Genetic sequences of hormone response elements share similarity with predicted alpha helices within DNA binding domains of steroid receptor proteins: A basis for site-specific recognition

AbstractThe 150 amino acid sequence comprising the DNA binding region of rat glucocorticoid receptor protein, RGRDBR, was compared to amino acid sequences of members of the superfamily of eukaryotic DNA regulatory proteins. Maximal similarity fell within the 86 amino acid sequence of RGRDBR reported to contain both DNA binding and transcription regulating properties and within the reported DNA binding regions of those proteins to which it was compared. Chou-Fasman secondary structure predictions within these DNA binding domains revealed a conserved alpha helix-beta turn-alpha helix motif. The 450 nucleotide sequence comprising the complementary DNA (cDNA) of amino acids making up RGRDBR was compared to a nucleotide sequence (−312 to −38) from mouse mammary tumor virus 5′ long terminal repeat, MMTV5LTR, known to contain glucocorticoid response elements (GREs). The maximally similar subsequence was found within the coding region for predicted alpha helix B of RGRDBR (nucleotides 1376 to 1412) and within a reported GRE of MMTV5LTR (nucleotides −199 to −131). This MMTV5LTR GRE sequence contains an imperfect palindrome of TGTTCT which is the specific recognition motif for DNA binding by both glucocorticoid and progesterone receptors. Since there are multiple coding possibilities for the majority of the 20 known amino acids, the exceptions being methionine and tryptophan which have a single codon, to thoroughly investigate the extent of genetic information conserved between RGRDBR and GRE, we converted this MMTV5LTR GRE nucleotide subsequence (−199 to −131) to amino acids in all three reading frames reading rightward and leftward in both strands. This procedure revealed all coding possibilities within the MMTV5LTR nucleotide subsequence, as well as the location of the codon sites. A comparison of these MMTV5LTR amino acid coding possibilities to RGRDBR predicted helix B amino acids revealed highly conserved genetic information localized within the GRE half-sites, predominantly in the right half-site containing the TGTTCT sequence. In the absence of atomic coordinates for eukaryotic DNA regulatory proteins, a computer model of a eukaryotic/procaryotic hybrid protein was created with RGRDBR predicted helix B replacing helix of F of E. coli cAMP-dependent regulatory protein (CRP) for which coordinates from X-ray crystallography were available. This hybrid protein was docked onto MMTV5LTR at the region of maximal similarity to helix B. Our computer model shows that the side chains of amino acids within RGRDBR helix B are oriented toward, and appear to be capable of interacting with, nucleotides on both strands of their respective codons within a functional GRE. Calculations of H-bonding in this model indicate that amino acids of helix B are forming H-bonds with nucleotides of their cognate codon/anti-codon sites within the major grooves of the GRE half-sites

Continuous Monitoring of Dynamical Systems and Master Equations

We illustrate the equivalence between the non-unitary evolution of an open quantum system governed by a Markovian master equation and a process of continuous measurements involving this system. We investigate a system of two coupled modes, only one of them interacting with external degrees of freedom, represented, in the first case, by a finite number of harmonic oscillators, and, in the second, by a sequence of atoms where each one interacts with a single mode during a limited time. Two distinct regimes appear, one of them corresponding to a Zeno-like behavior in the limit of large dissipation

Jumping on the 'bad'wagon? How group membership influences responses to the social exclusion of others

In four studies, we addressed whether group membership influences behavioral and neural responses to the social exclusion of others. Participants played a modified three-player Cyberball game (Studies 1–3) or a team-selection task (Study 4) in the absence or presence of a minimal group setting. In the absence of a minimal group, when one player excluded another player, participants actively included the excluded target. When the excluder was from the in-group and the excluded player from the out-group, participants were less likely to intervene (Studies 1–3) and also more often went along with the exclusion (Study 4). Functional magnetic resonance imaging results (Study 3) showed that greater exclusion in the minimal group setting concurred with increased activation in the dorsolateral pre-frontal cortex, a region associated with overriding cognitive conflict. Self-reports from Study 4 supported these results by showing that participants’ responses to the target’s exclusion were motivated by group membership as well as participants’ general aversion to exclude others. Together, the findings suggest that when people witness social exclusion, group membership triggers a motivational conflict between favoring the in-group and including the out-group target. This underscores the importance of group composition for understanding the dynamics of social exclusion.Social decision makin

Hubbard model versus t-J model: The one-particle spectrum

The origin of the apparent discrepancies between the one-particle spectra of the Hubbard and t-J models is revealed: Wavefunction corrections, in addition to the three-site terms, should supplement the bare t-J. In this way a quantitative agreement between the two models is obtained, even for the intermediate-$U$ values appropriate for the high-Tc cuprate superconductors. Numerical results for clusters of up to 20 sites are presented. The momentum dependence of the observed intensities in the photoemission spectra of Sr2CuO2Cl2 are well described by this complete strong-coupling approach.Comment: 4 two-column RevTeX pages, including 4 Postscript figures. Uses epsf. Accepted for publication in Physical Review B, Rapid Communicatio

