Biology subjects

Kalra, M.

Publications and source records attributed to Kalra, M..

5 recordsLinked to original sources

bioRxiv2026

HY5 orchestrates the transcriptional network controlling coumarin-mediated iron acquisition under elevated pH conditions

Iron (Fe) bioavailability is strongly limited in alkaline soils, where reduced Fe solubility severely restricts plant growth and productivity. To overcome this, Arabidopsis thaliana promotes Fe acquisition by secreting Fe-mobilizing coumarins, however, the transcriptional mechanisms coordinating this response is not clearly understood. Here we identify the ELONGATED HYPOCOTYL 5 (HY5), a bZIP transcription factor as a master regulator of coumarin mediated Fe acquisition under alkaline conditions. HY5 positively regulates genes required for coumarin biosynthesis, activation, secretion, and transcriptional control, and loss of HY5 markedly reduces their expression during high-pH-induced Fe deficiency. Chromatin immunoprecipitation analyses revealed that HY5 directly associates with the promoters of these genes, thereby establishing a transcriptional regulatory network that coordinates coumarin biosynthesis. Consistent with this regulatory function, hy5 mutants exhibit reduced coumarin accumulation, impaired root growth, chlorosis, and decreased Fe accumulation under alkaline conditions. Comparable phenotypes in coumarin-hy5 double mutants, together with the restoration of growth by exogenous fraxetin, demonstrate that HY5 functions upstream of coumarin-mediated Fe mobilization. Collectively, our findings identify HY5 as a molecular hub that integrates environmental pH signals with coumarin biosynthesis to promote adaptive Fe acquisition under alkaline conditions, providing a framework for improving crop performance on calcareous soils.

plant biology↗

bioRxiv2026

Enkephalin constrains fear learning via volume transmission to the lateral amygdala

Fear learning involves the formation of associations between cues and aversive outcomes, a process that must be tightly regulated to prevent excessive or generalised fear. Dopamine release in the lateral amygdala (LA) drives fear acquisition, whereas endogenous opioids constrain it. However, whether opioids are dynamically released within the amygdala circuits during learning, and how they exert this control remain unclear. Here we show that met-enkephalin is locally released within the amygdala during auditory fear conditioning, with signals shifting from the aversive outcome to its predictive cue as learning progresses. The amygdalo-striatal transition zone (ASt), is the principal source of this enkephalin, released from medium spiny neurons receiving strong auditory thalamic input. This enkephalin spreads from the ASt to the LA via volume transmission. Selective knockdown in the ASt abolished opioid signals and enhanced fear learning, demonstrating that this diffuse signal constrains fear memory formation. We further show that enkephalin suppresses dopamine release in both the ASt and LA via {micro}-opioid receptors, identifying the ASt as a neuromodulator hub coordinating opioid and dopaminergic signalling across amygdala fear circuits. Although demonstrated here for auditory fear learning, the ASt receives multimodal sensory input, suggesting a broader mechanism through which sensory experience recruits enkephalin release to gate associative learning

neuroscience↗

bioRxiv2026

Corepressor NCoR1-mediated regulation of mucin dynamics governs gut inflammation

Inflammatory bowel disease (IBD), comprising Ulcerative colitis (UC) and Crohns Disease, is a chronic relapsing immune-mediated inflammatory disorder of the gut. The intestinal mucus layer is a protective barrier that safeguards direct exposure of epithelium to luminal microbes and antigens. A prolonged disruption of the mucus layer may contribute to the development of IBD. Loss of mucin-producing goblet cells is a hallmark of UC. The underlying molecular mechanism controlling goblet regulation remains poorly understood. In the current work, we show a key role for NCoR1 (Nuclear corepressor 1) in goblet cell regulation. A specific downregulation of NCoR1 in intestinal crypts and goblet cells was observed in human UC and mice models. While NCoR1 was upregulated during goblet cell differentiation, inflammatory cues downregulated its expression. Experimental loss of NCoR1 resulted in exacerbated disease in a murine model of colitis, whereas its upregulation via Vitamin D led to a rescue. ChIP-seq led to the identification of KLF-16, a transcription factor, as a target of NCoR1. NCoR1 -KLF16 regulatory axis regulated key goblet cell proteins, including MUC2. Mechanistically, the regulation of MUC2 is modulated by the NCoR1-KLF16 axis, via mTOR signalling. In conclusion, this work shows a critical involvement of NCoR1-KLF16 in governing goblet cell function and intestinal homeostasis.

