Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

GdRh2_2Si2_2: An exemplary tetragonal system for antiferromagnetic order with weak in-plane anisotropy

The anisotropy of magnetic properties commonly is introduced in textbooks using the case of an antiferromagnetic system with Ising type anisotropy. This model presents huge anisotropic magnetization and a pronounced metamagnetic transition and is well-known and well-documented both, in experiments and theory. In contrast, the case of an antiferromagnetic $X$-$Y$ system with weak in-plane anisotropy is only poorly documented. We studied the anisotropic magnetization of the compound GdRh$_2$Si$_2$ and found that it is a perfect model system for such a weak-anisotropy setting because the Gd$^{3+}$ ions in GdRh$_2$Si$_2$ have a pure spin moment of S=7/2 which orders in a simple AFM structure with ${\bf Q} = (001)$. We observed experimentally in $M(B)$ a continuous spin-flop transition and domain effects for field applied along the $[100]$- and the $[110]$-direction, respectively. We applied a mean field model for the free energy to describe our data and combine it with an Ising chain model to account for domain effects. Our calculations reproduce the experimental data very well. In addition, we performed magnetic X-ray scattering and X-ray magnetic circular dichroism measurements, which confirm the AFM propagation vector to be ${\bf Q} = (001)$ and indicate the absence of polarization on the rhodium atoms

Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

Paramagnon dispersion in β\beta-FeSe observed by Fe LL-edge resonant inelastic x-ray scattering

We report an Fe $L$-edge resonant inelastic x-ray scattering (RIXS) study of the unusual superconductor $\beta$-FeSe. The high energy resolution of this RIXS experiment ($\approx\,$55$\,$meV FWHM) made it possible to resolve low-energy excitations of the Fe $3d$ manifold. These include a broad peak which shows dispersive trends between 100-200$\,$meV along the $(\pi,0)$ and $(\pi,\pi)$ directions of the one-Fe square reciprocal lattice, and which can be attributed to paramagnon excitations. The multi-band valence state of FeSe is among the most metallic in which such excitations have been discerned by soft x-ray RIXS

Similar temperature scale for valence changes in Kondo lattices with different Kondo temperatures

The Kondo model predicts that both the valence at low temperatures and its temperature dependence scale with the characteristic energy T_K of the Kondo interaction. Here, we study the evolution of the 4f occupancy with temperature in a series of Yb Kondo lattices using resonant X-ray emission spectroscopy. In agreement with simple theoretical models, we observe a scaling between the valence at low temperature and T_K obtained from thermodynamic measurements. In contrast, the temperature scale T_v at which the valence increases with temperature is almost the same in all investigated materials while the Kondo temperatures differ by almost four orders of magnitude. This observation is in remarkable contradiction to both naive expectation and precise theoretical predictions of the Kondo model, asking for further theoretical work in order to explain our findings. Our data exclude the presence of a quantum critical valence transition in YbRh2Si2

Liquorproteine bei der Neuromyelitis optica

Es werden zwei Fälle von Neuromyelitis optica beschrieben, die jeweils eine hochgradige Erhöhung der Proteine im Liquor aufwiesen. Während ein Patient nach 6monatigem Krankheitsverlauf starb und pathologisch-anatomisch untersucht werden konnte, überlebte der andere Patient mit erheblichen Residuen. Dieser Fall zeichnete sich dadurch aus, daß deutlich erhöhte IgA- und IgM-Werte sowohl im Liquor als auch im Serum vorlagen. Es wird diskutiert, ob die gefundenen Liquorveränderungen möglicherweise eine Abgrenzung entsprechender Fälle gegenüber der multiplen Sklerose zulassen

High-energy magnetic excitations in overdoped La2−x_{2-x}Srx_{x}CuO4_{4} studied by neutron and resonant inelastic X-ray scattering

We have performed neutron inelastic scattering and resonant inelastic X-ray scattering (RIXS) at the Cu-$L_3$ edge to study high-energy magnetic excitations at energy transfers of more than 100 meV for overdoped La$_{2-x}$Sr$_{x}$CuO$_{4}$ with $x=0.25$ ($T_c=15$ K) and $x=0.30$ (non-superconducting) using identical single crystal samples for the two techniques. From constant-energy slices of neutron scattering cross-sections, we have identified magnetic excitations up to ~250 meV for $x=0.25$. Although the width in the momentum direction is large, the peak positions along the (pi, pi) direction agree with the dispersion relation of the spin-wave in the non-doped La$_{2}$CuO$_{4}$ (LCO), which is consistent with the previous RIXS results of cuprate superconductors. Using RIXS at the Cu-$L_3$ edge, we have measured the dispersion relations of the so-called paramagnon mode along both (pi, pi) and (pi, 0) directions. Although in both directions the neutron and RIXS data connect with each other and the paramagnon along (pi, 0) agrees well with the LCO spin-wave dispersion, the paramagnon in the (pi, pi) direction probed by RIXS appears to be less dispersive and the excitation energy is lower than the spin-wave of LCO near (pi/2, pi/2). Thus, our results indicate consistency between neutron inelastic scattering and RIXS, and elucidate the entire magnetic excitation in the (pi, pi) direction by the complementary use of two probes. The polarization dependence of the RIXS profiles indicates that appreciable charge excitations exist in the same energy range of magnetic excitations, reflecting the itinerant character of the overdoped sample. A possible anisotropy in the charge excitation intensity might explain the apparent differences in the paramagnon dispersion in the (pi, pi) direction as detected by the X-ray scattering.Comment: 7 pages, 7 figure