Topogenesis and Homeostasis of Fatty Acyl-CoA Reductase 1

Peroxisomal fatty acyl-CoA reductase 1 (Far1) is essential for supplying fatty alcohols required for ether bond formation in ether glycerophospholipid synthesis. The stability of Far1 is regulated by a mechanism that is dependent on cellular plasmalogen levels. However, the membrane topology of Far1 and how Far1 is targeted to membranes remain largely unknown. Here, Far1 is shown to be a peroxisomal tail-anchored protein. The hydrophobic C terminus of Far1 binds to Pex19p, a cytosolic receptor harboring a C-terminal CAAX motif, which is responsible for the targeting of Far1 to peroxisomes. Far1, but not Far2, was preferentially degraded in response to the cellular level of plasmalogens. Experiments in which regions of Far1 or Far2 were replaced with the corresponding region of the other protein showed that the region flanking the transmembrane domain of Far1 is required for plasmalogen-dependent modulation of Far1 stability. Expression of Far1 increased plasmalogen synthesis in wild-type Chinese hamster ovary cells, strongly suggesting that Far1 is a rate-limiting enzyme for plasmalogen synthesis.     

Enzymic formation of di-D-fructose 1,2'; 2,1' dianhydride from inulobiose by Aspergillus fumigatus

The enzyme of Aspergillus fumigatus which produces di-D-fructose 1,2'; 2,1' dianhydride (difructose anhydride I) (Tanaka et al., 1979) was investigated for its mode of action. Fractionation and purification of the enzyme showed that it produced difructose anhydride I not from inulin but from inulobiose by the reverse reaction of the partial hydrolysis of difructose anhydride I.     

Mechanism of radiosensitizing effect of chloride ion on E. coli

Cells of E. coli capable of repairing DNA damage are sensitized to radiation in the presence of NaCl. However, the enhanced radiolethality was suppressed by the addition of compounds such as an amino acid to the irradiation buffer. The protective efficiencies of these compounds depend on their reactivities with Cl-.2 or OH.. ATP synthesis in the cells irradiated in the presence of NaCl was severely inhibited depending on the dose of irradiation. This reduced rate of ATP synthesis can account for the inhibition of protein, RNA and DNA synthesis in the irradiated cells with NaCl.     

Prediction of strength and strain of the proximal femur by a CT-based finite element method

Hip fractures are the most serious complication of osteoporosis and have been recognized as a major public health problem. In elderly persons, hip fractures occur as a result of increased fragility of the proximal femur due to osteoporosis. It is essential to precisely quantify the strength of the proximal femur in order to estimate the fracture risk and plan preventive interventions. CT-based finite element analysis could possibly achieve precise assessment of the strength of the proximal femur. The purpose of this study was to create a simulation model that could accurately predict the strength and surface strains of the proximal femur using a CT-based finite element method and to verify the accuracy of our model by load testing using fresh frozen cadaver specimens. Eleven right femora were collected. The axial CT scans of the proximal femora were obtained with a calibration phantom, from which the 3D finite element models were constructed. Materially nonlinear finite element analyses were performed. The yield and fracture loads were calculated, while the sites where elements failed and the distributions of the principal strains were determined. The strain gauges were attached to the proximal femoral surfaces. A quasi-static compression test of each femur was conducted. The yield loads, fracture loads and principal strains of the prediction significantly correlated with those measured (r=0.941, 0.979, 0.963). Finite element analysis showed that the solid elements and shell elements in undergoing compressive failure were at the same subcapital region as the experimental fracture site.     

Dual effect of AMD3100, a CXCR4 antagonist, on bleomycin-induced lung inflammation

The chemokine receptor CXCR4, which binds the chemokine stromal cell-derived factor 1, has been reported to be involved in the chemotaxis of inflammatory cells. In addition, AMD3100, an antagonist of CXCR4, has been reported to be an attractive drug candidate for therapeutic intervention in several disorders in which CXCR4 is critically involved. However, little is known about the therapeutic value of AMD3100 in the treatment of pulmonary fibrosis. In this study, we examined the effects of AMD3100 on a murine bleomycin-induced pulmonary fibrosis model. Concurrent administration of AMD3100 and bleomycin apparently attenuated bleomycin-induced pulmonary inflammation. In this process, an inhibition of neutrophil recruitment at early stage followed by the decrease of other inflammatory cell recruitment in the lung were observed. In addition, it also inhibited the expression of cytokines, including MCP-1, MIP-2, MIP-1alpha, and TGF-beta. In contrast, when AMD3100 was administered following bleomycin treatment, the bleomycin-induced lung inflammation progressed and resulted in severe pulmonary fibrosis. In this process, an increase of inflammatory cell recruitment, an up-regulation of lung MCP-1 and TGF-beta, and a remarkable activation of p44/42 MAPK in neutrophils were observed. U0126, an inhibitor of p44/42 MAPK, significantly abolished these effects. Thus, AMD3100 has dual effect on bleomycin-induced pulmonary fibrosis. Difference of inflammatory cell recruitment and activation might be associated with the dual effect of AMD3100 on bleomycin-induced pulmonary fibrosis.     

