral task in which head-restrained mice made binary decisions based on the total number of discrete odor pulses presented stochastically over several seconds. Mice readily learned this task, and their performance was well-described by widely used decision models. Logistic regression of binary choices against the timing of odor pulses within the respiratory cycle revealed that mice placed higher perceptual weight to stimuli arriving during inhalation than exhalation, a phase dependency that strongly correlated with the magnitude of responses in olfactory sensory neurons. The population response of anterior piriform cortex (APCx) neurons to odor pulses was also modulated by respiration phase, although individual neurons displayed varying levels of phase-dependence. Single APCx neurons responded stochastically and transiently to odor pulses, leading to a representation that carries signatures of sensory evidence, but not its accumulation. Our study reveals that mice can integrate intermittent odor signals across dozens of breaths, but respiratory modulation of sensory inputs imposes limits on information acquisition that cortical circuits cannot overcome to improve behavior.

neuroscience↗

bioRxiv2021

Efficient inhibition of HIV using CRISPR/Cas13d nuclease system

Recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas13 proteins are programmable RNA-guided ribonucleases that target single-stranded RNA (ssRNA). CRISPR/Cas13 mediated RNA targeting has emerged as a powerful tool for detecting and eliminating RNA viruses. Here, we demonstrate the effectiveness of CRISPR/Cas13d to inhibit HIV-1 replication. We designed guide RNAs (gRNAs) targeting highly conserved regions of HIV-1. RfxCas13d (CasRx) in combination with HIV-specific gRNAs efficiently inhibited HIV-1 replication in cell line models. Furthermore, simultaneous targeting of four distinct sites in the HIV-1 transcript resulted in robust inhibition of HIV-1 replication. We also show the effective HIV-1 inhibition in primary CD4+ T-cells and suppression of HIV-1 reactivated from latently infected cells using the CRISPR/Cas13d system. Our study demonstrates the utility of the CRISPR/Cas13d nuclease system to target acute and latent HIV infection and provides an alternative treatment modality against HIV.

molecular biology↗

bioRxiv2020

IP3/Ca2+ signals regulate larval to pupal transition under nutrient stress through the H3K36 methyltransferase dSET2

Persistent loss of dietary protein usually signals a shutdown of key metabolic pathways. In Drosophila larvae, that have crossed "critical weight" and can pupariate to form viable adults, such a metabolic shut-down would needlessly lead to death. IP3/Ca2+ signals in certain interneurons (vGlutVGN6341) allow Drosophila larvae to pupariate on a protein-deficient diet by partially circumventing this shutdown through upregulation of neuropeptide signaling and the expression of ecdysone synthesis genes. Here we show that IP3/Ca2+ signals in vGlutVGN6341 neurons drive expression of dSET2, a Drosophila Histone 3 Lysine 36 methyltransferase. Further, dSET2 expression is required for larvae to pupariate in the absence of dietary protein. IP3/Ca2+ signal-driven dSET2 expression upregulates key Ca2+ signaling genes through a novel positive feedback loop. Transcriptomic studies coupled with analysis of existing ChIP-seq datasets identified genes from larval and pupal stages, that normally exhibit robust H3K36 trimethyl marks on their gene bodies and concomitantly undergo stronger downregulation by knockdown of either an intracellular Ca2+ release channel the IP3R or dSET2. IP3/Ca2+ signals thus regulate gene expression through dSET2 mediated H3K36 marks on select neuronal genes for the larval to pupal transition.

developmental biology↗

bioRxiv2018

A Cortico- Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke

To facilitate the selection of an optimal therapy for a stroke patient with upper extremity hemiparesis, we propose a cortico-basal ganglia model capable of performing reaching tasks under normal and stroke conditions. The model contains two hemispherical systems, each organized into an outer sensory-motor cortical loop and an inner basal ganglia (BG) loop, controlling their respective hands. In addition to constraint induced movement therapy (CIMT), the model performs both unimanual and bimanual reaching tasks and the simulation results are in congruence with the experiment conducted by Rose et al (2004). Based on our study on the effect of lesion size on arm performance, we hypothesize that the effectiveness of a therapy could greatly depend on this factor. By virtue of the models ability to capture the experimental results effectively, we believe that it can serve as a benchmark for the development and testing of various rehabilitation strategies for stroke.

neuroscience↗

bioRxiv2017

A computational model that explores the effect of environmental geometries on grid cell representations

Grid cells are a special class of spatial cells found in the medial entorhinal cortex (MEC) characterized by their strikingly regular hexagonal firing fields. This spatially periodic firing pattern was originally considered to be invariant to the geometric properties of the environment. However, this notion was contested by examining the grid cell periodicity in environments with different polarity (Krupic et al 2015) and in connected environments (Carpenter et al 2015). Aforementioned experimental results demonstrated the dependence of grid cell activity on environmental geometry. Analysis of grid cell periodicity on practically infinite variations of environmental geometry imposes a limitation on the experimental study. Hence we analyze the grid cell periodicity from a computational point of view using a model that was successful in generating a wide range of spatial cells, including grid cells, place cells, head direction cells and border cells. We simulated the model in four types of environmental geometries such as: 1) connected environments, 2) convex shapes, 3) concave shapes and 4) regular polygons with varying number of sides. Simulation results point to a greater function for grid cells than what was believed hitherto. Grid cells in the model code not just for local position but also for more global information like the shape of the environment. The proposed model is interesting not only because it was able to capture the aforementioned experimental results but, more importantly, it was able to make many important predictions on the effect of the environmental geometry on the grid cell periodicity.

neuroscience↗