Oxidative stress and breast cancer biomarkers : the case of the cytochrome P450 2E1

Aim: The aim of the study is to investigate the impact of the cytochrome P450 2E1, which is the most efficient CYP450 family member in generating reactive oxygen species (ROS), on cellular energy metabolism of breast cancer cells and therefore the effects of CYP2E1 on breast carcinogenesis. Methods: The estrogen receptor positive MCF-7 and the triple negative MDAMB- 231 breast cancer cells were used as experimental system to estimate ROS generation in these cells overexpressing CYP2E1 and treated with the glycolytic inhibitors 3-bromopyruvate or 2-deoxyglucose in the presence or absence of the CYP2E1 inhibitor chlormethiazole. Adenosine triphosphate (ATP) assay was used to measure ATP production and lactate assay to quantify the efflux of lactic acid in breast cancer cells treated with the CYP2E1 inhibitor chlormethiazole, the mitochondrial membrane potential and cell viability assays were employed to assess the pathway of cellular energy production and cellular death respectively after treatment of MCF-7 and MDA-MB-231 with the CYP2E1 activator acetaminophen or the CYP2E1 inhibitor chlormethiazole. Results: T he r esults i ndicated i ncreased ROS generation i n b reast c ancer c ells overexpressing C YP2E1. ROS generation was differentially regulated in breast cancer cells upon treatment with the CYP2E1 inhibitor chlormethiazole. Chlormethiazole treated MCF-7 cells exhibited reduced lactate efflux implying that CYP2E1 directly or indirectly regulates the glycolytic rate in these cells. Furthermore the mitochondrial membrane potential of both MCF-7 and MDA-MB-231 cells was differentially affected by the CYP2E1 activator acetaminophen versus the CYP2E1 inhibitor chlormethiazole providing additional support for the involvement of CYP2E1 in energy metabolic pathways in breast cancer. Conclusion: Results presented in this study provide evidence to suggest that CYP2E1 regulates cellular energy metabolism of breast cancer cells in a manner dependent on cell type and potentially on the clinical staging of the disease therefore CYP2E1 is a possible breast cancer biomarker

Справа Івана Дзюби

У статті автор, використовуючи документи Галузевого державного архіву СБ України, досліджує постать видатного літературознавця, громадського діяча Івана Дзюби у контексті боротьби співробітників органів держбезпеки УРСР з «українським буржуазним націоналізмом».В статье автор, используя документы Отраслевого государственного архива СБ Украины, исследует личность выдающегося литературоведа, общественного деятеля Ивана Дзюбы в контексте борьбы сотрудников органов госбезопасности УССР с «украинским буржуазным национализмом».Using the documents of State branch archive of State Security of Ukraine, the author investigates the personality of Ivan Dzyuba during the struggle of KGB of the UkSSR against the «Ukrainian bourgeois nationalism»

Low- and Medium-Dispersion Spectropolarimetry of Nova V475 Sct (Nova Scuti 2003): Discovery of an Asymmetric High-Velocity Wind in a Moderately Fast Nova

We present low-resolution ($R\sim 90$) and medium-resolution ($R\sim 2500$) spectropolarimetry of Nova V475 Sct with the HBS instrument, mounted on the 0.91-m telescope at the Okayama Astrophysical Observatory, and with FOCAS, mounted on the 8.2-m Subaru telescope. We estimated the interstellar polarization toward the nova from the steady continuum polarization components and H$\alpha$ line emission components. After subtracting the interstellar polarization component from the observations, we found that the H$\alpha$ emission seen on 2003 October 7 was clearly polarized. In the polarized flux spectrum, the H$\alpha$ emission had a distinct red wing extending to $\sim +4900$ km s$^{-1}$ and a shoulder around $+3500$ km s$^{-1}$, showing a constant position angle of linear polarization \theta_{\rm *}\simeq 155\arcdeg\pm 15\arcdeg. This suggests that the nova had an asymmetric outflow with a velocity of $v_{\rm wind}\simeq 3500$ km s$^{-1}$ or more, which is six times higher than the expansion velocity of the ionized shell at the same epoch. Such a high-velocity component has not previously been reported for a nova in the `moderately fast' speed class. Our observations suggest the occurrence of violent mass-loss activity in the nova binary system even during the common-envelope phase. The position angle of the polarization in the H$\alpha$ wing is in good agreement with that of the continuum polarization found on 2003 September 26 ($p_{\rm *}\simeq 0.4$--0.6 %), which disappeared within the following 2 d. The uniformity of the PA between the continuum polarization and the wing polarization on October 7 suggests that the axis of the circumstellar asymmetry remained nearly constant during the period of our observations.Comment: 27 pages, 7 figures, accepted for publication in A

