Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one of the most prevalent cancers in the world and more than one million women are diagnosed leading to 410,000 deaths every year. In our previous studies new chalcone-imidazolone conjugates were prepared and evaluated for their anticancer activity in a panel of 53 human tumor cell lines and the lead compounds identified were 6 and 8. This prompted us to investigate the mechanism of apoptotic event.</p> <p>Results</p> <p>Involvement of pro-apoptotic protein (Bax), active caspase-9 and cleavage of retinoblastoma protein was studied. Interestingly, the compounds caused upregulation of p21, check point proteins (Chk1, Chk2) and as well as their phosphorylated forms which are known to regulate the DNA damage pathway. Increased p53BP1 foci by immunolocalisation studies and TRF1 suggested the possible involvement of telomere and associated proteins in the apoptotic event. The telomeric protein such as TRF2 which is an important target for anticancer therapy against human breast cancer was extensively studied along with proteins involved in proper functioning of telomeres.</p> <p>Conclusions</p> <p>The apoptotic proteins such as Bax, active caspase-9 and cleaved RB are up-regulated in the compound treated cells revealing the apoptotic nature of the compounds. Down regulation of TRF2 and upregulation of the TRF1 as well as telomerase assay indicated the decrease in telomeric length revealing telomeric dysfunction and thereby controlling the rapid rate of cell proliferation. In summary, chalcone-imidazolone conjugates displayed significant DNA damage activity particularly at telomeres and caused both apoptosis and senescence-like growth arrest which suggested that these compounds have potential activity against breast carcinoma.</p

Salinity tolerance and ion accumulation in chickpea (Cicer arietinum L.) subjected to salt stress

Chickpea (Cicer arietinum L.) is considered a salt sensitive species, but some genetic variation for salinity tolerance exists. The present study was initiated to determine the degree of salt tolerance among chickpea genotypes, and the relationship between salt tolerance and ion accumulation in leaves and reproductive tissues. Methods Three experiments were conducted in a glasshouse in Perth, Western Australia, in which up to 55 genotypes of chickpea were subjected to 0, 40 or 60 mM NaCl added to the soil to determine the variation in salt tolerance, and the association between salt tolerance and reproductive success. Pod and seed numbers, seed yield and yield components, pollen viability, in vitro pollen germination and in vivo pollen tube growth, were used to evaluate reproductive success. Leaves, flowers and seeds were sampled in the reproductive phase to measure the concentrations of sodium, potassium and chloride ions in these organs. Results When grown in soil with 40 mM NaCl, a 27-fold range in seed yield was observed among the 55 chickpea genotypes. The increased salt tolerance, as measured by yield under salinity or relative yield under saline conditions, was positively associated with higher pod and seed numbers, and higher shoot biomass, but not with time to 50 % flowering nor with the number of filled pods in the non-saline treatment. Pod abortion was higher in the salt sensitive genotypes, but pollen viability, in vitro pollen germination and in vivo pollen tube growth were not affected by salinity in either the salt tolerant or salt sensitive genotypes. The concentrations of sodium and potassium ions, but not chloride, in the seed were significantly higher in the sensitive (106 μmol g−1 DM of sodium and 364 μmol g−1 DM of potassium) than in the tolerant (74 and 303 μmol g−1 DM, respectively) genotypes. Sodium and potassium, but particularly chloride, ions accumulated in leaves and in pod wall, whereas accumulation in the seed was much lower. Conclusions Considerable genotypic variation for salt tolerance exists in chickpea germplasm. Selection for genotypes with high pod and/or seed numbers that accumulate low concentrations of salt in the seed will be beneficial

Drosophila Argonaute-1 is critical for transcriptional cosuppression and heterochromatin formation

Argonaute-1 (Ago-1) plays a crucial role in gene regulation and genome stability via biogenesis of small non-coding RNAs. Two “Argonaute” family genes, piwi and Ago-2 in Drosophila are involved in multiple silencing mechanisms in the nucleus, transgene cosuppression, long-distant chromosome interaction, nuclear organization and heterochromatin formation. To investigate whether Ago-1 also plays a similar role, we have generated a series of Ago-1 mutations by excising P element, inserted in the Ago-1 promoter (Ago-1k08121). AGO-1 protein is distributed uniformly in the nucleus and cytosol in early embryos but accumulated predominantly in the cytoplasm during the gastrulation stage. Repeat induced silencing produced by the mini-white (mw) array and transcriptional cosuppression of non-homologous transgenes Adh-w/w-Adh was disrupted by Ago-1 mutation. These effects of Ago-1 are distict from its role in microRNA processing because Dicer-1, a critical enzyme for miRNA biogenesis, has no role on the above silencing. Reduction of AGO-1 protein dislodged the POLYCOMB, EZ (enhancer of zeste) and H3me3K27 binding at the cosuppressed Adh-w transgene insertion sites suggesting its role in Polycomb dependent cosuppression. An overall reduction of methylated histone H3me2K9 and H3me3K27 from the polytene nuclei precisely from the mw promoters was also found that leads to concomitant changes in the chromatin structure. These results suggest a prominent role of Ago-1 in chromatin organization and transgene silencing and demonstrate a critical link between transcriptional transgene cosuppression, heterochromatin formation and chromatin organization. We propose Drosophila Ago-1 as a multifunctional RNAi component that interconnects at least two unrelated events, chromatin organization in the nucleus and microRNA processing in the cytoplasm, which may be extended to the other systems

A Survey: Trust Based Task Assignment in Service Oriented ADHOC Networks with Energy Efficient Optimization

Mobile Ad hoc Network (MANET) is an Infrastructure less network where mobile devices are connected without wires. Each device in MANET can move independently on its own. Thus MANET can change the location and configure by itself. Nowadays Energy Efficiency (EE) of the ADHOC nodes and Trust management becomes an essential aspect, as it is not possible to give sufficient power to the mobile devices of the ADHOC networks. This type of problem in ADHOC networks is a globally optimal problem where some customized branch and bound (BB) algorithm are effectively and efficiently used to solve it. In this paper a survey is done on the trust management protocol with energy efficient optimization

Genetic variability and correlation in pigeonpea genotypes

Forty nine pigeon pea genotypes were evaluated at Agricultural Research Station Tandur during kharif 2015-16. Genotypes were grouped into six clusters based on Mahalonobis D2 statistics. Days to maturity contributed to maximum genetic divergence followed by days to 50% flowering. Maximum inter cluster distance was observed between clusters II and VI and intra cluster distance in cluster I and II. Genotypes in cluster V recorded highest mean values for number of secondary branches/plant and number of pods/plant and seed yield. Broad sense heritability estimates were highest for days to maturity and days to 50% flowering. Significant and positive genotypic and phenotypic correlation was observed between seed yield and number of pods/plant and number of secondary branches/plant. The range of GCV observed was 4.55 to 22.07% for the traits under study indicating the extent of variability present among the pigeon pea genotypes. Path coefficient analysis revealed that days to maturity exhibited maximum direct effect followed by number of pods/plant