216 research outputs found
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 -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 is
smaller than the expected theoretical value, and increased slightly with
increasing temperature from 0.6 to . This small degree of anisotropy
was numerically confirmed by considering electron correlation effect. The
temperature dependence of the penetration depths followed a power
law() below 0.3, with 3.5 for both and
. Based on theoretical studies of iron-based superconductors, these
results suggest that the superconductivity of LiFeAs can be represented by an
extended -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
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