The role of p53 family members in myogenic differentiation and rhabdomyosarcoma development

Krebserkrankungen zeichnen sich häufig durch Störungen zellulärer Differenzierungsprozesse aus. So weisen Rhabdomyosarkome, die aus Muskelvorläuferzellen hervorgehen, Differenzierungsdefekte auf, die zur unkontrollierten Proliferation der Tumorzellen führen. Bislang ist ungeklärt, ob die Differenzierungsdefekte auf der verstärkten Expression von Inhibitoren, der defekten Funktion von Aktivatoren oder einer Kombination von beidem beruht. In dieser Arbeit wird gezeigt, dass im Unterschied zu normalen Muskelzellen RMS-Zellen verstärkt DeltaNp73, einen Pan-Inhibitor der p53-Tumorsuppressorfamilie, exprimieren. Die experimentelle Überexpression von DeltaNp73 in normalen Myoblasten blockierte die Muskeldifferenzierung und förderte in Kombination mit klassischen RMS-Onkogenen wie IGF2 oder PAX3/FKHR die maligne Transformation. Umgekehrt führte die Hemmung von DeltaNp73 durch RNAi zur Reduktion der Tumorigenität von RMS-Tumorzellen. Da DeltaNp73 als dominant-negativer Inhibitor der p53-Familie wirkt, lies die Hemmung von Differenzierungsprozessen durch DeltaNp73 vermuten, dass die p53-Familienmitglieder (p53, p63, und p73) an der Regulation der Muskeldifferenzierung beteiligt sind. Tatsächlich konnte in dieser Arbeit gezeigt werden, dass die drei p53-Familienmitglieder bei der Induktion später Differenzierungsstadien kooperieren, indem sie die Aktivität des Retinoblastoma-Proteins RB regulieren. Die Funktion von RB ist bekanntermassen sowohl für den permanenten Zellzyklusarrest als auch für die Aktivierung Muskel-spezifischer Gene notwendig. Während p53 die Proteinspiegel von RB reguliert, kontrollieren p63 und p73 den Aktivierungsgrad von RB, indem sie dessen Phoshphorylierungszustand über den Zyklin-abhängigen Kinaseinhibitor p57KIP2 modifizieren. Eine Hemmung dieser Funktionen blockiert das Differenzierungsprogramm und fördert die Tumorentstehung. Die Aktivierung zellulärer Differenzierungsprozesse stellt somit einen entscheidenden Bestandteil der Tumorsuppressoraktivität der p53-Familie dar und liefert eine Erklärung für die Häufigkeit von Mutationen im p53-Signalweg bei Rhabdomyosarkom-Patienten.Disruption of differentiation pathways is one of the hallmarks of cancer. In rhabdomyosarcoma (RMS), a human tumor arising from myogenic precursors, the muscle differentiation program is disabled resulting in uncontrolled proliferation. Whether the differentiation block is due to overexpression of inhibitors, deficient function of activators, or both remained unknown. This study shows that RMS cells but not non-neoplastic muscle cells overexpress DeltaNp73, a pan-inhibitor of the p53 family of tumor suppressor genes. Experimental overexpression of DeltaNp73 in normal muscle precursor cells inhibited myogenic differentiation and promoted malignant transformation in cooperation with the RMS oncogenes IGF2 and PAX3/FKHR. Vice versa, RNAi knockdown of DeltaNp73 reduced the tumorigenicity of established RMS tumor cells. As DeltaNp73 is a dominant-negative inhibitor of the p53 family, inhibition of differentiation by DeltaNp73 suggests that the p53 family members (p53, p63 and p73) are critically involved in myogenic differentiation control. Indeed, this study demonstrates that all three p53 family members cooperate to activate the late stages of the differentiation process by regulating the activity of the retinoblastoma protein RB. The function of RB is known to be required for both the permanent cell cycle exit and the activation of muscle-specific genes. Whereas p53 regulates RB protein levels, p63 and p73 control the activation state of RB by modifying its phosphorylation via the cyclin-dependent kinase inhibitor p57KIP2. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation. Induction of cellular differentiation therefore contributes to the tumor suppressor activities of the p53 family and provides an explanation for the high frequency of p53 pathway alterations in rhabdomyosarcoma patients

Iterative Receiver for DS-CDMA Systems in the Presence of Time-Varying Channels

In this paper, we present an efficient iterative receiver structure of tractable complexity for joint multiuser detection and multichannel estimation (JDE) of direct-sequence code-division multiple-access systems operating in the presence of time-varying flat fading channel. The time-varying channel is assumed to be modeled according to a piece-wise constant channel. An optimality criterion is defined and analytical expressions for the corresponding optimized weight coefficients are given. Monte-Carlo simulations of a synchronous scenario show that the proposed JDE receiver have excellent multiuser efficiency and are robust against errors in the estimation of the channel parameters

Multilevel/AES-LDPCC-CPFSK with channel equalization over WSSUS multipath environment

