Effect of mutations on the p53 IRES RNA structure Implications for de-regulation of the synthesis of p53 isoforms

Earlier we have demonstrated the presence of internal ribosome entry site (IRES) within tumor suppressor p53 mRNA. Here we have mapped the putative secondary structure of p53-IRES RNA using information from chemical probing and nuclease mapping experiments. Additionally, the secondary structure of the IRES element of the wild-type RNA was compared with cancer-derived silent mutant p53 RNAs. These mutations might result in the conformational alterations of p53-IRES RNAs. The results also indicate decreased IRES activities of the mutants as compared to wild-type RNA. Further, it was observed that some of the cytoplasmic trans-acting factors, critical for enhancing IRES function, were unable to bind mutant RNAs as efficiently as to wild-type. Our results suggest that hnRNP C1/C2 binds to p53-IRES and siRNA mediated partial silencing of hnRNP C1/C2 showed appreciable decrease in IRES function and consequent decrease in the level of the corresponding p53 isoform. Interestingly mutant p53 IRES showed lesser binding with hnRNP C1/C2 protein. Finally, upon doxorubicin treatment, the mutant RNAs were unable to show enhanced p53 synthesis to similar extent compared to wild type. Taken together, these observations suggest that mutations occurring in the p53 IRES might have profound implications for de-regulation of its expression and activity.

Planar triazinium cations from VO2+-assisted ring cyclizations: a remarkably efficient thiazole species for nuclear staining, PDT and anaerobic photocleavage of DNA

Planar triazinium cationic species, from VO2+-assisted cyclization of 1-(2-thiazolylazo)-2-naphthol, shows efficient DNA intercalative binding, visible light-induced anaerobic plasmid DNA photocleavage activity and photocytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway with selective localization of the compound in the nucleus as evidenced from the nuclear staining and confocal imaging.

Tunable Brownian vortex at the interface

A general kind of Brownian vortices is demonstrated by applying an external nonconservative force field to a colloidal particle bound by a conservative optical trapping force at a liquid-air interface. As the liquid medium is translated at a constant velocity with the bead trapped at the interface, the drag force near the surface provides enough rotational component to bias the particle's thermal fluctuations in a circulatory motion. The interplay between the thermal fluctuations and the advection of the bead in constituting the vortex motions is studied, and we infer that the angular velocity of the circulatory motion offers a comparative measure of the interface fluctuations.

Schiff base oxovanadium(IV) complexes of phenanthroline bases showing DNA photocleavage activity at near-IR light and photocytotoxicity

Oxovanadium(IV) complexes VO(L)(B)](ClO4) (1-3) of N-2-pyridylmethylidine-2-hydroxyphenylamine (HL) Schiff base and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d: 2',3'-f] quinoxaline (dpq in 2) or dipyrido3,2-a: 2',3'-c] phenazine (dppz in 3), were prepared, characterized and their DNA binding property, photo-induced DNA cleavage activity and photocytotoxicity in HeLa cells studied. The crystal structure of 1 shows the presence of a VO2+ moiety in VO2N4 coordination geometry. The complexes show a d-d band at similar to 830 nm in DMF. The complexes display an oxidative V(V)-V(IV) response near 0.5 V versus SCE and a reductive V(IV)/V(III) response near -0.65 V in DMF -0.1 M TBAP. The complexes that are avid binders to CT DNA giving K-b values within 7.1 x 10(4) to 3.2 x 10(5) M-1, do not show any significant chemical nuclease activity in presence of 3-mercaptopropionic acid or glutathione. The dpq and dppz complexes are photocleavers of pUC19 DNA in UV-A light of 365 nm forming both O-1(2) and (OH)-O-center dot radicals and in near-IR light of 785 nm forming (OH)-O-center dot radicals. The dppz complex exhibits photocytotoxicity in visible light in HeLa cells (IC50 = 6.8 mu M). Flow-cytometric study on this complex shows a high sub-G1 phase in light compared to dark indicating PDT effect. (C) 2011 Elsevier B. V. All rights reserved.

