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

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

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

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