The ultimate goal of this work was to detect the role of transcription factors (TFs) concordantly expressed with genes related to programmed cell death (PCD) during PCD and salt stress. This work was based on the hypothesis that TFs and their driven genes likely co-express under different stimuli. The conserved superfamily ethylene responsive factor (AP2/ERF) draw attention of the present study as it participates in the response to biotic and abiotic stimuli as well as to program cell death (PCD). RNA-Seq analysis was done for tobacco (N. benthamiana) leaves exposed to oxalic acid (OA) at 20 mM for 0, 2, 6, 12 and 24 h to induce PCD. Genes up-regulated after 2 h of OA treatment with known function during PCD were utilized as landmarks to select TFs with concordant expression. Knockdown mutants of these TFs were generated in tobacco via virus induced gene silencing (VIGS) in order to detect their roles during PCD. Based on the results of PCD assay, knockout (KO) T-DNA insertion mutants of Arabidopsis as well as over-expression lines of two selected TFs, namely ERF109 and TFIID5, analogs to those in tobacco, were tested under salt stress (0, 100, 150 and 200 mM NaCl). Results of knockdown mutant tobacco cells confirmed the influence of these two TFs during PCD. Knockout insertion mutants and over-expression lines indicated the role of ERF109 in conferring salt tolerance in Arabidopsis.

Calotropis procera is a wild plant species in the family Apocynaceae that is able to grow in harsh, arid and heat stressed conditions. Understanding how this highly adapted plant persists in harsh environments should inform future efforts to improve the hardiness of crop and forage plant species. To study the plant response to droμght and osmotic stress, we treated plants with polyethylene glycol and NaCl and carried out transcriptomic and metabolomics measurements across a time-course of five days. We identified a highly dynamic transcriptional response across the time-course including dramatic changes in inositol signaling, stress response genes and cytokinins. The resulting metabolome changes also involved sharp increases of myo-inositol, a key signaling molecule and elevated amino acid metabolites at later times. The data generated here provide a first glimpse at the expressed genome of C. procera, a plant that is exceptionally well adapted to arid environments. We demonstrate, through transcriptome and metabolome analysis that myo-inositol signaling is strongly induced in response to drought and salt stress and that there is elevation of amino acid concentrations after prolonged osmotic stress. This work should lay the foundations of future studies in adaptation to arid environments.

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

Colchicum luteum L. is an economically important and endangered medicinal plant of the Kashmir Himalaya. The corm extract is used for the treatment of rheumatism, gout, Behcet’s syndrome, and Alzheimer disease. It is also used extensively in plant breeding programs for the doubling of chromosomes. The present study was carried out for two years (2017–2019) to study the genetic diversity of C. luteum, an economically important and endangered medicinal plant of Kashmir Himalaya. The mapping of genetic diversity of C. luteum was estimated using Mahalanobis D² analysis in the Aharbal (Kulgam), Dhara (Theed), and Baera Baal Hills (Harwan) of Kashmir Valley. The results showed the presence of 5 clusters for 30 populations. There were 17 populations in cluster-1, 1 in cluster-2, 2 in cluster-3, 3 in cluster-4, and 7 in cluster-5. The majority of the population was a group in cluster-1 followed by cluster-5. The maximum intracluster distance (D² values) was observed in cluster-5 (46.55588) followed by cluster-3 (41.61871), and the maximum inter-cluster distance (D² values) was observed in cluster-3 (46.55588) followed by cluster-5 (41.61871). Our study revealed that plant species possessed sufficient genetic diversity among the populations. Cluster-5 showed superiority in plant⁻¹ respect of the maximum mean plant height (28.46 cm), leaf area (47.0 cm²), number of seeds plant⁻¹ (26.85), corm length (5.15 cm), corm width (3.17 cm), fresh weight of corm plant (6.87 g), and dry weight of corm plant (4.81 g) as compared to other clusters. Out of five clusters, cluster-5 is a promising one for better yield and yield attributing traits. The present study revealed that plant species possessed sufficient genetic diversity among the populations as 30 populations were arranged into 5 clusters. Therefore, cluster-5, consisting of seven populations from the undisturbed area of Harwan, and consequently the populations from the same cluster can be multiplied for initiating a conservation and breeding program and can serve as a tool for the scientific community to evolve better contemporary varieties of C. luteum with profitable characters such as more yield of corms, etc. This will assist farmers, particularly the marginal farmers, to alleviate their income.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

Antibiotics are drugs that are used to treat or prevent bacterial infections. They work by either killing or stopping bacteria from spreading. Nevertheless, it appeared in the last decade, Antibiotic-resistant bacteria are bacteria resistant to antibiotics and cannot be controlled or killed by them. In the presence of an antibiotic, they can live and even reproduce. The Neisseria gonorrhoeae bacteria is appearing to be a multidrug-resistant pathogen. Many factors contribute to antibiotic resistance, including unfettered access to antimicrobials, incorrect drug selection, misuse, and low-quality antibiotics. Here, we investigated in-silico docking screening and analysis for ten natural marine fungus extracted compounds. The resulted data were examined for the best binding affinity, toxicity, and chemical interactions. The most superior compound was elipyrone A with six hydrogen bonds, −8.5 of binding affinity, and preferable results in the SWISS-ADME examination. It is well known that “Declining corporate investment and a lack of innovation in the development of new antibiotics are weakening efforts to battle drug-resistant illnesses,” according to the World Health Organization (WHO). So, we extended our effort to predict a new natural compound to overcome the resistance of this bacteria.