MIMO Precoding With X- and Y- Codes

We consider a slow fading multiple-input multiple-output (MIMO) system with channel state information at both the transmitter and receiver. A well-known precoding scheme is based upon the singular value decomposition (SVD) of the channel matrix, which transforms the MIMO channel into parallel subchannels. Despite having low maximum likelihood decoding (MLD) complexity, this SVD precoding scheme provides a diversity gain which is limited by the diversity gain of the weakest subchannel. We therefore propose X- and Y-Codes, which improve the diversity gain of the SVD precoding scheme but maintain the low MLD complexity, by jointly coding information across a pair of subchannels. In particular, subchannels with high diversity gain are paired with those having low diversity gain. A pair of subchannels is jointly encoded using a 2 2 real matrix, which is fixed a priori and does not change with each channel realization. For X-Codes, these rotation matrices are parameterized by a single angle, while for Y-Codes, these matrices are left triangular matrices. Moreover, we propose X-, Y-Precoders with the same structure as X-, Y-Codes, but with encoding matrices adapted to each channel realization. We observed that X-Codes/Precoders are good for well-conditioned channels, while Y-Codes/Precoders are good for ill-conditioned channels.

Irreversibility-to-reversibility crossover in transient response of an optically trapped particle

We study the transient response of a colloidal bead which is released from different heights and allowed to relax in the potential well of an optical trap. Depending on the initial potential energy, the system's time evolution shows dramatically different behaviors. Starting from the short-time reversible to long-time irreversible transition, a stationary reversible state with zero net dissipation can be achieved as the release point energy is decreased. If the system starts with even lower energy, it progressively extracts useful work from thermal noise and exhibits an anomalous irreversibility. In addition, we have verified the Transient Fluctuation Theorem and the Integrated Transient Fluctuation Theorem even for the non-ergodic descriptions of our system. Copyright (C) EPLA, 2011

Micro and macroscopic features of impact failed defect induced carbon-epoxy composites

Laminated composite structures are susceptible to damage under impacts with attendant properly degradation. While studies on damage tolerance behaviour are emphasised and the findings reported, the citations correlating impacts with the fracture features are limited. In the present study, therefore, attempts have been made to depict how the transition of the fracture features take place depending on the type and extent of defect introduced onto the carbon-epoxy system. The test specimens were subjected to differing levels of low energy pendulum impacts with a view to have specimens with varying levels of intial impacts history. Into such specimens, additional defect in the form of slits of varying depths were introduced by a mechanical process. The test coupons were then allowed to fail by impact. The fracture surface was studied under scanning electron microscope. The fractographic features that appear, based on the induced/inserted defects, are presented in this paper. It was noticed that the energy absorbed for final fracture could be associated with the defect introduced into the system. It was also observed that the size of the mechanically inserted defect had a significant influence on the features of the fracture surface.

Precoding by Pairing Subchannels to Increase MIMO Capacity With Discrete Input Alphabets

We consider Gaussian multiple-input multiple-output (MIMO) channels with discrete input alphabets. We propose a non-diagonal precoder based on the X-Codes in 1] to increase the mutual information. The MIMO channel is transformed into a set of parallel subchannels using singular value decomposition (SVD) and X-Codes are then used to pair the subchannels. X-Codes are fully characterized by the pairings and a 2 x 2 real rotation matrix for each pair (parameterized with a single angle). This precoding structure enables us to express the total mutual information as a sum of the mutual information of all the pairs. The problem of finding the optimal precoder with the above structure, which maximizes the total mutual information, is solved by: i) optimizing the rotation angle and the power allocation within each pair and ii) finding the optimal pairing and power allocation among the pairs. It is shown that the mutual information achieved with the proposed pairing scheme is very close to that achieved with the optimal precoder by Cruz et al., and is significantly better than Mercury/waterfilling strategy by Lozano et al. Our approach greatly simplifies both the precoder optimization and the detection complexity, making it suitable for practical applications.

