Search for TeV γ\gamma -rays from H1426+428 during 2004-07 with the TACTIC telescope

The BL Lac object H1426+428 ($z\equiv 0.129$) is an established source of TeV $\gamma$-rays and detections of these photons from this object also have important implications for estimating the Extragalactic Background Light (EBL) in addition to the understanding of the particle acceleration and $\gamma$-ray production mechanisms in the AGN jets. We have observed this source for about 244h in 2004, 2006 and 2007 with the TACTIC $\gamma$-ray telescope located at Mt. Abu, India. Detailed analysis of these data do not indicate the presence of any statistically significant TeV $\gamma$-ray signal from the source direction. Accordingly, we have placed an upper limit of $\leq1.18\times10^{-12}$ $photons$ $cm^{-2}$ $s^{-1}$ on the integrated $\gamma$-ray flux at 3$\sigma$ significance level.Comment: 11 pages, 5 figures accepted for publication in Journal of Physics G: Nuclear and Particle Physic

Effects of oxalate on the re-initiation of DNA synthesis in LLC-PK1 cells do not involve p42/44 MAP kinase activation

Effects of oxalate on the re-initiation of DNA synthesis in LLC-PK1 cells do not involve p42/44 MAP kinase activation.BackgroundOxalate interaction with renal epithelial cells results in a program of events that include alterations in gene expression, re-initiation of DNA synthesis, cell growth and apoptosis. Our studies focused on understanding the mechanisms involved in the oxalate-induced re-initiation of the DNA synthesis. The effects of oxalate alone or in combination with epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and insulin were investigated to determine whether oxalate utilized the p42/44 mitogen activated protein (MAP) kinase pathway, which is a common pathway used by a majority of the mitogens.MethodsLLC-PK1 cells (a renal epithelial cell line of porcine origin) were exposed to oxalate in the presence or absence of three established growth factors, EGF, insulin and PDGF, and of the transcription/translation inhibitors, actinomycin-D and cycloheximide. DNA synthesis was assessed by [3H]-thymidine incorporation. p42/44 MAP kinase activity was assessed by super-shift analysis as well as by immunocomplex kinase assay.ResultsExposure of growth-arrested LLC-PK1 cells to oxalate resulted in the re-initiation of the DNA synthesis that had been abolished earlier by pretreatment with transcription/translation inhibitors. Oxalate (1mmol/L), EGF (50 ng/mL) and insulin (100 ng/mL) stimulated DNA synthesis in growth-arrested LLC-PK1 cells, while PDGF (50 ng/mL) had no effect. Effects of EGF and oxalate on DNA synthesis were additive. In contrast, oxalate and insulin had antagonistic effects on DNA synthesis. Additionally, oxalate did not activate the p42/44 MAP kinase pathway while EGF stimulated this pathway.ConclusionsThese findings demonstrate that oxalate does not activate the p42/44 MAP kinase pathway, and the effects of oxalate are mediated by pathways that are distinct from those of EGF, PDGF and insulin

Very High Energy gamma-ray observations of Mrk 501 using TACTIC imaging gamma-ray telescope during 2005-06

In this paper we report on the Markarian 501 results obtained during our TeV $\gamma$-ray observations from March 11 to May 12, 2005 and February 28 to May 7, 2006 for 112.5 hours with the TACTIC $\gamma$-ray telescope. During 2005 observations for 45.7 hours, the source was found to be in a low state and we have placed an upper limit of 4.62 $\times$ 10$^{-12}$ photons cm$^{-2}$ s$^{-1}$ at 3$\sigma$ level on the integrated TeV $\gamma$-ray flux above 1 TeV from the source direction. However, during the 2006 observations for 66.8h, detailed data analysis revealed the presence of a TeV $\gamma$-ray signal from the source with a statistical significance of 7.5$\sigma$ above $E_{\gamma}\geq$ 1 TeV. The time averaged differential energy spectrum of the source in the energy range 1-11 TeV is found to match well with the power law function of the form ($d\Phi/dE=f_0 E^{-\Gamma}$) with $f_0=(1.66\pm0.52)\times 10^{-11}cm^{-2}s^{-1}TeV^{-1}$ and $\Gamma=2.80\pm0.27$.Comment: 16 pages and 8 Figures Accepted for publication in the Journal of Physics

