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Salt stress is a major abiotic stress affecting the productivity of rice crop worldwide. This study screened a set of 71 rice genotypes collected from coastal parts of Goa and Karnataka states in India for seedling stage salinity tolerance to identify genotypes alternative to standard salt-tolerant donors Pokkali, FL478, etc. Phenotyping for seedling stage tolerance was carried out under micro plots at an induced salinity of 12 dS/m. For haplotyping, 14SaltolQTL linked simple sequence repeat (SSR) markers on chromosome 1 were utilized. On the basis of the response to salt stress, 10 genotypes were found tolerant, 16 moderately tolerant, 29 sensitive and 15 as highly sensitive. Among the SSR markers, marker RM10871 was the most polymorphic with a polymorphic information content of 0.90, exhibiting 14 different alleles followed by RM10793 (0.84) and RM3412 (0.80) with 8 and 7 alleles, respectively. These markers also exhibited high values for the effective number of alleles (Ne) and gene diversity (I). The haplotype analysis revealed that the allelic constitution of theSaltolregion of 10 tolerant genotypes from our study varied in comparison to the reference tolerant check FL478. Further, the haplotype of three tolerant genotypes, namely, Goa Dhan 2, Panvel 1 and Goa wild rice (GWR) 005 appears to be completely different from the FL478 haplotype indicating tolerance in these genotypes is controlled by genomic region other thanSaltol.These three genotypes with probable novel regions for seedling stage salt tolerance can be considered for enhancing salinity tolerance of rice cultivars.

Cellular plasticity, by large, is the ability through which cells morph into new phenotypic identity by trading-off with the previous one. This phenomenon has been observed in the normal and tumor cells in a very similar fashion. Occurrence of cellular plasticity, in malignancies like epithelial ovarian carcinoma (EOC) are well known but highly debated in terms of origin of the tumor for the inherent heterogeneity across subtypes. EOC has been termed as a clinically challenging malady for its subversive nature against chemotherapy. The management of ovarian cancer is mostly hindered by relapse with recalcitrance towards primary chemotherapy regimen e.g. platinum–taxol combination. Also, late detection preceded by peritoneal metastasis poses another challenge to the treatment. Underlying both these aspects of the disease, tumor heterogeneity turns out as the most critical factor. In the light of heterogeneity that can be across patients (inter-tumoral) and/or within a tumor (intra-tumoral), ovarian carcinoma is a multifactorial ailment. The governing factors behind this heterogeneity are—diverse genetic landscape among subtypes of EOC; the presence of cancer stem cell (CSC) niche and inherent plasticity of the cancer cells themselves. Apart from the well-studied mechanisms of plasticity, there are several emerging molecular players like lncRNAs, Hippo pathway and also phenomena like dedifferentiation of non-CSC neoplastic cells ,and transdifferentiation of CSCs. Here, we present an overview of the current knowledge on the evolution of EOC through cellular plasticity with emphasis on the three major aspects namely, subtype-specific genetic diversity; ovarian CSC and cancer cell duality between epithelial and mesenchymal lineages.

The present investigation was undertaken to assess the hybridity of experimental F1 plants derived from the crossing of salinity and/or submergence tolerant landraces with the high-yielding popular varieties of the west coast region of India. Seven microsatellite markers were utilized for confirming the hybridity of the 16 F1 plants developed from four cross combinations, viz. Karjat-3 X KS-19-2 (Cross 1), Goa dhan-3 X Jaddubatta (Cross 2), Jaya X KS-19-2 (Cross 3) and Karjat-3 X Jaddubatta (Cross 4). Polymorphism survey using above seven markers between the parents of all the four crosses revealed that six of them were polymorphic, whereas one marker was monomorphic. The marker RM21539 was found to be polymorphic in all the four cross combinations, followed by RM493, RM3412, RM206 and RM10843 exhibiting polymorphism in three crosses, while marker RM25181 was polymorphic in two crosses. The screening of F1s with polymorphic markers revealed that the F1s from Cross 3 exhibited heterozygosity (showing alleles from both the parents) at six marker loci, whereas the F1s from Cross 1 and Cross 4 at five loci and Cross 2 at two marker loci, thereby confirming hybridity in all the 16 tested F1 plants.

