Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Form factors and photoproduction amplitudes

We examine the use of phenomenological form factors in tree level amplitudes for meson photoproduction. Two common recipes are shown to be fundamentally incorrect. An alternate form consistent with gauge invariance and crossing symmetry is proposed.Comment: To be published in PR

Gauge-invariant tree-level photoproduction amplitudes with form factors

We show how the gauge-invariance formulation given by Haberzettl is implemented in practice for photoproduction amplitudes at the tree level with form factors describing composite nucleons. We demonstrate that, in contrast to Ohta's gauge-invariance prescription, this formalism allows electric current contributions to be multiplied by a form factor, i.e., it does not require that they be treated like bare currents. While different in detail, this nevertheless lends support to previous ad hoc approaches which multiply the Born amplitudes by an overall form factor. Numerical results for kaon photoproduction off the nucleon are given. They show that the gauge procedure by Haberzettl leads to much improved $\chi^2$ values as compared to Ohta's prescription.Comment: 5 pages, RevTeX, two eps figure

Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

<p>Abstract</p> <p>Background</p> <p>Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of <it>Saccharomyces cerevisiae</it>. The three factors we considered were specific growth rate, nutrient limitation, and oxygen availability.</p> <p>Results</p> <p>We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which mRNA expression changes are significantly associated. Among key metabolic pathways, this analysis revealed <it>de novo </it>synthesis of pyrimidine ribonucleotides and ATP producing and consuming reactions at fast cellular growth. By scoring the significance of overlap between growth rate dependent genes and known transcription factor target sets, transcription factors that coordinate balanced growth were also identified. Our analysis shows that Fhl1, Rap1, and Sfp1, regulating protein biosynthesis, have significantly enriched target sets for genes up-regulated with increasing growth rate. Cell cycle regulators, such as Ace2 and Swi6, and stress response regulators, such as Yap1, were also shown to have significantly enriched target sets.</p> <p>Conclusion</p> <p>Our work, which is the first genome-wide gene expression study to investigate specific growth rate and consider the impact of oxygen availability, provides a more conservative estimate of growth rate dependent genes than previously reported. We also provide a global view of how a small set of transcription factors, 13 in total, contribute to control of cellular growth rate. We anticipate that multi-factorial designs will play an increasing role in elucidating cellular regulation.</p

Predicting functionality of protein–DNA interactions by integrating diverse evidence

Chromatin immunoprecipitation (ChIP-chip) experiments enable capturing physical interactions between regulatory proteins and DNA in vivo. However, measurement of chromatin binding alone is not sufficient to detect regulatory interactions. A detected binding event may not be biologically relevant, or a known regulatory interaction might not be observed under the growth conditions tested so far. To correctly identify physical interactions between transcription factors (TFs) and genes and to determine their regulatory implications under various experimental conditions, we integrated ChIP-chip data with motif binding sites, nucleosome occupancy and mRNA expression datasets within a probabilistic framework. This framework was specifically tailored for the identification of functional and non-functional DNA binding events. Using this, we estimate that only 50% of condition-specific protein–DNA binding in budding yeast is functional. We further investigated the molecular factors determining the functionality of protein–DNA interactions under diverse growth conditions. Our analysis suggests that the functionality of binding is highly condition-specific and highly dependent on the presence of specific cofactors. Hence, the joint analysis of both, functional and non-functional DNA binding, may lend important new insights into transcriptional regulation

Extraction of the D13(1520) photon-decay couplings from pion- and eta-photoproduction data

We compare results for the D13(1520) photon-decay amplitudes determined in analyses of eta- and pion-photoproduction data. The ratio of helicity amplitudes (A_3/2 / A_1/2), determined from eta-photoproduction data, is quite different from that determined in previous analyses of pion-photoproduction data. We consider how strongly the existing pion-photoproduction data constrain both this ratio and the individual photon-decay amplitudes.Comment: 7 pages, 2 figure

Slow early growers have more muscle in relation to adult activity: evidence from Cebu, Philippines

Adult skeletal muscle mass (SMM) protects against type 2 diabetes but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. Additionally, we examined whether increases in SMM associated with adult muscle-building exercise varied according to early growth

Virtual-pion and two-photon production in pp scattering

Two-photon production in pp scattering is proposed as a means of studying virtual-pion emission. Such a process is complementary to real-pion emission in pp scattering. The virtual-pion signal is embedded in a background of double-photon bremsstrahlung. We have developed a model to describe this background process and show that in certain parts of phase space the virtual-pion signal gives significant contribution. In addition, through interference with the two-photon bremsstrahlung background, one can determine the relative phase of the virtual-pion process

Coherent Pair State of Pion in Constituent Quark Model

A coherent state of pions is introduced to the nonrelativistic quark model. The coherent pair approximation is employed for the pion field in order to maintain the spin-isospin symmetry. In this approximation the pion is localized in the momentum space, and the vertex form factor in the pion-quark interaction is derived from this localization. The nucleon masses and wave functions are calculated using this model, and our results are compared to those of the quark model with the one pion exchange potential. Similar result is obtained for the mass spectrum, but there exists a clear difference in the internal structure of nucleon resonances.Comment: 17 pages, 2 figures, revtex, submitted to Phys. Rev.

The energies and residues of the nucleon resonances N(1535) and N(1650)

We extract pole positions for the N(1535) and N(1650) resonances using two different models. The positions are determined from fits to different subsets of the existing $\pi N\to\pi N$, $\pi N\to\eta N$ and $\gamma p\to\eta p$ data and found to be 1515(10)--i85(15)MeV and 1660(10)--i65(10)MeV, when the data is described in terms of two poles. Sensitivity to the choice of fitted data is explored. The corresponding $\pi \pi$ and $\eta \eta$ residues of these poles are also extracted.Comment: 9 page