Regulation of SPDEF expression by DNA methylation in advanced prostate cancer

IntroductionProstate cancer (PCa) presents a significant health challenge in men, with a substantial number of deaths attributed to metastatic castration resistant PCa (mCRPC). Moreover, African American men experience disproportionately high mortality rates due to PCa. This study delves into the pivotal role of SPDEF, a prostate specific Ets transcription factor, and its regulation by DNA methylation in the context of PCa progression.MethodsWe performed Epigenetic reprogramming using daily treatment with non-toxic dose of 5Aza-2-deoxycytidine (5Aza-dC) for two weeks to assess its impact on PDEF expression in prostate cancer cells. Next, we conducted functional studies on reprogrammed cells, including cell migration (wound-healing assay), invasion (Boyden-Chamber test), and proliferation (MTT assay) to comprehensively evaluate the consequences of altered PDEF expression. We used bisulfite sequencing (BSP) to examine DNA methylation at SPDEF promoter. Simultaneously, we utilized siRNA-mediated targeting of key DNMTs (DNMT1, DNMT3A, and DNMT3B) to elucidate their specific role in regulating PDEF. We measured mRNA and protein expressions using qRT-PCR and immune-blotting techniques, respectively.ResultsIn this report, we observed that: a) there is a gradual decrease in SPDEF expression with a concomitant increase in methylated CpG sites within the SPDEF gene during prostate cancer progression from lower to higher Gleason grade; b) Expression of DNMT’s (DNMT1, 3a and 3b) is increased during prostate cancer progression, and there is an inverse correlation between SPDEF and DNMT expression; c) SPDEF levels are decreased in RC77/T, a line of PCa cells from African American origin similar to PC3 and DU145 cells (CRPC cells), as compared to LNCaP cells , a line of androgen dependent cells,; d) the 5′ CpG island of SPDEF gene are hypermethylated in SPDEF-negative CRPC ( PC3, DU145 and RC77/T) cell lines but the same regions are hypomethylated in SPDEF-positive castrate sensitive (LNCaP) cell line ; (e) expression of SPDEF in PCa cells lacking SPDEF decreases cell migration and invasion, but has no significant effect on cell proliferation, and; (f) treatment with the demethylating agent, 5-aza-2′-deoxycytidine, or silencing of the DNMT’s by siRNA, partially restores SPDEF expression in SPDEF-negative PCa cell lines, and decreases cell migration and invasion.DiscussionThese results indicate hypermethylation is a prevalent mechanism for decreasing SPDEF expression during prostate cancer progression. The data demonstrate that loss of SPDEF expression in prostate cancer cells, a critical step in cellular plasticity, results from a potentially reversible process of aberrant DNA methylation. These studies suggest DMNT activity as a potential therapeutic vulnerability that can be exploited for limiting cellular plasticity, tumor progression, and therapy resistance in prostate cancer

Observations of TeV gamma-rays from Mrk 421 during Dec. 2005 to Apr. 2006 with the TACTIC telescope

The TACTIC $\gamma$-ray telescope has observed Mrk 421 on 66 clear nights from Dec. 07, 2005 to Apr. 30, 2006, totalling $\sim$ 202 hours of on-source observations. Here, we report the detection of flaring activity from the source at $\geq$ 1 TeV energy and the time-averaged differential $\gamma$-ray spectrum in the energy range 1-11 TeV for the data taken between Dec. 27, 2005 to Feb. 07, 2006 when the source was in a relatively higher state as compared to the rest of the observation period. Analysis of this data spell, comprising about $\sim$97h reveals the presence of a $\sim 12.0 \sigma$ $\gamma$-ray signal with daily flux of $>$ 1 Crab unit on several days. A pure power law spectrum with exponent $-3.11\pm0.11$ as well as a power law spectrum with an exponential cutoff $(\Gamma = -2.51\pm0.26$ and $E_0=(4.7\pm2.1) TeV)$ are found to provide reasonable fits to the inferred differential spectrum within statistical uncertainties. We believe that the TeV light curve presented here, for nearly 5 months of extensive coverage, as well as the spectral information at $\gamma$-ray energies of $>$ 5 TeV provide a useful input for other groups working in the field of $\gamma$-ray astronomy.Comment: 13pages,4figures; Accepted for publication in Astroparticle Physic