16,617 research outputs found

    Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity

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    The NAD+-dependent deacetylase SIRT1 is involved in diverse cellular processes, and has also been linked with multiple disease states. Among these, SIRT1 expression negatively correlates with cancer survival in both laboratory and clinical studies. Active regulator of SIRT1 (AROS) was the first reported post-transcriptional regulator of SIRT1 activity, enhancing SIRT1-mediated deacetylation and downregulation of the SIRT1 target p53. However, little is known regarding the role of AROS in regulation of SIRT1 during disease. Here, we report the cellular and molecular effects of RNAi-mediated AROS suppression, comparing this with the role of SIRT1 in a panel of human cell lines of both cancerous and non-cancerous origins. Unexpectedly, AROS is found to vary in its modulation of p53 acetylation according to cell context. AROS suppresses p53 acetylation only following the application of cell damaging stress, whereas SIRT1 suppresses p53 under all conditions analysed. This supplements the original characterization of AROS but indicates that SIRT1 activity can persist following suppression of AROS. We also demonstrate that knockdown of AROS induces apoptosis in three cancer cell lines, independent of p53 activation. Importantly, AROS is not required for the viability of three non-cancer cell lines indicating a putative role for AROS in specifically promoting cancer cell survival

    Molecular genetic analysis of the Chinese Erhualian pig breed

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    The Chinese Erhualian is one of the most prolific pig breeds in the world, but it is in danger of being replaced by other exotic pig breeds because of its slow growth rate and high fat content in the body. To obtain some genetic information for conservation, we analysed the Erhualian pigs by using a PCR-RFLP for the calcium-release-channel (CRC) gene, nine polymorphic microsatellites and the complete mtDNA D-loop sequences, and compared these data with those from other pig breeds from Europe and Asian. The PCR-RFLP analysis of the CRC gene showed that the frequency of the C allele associated with stress resistance was 100% in the Erhualian pigs. Neighbour-Joining trees constructed on the basis of mtDNA D-loop sequences and the microsatellite analysis clearly showed that the Erhualian pigs were located in a separate branch. These data suggest that the Erhualian pigs are different from other breeds. Microsatellite analysis showed that the average allele number (5.3/locus) in the Erhualian pig was intermediate as compared with that (4.8-7.0/locus) in the three European pig breeds. The expected heterozygosity was higher in the Erhualian pig (0.78) than that in these European pig breeds (0.59-0.72), whereas the observed heterozygosity was higher in the European breeds (0.51-0.64) than in the Erhualian pig (0.46). In the Erhualian pig, the fixation index (FIS) was as high as 0.41. These data suggest a high level of inbreeding and/or subpopulation in the Erhualian pigs. For conservation of the germplasm in the Erhualian pigs, it is necessary to take measures to reduce inbreeding and/or subpopulation. Keywords: Erhualian pig, Genetic diversity, Conservation, DNA markers South African Journal of Animal Science Vol.33(3) 2003: 159-16

    Bayesian computation for contingency tables with incomplete cell-counts

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    This article studies Bayesian analysis of contingency tables (or multinomial data) where the cell counts are not fully observed due to reasons such as nonresponse and misclassification, and derives the posterior distributions of the unknown cell probabilities in terms of various types of generalized Dirichlet distributions. For some special situations such as grouped and nested Dirichlet distributions, the posterior means of the unknown cell probabilities can be obtained in closed form by using inverse Bayes formulae and/or stochastic representation. When closed-form expressions do not exist, we suggest using importance sampling with a feasible proposal density to approximately compute the posterior quantities, and propose a procedure for choosing an effective proposal density. Applications are illustrated by sample surveys with nonresponse, crime survey data, death penalty attitude data, and misclassified multinomial data.published_or_final_versio

    Nuclear forward scattering in particulate matter: dependence of lineshape on particle size distribution

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    In synchrotron Moessbauer spectroscopy, the nuclear exciton polariton manifests itself in the lineshape of the spectra of nuclear forward scattering (NFS) Fourier-transformed from time domain to frequency domain. This lineshape is generally described by the convolution of two intensity factors. One of them is Lorentzian related to free decay. We derived the expressions for the second factor related to Frenkel exciton polariton effects at propagation of synchrotron radiation in Moessbauer media. Parameters of this Frenkelian shape depend on the spatial configuration of Moessbauer media. In a layer of uniform thickness, this factor is found to be a simple hypergeometric function. Next, we consider the particles spread over a 2D surface or diluted in non-Moessbauer media to exclude an overlap of ray shadows by different particles. Deconvolving the purely polaritonic component of linewidths is suggested as a simple procedure sharpening the experimental NFS spectra in frequency domain. The lineshapes in these sharpened spectra are theoretically expressed via the parameters of the particle size distributions (PSD). Then, these parameters are determined through least-squares fitting of the line shapes.Comment: 13 pages, 12 figure

