AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model

Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Canada Day Theorem

The Canada Day Theorem is an identity involving sums of $k \times k$ minors of an arbitrary $n \times n$ symmetric matrix. It was discovered as a by-product of the work on so-called peakon solutions of an integrable nonlinear partial differential equation proposed by V. Novikov. Here we present another proof of this theorem, which explains the underlying mechanism in terms of the orbits of a certain abelian group action on the set of all $k$-edge matchings of the complete bipartite graph $K_{n,n}$.Comment: 16 pages. pdfLaTeX + AMS packages + TikZ. Fixed a hyperlink problem and a few typo

Income Convergence: The Dickey-Fuller Test under the Simultaneous Presence of Stochastic and Deterministic Trends

We investigate the efficiency of the Dickey-Fuller (DF) test as a tool to examine the convergence hypothesis. In doing so, we first describe two possible outcomes, overlooked in previous studies, namely Loose Catching-up and Loose Lagging-behind. Results suggest that this test is useful when the intention is to discriminate between a unit root process and a trend stationary process, though unreliable when used to differentiate between a unit root process and a process with both deterministic and stochastic trends. This issue may explain the lack of support for the convergence hypothesis in the aforementioned literature.Divergence, Loose Catching-up/Lagging-behind, Convergence, Deterministic and Stochastic trends

Testing for a Deterministic Trend when there is Evidence of Unit-Root

Whilst the existence of a unit root implies that current shocks have permanent effects, in the long run, the simultaneous presence of a deterministic trend obliterates that consequence. As such, the long-run level of macroeconomic series depends upon the existence of a deterministic trend. This paper proposes a formal statistical procedure to distinguish between the null hypothesis of unit root and that of unit root with drift. Our procedure is asymptotically robust with regard to autocorrelation and takes into account a potential single structural break. Empirical results show that most of the macroeconomic time series originally analyzed by Nelson and Plosser (1982) are characterized by their containing both a deterministic and a stochastic trend.Unit Root, Deterministic Trend, Trend Regression, R2

Nonsmooth Morse-Sard theorems

We prove that every function $f:\mathbb{R}^n\to \mathbb{R}$ satisfies that the image of the set of critical points at which the function $f$ has Taylor expansions of order $n-1$ and non-empty subdifferentials of order $n$ is a Lebesgue-null set. As a by-product of our proof, for the proximal subdifferential $\partial_{P}$, we see that for every lower semicontinuous function $f:\mathbb{R}^2\to\mathbb{R}$ the set $f(\{x\in\mathbb{R}^2 : 0\in\partial_{P}f(x)\})$ is $\mathcal{L}^{1}$-null.Comment: Final version. The main result has been strengthened thanks to the suggestions of a refere

Steady-State Magnetohydrodynamic Flow Around an Unmagnetized Conducting Sphere

The non-collisional interaction between conducting obstacles and magnetized plasma winds can be found in different scenarios, from the interaction occurring between regions inside galaxy clusters to the interaction between the solar wind and Mars, Venus, active comets or even the interaction between Titan and the Saturnian's magnetospheric flow. These objects generate, through several current systems, perturbations in the streaming magnetic field leading to its draping around the obstacle's effective conducting surface. Recent observational results suggest that several properties associated with the magnetic field draping, such as the location of the polarity reversal layer of the induced magnetotail, are affected by variations in the conditions of the streaming magnetic field. To improve our understanding of these phenomena, we perform a characterization of several magnetic field draping signatures by analytically solving an ideal problem in which a perfectly conducting magnetized plasma (with frozen-in magnetic field conditions) flows around a spherical body for various orientations of the streaming magnetic field. In particular, we compute the shift of the inverse polarity reversal layer as the orientation of the background magnetic field is changed.Comment: Preprint submitted to Astrophysical Journa