Plant genomes are complex and contain large amounts of repetitive DNA including microsatellites that are distributed across entire genomes. Whole genome sequences of several monocot and dicot plants that are available in the public domain provide an opportunity to study the origin, distribution and evolution of microsatellites, and also facilitate the development of new molecular markers. In the present investigation, a genome-wide analysis of microsatellite distribution in monocots (Brachypodium, sorghum and rice) and dicots (Arabidopsis, Medicago and Populus) was performed. A total of 797,863 simple sequence repeats (SSRs) were identified in the whole genome sequences of six plant species. Characterization of these SSRs revealed that mono-nucleotide repeats were the most abundant repeats, and that the frequency of repeats decreased with increase in motif length both in monocots and dicots. However, the frequency of SSRs was higher in dicots than in monocots both for nuclear and chloroplast genomes. Interestingly, GC-rich repeats were the dominant repeats only in monocots, with the majority of them being present in the coding region. These coding GC-rich repeats were found to be involved in different biological processes, predominantly binding activities. In addition, a set of 22,879 SSR markers that were validated by e-PCR were developed and mapped on different chromosomes in Brachypodium for the first time, with a frequency of 101 SSR markers per Mb. Experimental validation of 55 markers showed successful amplification of 80% SSR markers in 16 Brachypodium accessions. An online database ‘BraMi’ (Brachypodium microsatellite markers) of these genome-wide SSR markers was developed and made available in the public domain. The observed differential patterns of SSR marker distribution would be useful for studying microsatellite evolution in a monocot–dicot system. SSR markers developed in this study would be helpful for genomic studies in Brachypodium and related grass species, especially for the map based cloning of the candidate gene(s).
Large number of well-filled grains per panicle is an important yield component trait in rice. A combination of QTL mapping and transcriptome profiling was used to identify candidate genes for grain number. A framework linkage map was constructed using 166 SSR markers evenly distributed over the 12 rice chromosomes. QTL mapping using 3 years phenotyping data on a set of recombinant inbred lines derived from a cross between Pusa 1266 (high grain number) and Pusa Basmati 1 (low grain number) identified one consistent QTL qGN4-1 on the long arm of chromosome 4 with major effect on grain number. This QTL was co-localized with major QTLs for primary and secondary branches per panicle, and number of panicles per plant. The QTL interval was narrowed down to 11.1 cM (0.78 Mbp) by targeted enrichment of the region with six additional markers. Microarray transcriptome profiling revealed eight genes in the qGN4-1 region differentially expressed between the two parents during early panicle development. Synteny of this QTL and potential candidates was examined in wheat, barley, maize, sorghum, and Brachypodium to further validate the association.
Structural diversity of flavonoids and biological activities has remained an important discourse in the mainstream of flavonoid research. In the present studies different class of flavonoids such as flavones, flavanones and flavanolols were evaluated for their antiangiogenic, cytotoxic and antioxidant activities. The anti-angiogenic activity was evaluated using in vivo chorioallantoic membrane model (CAM), antioxidant potential and kinetics of free radical scavenging activity was determined using DPPH (2, 2-diphenyl-1-picryl hydrazine) and superoxide anion radical (SOR) scavenging assays, while cytotoxicity against selected cancer cell lines was carried out using MTT cell viability assay. The physicochemical properties/quantum chemical discriptors of the selected flavonoids were calculated using BioMed CAChe 6.1.10 drug. The selected flavonoids were docked in silico onto the proangiogenic peptides such as vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF-1α), and vascular endothelial growth factor receptor-2 (VEGFR2) and others from human origin. The results of the present investigation are discussed in the mainstream of structure activity relationship which may be useful in translating flavonoids as therapeutic molecules targeting angiogenesis. References 1. Gacche R. N. Shegokar Harshala, Gond Dhananjay , A. D. Jadhav and Ghole Vikram. (2010). Effect of Hydroxyl Substitution of Flavone on Antiangiogenic and Free Radical Scavenging Activities: A Structure Activity Relationship Studies Using Computational Tools. European J. Pharmaceutical Science 39, 37-44. 2. Gacche R. N. Shegokar Harshala, Gond Dhananjay , Zhenzhou Yang, A. D. Jadhav (2011). Evaluation of selected flavonoids as antiangiogenic, anticancer and radical scavenging agents: an experimental and in silico analysis. Cell Biochemistry and Biophysics 61, 651-663. DOI 10.1007/s12013-011-9252-z. 3. Gacche RN and Meshram RJ (2013) Targeting Tumor Micro-environment for Design and Development of Novel Anti-angiogenic Agents Arresting Tumor Growth. Progress in Biophysics & Molecular Biology 113 (2013) 333-354. Note: This abstract was not presented at the meeting. Citation Format: Raju N. Gacche, Harshala D. Shegokar, Dhananjay S. Gond, Rohan J. Meshram. Structural peculiarities of flavonoids influence anti-angiogenic, cytotoxic and antioxidant effects: experimental and insilico analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1006. doi:10.1158/1538-7445.AM2014-1006
The evolving drug resistance and cancer heterogeneity is limiting the efficacy of current chemotherapy drugs. In the present state of the art, natural product and drug discovery has remained a significant hope for the identification of novel leads against series anti-cancer drug targets. The major issue is to convert the traditional knowledge into clinical reality by applying omics approaches. As a part of our continues efforts in exploring the efficacy of Prosopis juliflora as possible resource for the management of cancer, we have carried out the efficacy of P. juliflora against melanoma cancer using B16F10 as a melanoma model. The rational in selecting the melanoma lies in its aggressive metastatic phenotype and resistance to present chemotherapy drugs. Prosopis juliflora leaves methanol extract (PJLME) was assessed for its anticancer activity against B16F10 skin melanoma cancer cell line. Series of in vitro and in vivo experiments demonstrated that PJLME is cytotoxic (IC5017ug/ml), inhibited the migration ability of cells, inhibited the colony formation, arrested cell cycle at G0-G1 phase, induced apoptosis by up regulating the pro-apoptic markers like Bax & Bad, along with successful cleavage of Caspase-9 and PARP-1 and down regulated the anti-apoptotic marker Bcl2. The PJLME also suppressed the expression of Akt, mTOR and ERK signalling pathways. The in vivo xenograft studies in BALB/c mice model demonstrated impressive activity against the melanoma cancer. As a part of understanding the possible mechanism of action, our studies indicate that, PJLME induces cell death via apoptosis mechanism and by down regulating the cell proliferation signalling pathways. The HPLC-MS analysis of PJLME indicates the diversity of compounds, few of them are known for their anticancer effects. Our studies unraveled the significance of PJLME as a novel natural source for the management of melanoma cancer. Citation Format: Raju Nivarti Gacche. Novel leads from Prosopis juliflora (Sw.) arrest the growth of B16F10 melanoma cancer cells by inducing apoptosis and down regulating the cell proliferating signalling pathways [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6551.
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