275 research outputs found

    Protein-protein interactions of the androgen receptor in living cells

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    Protein-protein interactions of the androgen receptor in living cells

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    Ratios of BB and DD Meson Decay Constants in Relativistic Quark Model

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    We calculate the ratios of BB and DD meson decay constants by applying the variational method to the relativistic hamiltonian of the heavy meson. We adopt the Gaussian and hydrogen-type trial wave functions, and use six different potentials of the potential model. We obtain reliable results for the ratios, which are similar for different trial wave functions and different potentials. The obtained ratios show the deviation from the nonrelativistic scaling law, and they are in a pretty good agreement with the results of the Lattice calculations.Comment: 13 pages, 1 Postscript figur

    Androgen receptor complexes probe DNA for recognition sequences by short random interactions

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    Owing to the tremendous progress in microscopic imaging of fluorescently labeled proteins in living cells, the insight into the highly dynamic behavior of transcription factors has rapidly increased over the past decade. However, a consistent quantitative scheme of their action is still lacking. Using the androgen receptor (AR) as a model system, we combined three different fluorescence microscopy assays: single-molecule microscopy, photobleaching and correlation spectroscopy, to provide a quantitative model of the action of this transcription factor. This approach enabled us to distinguish two types of AR-DNA binding: very brief interactions, in the order of a few hundred milliseconds, and hormone-induced longer-lasting interactions, with a characteristic binding time of several seconds. In addition, freely mobile ARs were slowed down in the presence of hormone, suggesting the formation of large AR-co-regulator complexes in the nucleoplasm upon hormone activation. Our data suggest a model in which mobile hormone-induced complexes of transcription factors and co-regulators probe DNA by briefly binding at random sites, only forming relatively stable transcription initiation complexes when bound to specific recognition sequences

    Extended van Royen-Weisskopf formalism for lepton-antilepton meson decay widths within non-relativistic quark models

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    The classical van Royen-Weisskopf formula for the decay width of a meson into a lepton-antilepton pair is modified in order to include non-zero quark momentum contributions within the meson as well as relativistic effects. Besides, a phenomenological electromagnetic density for quarks is introduced. The meson wave functions are obtained from two different models: a chiral constituent quark model and a quark potential model including instanton effects. The modified van Royen-Weisskopf formula is found to improve systematically the results for the widths, giving an overall good description of all known decays.Comment: 22 pages, 3 figures, RevTex, epsfig. To be published in Nucl. Phys.

    Three-dimensional microscopic analysis of clinical prostate specimens

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    __Aims:__ Microscopic evaluation of prostate specimens for both clinical and research purposes is generally performed on 5-ÎŒm-thick tissue sections. Because cross-sections give a two-dimensional (2D) representation, little is known about the actual underlying three-dimensional (3D) architectural features of benign prostate tissue and prostate cancer (PCa). The aim of this study was to show that a combination of tissue-clearing protocols and confocal microscopy can successfully be applied to investigate the 3D architecture of human prostate tissue. __Methods and results:__ Optical clearing of intact fresh and formalin-fixed paraffin-embedded (FFPE) clinical prostate specimens allowed us to visualize tissue structures up to a depth of 800 ÎŒm, whereas, in uncleared tissue, detection of fluorescence was only possible up to 70 ÎŒm. Fluorescent labelling with a general nuclear dye and antibodies against cytokeratin (CK) 5 and CK8-18 resulted in comprehensive 3D imaging of benign peripheral and transition prostate zones, as well as individual PCa growth patterns. After staining, clearing, and imaging, samples could still be processed for 2D (immuno)histochemical staining and DNA analysis, enabling additional molecular and diagnostic characterization of small tissue specimens. __Conclusions:__ In conclusion, the applicability of 3D imaging to archival FFPE and fresh clinical specimens offers unlimited opportunities to stud

    Compartmentalization of androgen receptor protein–protein interactions in living cells

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    Steroid receptors regulate gene expression in a ligand-dependent manner by binding specific DNA sequences. Ligand binding also changes the conformation of the ligand binding domain (LBD), allowing interaction with coregulators via LxxLL motifs. Androgen receptors (ARs) preferentially interact with coregulators containing LxxLL-related FxxLF motifs. The AR is regulated at an extra level by interaction of an FQNLF motif in the N-terminal domain with the C-terminal LBD (N/C interaction). Although it is generally recognized that AR coregulator and N/C interactions are essential for transcription regulation, their spatiotemporal organization is largely unknown. We performed simultaneous fluorescence resonance energy transfer and fluorescence redistribution after photobleaching measurements in living cells expressing ARs double tagged with yellow and cyan fluorescent proteins. We provide evidence that AR N/C interactions occur predominantly when ARs are mobile, possibly to prevent unfavorable or untimely cofactor interactions. N/C interactions are largely lost when AR transiently binds to DNA, predominantly in foci partly overlapping transcription sites. AR coregulator interactions occur preferentially when ARs are bound to DNA

    A study on the rare radiative decay Bc→Ds∗γB_c \to D_s^* \gamma

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    We study the decay Bc→Ds∗γB_c \rightarrow D_s^* \gamma. There are two mechanisms contributing to the process. One proceeds through the short distance b→sÎłb{\rightarrow}s\gamma transition and the other occurs through weak annihilation accompanied by a photon emission.The electromagnetic penguin contribution is estimated by perturbative QCD and found to be 4.68×10−184.68\times10^{-18} GeV. In particular, we find the contribution of the weak annihilation is 6.25×10−18GeV6.25\times10^{-18}GeV which is in the same order as that of the electromagnetic penguin. The total decay rate Γ(Bc→Ds∗γ)\Gamma(B_c \rightarrow D_s^* \gamma) is predicted to be 1.45×10−17GeV1.45\times10^{-17}GeV and the branching ratio Br(Bc→Ds∗γ)Br(B_c \rightarrow D_s^* \gamma) is predicted to be 2.98×10−52.98\times 10^{-5} for τBc=1.35ps\tau_{B_c}=1.35ps. The the decays Bc→Ds∗γB_c \rightarrow D_s^* \gamma can be well studied at LHC in the near future.Comment: 13 pages, in LaTeX, to be appear in Phys. Lett.

    Compartmentalization of androgen receptors at endogenous genes in living cells

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    A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.</p

    Compartmentalization of androgen receptors at endogenous genes in living cells

    Get PDF
    A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.</p
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