In this paper, in order to ensure secure and robust communication, a new type of data encryption and error correction mechanism called Multilevel/Advanced Encryption Standard-Low Density Parity Check Coded-Continuous Phase Frequency Shift Keying (Multilevel/AES-LDPCC-CPFSK) is carried out. Here, we have chosen AES for data encryption, LDPC codes for error correction and CPFSK for modulation. We have evaluated error performance of this scheme over Wide-Sense Stationary Uncorrelated Scattering (WSSUS) multipath channels with channel equalization. We have simulated 5-level AES, 2-level LDPC for 4CPFSK and 16CPFSK over WSSUS channels modeled by Cooperation in the field of Science & Technology, Project #207 (COST207). We have concluded that our proposed structure has promising results compared to Turbo Codes for all SNR values in WSSUS channels. (C) 2011 Elsevier GmbH. All rights reserved

Cooperative communications with multilevel/AES-SD4-CPFSK in wireless sensor networks

In this paper, a new joint multilevel data encryption and channel coding mechanism is proposed, which is called "multilevel/advanced encryption standard-systematic distance 4-continuous phase frequency shift keying" (ML/AES-SD4-CPFSK). In the proposed scheme, we have not only taken advantage of spatial diversity gains but also optimally allocated energy and bandwidth resources among sensor nodes as well as providing high level of security and error protection for cooperative communications in wireless sensor networks. Relay protocols of cooperative communications, such as amplify-and-forward and decode-and-forward with/without adversary nodes, have been studied for 4CPFSK, 8CPFSK, and 16CPFSK of ML/AES-SD4-CPFSK. We have evaluated the error performances of multilevel AES for data encryption, multilevel SD-4 for channel coding, and various CPFSK types for modulation utilizing cooperative communications in wireless sensor networks. According to computer simulation results, significant diversity gain and coding gain have been achieved. As an example, bit error rate (BER) performance of 10(-5) value has been obtained at a signal-to-noise ratio (SNR) of -6 dB for SD-4-CPFSK scheme in a compared related journal paper, whereas in our proposed system, we have reached the same BER value at a SNR of -23 dB with amplify-and-forward with direct path signal protocol in 16-level AES, two-level SD-4 coded 16CPFSK, and at the same time, we have reached the same BER value at a SNR of -22 dB with amplify-and-forward without direct path signal protocol in 16-level AES, two-level SD-4 coded 16CPFSK

Radiation shielding properties of Poly(hydroxylethyl methacrylate)/Tungsten(VI) oxide composites

AKAT, HAKAN/0000-0003-4002-5352WOS: 000503099500022In this study, it has been demonstrated that poly(hydroxyethyl methacrylate) (PHEMA) -composites containing tungsten(VI) oxide (10%-50%) moieties were successfully prepared by using "radical polymerization method". For this purpose, hydroxyethyl methacrylate was polymerized with Azobisizobiltironitril in dimethyl formamide (DMF) for 0.5 hat 70 degrees C in order to give the corresponding polymer. the synthesized PHEMA was characterized by H-1 NMR, FTIR spectroscoples and GPC. PHEMA - tungsten(VI) oxide composites were prepared at 80 degrees C and their gamma-ray attenuation coefficients were measured using NaI(Tl) scintillation detector. the linear attenuation coefficients of all composites were also calculated theoretically with the XCOM program by considering the elemental analysis of the composites and compared with the experimental results. According to the results of SEM analysis, there is a homogenous dispersion between PHEMA and tungsten(VI) oxide particles. the transmission parameters the half-value layer (HVL), the tenth-value layer (TVL) and the mean free path (MFP) were obtained. It was found that the best shielding material among the studied composites was the PHEMA+50% WO3 with higher linear attenuation coefficient and lower absorption thicknesses

Styrene-based unsaturated polyester-tungsten(VI) oxide composites: Preparation and investigation of their radiation shielding and thermal properties

In this study, the thermal and radiation shielding properties of composites obtained using different ratios of tungsten(VI) oxide unsaturated polyester were investigated. Composites were prepared using WO3.2H(2)O powder in different ratios (10%, 20%, 30%, 40%, and 50%.), and based on Styrene unsaturated polyester were used as resins. The linear attenuation coefficients of the composites were measured by the NaI(Tl) gamma spectrometry system. The attenuation coefficients were also calculated theoretically by the XCOM platform, taking into consideration the basic analysis of composites, and compared with empirical outcomes. According to the results of XRD and particle size distribution of WO3.2H(2)O powder demonstrated had obvious diffraction peaks and its pore size distribution values were good. When the thermal degradation curves of the composites are examined, it is seen that the remaining ash amounts of the prepared composites and the % mass of the prepared composites overlap. It was clear that the best shielding material in the studied composites was styrene-based unsaturated polyester +50% WO3.2H(2)O with a higher linear attenuation coefficient

The relationship between the coronary artery anatomy and the subeustachian isthmus, coronary sinus Os-middle cardiac vein and floor of coronary sinus

56th Annual Scientific Session of the American-College-of-Cardiology -- MAR 24-27, 2007 -- New Orleans, LAWOS: 000244651800102Amer Coll Cardio