The Bicoid (Bcd) protein gradient in Drosophila serves as a paradigm for gradient formation in textbooks. To explain the generation of the gradient, the ARTS model, which is based on the observation of a bcd mRNA gradient, proposes that the bcd mRNA, localized at the anterior pole at fertilization, migrates along microtubules (MTs) at the cortex to the posterior to form a bcd mRNA gradient which is translated to form a protein gradient. To fulfil the criteria of the ARTS model, an early cortical MT network is thus a prerequisite. We report hitherto undiscovered MT activities in the early embryo important for bcd mRNA transport: (i) an early and omnidirectional MT network exclusively at the anterior cortex of early nuclear cycle embryos showing activity during metaphase and anaphase only, (ii) long MTs up to 50 µm extending into the yolk at blastoderm stage to enable basal-apical transport. The cortical MT network is not anchored to the actin cytoskeleton. The posterior transport of the mRNA via the cortical MT network critically depends on maternally-expressed αTubulin67C and the minus-end motor Ncd. In either mutant, cortical transport of the bcd mRNA does not take place and the mRNA migrates along another yet undisclosed interior MT network, instead. Our data strongly corroborate the ARTS model and explain the occurrence of the bcd mRNA gradient.

The use of silver nanoparticles (AgNPs) against various pathogens is now being well recognized in the agriculture and health sector. Nanoparticles have been shown to exhibit various novel properties and these properties, on other hand, rely upon the size, shape, and morphology of these particles. Moreover, these physical characteristics enable them to interact with microbes, plants, and animals. Smaller-sized particles have shown more toxicity than larger-sized nanoparticles. AgNPs have shown growth inhibition of many fungi like Aspergillus fumigates, A. niger, A. flavus, Trichophyton rubrum, Candida albicans, and Penicillium species. According to the current hypothesis, AgNPs act by producing reactive oxygen species and free radicals, which cause protein denaturation, nucleic acid and proton pump damage, lipid peroxidation, and cell wall damage. Therefore, they alter the cell membrane permeability, causing cell death. This mini-review summarizes the use of silver nanoparticles against fungal pathogens and fungal biofilm in the agricultural sector.

Several lines of evidence indicate that Fibronectin Extra Domain A (EDA) promotes metastatic capacity of tumor cells by engaging cell surface α9β1 integrins. This interaction mediated by the C-C loop of EDA activates pro-oncogenic signaling pathways leading to epithelial to mesenchymal transition (EMT) of tumor cells, thus signifying its importance in control of metastatic progression. In this context the present study was designed to explore the active compounds from selected ethno-medicinal plants of western Himalayan region for targeting EDA of Fibronectin in lung carcinoma cells. Structure based informatics for drug designing and screening was employed to generate a lead compound(s) feed that were conformationally and energetically viable. Out of 120 compounds selected, Irigenin showed best binding-affinity with C-C loop of EDA. Irigenin specifically targeted α9β1 and α4β1 integrin binding sites on EDA comprising LEU46, PHE47, PRO48, GLU58, LEU59 and GLN60 in its C-C loop as evaluated by energy decomposition per residue of Irigenin–EDA complex. In-vitro cell motility assays complemented with EDA knock-in and knockdown assays distinctively demonstrated that Irigenin prevents metastatic capacity of lung cancer cells by selectively blocking EDA. The results presented thus project Irigenin as a lead compound to overcome Fibronectin EDA induced metastatic progression in lung carcinoma cells.

Aim: The implications of molecular biomarkers IDH1/2 mutations and MGMT gene promoter methylation were evaluated for prognostic outcome of glioma patients. Materials & methods: Glioma cases were analyzed for IDH1/2 mutations and MGMT promoter methylation by DNA sequencing and methylation-specific PCR, respectively. Results: Mutations found in IDH1/2 genes totaled 63.4% (N = 40) wherein IDH1 mutations were significantly associated with oligidendrioglioma (p = 0.005) and astrocytoma (p = 0.0002). IDH1 mutants presented more, 60.5% in MGMT promoter-methylated cases (p = 0.03). IDH1 mutant cases had better survival for glioblastoma and oligodendrioglioma (log-rank p = 0.01). Multivariate analysis confirmed better survival in MGMT methylation carriers (hazard ratio [HR]: 0.59; p = 0.031). Combination of both biomarkers showed better prognosis on temozolomide (p < 0.05). Conclusion: IDH1/2 mutations proved independent prognostic factors in glioma and associated with MGMT methylation for better survival.

Tumor-associated macrophages (TAMs) play a pivotal role in facilitating tumor growth and metastasis. This tumor-promoting propensity of TAMs sets in as a result of their complex cross-talk with tumor cells mediated primarily by tumor cell-secreted proteins in the tumor microenvironment. To explore such interactions, we employed an immunoscreening approach involving the immunization of Balb-c mice with model human lung carcinoma cell line, A549. From serological examination combined with mass spectrometric analysis, EDA-containing fibronectin (EDA FN) was identified as a conspicuous immunogenic protein in A549 cell secretome. We showed that A549 secreted EDA FN engages TLR-4 on THP-1 monocytes to drive the proinflammatory response via NF-κB signaling cascade. Conversely, A549 derived EDA FN potentiates their metastatic capacity by inducing epithelial-mesenchymal transition through its autocrine activity. In conclusion, the study proposes a possible mechanism of cellular cross-talk between lung cancer cells and associated monocytes mediated by lung cancer-derived EDA FN and resulting in the establishment of proinflammatory and metastatic tumor microenvironment.