Metabolite essentiality elucidates robustness of Escherichia coli metabolism

Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens.Comment: Supplements available at http://stat.kaist.ac.kr/publication/2007/PJKim_pnas_supplement.pd

A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3 beta/JNK axis

We examined the role of phospholipase D2 (PLD2) on acetaminophen (APAP)-induced acute liver injury using a PLD2 inhibitor (CAY10594). 500 mg/kg of APAP challenge caused acute liver damage. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. During the pathological progress of acute liver injury, GSH levels are decreased, and this is significantly recovered upon the administration of CAY10594 at 6 hours post APAP challenge. GSK-3 beta (Serine 9)/JNK phosphorylation is mainly involved in APAPinduced liver injury. CAY10594 administration strongly blocked GSK-3 beta (Serine 9)/JNK phosphorylation in the APAP-induced acute liver injury model. Consistently, sustained JNK activation in the cytosol and mitochondria from hepatocytes were also decreased in CAY10594-treated mice. Many types of immune cells are also implicated in APAP-induced liver injury. However, neutrophil and monocyte populations were not different between vehicle- and CAY10594-administered mice which are challenged with APAP. Therapeutic administration of CAY10594 also significantly attenuated liver damage caused by the APAP challenge, eliciting an enhanced survival rate. Taken together, these results indicate that PLD2 is involved in the intrinsic response pathway of hepatocytes driving the pathogenesis of APAP-induced acute liver injury, and PLD2 may therefore represent an important therapeutic target for patients with drug-induced liver injury.11Ysciescopu

Measurement and physical interpretation of the mean motion of turbulent density patterns detected by the BES system on MAST

The mean motion of turbulent patterns detected by a two-dimensional (2D) beam emission spectroscopy (BES) diagnostic on the Mega Amp Spherical Tokamak (MAST) is determined using a cross-correlation time delay (CCTD) method. Statistical reliability of the method is studied by means of synthetic data analysis. The experimental measurements on MAST indicate that the apparent mean poloidal motion of the turbulent density patterns in the lab frame arises because the longest correlation direction of the patterns (parallel to the local background magnetic fields) is not parallel to the direction of the fastest mean plasma flows (usually toroidal when strong neutral beam injection is present). The experimental measurements are consistent with the mean motion of plasma being toroidal. The sum of all other contributions (mean poloidal plasma flow, phase velocity of the density patterns in the plasma frame, non-linear effects, etc.) to the apparent mean poloidal velocity of the density patterns is found to be negligible. These results hold in all investigated L-mode, H-mode and internal transport barrier (ITB) discharges. The one exception is a high-poloidal-beta (the ratio of the plasma pressure to the poloidal magnetic field energy density) discharge, where a large magnetic island exists. In this case BES detects very little motion. This effect is currently theoretically unexplained.Comment: 28 pages, 15 figures, submitted to PPC

An investigation into seasonal and regional aerosol characteristics in East Asia using model-predicted and remotely-sensed aerosol properties

International audienceIn this study, the spatio-temporal and seasonal distributions of EOS/Terra Moderate Resolution Imaging Spectroradiometer (MODIS)-derived aerosol optical depth (AOD) over East Asia were analyzed in conjunction with US EPA Models-3/CMAQ v4.3 modeling. In this study, two MODIS AOD products (? MODIS:?M-BAER and ?NASA) retrieved through a modified Bremen Aerosol Retrieval (M-BAER) algorithm and NASA collection 5 (C005) algorithm were compared with the AOD (?CMAQ) that was calculated from the US EPA Models-3/CMAQ model simulations. In general, the CMAQ-predicted AOD values captured the spatial and temporal variations of the two MODIS AOD products over East Asia reasonable well. Since ?MODIS cannot provide information on the aerosol chemical composition in the atmosphere, different aerosol formation characteristics in different regions and different seasons in East Asia cannot be described or identified by ?MODIS itself. Therefore, the seasonally and regionally varying aerosol formation and distribution characteristics were investigated by the US EPA Models-3/CMAQ v4.3 model simulations. The contribution of each particulate chemical species to ?M-BAER, ?NASA, and ?CMAQ showed strong spatial, temporal and seasonal variations. For example, during the summer episode, ?M-BAER, ?NASA, and ?CMAQ were mainly raised due to high concentrations of (NH4)2SO4 over Chinese urban and industrial centers and secondary organic aerosols (SOAs) over the southern parts of China, whereas during the winter episode, ?M-BAER, ?NASA, and ?CMAQ were higher due largely to high levels of NH3NO3 formed over the urban and industrial centers, as well as in areas with high NH3 emissions. In addition, the accuracy of ?M-BAER and ?NASA was evaluated by a comparison with the AOD (?AERONET) from the AERONET sites in East Asia. Both ?M-BAER and ?NASA showed a strong correlation with ?AERONETR around the 1:1 line (R=0.79), indicating promising potential for the application of both the M-BAER and NASA aerosol retrieval algorithms to satellite-based air quality monitoring studies in East Asia

Genetic noise control via protein oligomerization

Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Here we have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise

Single crystal growth and superconducting properties of LiFeAs

We report the successful growth of high quality single crystals of LiFeAs with lateral sizes up to 5 x 5 mm2 by the Sn-flux method. Electrical resistivity studies reveal that the superconducting onset temperature is 18.2 K with a transition width less than 1.1 K and the ratio of room temperature to residual resistivity is about 24. Bulk superconductivity is supported by perfect shielding in the magnetic susceptibility and a clear jump in the specific heat Cp, resulting in deltaCp/T ~ 20.0 mJ/mol*K2. Upper critical field slopes of dHc2c/dT ~ -1.39 and dHc2ab/dT ~ -2.99 T/K near Tc predict zero temperature upper critical fields of Hc2c(0) ~ 17.2 and Hc2ab(0) ~ 36.9 T and coherence lengths of Xi_ab = 4.4 and Xi_c = 2.0 nm in a single band model. This result points to a modest superconducting anisotropy about 2.3 in LiFeAs.Comment: 18 pages, 4 figure

Small anisotropy of the lower critical field and s±s_\pm-wave two-gap feature in single crystal LiFeAs

The in- and out-of-plane lower critical fields and magnetic penetration depths for LiFeAs were examined. The anisotropy ratio $\gamma_{H_{c1}}(0)$ is smaller than the expected theoretical value, and increased slightly with increasing temperature from 0.6$T_c$ to $T_c$. This small degree of anisotropy was numerically confirmed by considering electron correlation effect. The temperature dependence of the penetration depths followed a power law($\sim$$T^n$) below 0.3$T_c$, with $n$$>$3.5 for both $\lambda_{ab}$ and $\lambda_c$. Based on theoretical studies of iron-based superconductors, these results suggest that the superconductivity of LiFeAs can be represented by an extended $s_\pm$-wave due to weak impurity scattering effect. And the magnitudes of the two gaps were also evaluted by fitting the superfluid density for both the in- and out-of-plane to the two-gap model. The estimated values for the two gaps are consistent with the results of angle resolved photoemission spectroscopy and specific heat experiments.Comment: 10 pages, 5 figure