Some dinophycean red tide plankton species generate a superoxide scavenging substance

Recent studies indicate that some raphidophycean red tide flagellates produce substances able to scavenge superoxide, whereas there have been no reports on superoxide scavenger production by dinophycean red tide flagellates. In this study, we examined the superoxide-scavenging activity of aqueous extracts from dinophycean red tide flagellates, Gymnodinium spp., Scrippsiella trochoidea, and Karenia sp., by a luminol analog L-012-dependent chemiluminescence (CL) method and an electron spin resonance (ESR)-spin trapping method, and compared the activity to that of raphidophycean red tide flagellates, Chattonella spp., Heterosigma akashiwo, and Fibrocapsa japonica. In the experiment applying the L-012-dependent CL method, only the aqueous extracts from raphidophycean red tide flagellates showed superoxide-scavenging activity. On the other hand, applying the ESR-spin trapping method, we found that the aqueous extracts from dinophycean red tide flagellates also showed superoxide-scavenging activity. This is the first report on the production of a superoxide-scavenger by dinophycean red tide flagellates.     

Role of Pax3 acetylation in the regulation of Hes1 and Neurog2

Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell maintenance and neurogenesis. A mechanism for Pax3 regulation of these two opposing events, during caudal neural tube development, is examined in this study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be critical for proper regulation of Hes1 and Neurog2. Removal of these lysine residues increased Hes1 but decreased Neurog2 promoter activity. SIRT1 deacetylase may be a key component in regulating Pax3 acetylation. Chromatin immunoprecipitation assays showed that SIRT1 is associated with Hes1 and Neurog2 promoters during murine embryonic caudal neural tube development at E9.5, but not at E12.5. Overexpression of SIRT1 decreased Pax3 acetylation, Neurog2 and Brn3a positive staining. Conversely, siRNA-mediated silencing of SIRT1 increased these factors. These studies suggest that Pax3 acetylation results in decreased Hes1 and increased Neurog2 activity, thereby promoting sensory neuron differentiation.     

Effect of linear polarized near-infrared light irradiation and light exercise on muscle performance

This study aimed to determine the effect of active warm-up by local muscle light exercise and passive warm-up by polarized light irradiation on skin and muscle temperatures and forearm muscle performance (muscle strength, power, endurance, and controlled force-exertion). Ten healthy males performed various grip tests before and after active (local muscle light exercise) and passive (linear polarized near-infrared light irradiation) warm-ups. An active warm-up involved intermittent gripping exercise (contraction: 1 second and relaxation: 1 second) for 10 minutes using a sponge. A passive warm-up consisted of polarized light irradiation to the forearm (superficial digital flexor) for 10 minutes (irradiation: 5 seconds and rest: 1 second). Skin and muscle temperatures were measured during both warm-ups. Skin and muscle temperatures increased significantly after 5 minutes of local muscle light exercise and after 10 minutes of polarized light irradiation. Temperatures were significantly higher after 6 minutes of local muscle light exercise than after 6 minutes of polarized light irradiation. There were no significant differences of muscle strength, power, and controlled force-exertion before and after either warm-up. Average force outputs in all conditions significantly decreased with exertion time, and at 30, 60, 90, and 120 seconds they were higher in both warm-up conditions than in the non-warm-up condition. In conclusion, both warm-ups may contribute to improve muscle endurance performance in the decreasing force phase.     

Synthesis and in vitro insulin-mimetic activities of zinc(ii) complexes of ethyl 2,5-dihydro-4-hydroxy-5-oxo-1H-pyrrole-3-carboxylates

Several Zn(II) complexes (2a-e) of 1-arylmethyl-2,5-dihydro-4-hydroxy-5-oxo-1H-pyrrole-3-carboxylates (1a-e), known drug candidates for diabetic complications, were synthesized and proved to have in vitro insulin-mimetic activities, suggesting that these complexes are potential chemotherapeutics that are effective against both diabetes and diabetic complications.