Development of P450-BM3 using molecular dynamics simulations- A tribute to the late Professor Hideaki Yamada

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Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells

Microorganisms in animal gut produce unusual fatty acids from the ingested diet. Two types of hydroxy fatty acids (HFAs), 10-hydroxy-cis-12-octadecenoic acid (HYA) and 10-hydroxy-octadecanoic acid (HYB), are linoleic acid (LA) metabolites produced by Lactobacillus plantarum. In this study, we investigated the metabolism of these HFAs in mammalian cells. When Chinese hamster ovary (CHO) cells were cultured with HYA, approximately 50% of the supplemented HYA disappeared from the dish within 24 hours. On the other hand, the amount of HYA that disappeared from the dish of peroxisome (PEX)-deficient CHO cells was lower than 20%. Significant amounts of C2- and C4-chain-shortened metabolites of HYA were detected in culture medium of HYA-supplemented CHO cells, but not in medium of PEX-deficient cells. These results suggested that peroxisomal β-oxidation is involved in the disappearance of HYA. The PEX-dependent disappearance was observed in the experiment with HYB, but not with LA. We also found that HYA treatment up-regulates peroxisomal β-oxidation activity of human gastric MKN74 cells and intestinal Caco-2 cells. These results indicate a possibility that HFAs produced from gut bacteria affect lipid metabolism of host via modulation of peroxisomal β-oxidation activity

3D garment digitisation for virtual wardrobe using a commodity depth sensor

5-Aminovaleric acid (5AVA) is an important five-carbon platform chemical that can be used for the synthesis of polymers and other chemicals of industrial interest. Enzymatic conversion of L-lysine to 5AVA has been achieved by employing lysine 2-monooxygenase encoded by the davB gene and 5-aminovaleramidase encoded by the davA gene. Additionally, a recombinant Escherichia coli strain expressing the davB and davA genes has been developed for bioconversion of L-lysine to 5AVA. To use glucose and xylose derived from lignocellulosic biomass as substrates, rather than L-lysine as a substrate, we previously examined direct fermentative production of 5AVA from glucose by metabolically engineered E. coli strains. However, the yield and productivity of 5AVA achieved by recombinant E. coli strains remain very low. Thus, Corynebacterium glutamicum, a highly efficient L-lysine producing microorganism, should be useful in the development of direct fermentative production of 5AVA using L-lysine as a precursor for 5AVA. Here, we report the development of metabolically engineered C. glutamicum strains for enhanced fermentative production of 5AVA from glucose.Various expression vectors containing different promoters and origins of replication were examined for optimal expression of Pseudomonas putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. Among them, expression of the C. glutamicum codon-optimized davA gene fused with His-Tag at its N-Terminal and the davB gene as an operon under a strong synthetic H promoter (plasmid p36davAB3) in C. glutamicum enabled the most efficient production of 5AVA. Flask culture and fed-batch culture of this strain produced 6.9 and 19.7\ua0g/L (together with 11.9\ua0g/L glutaric acid as major byproduct) of 5AVA, respectively. Homology modeling suggested that endogenous gamma-aminobutyrate aminotransferase encoded by the gabT gene might be responsible for the conversion of 5AVA to glutaric acid in recombinant C. glutamicum. Fed-batch culture of a C. glutamicum gabT mutant-harboring p36davAB3 produced 33.1\ua0g/L 5AVA with much reduced (2.0\ua0g/L) production of glutaric acid.Corynebacterium glutamicum was successfully engineered to produce 5AVA from glucose by optimizing the expression of two key enzymes, lysine 2-monooxygenase and delta-aminovaleramidase. In addition, production of glutaric acid, a major byproduct, was significantly reduced by employing C. glutamicum gabT mutant as a host strain. The metabolically engineered C. glutamicum strains developed in this study should be useful for enhanced fermentative production of the novel C5 platform chemical 5AVA from renewable resources

Microstructural and Corrosion Properties of Ti-to-Zr Dissimilar Alloy Joints Brazed with a Zr-Ti-Cu-Ni Amorphous Filler Alloy

