1,089 research outputs found
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
Molecular characterization of polish blueberry red ringspot virus isolate
In this study, we determined the complete sequence of the genomic DNA of a Polish isolate of Blueberry red ringspot virus (BRRSV24) and compared it with a Czech (Darrow 5), and the US isolates of the virus and those of other Caulimoviridae family. The genomic DNA of BRRSV24 consists of 8,265 nucleotides and encodes eight open reading frames (ORFs). The sequence homologies of the eight ORFs of BRRSV24 were from 95 to 98% in respect of Darrow 5 and from 91 to 98% in respect of the US isolates at the amino acid level. This high level of amino acid sequence identity within the coding regions among the Czech, the US and Polish BRRSV isolates is suggestive of their common origin
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
Sperm parameters and epididymis function in transgenic rats overexpressing the Ca-2-binding protein regucalcin: a hidden role for Ca-2 in sperm maturation?
Sperm undergo maturation acquiring progressive motility and the ability to fertilize oocytes through exposure to the components of the epididymal fluid (EF). Although the establishment of a calcium (Ca-2) gradient along the epididymis has been described, its direct effects on epididymal function remain poorly explored. Regucalcin (RGN) is a Ca-2-binding protein, regulating the activity of Ca-2-channels and Ca-2-ATPase, for which a role in male reproductive function has been suggested. This study aimed at comparing the morphology, assessed by histological analysis, and function of epididymis, by analysis of sperm parameters, antioxidant potential and Ca-2 fluxes, between transgenic rats overexpressing RGN (Tg-RGN) and their wild-type littermates. Tg-RGN animals displayed an altered morphology of epididymis and lower sperm counts and motility. Tissue incubation with Ca-45(2) showed also that epididymis of Tg-RGN displayed a diminished rate of Ca-2-influx, indicating unbalanced Ca-2 concentrations in the epididymal lumen. Sperm viability and the frequency of normal sperm, determined by the one-step eosin-nigrosin staining technique and the Diff-Quik staining method, respectively, were higher in Tg-RGN. Moreover, sperm of Tg-RGN rats showed a diminished incidence of tail defects. Western blot analysis demonstrated the presence of RGN in EF as well as its higher expression in the corpus region. The results presented herein demonstrated the importance of maintaining Ca-2-levels in the epididymal lumen and suggest a role for RGN in sperm maturation. Overall, a new insight into the molecular mechanisms driving epididymal sperm maturation was obtained, which could be relevant to development of better approaches in male infertility treatment and contraception.Portuguese Foundation for Science and Technology (FCT) under Program COMPETE [PEst-C/SAU/UI0709/2011]; FCT; FCT fellowships [SFRH/BD/60945/2009, SRFH/BPD/80451/2011]info:eu-repo/semantics/publishedVersio
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 (t1s) 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
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
The next detectors for gravitational wave astronomy
This paper focuses on the next detectors for gravitational wave astronomy
which will be required after the current ground based detectors have completed
their initial observations, and probably achieved the first direct detection of
gravitational waves. The next detectors will need to have greater sensitivity,
while also enabling the world array of detectors to have improved angular
resolution to allow localisation of signal sources. Sect. 1 of this paper
begins by reviewing proposals for the next ground based detectors, and presents
an analysis of the sensitivity of an 8 km armlength detector, which is proposed
as a safe and cost-effective means to attain a 4-fold improvement in
sensitivity. The scientific benefits of creating a pair of such detectors in
China and Australia is emphasised. Sect. 2 of this paper discusses the high
performance suspension systems for test masses that will be an essential
component for future detectors, while sect. 3 discusses solutions to the
problem of Newtonian noise which arise from fluctuations in gravity gradient
forces acting on test masses. Such gravitational perturbations cannot be
shielded, and set limits to low frequency sensitivity unless measured and
suppressed. Sects. 4 and 5 address critical operational technologies that will
be ongoing issues in future detectors. Sect. 4 addresses the design of thermal
compensation systems needed in all high optical power interferometers operating
at room temperature. Parametric instability control is addressed in sect. 5.
Only recently proven to occur in Advanced LIGO, parametric instability
phenomenon brings both risks and opportunities for future detectors. The path
to future enhancements of detectors will come from quantum measurement
technologies. Sect. 6 focuses on the use of optomechanical devices for
obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum
measurement options
Functional characterization of two defensin isoforms of the hard tick Ixodes ricinus
<p>Abstract</p> <p>Background</p> <p>The immune system of ticks is stimulated to produce many pharmacologically active molecules during feeding and especially during pathogen invasion. The family of cationic peptides - defensins - represents a specific group of antimicrobial compounds with six conserved cysteine residues in a molecule.</p> <p>Results</p> <p>Two isoforms of the defensin gene <it>(def1 </it>and <it>def2</it>) were identified in the European tick <it>Ixodes ricinus</it>. Expression of both genes was induced in different tick organs by a blood feeding or pathogen injection. We have tested the ability of synthetic peptides def1 and def2 to inhibit the growth or directly kill several pathogens. The antimicrobial activities (expressed as minimal inhibition concentration and minimal bactericidal concentration values) against Gram positive bacteria were confirmed, while Gram negative bacteria, yeast, Tick Borne Encephalitis and West Nile Viruses were shown to be insensitive. In addition to antimicrobial activities, the hemolysis effect of def1 and def2 on human erythrocytes was also established.</p> <p>Conclusions</p> <p>Although there is nothing known about the realistic concentration of defensins in <it>I. ricinus </it>tick body, these results suggest that defensins play an important role in defence against different pathogens. Moreover this is a first report of a one amino acid substitution in a defensins molecule and its impact on antimicrobial activity.</p
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