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Kumar Sinha, D.

Publications and source records attributed to Kumar Sinha, D..

2 recordsLinked to original sources

Lipid Droplet metabolism dependent microbial defense in pre-immune zebrafish embryos

Microbes present survival challenge to pre-immune embryos. Our study provides evidence for antimicrobial-secretion-based strategy of zebrafish embryos against microbes during pre-immune stages. Chorion prevents physical contact between embryos and microbes, yet microbes compromise embryonic survival through their secretions. Development of embryos in microbe-free medium involves secretion of pro-microbial compounds that bacteria utilize to accelarete growth. Embryo senses presence of microbes through microbial secretions. They respond by altering their secretions to include antimicrobial compounds along with regular pro-microbial ones. Upon sensing embryonic anti-microbial secretions, microbes too alter their secretions to include more potent toxins for embryos. In response to this embryos alter their secretions to include more potent antimicrobial compounds. Ability of embryos to secrete antimicrobial compounds is positively correlated with amount of lipid droplets (LDs) in them. Inhibition of LD metabolism prevents antimicrobial secretions by embryos. Thus, LDs protect zebrafish embryos from microbes. This manuscript establishes that pre-immune embryos employ dynamically evolving biochemical warfare to protect themselves from harmful microbes.

developmental biology↗

3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-{kappa}{beta} activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather its the adhesion which triggers the differentiation of monocytes. MAPK, and NF-{kappa}{beta} being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.\n\nSummary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.

cell biology↗