Titanium and Zircaloy-4 dissimilar alloys were brazed with a zirconium-titanium-copper-nickel amorphous filler alloy, and the resulting joint structures as well as their corrosion properties were examined. The microstructure of the brazed joints was investigated according to brazing holding time at 850 degrees C, and the corrosion property was analyzed by potentiodynamic polarization. During brazing, joints were produced by diffusion-induced isothermal solidification of the molten filler alloy. At a relatively brief brazing holding time of 5 min, a large segregation zone consisting of an active alpha-phase and a nobler intermetallic phase was generated in the joint center, which suffered from micro-galvanic corrosion. The presence of alloyed titanium deteriorated the nobility of the alpha-zirconium phase near the joint and induced galvanic coupling with cathodic base metals, resulting in massive localized corrosion. This localized corrosion caused the pitting behavior at the applied potential of -51.1 similar to 187.5 mV during anodic polarization. With a brazing holding time of 20 min, the concentration of the alloying elements was homogenized to eliminate the electrochemical potential difference and minimize the galvanic corrosion susceptibility of the joint region. This homogeneous joint resulted in a highly passive corrosion behavior comparable to that of the titanium base metal

Successful Treatment of Stereotactic Body Radiation Therapy Combined with Transarterial Chemolipiodolization for Hepatocellular Carcinoma with Biliary Obstruction

Conventional radiation therapy (RT) is a widely recognized treatment for hepatocellular carcinoma (HCC). However, conventional RT plays only a limited role in HCC treatment because of its low efficacy and the low tolerance of the liver for this modality. Stereotactic body radiation therapy (SBRT) was recently developed and represents the most advanced radiation therapy technique currently available. It can deliver a high dose in a short time to well-defined hepatic tumors, with rapid dose fall-off gradients. We believe that SBRT with transarterial chemolipiodolization (TACL) may prove promising as a combined treatment modality for HCC due to its precision and relative safety. Here we present a case of successful treatment of advanced HCC with obstructive jaundice using this combined modality

Towards Al3+-Induced Manganese-Containing Superoxide Dismutase Inactivation and Conformational Changes: An Integrating Study with Docking Simulations

Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in skins exposed to oxygen. We studied the inhibitory effects of Al3+ on the activity and conformation of manganese-containing SOD (Mn-SOD). Mn-SOD was significantly inactivated by Al3+ in a dose-dependent manner. The kinetic studies showed that Al3+ inactivated Mn-SOD follows the first-order reaction. Al3+ increased the degree of secondary structure of Mn-SOD and also disrupted the tertiary structure of Mn-SOD, which directly resulted in enzyme inactivation. We further simulated the docking between Mn-SOD and Al3+ (binding energy for Dock 6.3: −14.07 kcal/mol) and suggested that ASP152 and GLU157 residues were predicted to interact with Al3+, which are not located in the Mn-contained active site. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of Al3+ and allow us to describe a ligand binding via inhibition kinetics combined with the computational prediction

Bimodal Mesoporous Titanium Nitride/Carbon Microfibers as Efficient and Stable Electrocatalysts for Li–O_2 Batteries

The rechargeable Li–O_2 battery has been considered as a sustainable chemical power source for electric vehicles and grid energy storage systems due to the high theoretical specific energy (∼3500 Wh/kg). The practical performance of Li–O_2 batteries is, however, still far below expectations. This is mainly attributed to the (1) intrinsic sluggish reaction kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), (2) passivation of the electrodes by electrical isolation and pore blocking, and (3) chemical instability of the organic cell components, i.e., electrolyte, polymer binder, and carbon electrode, in the presence of O_2•– and Li_2O_2. It is crucial to develop highly porous, three-dimensional, conducting cathode catalyst/gas diffusion layer (GDL) architectures possessing superior catalytic activity and stability with respect to the ORR and the OER in order to address these issues. All of these requirements prompted us to examine the catalytic performance of porous framework metal nitride electrodes for Li–O_2 batteries

Seq-Scope protocol in MiSeq system for profiling hepatic and colonic spatial transcriptome.

http://deepblue.lib.umich.edu/bitstream/2027.42/168395/5/Seq-Scope Protocol M1.0.0 version.pdfSEL

Bimodal Mesoporous Titanium Nitride/Carbon Microfibers as Efficient and Stable Electrocatalysts for Li–O_2 Batteries

The rechargeable Li–O_2 battery has been considered as a sustainable chemical power source for electric vehicles and grid energy storage systems due to the high theoretical specific energy (∼3500 Wh/kg). The practical performance of Li–O_2 batteries is, however, still far below expectations. This is mainly attributed to the (1) intrinsic sluggish reaction kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), (2) passivation of the electrodes by electrical isolation and pore blocking, and (3) chemical instability of the organic cell components, i.e., electrolyte, polymer binder, and carbon electrode, in the presence of O_2•– and Li_2O_2. It is crucial to develop highly porous, three-dimensional, conducting cathode catalyst/gas diffusion layer (GDL) architectures possessing superior catalytic activity and stability with respect to the ORR and the OER in order to address these issues. All of these requirements prompted us to examine the catalytic performance of porous framework metal nitride electrodes for Li–O_2 batteries