An active fluidic microenvironment governs peritoneal metastasis in epithelial ovarian cancer (EOC), but its critical functional/molecular cues are not fully understood. Utilizing co-culture models of NIH3T3 cells (differentially overexpressing Jagged1) and SKOV3 cells expressing a Notch3 luciferase reporter-sensor (SNFT), we showed that incremental expression of Jagged1 led to proportional Notch3 activation in SNFT. With no basal luciferase activity, this system efficiently recorded dose-dependent Notch3 activation by rh-Jag1 peptide and the non-appearance of such induction in co-culture with NIH3T3Δjag1 cells indicates its sensitivity and specificity. Similar Notch3 modulation was shown for the first time in co-cultures with HGSOC patients’ ascites-derived cancer-associated fibroblasts and Jagged1-expressing EOC cell lines. NIH3T3J1-A and OVCAR3 co-cultured SNFT cells showed maximum proliferation, invasion, and cisplatin resistance among all the heterotypic/homotypic cellular partners. VEGFA and CDKN1A are the two most upregulated genes identified across co-cultures by the gene profiler array. Co-culture induced VEGFA secretion from SNFT cells which also reduced cancer stem cell differentiation in platinum-resistant A2780 cells. rh-Jag1-peptide promoted enhanced nuclear-cytoplasmic p21 expression. Additionally, metastatic HGSOC tumors had higher VEGFA than corresponding primary tumors. This study thus demonstrates the tumoral and non-tumoral cell-mediated differential Notch3 activation imparting its tumorigenic effects through two critical molecular regulators, VEGFA and p21, during EOC progression.

Alterations in key kinases and signaling pathways can fine-tune autophagic flux to promote the development of chemoresistance. Despite empirical evidences of strong association between enhanced autophagic flux with acquired chemoresistance, it is still not understood whether an ongoing autophagic flux is required for both initiation, as well as maintenance of chemoresistance, or is sufficient for one of the either steps. Utilizing indigenously developed cisplatin–paclitaxel-resistant models of ovarian cancer cells, we report an intriguing oscillation in chemotherapy-induced autophagic flux across stages of resistance, which was found to be specifically elevated at the early stages or onset of chemoresistance. Conversely, the sensitive cells and cells at late stages of resistance showed stalled and reduced autophagic flux. This increased flux at early stages of resistance was found to be dictated by a hyperactive ERK1/2 signaling, which when inhibited either pharmacologically (U0126/Trametinib) or genetically, reduced p62 degradation, number of LC3+veLAMP1+ve puncta, autophagolysosome formation, and led to chemo-sensitization and apoptosis. Inhibition of ERK1/2 activation also altered the level of UVRAG and Rab7, the two key proteins involved in autophagosome–lysosome fusion. Noninvasive imaging of autophagic flux using a novel autophagy sensor (mtFL-p62 fusion reporter) showed that combinatorial treatment of platinum–taxol along with Trametinib/chloroquine blocked autophagic flux in live cells and tumor xenografts. Interestingly, Trametinib was found to be equally effective in blocking autophagic flux as chloroquine both in live cells and tumor xenografts. Combinatorial treatment of Trametinib and platinum–taxol significantly reduced tumor growth. This is probably the first report of real-time monitoring of chemotherapy-induced autophagy kinetics through noninvasive bioluminescence imaging in preclinical mouse model. Altogether our data suggest that an activated ERK1/2 supports proper completion of autophagic flux at the onset of chemoresistance to endure initial chemotherapeutic insult and foster the development of a highly chemoresistant phenotype, where autophagy becomes dispensable.