Interleukin‐1 receptor‐associated kinase‐1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP‐1 derived macrophages and human monocyte‐derived macrophages (HMDMs). Ox‐LDL (40 μg/mL, 15 minutes–48 hours) treatment induced time‐dependent increase in IRAK1, IRAK4, and Stat1 activation in THP‐1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI‐Ox‐LDL binding, and uptake while (...) cholesterol efflux to apoAI and HDL was enhanced in THP‐1 derived macrophages and HMDMs. Ox‐LDL treatment significantly increased the mRNA expression of CD36, LOX‐1, SR‐A, ABCA1, ABCG1, Caveolin‐1, CYP27A1 while that of SR‐BI was decreased. IRAK1/4 inhibition or IRAK1 knockdown, however, attenuated Ox‐LDL‐induced CD36 expression; augmented ABCA1 and ABCG1 expression while expression of others was unaffected in THP‐1 derived macrophages and HMDMs. Moreover, IRAK1/4 inhibition had no significant effect on genes involved in lipid biosynthesis. In IRAK1/4 INH pre‐treated THP‐1 derived macrophages Ox‐LDL‐induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRα expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36‐mediated uptake and ABCA1‐, ABCG1‐dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation. (shrink)

There seems to exist a dilemma in the literature as to the correct relativistic formula for the Sagnac phase-shift. The paper addresses this issue in the light of a novel, kinematically equivalent linear Sagnac-type thought experiment, which provides a vantage point from which the effect of rotation in the usual Sagnac effect can be analyzed. The question is shown to be related to the so-called rotating disc problem known as the Ehrenfest paradox. The relativistic formula for the Sagnac phase-shift seems (...) to depend on the way the paradox is resolved. Kinematic resolution of the Ehrenfest paradox proposed by some authors predicts the usually quoted formula for the Sagnac delay but the resolution itself is shown to be based upon some implicit assumptions regarding the behaviour of solid bodies under acceleration. In order to have a greater insight into the problem, a second version of the thought experiment involving linear motion of a “special type” of a non-rigid frame of reference is discussed. It is shown by analogy that the usually quoted special relativistic formula for the Sagnac delay follows, provided the material of the disc matches the “special type.”. (shrink)

FAO has a unique and essential rolein addressing the ethical problems facinghumanity and in making these problems intoopportunities for practical resolution. A broadrange of ethical issues in agriculture,fisheries, and forestry were identified byanalysis of the literature and by interviewswith FAO staff. Issues include sharing accessto and preserving natural resources,introduction of new technology, conservatismover the use of genetic engineering, ethics inanimal agriculture, access to information, foodsecurity, sustainable rural development,ensuring participation of all people indecision making and in receiving benefits ofagriculture, reducing corruption, (...) andinvolvement of private and public sectors indecision making. Rather than viewing theseissues as problems, they should be viewed asopportunities for debate, learning aboutothers' views, and resolution. The UnitedNations has an important role to play in howdecisions are made in the global ethical debatein food and agriculture. The ethical role ofFAO is to promote global food security,balanced conservation, management andutilization of natural resources, andsustainable rural development. FAO should fullyand publicly assume its ethicalresponsibilities, gathering and sharinginformation on ethics in its areas of mandate,acting as an interactive forum, and providingexpert guidance on policy options and choicesbased on practical ethical analysis. (shrink)