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Most chemotherapeutics harm normal cells causing severe side effects and induce the development of resistance in cancer cells. Antimicrobial peptides (AMPs), recognized as anticancer agents, may overcome these limitations. The most studied mechanism underlying multidrug resistance (MDR) is the over-expression of cell membrane transporter P-glycoprotein (P-gp), which extrudes a variety of hydrophobic drugs. Additionally, P-gp contributes to cell membrane composition and increases the net negative charge on cell surface. We postulated that NK-lysin derived cationic peptide NK-2 might discriminate and preferentially eliminate P-gp over-expressing cancer cells. To test this hypothesis, we employed MDR non-small cell lung carcinoma (NCI-H460/R) and colorectal carcinoma (DLD1-TxR) cell lines with high P-gp expression. MDR cancer cells that survived NK-2 treatment had decreased P-gp expression and were more susceptible to doxorubicin. We found that NK-2 more readily eliminated P-gp high-expressing cells. Acting in 'carpet-like' manner NK-2 co-localized with P-gp on the MDR cancer cell membrane. The inhibition of P-gp reduced the NK-2 effect in MDR cancer cells and, vice versa, NK-2 decreased P-gp transport activity. In conclusion, NK-2 could modulate MDR in unique way, eliminating the P-gp high-expressing cells from heterogeneous cancers and making them more vulnerable to classical drug treatment. (C) 2012 Elsevier Inc. All rights reserved. Ministry of Education, Science and Technological Development of Republic of Serbia [III41031]; German Science Foundation (DFG) [AN301/5-1]

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The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved. Ministry of Education and Science, Republic of Serbia [III41031]

This paper presents realization of a digital embedded system for measuring electrical breakdown time delay. The proposed system consists of three major parts: dc voltage supply, analog subsystem, and a digital subsystem. Any dc power source with the range from 100 to 1000 V can be used in this application. The analog subsystem should provide fast and accurate voltage switching on the testing device as well as transform the signals that represent the voltage pulse on the device and the device breakdown into the form suitable for detection by a digital subsystem. The insulated gate bipolar transistor IRG4PH40KD driven by TC429 MOSFET driver is used for high voltage switching on the device. The aim of a digital subsystem is to detect the signals from the analog subsystem and to measure the elapsed time between their occurrences. Moreover, the digital subsystem controls various parameters that influence time delay and provides fast data storage for a large number of measured data. For this propose, we used the PIC18F4550 microcontroller with a full-speed compatible universal serial bus (USB) engine. Operation of this system is verified on different commercial and custom made gas devices with different structure and breakdown mechanisms. The electrical breakdown time delay measurements have been carried out as a function of several parameters, which dominantly influence electrical breakdown time delay. The obtained results have been verified using statistical methods, and they show good agreement with the theory. The proposed system shows good repeatability, sensitivity, and stability for measuring the electrical breakdown time delay.

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Accurate normalization is the prerequisite for obtaining reliable results in the quantification of gene expression. Using TaqMan Real Time RT-PCR, we carried out an extensive evaluation of five most commonly used endogenous controls, gapdh, beta-actin, 18S rRNA, hprt and cypB, for their presumed stability of expression, in rat cortex and hippocampus, during aging, under dietary restriction and dexamethasone treatment. Valid reference genes (HKGs) were identified using GeNorm and NormFinder software packages and by direct comparison of Ct values. Analysis revealed gapdh and P-actin as the most stable HKGs for all treatments analyzed, combined or separately, in the cortex, while in the hippocampus gapdh/ hprt and beta-actin/hprt are the combination of choice for the single or combined effects of dietary restriction/dexamethasone, respectively. All treatments significantly influenced expression of 18S rRNA and cypB in both structures. In addition, we used gapdh and normalization factor, calculated by GeNorm, to compare the expression of a-syn in the cortex. Our results demonstrate the importance of the right choice of HKG and suggest the appropriate endogenous control to be used for TaqMan RT-PCR analysis of mRNA expression in rat cortex and hippocampus for selected experimental paradigms. null

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Dietary restriction (DR) is one of the promising environmental interventions known to attenuate aging and decrease risk of age-related neurodegenerative disorders. The aim of this study was to assess the effects of DR on expression of a-synuclein, a presynaptic protein involved in pathogenesis of Parkinson's and some other neurodegenerative diseases, in the cortex and hippocampus of adult, middle-aged, late middle-aged, and aged rats. Using Real Time RT-PCR, the authors report that aging regulates the expression of alpha-synuclein in a tissue-specific manner and that long-term DR reverts the late age-related changes of alpha-synuclein expression. (c) 2007 Wiley-Liss, Inc. null

Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (

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Kinetics of positive ions and electrically neutral active particles formed during breakdown and successive discharge in neon-filled tube at 6.6 millibars pressure had been analyzed. This analysis was performed on the basis of mean value of electrical breakdown time delay t¯d dependence on afterglow period τ (memory curve). It was shown that positive ions are present in the 1μs 3 s, breakdown is initiated by cosmic rays and natural radioactivity. The increase of discharge current leads to ...

The processes which are a consequence of neutral active particles presence in post-discharge nitrogen-filled tube at 13.3 mbar pressure have been analyzed. The analysis has been performed based on the experimental data of electrical breakdown time delay as a function of afterglow period τ. The most significant parameters such as applied voltage, discharge current, time, and exposure to radiation have been varied. It has been shown that the increase in applied voltage and discharge time, as well as exposure to UV radiation, leads to the decrease of the mean value of electrical breakdown time delay t¯d. This decrease occurs for τ>70 ms, when N(S4) atoms play a dominant role in breakdown initiation. The increase in discharge current leads to the decrease of t¯d values for τ≤70 ms, when positive ions dominantly induce breakdown. The most important reactions which lead to formation of positive ions and neutral active particles are also presented in the paper.

Memory effect in nitrogen based on experimental data of electrical breakdown time delay as a function of afterglow period in the presence of additional electrons has been investigated. The additional electrons were supplied as a result of extraction from the auxiliary electrode pair or nitrogen irradiation with the radioactive source of low activity. The results show that these electrons have an important role in the recombination of positive ions formed in mutual metastable molecules' collisions and collisions between metastable and highly vibrationally excited molecules in the early afterglow. As a consequence of the ion–electron recombination N(4S) atoms are formed which, as well as N(4S) atoms formed in previous discharge, have a significant influence on the memory effect in late afterglow. The presence of N(4S) atoms in the late afterglow is tracked by monitoring the secondary emission which they induce via catalytic recombination on the cathode of a nitrogen-filled tube. Also, it has been shown that the contribution of secondary electrons which originate from N(4S) atoms and Compton electrons when the radioactive source is and isn't present can be distinguished.