Search

MicroRNAs (miRNAs) repress protein expression by binding to the target mRNAs. Exploring whether the expression of one miRNA can regulate the abundance and activity of other miRNAs, we noted the coordinated biogenesis of miRNAs in activated macrophages. miRNAs with higher numbers of binding sites (the "primary" miRNAs) induce expression of other miRNAs ("secondary" miRNAs) having binding sites on the 3' untranslated region (UTR) of common target mRNAs. miR-146a-5p, in activated macrophages, acts as a "primary" miRNA that coordinates biogenesis of "secondary" miR-125b, miR-21, or miR-142-3p to target new sets of mRNAs to balance the immune responses. During coordinated biogenesis, primary miRNA drives the biogenesis of secondary miRNA in a target mRNA- and Dicer1 activity-dependent manner. The coordinated biogenesis of miRNAs was observed across different cell types. The target-dependent coordinated miRNA biogenesis also ensures a cumulative mode of action of primary and secondary miRNAs on the secondary target mRNAs. Interestingly, using the "primary" miR-146a-5p-specific inhibitor, we could inhibit the target-dependent biogenesis of secondary miRNAs that can stop the miRNA-mediated buffering of cytokine expression and inflammatory response occurring in activated macrophages. Computational analysis suggests the prevalence of coordinated biogenesis of miRNAs also in other contexts in human and in mouse.

Biofilm is the conglomeration of microbial cells which is associated with a surface. In the recent times, the study of biofilm has gained popularity and vivid research is being done to know about the effects of biofilm and that it consists of many organisms which are symbiotic in nature, some of which are human pathogens. Here, in this study, we have discussed about biofilms, its formation, relevance of its presence in the biosphere, and the possible remediations to cope up with its negative effects. Since removal of biofilm is difficult, emphasis has been made to suggest ways to prevent biofilm formation and also to devise ways to utilize biofilm in an economically and environment-friendly method.

Leishmania donovani, the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells of the mammalian host. It is not clear how the parasite infected cells cross-talk with the non-infected cells in the infection niche to regulate the infection process. Interestingly, miRNAs, the regulatory small RNAs of the host, could get trafficked into and out of infected cells as part of extracellular vesicles to ensure exchange of the epigenetic signals and can regulate the expression of their target genes in both donor and recipient cells. Leishmania, for its survival in host macrophage, adopts a dual strategy to regulate the intercellular transport of host miRNAs. The parasite, by preventing mitochondrial function of the host cells, restricts the entry of liver cell derived miR-122 containing extracellular vesicles in infected macrophage to curtail the inflammatory response by miR-122. The parasite reciprocally upregulates the extracellular export of anti-inflammatory miR-146a from the infected cells. The exported miR-146a restricts miR-122 production in liver cells and polarizes neighbouring naïve macrophages to the M2 state. miR-146a upregulates IL-10 in neighbouring macrophages where miR-146a dominates the RNA binding and miRNA suppressor protein HuR to inhibit the expression of proinflammatory cytokine mRNAs having HuR-interacting AU-rich elements and polarized the recipient cells to M2 stage.Graphical AbstractKey FindingsLeishmania stops vesicular entry of inflammatory miR-122 in infected cells by causing mitochondrial depolarizationLeishmania secrets miR-146a from infected cells to stop miR-122 production in neighbouring hepatocytesmiR-146a containing vesicles secreted by infected cells stops inflammatory response in recipient naïve macrophagemiR-146 targets RNA binding protein HuR to stop inflammatory cytokine production

The nature of fractality and correlations in relativistic heavy-ion interactions of $$^{16}$$ O–Ag/Br at collision energy 60 A GeV are investigated in the framework of the sandbox algorithm using the concept of isotropy and anisotropy of phase space. In this work, we have attempted to find the deterministic information in $$\eta -\phi $$ space using the concept of Hurst exponent (H) by means of precise determination of topological parameters from the complex network perspective. The experimental data have been compared with Monte Carlo (MC) generated events to extract non-statistical dynamics. It has been observed that the process under study is multifractal in nature. It is also observed that the process is ruled by a small number of large fluctuations and contributes to correlated stochastic long-term positive auto-correlations. The characteristics of the multiparticle production process under study are independent of the spatial distribution of $$\eta $$ and $$\phi $$ space, where $$\eta $$ is pseudorapidity and $$\phi $$ is the azimuthal angle, but the degree of multifractality depends on the spatial distribution of pions in anisotropic phase space during the multiparticle production process. It is also observed that for different Hurst exponents, the multifractality of the experimental data sets are significantly different from the MC-simulated events.