Efficient Conversion of Phenylpyruvic Acid to Phenyllactic Acid by Using Whole Cells of Bacillus coagulans SDM

Background: Phenyllactic acid (PLA), a novel antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi, can be produced by many microorganisms, especially lactic acid bacteria. However, the concentration and productivity of PLA have been low in previous studies. The enzymes responsible for conversion of phenylpyruvic acid (PPA) into PLA are equivocal. Methodology/Principal Findings: A novel thermophilic strain, Bacillus coagulans SDM, was isolated for production of PLA. When the solubility and dissolution rate of PPA were enhanced at a high temperature, whole cells of B. coagulans SDM could effectively convert PPA into PLA at a high concentration (37.3 g l 21) and high productivity (2.3 g l 21 h 21) under optimal conditions. Enzyme activity staining and kinetic studies identified NAD-dependent lactate dehydrogenases as the key enzymes that reduced PPA to PLA. Conclusions/Significance: Taking advantage of the thermophilic character of B. coagulans SDM, a high yield and productivity of PLA were obtained. The enzymes involved in PLA production were identified and characterized, which makes possible the rational design and construction of microorganisms suitable for PLA production with metaboli

Performance evaluation of on-chip wavelength conversion based on InP/In1−x_{1-x}Gax_xAsy_yP1−y_{1-y} semiconductor waveguide platforms

We propose and design the high confinement InP/In1-xGaxAsyP1-y semiconductor waveguides and report the results of effective wavelength conversion based on this platform. Efficient confinement and mode field area fluctuation at different wavelength is analyzed to achieve the high nonlinear coefficient. The numerical results show that nearly zero phase-mismatch condition can be satisfied through dispersion tailoring of InP/In1-xGaxAsyP1-y waveguides, and the wavelength conversion ranging over 40 nm with the maximum conversion efficiency -26.3 dB is achieved for fixing pump power 100 mW. Meanwhile, the influences of the doping parameter y and pumping wavelength on the bandwidth and conversion efficiency are also discussed and optimized. It is indicated the excellent optical properties of the InP/In1-xGaxAsyP1-y waveguides and pave the way towards direct integration telecom band devices on stand semiconductor platforms.Comment: 21 page

Resveratrol differentially modulates inflammatory responses of microglia and astrocytes

<p>Abstract</p> <p>Background</p> <p>Inflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.</p> <p>Methods</p> <p>A murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-κB and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.</p> <p>Results</p> <p>We found that LPS stimulated the expression of TNF-α, IL-1β, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-κB and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-α, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1β in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-κB activation in both cell types, but inhibited AP-1 activation only in microglia.</p> <p>Conclusion</p> <p>These results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.</p

Crucial Roles of 5-HT and 5-HT2 Receptor in Diabetes-Related Lipid Accumulation and Pro-Inflammatory Cytokine Generation in Hepatocytes

Background/Aims: Previously, we confirmed that liver-synthesized 5-HT rather than non-liver 5-HT, acting on the 5-HT2 receptor (5-HT2R), modulates lipid-induced excessive lipid synthesis (ELS). Here, we further revealed the effects of the hepatocellular 5-HT system in diabetes-related disorders. Methods: Studies were conducted in male ICR mice, human HepG2 cells, and primary mouse hepatocytes (PMHs) under gene or chemical inhibition of the 5-HT system, key lipid metabolism, and inflammation-related factors. Protein and messenger RNA expression and levels of the factors were determined via western blotting, reverse transcription PCR, and quantitative assay kits, respectively. Hepatic steatosis with inflammation and fibrosis, intracellular lipid droplet accumulation (LDA), and reactive oxygen species (ROS) location were determined via hematoxylin and eosin, Masson’s trichrome, Oil red O, and fluorescent-specific staining, respectively. Results: Palmitic acid induced the activation of the 5-HT system: the activation of 5-HT2R, primarily 5-HT2AR, in addition to upregulating monoamine oxidase A (MAO-A) expression and 5-HT synthesis, by activating the G protein/ phospholipase C pathway modulated PKCε activation, resulting in ELS with LDA; the activation of NF-κB, which mediates the generation of pro-inflammatory cytokines, was primarily due to ROS generation in the mitochondria induced by MAO-A–catalyzed 5-HT degradation, and secondarily due to the activation of PKCε. These effects of the 5-HT system were also detected in palmitic acid- or high glucose-treated PMHs and regulated multiple inflammatory signaling pathways. In diabetic mice, co-treatment with antagonists of both 5-HT synthesis and 5-HT2R significantly abolished hepatic steatosis, inflammation, and fibrosis as well as hyperglycemia and dyslipidemia. Conclusion: Activation of the hepatocellular 5-HT system plays a crucial role in inducing diabetes-related hepatic dysfunction and is a potential therapeutic target

Holocene variability of East Asian summer monsoon as viewed from the speleothem δ18O records in central China

Monsoon precipitation in East China shows distinct spatial distribution and its variability is closely linked with the changes of the East Asian summer monsoon (EASM). Located in the transition zone between the southern subtropical humid climate and the northern warm temperate semi-humid climate, central China is a core region for recognizing and understanding the spatio-temporal variability of the EASM. Using U-series dating and stable isotope analysis on five stalagmites (MG-1, MG-2, MG-7, MG-40 and MG-64) from Magou Cave, Henan Province, Central China, we construct a high-resolution and precisely dated composite stalagmite O time series covering most of the Holocene. This composite record reveals variations in precipitation O between 11.7 and 1.1 ka BP with average resolution of ∼4 yrs. The Magou composite record demonstrates that EASM intensity dominates long-term changes in precipitation O, which generally follows the northern hemisphere summer insolation (NHSI) trend. Both, Ensemble Empirical Mode Decomposition (EEMD) and wavelet filtering analyses real that the amplitudes of long-term (100-500 and 500-3000 yrs) components were slightly reduced between 8.5 and 4.9 ka BP, implying a weakened influence of climatic forcings on centennial and even millennial timescales during this warm period. Variance on 1-30-yr timescales is relatively low and ascribed to sampling resolution. Fourteen weak EASM intervals, including the 8.2 ka event, were identified within the period corresponding broadly with the Holocene Megathermal. Since no cold excursions other than the 8.2 ka event are found in the Greenland ice core records, we tentatively propose that oscillations in tropical sea surface temperature (SST) likely play an important role in steering other weak monsoon events. Aligning the Magou composite record and other moisture records with archaeological records from the study region, it seems that climate change influenced both the spatial distribution and agricultural practices of ancient cultures. However, overall moderate climatic changes in this region, most likely characterized by shifts between subtropical humid climate and warm temperate semi-humid climate, supported a generally consecutive development of ancient cultures without major hiatuses

Associations of Amylin with Inflammatory Markers and Metabolic Syndrome in Apparently Healthy Chinese

BACKGROUND: Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese. METHODS: A population-based sample of 1,011 Chinese men and women aged 35-54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR. CONCLUSIONS: Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively

Biophysical Characterization of the Strong Stabilization of the RNA Triplex poly(U)•poly(A)*poly(U) by 9-O-(ω-amino) Alkyl Ether Berberine Analogs

Background: Binding of two 9-O-(v-amino) alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U)Npoly(A)*poly(U) was studied by various biophysical techniques. Methodology/Principal Findings: Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5uC compared to a 17.5uC stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain. Conclusions/Significance: Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena