22 research outputs found
Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin
No full textThe role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 mu M. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.NIT-Rourkela; DST, Government of Indi
Loss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response
No full textAbstract
Background
Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage. Therefore, as a prerequisite to maintain sustained proliferation in fibroblasts, activation of distinct DNA repair mechanism is essential.
Result
In this study, we report that TET3, a DNA demethylating enzyme, which has been shown to be reduced in cardiac fibrosis and to exert antifibrotic effects does so not only through its demethylating activity but also through maintaining genomic integrity by facilitating error-free homologous recombination (HR) repair of DNA damage. Using both in vitro and in vivo models of cardiac fibrosis as well as data from human heart tissue, we demonstrate that the loss of TET3 in cardiac fibroblasts leads to spontaneous DNA damage and in the presence of TGF-β to a shift from HR to the fast but more error-prone non-homologous end joining repair pathway. This shift contributes to increased fibroblast proliferation in a fibrotic environment. In vitro experiments showed TET3’s recruitment to H2O2-induced DNA double-strand breaks (DSBs) in mouse cardiac fibroblasts, promoting HR repair. Overexpressing TET3 counteracted TGF-β-induced fibroblast proliferation and restored HR repair efficiency. Extending these findings to human cardiac fibrosis, we confirmed TET3 expression loss in fibrotic hearts and identified a negative correlation between TET3 levels, fibrosis markers, and DNA repair pathway alteration.
Conclusion
Collectively, our findings demonstrate TET3’s pivotal role in modulating DDR and fibroblast proliferation in cardiac fibrosis and further highlight TET3 as a potential therapeutic target.
Graphical abstract
Schematic representation illustrating the role of TET3 in modulating the DDR response in healthy and fibrotic fibroblasts.Open-Access-Publikationsfonds 202
TET3 IMPACTS CARDIAC FIBROSIS PARTIALLY VIA REGULATION OF DNA DAMAGE RESPONSE
No full textActivation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage. Therefore, as a prerequisite to maintain sustained proliferation in fibroblasts, activation of distinct DNA repair mechanism is essential. We have previously shown a protective epigenetic role of TET3 in organ fibrosis. Here, we demonstrate that TET3 additionally impacts DNA damage response (DDR) mechanisms via orchestrating checkpoint-assisted homologous recombination (HR)-mediated DDR, and that TGF-ß, in combination with lack of TET3 in cardiac fibrosis, leads to an increase of a checkpoint-arrest independent non-homologous end joining (NHEJ) DDR. Finally, we provide evidence that overexpression of TET3 reduces the increased proliferation rate of fibrotic fibroblasts by shifting the DDR response from NHEJ to HR
The Theme of Betrayal in Tagore’s Home and The World
No full textRabindranath Tagore was a prolific author who earned name and fame worldwide for his contribution in literature. Tagore depicts the different shades of man’s life through the characters of his novels. Tagore touches the different issues like : the struggle for freedom, the existence of good and evil of the world. Tagore’s The Home and the World deals with the theme of betrayal and the relationship of husband and wife and how the wife realizes her mistake at the end of the novel This paper is a sincere effort to display how the betrayal of Bimala effects Nikhil’s life and how she is deceived by her idol Sandip
Impact of Time-dependent Annealing on TiO2 Films for CMOS application
No full textPost-deposition annealing (PDA) is the inherent part of sol-gel fabrication process to achieve the optimum device performance, especially in CMOS applications. The annealing removes the oxygen vacancies and improves the structural order of dielectric films. The process also reduces the interface related defects and improves the interfacial properties. In this work, we have integrated the sol-gel spin-coating deposited high-TiO2 films in MOS. The films are fired at 400 degrees C for the duration of 20, 40, 60 and 80 min. The thicknesses of the films were found to be of similar to 30 nm using ellipsometry. The (Al/TiO2/p-Si) devices were examined with current-voltage (I-V) and capacitance-voltage (C-V) at room temperature to understand the influence of firing time. The C-V and I-V characteristic showed a significant dependence on annealing time such as variation in dielectric constant and leakage current. The accumulation capacitance (Cox), dielectric constant (kappa) and the equivalent oxide thickness (EOT) of the film fired for 60 min were found to be 458 pF, 33, and 4.25nm, respectively with a low leakage current density (1.09 10(-6) A/cm(2)) fired for 80 min at + 1 V
Band Alignment and Electrical Investigations of Ultra-Thin Al2O3 on Si by E-beam Evaporation
No full textThe continuous downscaling leads the search of high-gate dielectrics. The films amorphous in nature offered good mechanical flexibility, smooth surfaces and better uniformity associated with low leakage current density. In this work, 16 nm thick amorphous Al2O3 films on silicon substrate are fabricated by E-beam evaporation. The high value of refractive index (1.76) extracted from ellipsometry analysis directs the deposition of compact film. The AFM analysis reveal a flat surface with small RMS surface roughness 1.5 angstrom. The band gap is extracted from O-1s electron loss spectra and was found 6.7 eV and band alignment of Al2O3/Si is derived from the UPS measurements. The films are incorporated in Metal Insulator -Semiconductor (MIS) capacitor to perform the electrical measurement. The flat band voltage (V-FB), dielectric constant () and oxide trapped charges (Q(ot)) extracted from high frequency (1 MHz) C-V curve are - 0.4 V, 8.4 and 2 x 10(11) cm(-2), respectively. The small flat band voltage - 0.4 V, narrow hysteresis and very little frequency dispersion suggest an exceptional good Al2O3/Si interface with small quantity of trapped charges in the oxide. The leakage current density was 4.27 x 10(-8) A/cm(2) at 1 V. The moderate dielectric constant and low leakage current density with ultra-smooth surface is quite useful towards its application in future CMOS and memory devices
Institutional investment, equity volume and volatility spillover: Causalities and asymmetries
No full textAbstractWe study four-varyingly liberalized emerging markets, precisely, India, Korea, Taiwan and Vietnam, to test causalities and asymmetries of price volume relationship in the conditional second moment. Unlike past literature, equity volume appears as endogenous dynamic information evolving simultaneously with volatility. We extend past researches correlating equity return and volume after splitting into domestic and foreign institutional investor purchases. Uniquely, volatility led impact on volume is much bigger than the volume led impact on volatility. Among other results, we highlight that conditional correlation between volume dispersion and returns dispersion triggers and plays an important role in the stabilization of equity markets
Software Quality Assesment using COCOMO-II Metrics with ABC and NN
No full textTime, cost and quality predictions are the key aspects of any software development system. Loses that result due to wrong estimations may lead to irresistible damage. It is observed that a badly estimated project always results into a bad quality output as the efforts are put in the wrong direction. In the present study, author proposed ABC-COCOMO-II as a new model and tried to enhance the extent of accuracy in effort quality assessment through effort estimation. In the proposed model author combined the strengths of COCOMO-II (Constructive Cost Model) with the Artificial Bee Colony (ABC) and Neural Network (NN). In the present work, ABC algorithm is used to select the best solution, NN is used for the classification purpose to improve the quality estimation using COCOMO-II. The results are compared and evaluated with the pre-existing effort estimation models. The simulation results had shown that the proposed combination outperformed in terms of quality estimation with small variation of 5-10% in comparison to the actual effort, which further leads to betterment of the quality. More than 90% projects results into high quality output for the proposed algorithmic architecture
