Phytosphingosine degradation pathway includes fatty acid alpha-oxidation reactions in the endoplasmic reticulum

Although normal fatty acids (FAs) are degraded via beta-oxidation, unusual FAs such as 2-hydroxy (2-OH) FAs and 3-methyl-branched FAs are degraded via alpha-oxidation. Phytosphingosine (PHS) is one of the long-chain bases (the sphingolipid components) and exists in specific tissues, including the epidermis and small intestine in mammals. In the degradation pathway, PHS is converted to 2-OH palmitic acid and then to pentadecanoic acid (C15:0-COOH) via FA alpha-oxidation. However, the detailed reactions and genes involved in the alpha-oxidation reactions of the PHS degradation pathway have yet to be determined. In the present study, we reveal the entire PHS degradation pathway: PHS is converted to C15: 0-COOH via six reactions [phosphorylation, cleavage, oxidation, CoA addition, cleavage (C1 removal), and oxidation], in which the last three reactions correspond to the alpha-oxidation. The aldehyde dehydrogenase ALDH3A2 catalyzes both the first and second oxidation reactions (fatty aldehydes to FAs). In Aldh3a2-deficient cells, the unmetabolized fatty aldehydes are reduced to fatty alcohols and are incorporated into ether-linked glycerolipids. We also identify HACL2 (2-hydroxyacyl-CoA lyase 2) [previous name, ILVBL; ilvB (bacterial acetolactate synthase)-like] as the major 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the FA alpha-oxidation of the PHS degradation pathway. HACL2 is localized in the endoplasmic reticulum. Thus, in addition to the already-known FA alpha-oxidation in the peroxisomes, we have revealed the existence of FA alpha-oxidation in the endoplasmic reticulum in mammals

Design, Development and Evaluation of Thought Externalization Environment based on Information Structure Open Approach

広島大学(Hiroshima University)博士(工学)Doctor of Engineeringdoctora

A fully decentralized control of an amoeboid robot by exploiting the law of conservation of protoplasmic mass

2008 IEEE International Conference on Robotics and Automation, Pasadena, CA, USA, May 19-23, 200

Biocatalytic synthesis of flavones and hydroxyl-small molecules by recombinant Escherichia coli cells expressing the cyanobacterial CYP110E1 gene

Background: Cyanobacteria possess several cytochrome P450s, but very little is known about their catalytic functions. CYP110 genes unique to cyanaobacteria are widely distributed in heterocyst-forming cyanobacteria including nitrogen-fixing genera Nostoc and Anabaena. We screened the biocatalytic functions of all P450s from three cyanobacterial strains of genus Nostoc or Anabaena using a series of small molecules that contain flavonoids, sesquiterpenes, low-molecular-weight drugs, and other aromatic compounds. Results: Escherichia coli cells carrying each P450 gene that was inserted into the pRED vector, containing the RhFRed reductase domain sequence from Rhodococcus sp. NCIMB 9784 P450RhF (CYP116B2), were co-cultured with substrates and products were identified when bioconversion reactions proceeded. Consequently, CYP110E1 of Nostoc sp. strain PCC 7120, located in close proximity to the first branch point in the phylogenetic tree of the CYP110 family, was found to be promiscuous for the substrate range mediating the biotransformation of various small molecules. Naringenin and (hydroxyl) flavanones were respectively converted to apigenin and (hydroxyl) flavones, by functioning as a flavone synthase. Such an activity is reported for the first time in prokaryotic P450s. Additionally, CYP110E1 biotransformed the notable sesquiterpene zerumbone, anti-inflammatory drugs ibuprofen and flurbiprofen (methylester forms), and some aryl compounds such as 1-methoxy and 1-ethoxy naphthalene to produce hydroxylated compounds that are difficult to synthesize chemically, including novel compounds. Conclusion: We elucidated that the CYP110E1 gene, C-terminally fused to the P450RhF RhFRed reductase domain sequence, is functionally expressed in E. coli to synthesize a robust monooxygenase, which shows promiscuous substrate specificity (affinity) for various small molecules, allowing the biosynthesis of not only flavones (from flavanones) but also a variety of hydroxyl-small molecules that may span pharmaceutical and nutraceutical industries

Cold-Induced Interveinal Chlorosis and Defective Root Formation Observed in Lilium × formolongi

We tried to identify the frequency of chlorosis occurrence and defective root formation under the low temperature conditions observed in Lilium × formolongi using a cultivar ‘Green Lily Alp’(‘Alp’) as a model. First, we confirmed that ‘Alp’ plants exhibited more severe interveinal chlorosis than did L. × formolongi plants. The highest index for interveinal chlorosis in ‘Alp’ plants occurred in a study from November 2016 to April 2017 and was 4.1, compared with an index for L. × formolongi. A significant difference was observed in root dry weights, with stem roots weighing 60 mg and 260 mg and basal roots weighing 240 mg and 780 mg per plant in symptomatic and asymptomatic ‘Alp’ plants, respectively. The index for interveinal chlorosis occurrence was 0 under the control 25/10˚C (day/night) temperature treatment but 0.7 under the cooler 15–19/10˚C treatment. Total chlorophyll content and basal root dry weight were significantly lower (P＜0.05) under 15–19/10˚C treatment than under the control. These results suggest that the extreme frequency and occurrence of low temperature-induced interveinal chlorosis and defective root formation in ‘Alp’ plants is induced by the low root zone temperature.Article信州大学農学部AFC報告 18: 37-47(2020)departmental bulletin pape

Development of Quadruped Achieving High Terrain Adaptability (DOF Configuration Consideration for Redundant Leg Structures)

Abstract Legged locomotion is suitable to move on uneven terrain. However, advantages of legged robots have not been achieved yet. In this study, a relationship between combinations of the joints and generated force or torque will be discussed. Legs with four joints were considered. These legs have a possibility to adapt a rough terrain because of their redundancy. Redundant joint can change the direction of maximum output force without changing output force distribution. After several considerations, three legs out of 81 combinations are examined to simulate. Output force distributions during walking on flat ground and slope are reported

Modeling and emergence of flapping flight of butterfly based on experimental measurements

The objective of this paper is to clarify the principle of stabilization in flapping-of-wing flight of a butterfly, which is a rhythmic and cyclic motion. For this purpose, a dynamics model of a butterfly is derived by Lagrange’s method, where the butterfly is considered as a rigid multi-body system. For the aerodynamic forces, a panel method is applied. Validity of the mathematical models is shown by an agreement of the numerical result with the measured data. Then, periodic orbits of flapping-of-wing flights are searched in order to fly the butterfly models. Almost periodic orbits are obtained, but the model in the searched flapping-of-wing flight is unstable. This research, then, studies how the wake-induced flow and the flexibly torsional wing’s effect on the flight stability. Numerical simulations demonstrate that both the wake-induced flow and the flexible torsion reduces the flight instability. Because the obtained periodic flapping-of-wing flight is unstable, a feedback control system is designed, and a stable flight is realized

A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation

A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia

Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD.</p> <p>Results</p> <p>In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B.</p> <p>Conclusions</p> <p>The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.</p