    Magnetically tunable properties related with carriers density in self-doped La1−xMnO3/y wt %Nb-SrTiO3 heteroepitaxial junctions

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    The self-doped La1−xMnO3 (x=0.1 and 0.3) thin films deposited on Nb-doped (wt % y) SrTiO3 (y=0.05 and 0.8) crystals to form heteroepitaxial junctions have been prepared by the pulse laser deposition method. The current-voltage loops of junction were measured at several fixed magnetic fields for the temperature from 10 to 300 K. We have focused on the effects of doping level and annealing time on the magnetically tunable property of the junction. The results show that these junctions have a typical temperature-dependent rectifying characteristics and asymmetrical hysteresis. The magnetically tunable property of the junction was related with the annealing time for the self-doped La1−xMnO3−δ thin film and the doping level in the Nb-doped SrTiO3 (STON) crystal. In the self-doped La0.9MnO3/0.05-STON junction annealed at 900 °C for 5 h, the relative ratio of voltage [Vb(0)−Vb(H)] /Vb(0) is about 70% at H=6 T and T=70 K for I=0.1 mA, showing a large magnetically tunable property. These results reveal the great potential of the manganites in configuring artificial devices.published_or_final_versio

    The determinants of vulnerability to currency crises: country-specific factors versus regional factors

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    We investigate the determinants of exchange market pressures (EMP) for some new EU member states at both the national and regional levels, where macroeconomic and financial variables are considered as potential sources. The regional common factors are extracted from these variables by using dynamic factor analysis. The linear empirical analysis, in general, highlights the importance of country-specific factors to defend themselves against vulnerability in their external sectors. Yet, given a significant impact of the common component in credit on EMP, a contagion effect is apparent through the conduit of credit market integration across these countries under investigation

    Molecular characterizations of PCR-positive Mycoplasma pneumoniae specimen collected from Australia and China.

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    Mycoplasma pneumoniaeis an important cause of community-acquired pneumonia (CAP). In this study,M. pneumoniae strains in PCR-positive specimens collected from patients in Sydney, Australia (30 samples), and Beijing, China (83 samples), were characterized using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA), P1-restriction fragment length polymorphism (RFLP) analysis, and sequencing of domain V of the 23S rRNA gene to compare genotype distribution and macrolide resistance rates between locations. Eighteen distinct MLVA types were identified in specimens from Sydney, of which 10 were known (types E, G, J, M, N, P, U, V, S, and X) and 8 previously unknown. Strains were equally distributed between P1-RFLP type 1 and type 2 variants. Among samples from Beijing, MLVA types E, G, J, P, U, X, and Z and four new types were identified. Most specimens belonged to P1-RFLP type 1. A nomenclature based on five VNTR loci is proposed to designate MLVA patterns. Macrolide resistance-associated mutations were identified in only 1 of 30 specimens (3.3%) from Sydney and 71 of 83 (85.5%) from Beijing (P<0.05). This study demonstrated that although multiple individualM. pneumoniaestrains were circulating in Beijing, the genotypes were less diverse than those in Sydney. However, the greatest regional difference was in the incidence of macrolide resistance, which may reflect differences in antibiotic use and/or measures in resistance controlthe Beijing Natural Science Foundation (7112019) and the Beijing City talent training project fund (20071 A0303200118

    Accurate prediction of heat of formation by combining Hartree-Fock/density functional theory calculation with linear regression correction approach

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    A linear regression correction (LRC) approach was developed to account for the electron correlation energy missing in Hartree-Fock (HF) calculation. This method was applied to evaluate the standard heats of formation of 180 small-sized to medium-sized organic molecules at 298.15 K. The descriptors in the LRC scheme are the number of lone-pair electrons, bonding electrons and inner layer electrons in molecules, and the number of unpaired electrons in ground state atoms. It is observed that the large systematic deviations for the calculated heat of formation are reduced drastically, in particular, for the HF results.published_or_final_versio
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