Two timescale analysis of the Alopex algorithm for optimization

Alopex is a correlation-based gradient-free optimization technique useful in many learning problems. However, there are no analytical results on the asymptotic behavior of this algorithm. This article presents a new version of Alopex that can be analyzed using techniques of two timescale stochastic approximation method. It is shown that the algorithm asymptotically behaves like a gradient-descent method, though it does not need (or estimate) any gradient information. It is also shown, through simulations, that the algorithm is quite effective.

Role of TGF-beta beta and BMP7 in the pathogenesis of oral submucous fibrosis

To understand the molecular pathogenesis of oral submucous fibrosis (OSF), which is a chronic inflammatory disease, gene expression profiling was performed in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results revealed differential expression of 5288 genes (P < a parts per thousand currency sign 0.05 and fold change >= a parts per thousand yen 1.5). Among these, 2884 are upregulated and 2404 are downregulated. Validation employing quantitative real-time PCR and immunohistochemistry confirmed upregulation of transforming growth factor-beta beta 1 (TGF-beta beta 1), TGFBIp, THBS1, SPP1, and TIG1 and downregulation of bone morphogenic protein 7 (BMP7) in OSF tissues. Furthermore, activation of TGF-beta beta pathway was evident in OSF as demonstrated by pSMAD2 strong immunoreactivity. Treatment of keratinocytes and oral fibroblasts by TGF-beta beta confirmed the regulation of few genes identified in microarray including upregulation of connective tissue growth factor, TGM2, THBS1, and downregulation of BMP7, which is a known negative modulator of fibrosis. Taken together, these data suggest activation of TGF-beta beta signaling and suppression of BMP7 expression in the manifestation of OSF.

On the utility of an instrumented impact set-up to characterise the response of discontinuous buffer strips in carbon–epoxy systems in dry and wet conditions

The use of an instrumented impact test set-up to evaluate the influence of water ingress on the impact response of a carbon–epoxy (C–E) laminated composite system containing discontinuous buffer strips (BS) has been examined. The data on the BS-free C–E sample in dry conditions are used as reference to compare with the data derived from those immersed in water. The work demonstrated the utility of an instrumented impact test set-up in characterising the response, first owing to the architectural difference due to introduction of buffer strips and then due to the presence of an additional phase in the form of water ingressed into the sample. The presence of water was found to enhance the energy absorption characteristics of the C–E system with BS insertions. It was also noticed that with an increasing number of BS layer insertions, the load–time plots displayed characteristic changes. The ductility indices (DI) were found to display a lower value for the water immersed samples compared to the dry ones.

Synthesis and metallic probe induced conductance of Au tipped ultranarrow PbS rods

Au tipped ultranarrow PbS nanorods are synthesized. DFT electronic structure calculations and transport studies show that Au probes modify the nature and energies of PbS nanorod orbitals creating efficient electron conduction channels for enhanced conductance even at low applied bias.

Characterization of recombinant diaminopropionate ammonia-lyase from Escherichia coli and Salmonella typhimurium

Diaminopropionate ammonia-lyase gene from Escherichia coli and Salmonella typhimurium was cloned and the overexpressed enzymes were purified to homogeneity. The k(cat) Values, determined for the recombinant enzymes with DL-DAP, D-serine, and L-serine as substrates, showed that the enzyme from S. typhimurium was more active than that from E coli and the K-m values were found to be similar. The purified enzymes had an absorption maximum (lambda(max)) at 412 nm, typical of PLP dependent enzymes. A red shift in lambda(max) was observed immediately after the addition Of 10 MM DL-DAP, which returned to the original lambda(max) of 412 nm in about 4 min. This red shift might reflect the formation of an external aldimine and/or other transient intermediates of the reaction. The apoenzyme of E coli and S. typhimurium prepared by treatment With L-cysteine could be partially (60%) reconstituted by the addition of PLP. The holo, apo, and the reconstituted enzymes were shown to be present as homo dimers by size exclusion chromatography. (C) 2003 Elsevier Science (USA). All rights reserved.