Membrane dynamics as seen by Fourier transform infrared spectroscopy in a cyanobacterium, Synechocystis PCC 6803 The effects of lipid unsaturation and the protein-to-lipid ratio

AbstractThe roles of lipid unsaturation and lipid-protein interactions in maintaining the physiologically required membrane dynamics were investigated in a cyanobacterium strain, Synechocystis PCC 6803. The specific effects of lipid unsaturation on the membrane structure were addressed by the use of desaturase-deficient (desA−/desD−) mutant cells (which contain only oleic acid as unsaturated fatty acid species) of Synechocystis PCC 6803. The dynamic properties of the membranes were determined from the temperature dependence of the symmetric CH2 stretching vibration frequency, which is indicative of the lipid fatty acyl chain disorder. It was found that a similar membrane dynamics is maintained at any growth temperature, in both the wild-type and the mutant cell membranes, with the exception of mutant cells grown at the lower physiological temperature limit. It seems that in the physiological temperature range the desaturase system of the cells can modulate the level of lipid desaturation sufficiently to maintain similar membrane dynamics. Below the range of normal growth temperatures, however, the extent of lipid disorder was always higher in the thylakoid than in the cytoplasmic membranes prepared from the same cells. This difference was attributed to the considerable difference in protein-to-lipid ratio in the two kinds of membranes, as determined from the ratio of the intensities of the protein amide I band and the lipid ester CO vibration. The contributions to the membrane dynamics of an ab ovo present ‘structural’ lipid disorder due to the protein–lipid interactions and of a thermally induced ‘dynamic’ lipid disorder could be distinguished

Pseudogap Phase Boundary in Overdoped Bi_2Sr_2CaCu_2O_8 Studied by Measuring Out-of-plane Resistivity under the Magnetic Fields

The characteristic pseudogap temperature T* in Bi2Sr2CaCu2O8 system has been systematically evaluated as a function of doping, especially focusing on its overdoped region, by measuring the out-of-plane resistivity under the magnetic fields. Overdoped samples have been prepared by annealing TSFZ-grown Bi2Sr2CaCu2O8 single crystals under the high oxygen pressures (990 kgf/cm2). At a zero field, the out-of-plane resistivity showed a metallic behavior down to Tc (= 62 K), while under the magnetic fields of over 3 T,it showed typical upturn behavior from around 65 K upon decreasing temperature. This result suggests that the pseudogap and superconductivity are different phenomena.Comment: 2 pages, 2 figures. Final version accepted for the Proceedings of the M2S-IX Conference (Tokyo, September 2009

Both the anaerobic pathway and aerobic desaturation are involved in the synthesis of unsaturated fatty acids in Vibrio sp. strain ABE-1

AbstractVibrio sp. strain ABE-1 is a unique marine bacterium in terms of its ability to synthesize Δ9-trans-hexadecenoic acid and Δ7-cis-tetradecenoic acid (14:1(7c); Okuyama, H., Sasaki, S., Higashi, S. and Murata, N. (1990) J. Bacteriol. 172, 3515-3518). The present study, involving labeling with [1-14C]acetate, demonstrated that 14:1 is synthesized by the anaerobic pathway. When cells of this bacterium were grown in the presence of [1-14C]myristic acid (14:0), this compound was converted to palmitic (16:0) and hexadecenoic (16:1) acids but not to 14:1, under aerobic conditions. These results suggest that the incorporated 14:0 was elongated to 16:0 and then converted to 16:1 by the aerobic desaturation of 16:0. It appears that the anaerobic pathway and aerobic desaturation are both involved in the synthesis of unsaturated fatty acids during aerobic growth of Vibrio sp. strain ABE-1

Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke

<p>Abstract</p> <p>Background</p> <p>The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy.</p> <p>Results</p> <p>Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 ± 57 mm³saline controls; 309 ± 58 mm³NBO; 201 ± 78 mm³tPA; 138 ± 30 mm³tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality.</p> <p>Conclusion</p> <p>NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.</p

Free fatty acid receptors, G protein-coupled receptor 120 and G protein-coupled receptor 40, are essential for oil-induced gastric inhibitory polypeptide secretion

Aims/Introduction: Incretin hormone glucose‐dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) plays a key role in high‐fat diet‐induced obesity and insulin resistance. GIP is strongly secreted from enteroendocrine K cells by oil ingestion. G protein‐coupled receptor (GPR)120 and GPR40 are two major receptors for long chain fatty acids, and are expressed in enteroendocrine K cells. In the present study, we investigated the effect of the two receptors on oil‐induced GIP secretion using GPR120‐ and GPR40‐double knockout (DKO) mice. Materials and Methods: Global knockout mice of GPR120 and GPR40 were crossbred to generate DKO mice. Oral glucose tolerance test and oral corn oil tolerance test were carried out. For analysis of the number of K cells and gene expression in K cells, DKO mice were crossbred with GIP‐green fluorescent protein knock‐in mice in which visualization and isolation of K cells can be achieved. Results: Double knockout mice showed normal glucose‐induced GIP secretion, but no GIP secretion by oil. We then investigated the number of K cells and gene characteristics in K cells isolated from GIP‐green fluorescent protein knock‐in mice. Deficiency of both receptors did not affect the number of K cells in the small intestine or expression of GIP messenger ribonucleic acid in K cells. Furthermore, there was no significant difference in the expression of the genes associated with lipid absorption or GIP secretion in K cells between wild‐type and DKO mice. Conclusions: Oil‐induced GIP secretion is triggered by the two major fatty acid receptors, GPR120 and GPR40, without changing K‐cell number or K‐cell characteristics

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan

Abstract Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. Methods A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Findings Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US$1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US$22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US$67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Conclusion Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF

A Substellar Companion to the Intermediate-Mass Giant 11 Com

We report the detection of a substellar companion orbiting the intermediate-mass giant star 11 Com (G8 III). Precise Doppler measurements of the star from Xinglong station and Okayama Astrophysical Observatory (OAO) revealed Keplerian velocity variations with an orbital period of 326.03 +/- 0.32 days, a semiamplitude of 302.8 +/- 2.6 m/s, and an eccentricity of 0.231 +/- 0.005. Adopting a stellar mass of 2.7 +/- 0.3 M_solar, the minimum mass of the companion is 19.4 +/- 1.5 M_Jup, well above the deuterium burning limit, and the semimajor axis is 1.29 +/- 0.05 AU. This is the first result from the joint planet search program between China and Japan aiming at revealing statistics of substellar companions around intermediate-mass giants. 11 Com b emerged from 300 targets of the planet search program at OAO. The current detection rate of a brown dwarf candidate seems to be comparable to that around solar-type stars within orbital separations of $\sim$3 AU.Comment: 19 pages, 4 figures, accepted by Ap