Theta angle versus CP violation in the leptonic sector

Assuming that the axion mechanism of solving the strong CP problem does not exist and the vanishing of theta at tree level is achieved by some model-building means, we study the naturalness of having large CP-violating sources in the leptonic sector. We consider the radiative mechanisms which transfer a possibly large CP-violating phase in the leptonic sector to the theta parameter. It is found that large theta cannot be induced in the models with one Higgs doublet as at least three loops are required in this case. In the models with two or more Higgs doublets the dominant source of theta is the phases in the scalar potential, induced by CP violation in leptonic sector. Thus, in the MSSM framework the imaginary part of the trilinear soft-breaking parameter A_l generates the corrections to the theta angle already at one loop. These corrections are large, excluding the possibility of large phases, unless the universality in the slepton sector is strongly violated.Comment: 5 pages, 2 figure

Parathyroid hormone induces bone cell motility and loss of mature osteocyte phenotype through L-calcium channel dependent and independent mechanisms

Parathyroid Hormone (PTH) can exert both anabolic and catabolic effects on the skeleton, potentially through expression of the PTH type1 receptor (PTH1R), which is highly expressed in osteocytes. To determine the cellular and molecular mechanisms responsible, we examined the effects of PTH on osteoblast to osteocyte differentiation using primary osteocytes and the IDG-SW3 murine cell line, which differentiate from osteoblast to osteocyte-like cells in vitro and express GFP under control of the dentin matrix 1 (Dmp1) promoter. PTH treatment resulted in an increase in some osteoblast and early osteocyte markers and a decrease in mature osteocyte marker expression. The gene expression profile of PTH-treated Day 28 IDG-SW3 cells was similar to PTH treated primary osteocytes. PTH treatment induced striking changes in the morphology of the Dmp1-GFP positive cells in IDG-SW3 cultures and primary cells from Dmp1-GFP transgenic mice. The cells changed from a more dendritic to an elongated morphology and showed increased cell motility. E11/gp38 has been shown to be important for cell migration, however, deletion of the E11/gp38/podoplanin gene had no effect on PTH-induced motility. The effects of PTH on motility were reproduced using cAMP, but not with protein kinase A (PKA), exchange proteins activated by cAMP (Epac), protein kinase C (PKC) or phosphatidylinositol-4,5-bisphosphonate 3-kinase (Pi3K) agonists nor were they blocked by their antagonists. However, the effects of PTH were mediated through calcium signaling, specifically through L-type channels normally expressed in osteoblasts but decreased in osteocytes. PTH was shown to increase expression of this channel, but decrease the T-type channel that is normally more highly expressed in osteocytes. Inhibition of L-type calcium channel activity attenuated the effects of PTH on cell morphology and motility but did not prevent the downregulation of mature osteocyte marker expression. Taken together, these results show that PTH induces loss of the mature osteocyte phenotype and promotes the motility of these cells. These two effects are mediated through different mechanisms. The loss of phenotype effect is independent and the cell motility effect is dependent on calcium signaling.Matthew Prideaux, Sarah L. Dallas, Ning Zhao, Erica D. Johnsrud, Patricia A. Veno, Dayong Guo, Yuji Mishina, Stephen E. Harris, Lynda F. Bonewal

Motion of a driven tracer particle in a one-dimensional symmetric lattice gas

We study the dynamics of a tracer particle subject to a constant driving force $E$ in a one-dimensional lattice gas of hard-core particles whose transition rates are symmetric. We show that the mean displacement of the driven tracer grows in time, $t$, as $\sqrt{\alpha t}$, rather than the linear time dependence found for driven diffusion in the bath of non-interacting (ghost) particles. The prefactor $\alpha$ is determined implicitly, as the solution of a transcendental equation, for an arbitrary magnitude of the driving force and an arbitrary concentration of the lattice gas particles. In limiting cases the prefactor is obtained explicitly. Analytical predictions are seen to be in a good agreement with the results of numerical simulations.Comment: 21 pages, LaTeX, 4 Postscript fugures, to be published in Phys. Rev. E, (01Sep, 1996

Retirement from sport and the loss of athletic identity

The purpose of this study was to examine how a sample of elite athletes coped with distressful reactions to retirement from sport. As part of a larger research project, 15 former elite athletes were identified as having experienced severe emotional difficulties upon athletic career termination. Through use of a micronarrative methodology, it was determined that account making can be a significant moderator of distress during the career transition process. In addition, the quality of the account making was found to be related to present affect and overall success in coping with athletic retirement. Finally, changes in athletic identity were found to be significant determinants of adjustment for athletes upon career termination. Suggestions are presented for future research on treatment strategies for distressful reactions to retirement from sport