绵羊的故事

1999年,我们将庆祝应用科学中伟大的维多利亚时代的赞歌之一、由JamesCaird撰写的书籍──《自由盟为下的高农场：保护最好的代用品》出版150周年。当英国人首次进行自由贸易试验时,这场论战从19世纪中叶就开始了,人们并不鼓励农民依靠进口税收,而是鼓励农民转向科学以增强生产效率和利润,开创新技术的农业则被称为“高农场”。1997年,这一年的科学成就──多利,在苏格兰罗斯林研究所诞生了,那里是Caird的家乡,他是与高地和农业社会相关的农业改革的开拓者。在18和19世纪,这个在地貌上起伏不平的国家成了科学、技术和人类之间的…     

Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli

The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans. Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages, suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity. We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis. These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor. This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria. Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified. Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo. Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection. Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria. Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis.     

Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair

The Ku heterodimer (Ku70 and Ku80 subunits) contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. The crystal structure of the human Ku heterodimer was determined both alone and bound to a 55-nucleotide DNA element at 2.7 and 2.5 A resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA. The binding site can cradle two full turns of DNA while encircling only the central 3-4 base pairs (bp). Ku makes no contacts with DNA bases and few with the sugar-phosphate backbone, but it fits sterically to major and minor groove contours so as to position the DNA helix in a defined path through the protein ring. These features seem well designed to structurally support broken DNA ends and to bring the DNA helix into phase across the junction during end processing and ligation.     

Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms

Stargazer, an ataxic and epileptic mutant mouse, lacks functional AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate) receptors on cerebellar granule cells. Stargazin, the mutated protein, interacts with both AMPA receptor subunits and synaptic PDZ proteins, such as PSD-95. The interaction of stargazin with AMPA receptor subunits is essential for delivering functional receptors to the surface membrane of granule cells, whereas its binding with PSD-95 and related PDZ proteins through a carboxy-terminal PDZ-binding domain is required for targeting the AMPA receptor to synapses. Expression of a mutant stargazin lacking the PDZ-binding domain in hippocampal pyramidal cells disrupts synaptic AMPA receptors, indicating that stargazin-like mechanisms for targeting AMPA receptors may be widespread in the central nervous system.     

An updatable holographic three-dimensional display

Holographic three-dimensional (3D) displays provide realistic images without the need for special eyewear, making them valuable tools for applications that require situational awareness, such as medical, industrial and military imaging. Currently commercially available holographic 3D displays use photopolymers that lack image-updating capability, resulting in restricted use and high cost. Photorefractive polymers are dynamic holographic recording materials that allow updating of images and have a wide range of applications, including optical correlation, imaging through scattering media and optical communication. To be suitable for 3D displays, photorefractive polymers need to have nearly 100% diffraction efficiency, fast writing time, hours of image persistence, rapid erasure, and large area-a combination of properties that has not been shown before. Here, we report an updatable holographic 3D display based on photorefractive polymers with such properties, capable of recording and displaying new images every few minutes. This is the largest photorefractive 3D display to date (4 x 4 inches in size); it can be recorded within a few minutes, viewed for several hours without the need for refreshing, and can be completely erased and updated with new images when desired.     

MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome

Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, syndactyly and cardiac defect. We show here that heterozygous mutations in the gene MYCN are present in Feingold syndrome. All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain growth in humans are tightly regulated by MYCN dosage.