Methods for Reducing False Alarms in Searches for Compact Binary Coalescences in LIGO Data

The LIGO detectors are sensitive to a variety of noise transients of non-astrophysical origin. Instrumental glitches and environmental disturbances increase the false alarm rate in the searches for gravitational waves. Using times already identified when the interferometers produced data of questionable quality, or when the channels that monitor the interferometer indicated non-stationarity, we have developed techniques to safely and effectively veto false triggers from the compact binary coalescences (CBCs) search pipeline

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

Senescence marker protein 30 in acute liver failure: validation of a mass spectrometry proteomics assay

<p>Abstract</p> <p>Background</p> <p>Our previous proteomic study showed that the senescence marker protein (SMP30) is selectively present in the plasma of a murine model of acute liver failure (ALF). The aim of this study was to validate this SMP30 expression in the plasma and liver tissues of mice and humans with ALF.</p> <p>Methods</p> <p>After the proteomic analysis of plasma from a murine model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced ALF by two-dimensional electrophoresis (2-DE) and mass spectrometry, the expression levels of SMP30 in the plasma and liver tissues were validated by western blot and RT-PCR analyses. These results were then confirmed in plasma samples from humans.</p> <p>Results</p> <p>These data validate the results of 2-DE, and western blot showed that SMP30 protein levels were only elevated in the plasma of ALF mice. Further analysis revealed that GalN/LPS induced the downregulation of SMP30 protein levels in liver tissues (by approximately 25% and 16% in the GalN/LPS-treated mice and in the treated mice that survived, respectively; <it>P </it>< 0.01). Hepatic SMP30 mRNA levels decreased by about 90% only in the mice that survived the GalN/LPS treatment. Importantly, plasma obtained from patients with ALF also contained higher levels of SMP30, about (3.65 ± 0.34) times those observed in healthy volunteers.</p> <p>Conclusion</p> <p>This study shows that SMP30 is not only a potential biomarker for the diagnosis and even prognosis of ALF. It also plays a very important role in a self-protective mechanism in survival and participates in the pathophysiological processes of ALF.</p

Spectropolarimetry of R Coronae Borealis in 1998--2003: Discovery of Transient Polarization at Maximum Brightness

We present an extended optical spectropolarimetry of R CrB from 1998 January to 2003 September. The polarization was almost constant in the phase of maximum brightness, being consistent with past observations. We detected, however, temporal changes of polarization ($\sim 0.5$ %) in 2001 March and August, which were the first detection of large polarization variability in R CrB near maximum brightness. The amplitude and the position angle of the `transient polarization' were almost constant with wavelength in both two events. There was a difference by about 20 degrees in the position angle between the two events. Each event could be explained by light scattering due to short-lived dust puff occasionally ejected off the line of sight. The flatness of the polarization against the wavelength suggests that the scatterer is a mixture of dust grains having various sizes. The rapid growth and fading of the transient polarization favors the phenomenological model of dust formation near the stellar photosphere (e.g., within two stellar radii) proposed for the time evolution of brightness and chromospheric emission lines during deeply declining periods, although the fading timescale can hardly be explained by a simple dispersal of expanding dust puff with a velocity of $\sim 200-350$ km s $^{-1}$. Higher expansion velocity or some mechanism to destroy the dust grains should be needed.Comment: 22 pages, 10 figures, accepted for publication in A

Identification of long-duration noise transients in LIGO and Virgo

The LIGO and Virgo detectors are sensitive to a variety of noise sources, such as instrumental artifacts and environmental disturbances. The Stochastic Transient Analysis Multi-detector Pipeline (STAMP) has been developed to search for long-duration (t$\gtrsim$1s) gravitational-wave (GW) signals. This pipeline can also be used to identify environmental noise transients. Here we present an algorithm to determine when long-duration noise sources couple into the interferometers, as well as identify what these noise sources are. We analyze the cross-power between a GW strain channel and an environmental sensor, using pattern recognition tools to identify statistically significant structure in cross-power time-frequency maps. We identify interferometer noise from airplanes, helicopters, thunderstorms and other sources. Examples from LIGO's sixth science run, S6, and Virgo's third scientific run, VSR3, are presented.Comment: 10 pages, 7 figures, Gravitational-wave Physics & Astronomy Worksho