Platensimycin is a selective FabF inhibitor with potent antibiotic properties

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.     

Seismic reflection images of the Moho underlying melt sills at the East Pacific Rise

The determination of melt distribution in the crust and the nature of the crust-mantle boundary (the 'Moho') is fundamental to the understanding of crustal accretion processes at oceanic spreading centres. Upper-crustal magma chambers have been imaged beneath fast- and intermediate-spreading centres but it has been difficult to image structures beneath these magma sills. Using three-dimensional seismic reflection images, here we report the presence of Moho reflections beneath a crustal magma chamber at the 9 degrees 03' N overlapping spreading centre, East Pacific Rise. Our observations highlight the formation of the Moho at zero-aged crust. Over a distance of less than 7 km along the ridge crest, a rapid increase in two-way travel time of seismic waves between the magma chamber and Moho reflections is observed, which we suggest is due to a melt anomaly in the lower crust. The amplitude versus offset variation of reflections from the magma chamber shows a coincident region of higher melt fraction overlying this anomalous region, supporting the conclusion of additional melt at depth.     

机械振动对铸造A308 (LM21)铝合金物理、冶金和力学性能的影响

本文研究了A308压铸合金在机械振动作用下凝固过程中的组织、物理和力学性能。采用功率放大器作为功率输入器件，在31 μm的恒定振幅下，采用不同频率(0、20、30、40、50 Hz)进行功率输入。采用X射线衍射、光学显微镜和扫描电子显微镜观察了固定和振动条件下铸态试样的形态变化。利用ImageJ软件对铸件的金相特征进行了评价。在30 Hz频率下，与固定铸造相比，初晶α-Al晶粒尺寸、枝晶臂间距、共晶硅平均面积、长径比和孔隙率等冶金特征平均值分别降低了34%、59%、56%、22%和62%。力学性能测试表明，在30 Hz频率下，铸件的屈服强度(YS)、抗拉强度(UTS)、伸长率(EL)和显微硬度(HV)分别比固定铸造提高了8%、13%、17%和16%。拉伸试样的断口表现为脆性面、解理面、韧性撕裂和韧窝形貌的混合断裂行为。小韧窝的存在表明在断裂前发生了塑性变形。