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Lee JM  Lee YK  Mamrosh JL  Busby SA  Griffin PR  Pathak MC  Ortlund EA  Moore DD 《Nature》2011,474(7352):506-510
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.  相似文献   
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We studied theoretically and experimentally a biomimetic propulsion system inspired by the motility mechanisms of bacteria such as E. coli. Our goal was to investigate the effect of the ??complex?? filament of Rhizobium Meliloti bacteria on thrust force. The complex filament is a helically perturbed filament, similar to a plain filament threaded through a small helix. The propulsive performance of this system was estimated by modeling the dynamics of helical wave motion in viscous fluid. The model consists of a helical filament which is axially rotated at angular velocity ??. Resistive force theory (RFT) was applied to this model to calculate the thrust force and required torque. The Buckingham PI theorem (non-dimensional analysis) was also used to analyze the theoretical results. The procedure for making a complex filament with various pitch angles ?? s from a small helix and plain filament is explained in detail. To validate the theoretical results for helical wave propulsion and compare the characteristics of complex and plain filaments together, an experiment was performed to measure the thrust forces in silicone oil. The experimental results agreed with the theoretical values predicted by RFT. The thrust forces of complex filaments depended on the shape of small helix winding. The maximum thrust force was achieved at a small helix pitch angle of ?? s = 45°. In addition, we found that the thrust force generated by a complex filament had a value about 10% higher than that of a plain filament with the same equivalent diameter d e .  相似文献   
335.
Detailed high-resolution observations of the innermost regions of nearby galaxies have revealed the presence of supermassive black holes. These black holes may interact with their host galaxies by means of 'feedback' in the form of energy and material jets; this feedback affects the evolution of the host and gives rise to observed relations between the black hole and the host. Here we report observations of the ultraviolet emissions of massive early-type galaxies. We derive an empirical relation for a critical black-hole mass (as a function of velocity dispersion) above which the outflows from these black holes suppress star formation in their hosts by heating and expelling all available cold gas. Supermassive black holes are negligible in mass compared to their hosts but nevertheless seem to play a critical role in the star formation history of galaxies.  相似文献   
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Many types of bacteria produce extracellular polysaccharides (EPSs). Some are secreted polymers and show only limited association with the cell surface, whereas others are firmly attached to the cell surface and form a discrete structural layer, the capsule, which envelopes the cell and allows the bacteria to evade or counteract the host immune system. EPSs have critical roles in bacterial colonization of surfaces, such as epithelia and medical implants; in addition some EPSs have important industrial and biomedical applications in their own right. Here we describe the 2.26 A resolution structure of the 340 kDa octamer of Wza, an integral outer membrane lipoprotein, which is essential for group 1 capsule export in Escherichia coli. The transmembrane region is a novel alpha-helical barrel. The bulk of the Wza structure is located in the periplasm and comprises three novel domains forming a large central cavity. Wza is open to the extracellular environment but closed to the periplasm. We propose a route and mechanism for translocation of the capsular polysaccharide. This work may provide insight into the export of other large polar molecules such as DNA and proteins.  相似文献   
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镁是最轻的金属结构材料。然而,镁合金板材具有织构强,室温成形性差的瓶颈难题,限制其广泛应用。虽然研究发现在Mg–Zn–Zr合金体系同添加钙或钆能弱化织构,提高成形性,但这两种元素添加后对的效果尚未有过系统比较和研究。本文旨在展现微合金添加钆和钙对于显微结构和力学性能的影响规律。本文发现,Mg–Zn–Gd–Zr 与 Mg–Zn–Ca–Zr轧板有类似的弱织构,但是Mg–Zn–Gd–Zr轧板的延伸率和成形性高于Mg–Zn–Ca–Zr。当在Mg–1Zn–0.5Zr合金中添加0.4wt%钆、0.2wt%钙时能获得最高的室温延伸率,其深冲成形性可以和铝合金板材6016相媲美。当钙的含量从0.2wt%提升至0.5wt%后,合金板材的延伸率与成形性下降,其主要原因是钙的过量添加导致了晶界脆化,降低了晶界韧性从而裂纹容易从晶界处萌生并扩展。  相似文献   
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