molecular biology↗

bioRxiv2026

Carbon Cybernetics Array: a miniaturized carbon-based microelectrode array for intracortical recording

Implantable brain-machine interfaces, capable of capturing high-resolution neural signals, hold great promise for treating neurological conditions and advancing neuroscience research. As the field moves toward chronic, fully implantable systems, ensuring the long-term safety and stability of the microelectrode arrays, the core component of these interfaces, remains a significant challenge. Hermetic sealing, which prevents moisture and contaminants from entering the device, is a critical yet often overlooked factor in array designs. This study reports the Carbon Cybernetics Array, a hermetically sealed, carbon-based microelectrode array for neural interfacing. Carbon fiber electrodes are anchored on a diamond substrate via a hermetic feedthrough structure, with hermeticity validated through helium leak testing. These ultrathin and flexible carbon fibers require minimal insertion force, cause little tissue damage after six months of implantation in rats and enable single-unit neural recordings. Furthermore, a low-cost, manually controllable insertion toolset is developed for precise array implantation in the sheep brain through a small burr hole, demonstrating a step toward clinical translation. Finally, the scalability of the fabrication approach is exemplified by arrays with over 1000 fibers. Together, this hermetically sealed feedthrough structure will lay the foundation for a future fully implantable device with wireless capabilities.

bioengineering↗

bioRxiv2020

Evolution-guided mutagenesis of the cytoplasmic incompatibility proteins: Identifying CifAs complex functional repertoire and new essential regions in CifB

Wolbachia are the worlds most common, maternally-inherited, arthropod endosymbionts. Their worldwide distribution is due in part to a selfish drive system termed cytoplasmic incompatibility (CI) that confers a relative fitness advantage to females that transmit Wolbachia to their offspring. CI results in embryonic death when infected males mate with uninfected females but not infected females. Under the Two-by-One genetic model of CI, males expressing the two phage WO proteins CifA and CifB cause CI, and females expressing CifA rescue CI. While each protein is predicted to harbor three functional domains, there is no knowledge on how sites across these Cif domains, rather than in any one particular domain, contribute to CI and rescue. Here, we use evolution-guided, substitution mutagenesis of conserved amino acids across the Cif proteins, coupled with transgenic expression in uninfected Drosophila melanogaster, to determine the functional impacts of conserved residues evolving mostly under purifying selection. We report that amino acids in CifAs N-terminal unannotated region and annotated catalase-related domain are important for both complete CI and rescue, whereas C-terminal residues in CifAs putative domain of unknown function are solely important for CI. Moreover, conserved CifB amino acids in the predicted nucleases, peptidase, and unannotated regions are essential for CI. Taken together, these findings indicate that (i) all CifA amino acids determined to be involved in rescue are correspondingly involved in CI, (ii) an additional set of CifA amino acids are uniquely important in CI, and (iii) CifB amino acids across the protein, rather than in one particular domain, are all essential for CI. We discuss how these findings advance an expanded view of Cif protein evolution and function, inform the mechanistic and biochemical bases of Cif-induced CI/rescue, and continue to substantiate the Two-by-One genetic model of CI. Article summaryWolbachia are maternally-transmitted, intracellular bacteria that occur in approximately half of arthropod species worldwide. They can spread rapidly though host populations via the cytoplasmic incompatibility (CI) drive system. CI causes embryonic death when infected males mate with infected females, but offspring of infected females are rescued. Two proteins, CifA and CifB, underlie the genetic basis of CI and rescue, but how amino acid sites across these proteins contribute to CI and/or rescue remain unknown. Here, we employed evolution-guided, combinatorial mutagenesis on conserved amino acids to understand their relative contributions to CI and rescue. The results of this study reveal a phenotypic complexity underlying the expression of these proteins and provide relevance to the biochemical and mechanistic bases of CI and rescue.

microbiology↗