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研前沿的 &ruo; 研前沿Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss). Wu et al. (p. 856, published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike. Zhou et al. (p. 811, published online 8 July) analyzed the crystal structure for one of these antibodies, VRC01, in complex with an HIV-1 gp120. VRC01 focuses its binding onto a conformationally invariant domain that is the site of initial CD4 attachment, which allows the antibody to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. The epitopes recognized by these antibodies suggest potential immunogens that can inform vaccine design.
Protein misfolding diseases often lead to the retention and degradation of important proteins within the endoplasmic reticulum (ER). Strategies to reduce the stringency of ER quality control that allow the proteins to carry on through the secretory pathway to reach their destination at the cell surface have shown some promise. Okiyoneda et al. (p. 805, published online 1 July; see the Perspective by Hutt and Balch) wanted to understand how, even if a protein reaches its destination, it may still be subjected to a second level of quality control and be cleared from the plasma membrane. Using functional small-interfering RNA screens in cells expressing the common cystic fibrosis mutation F508CFTR, the authors identified a pair of chaperones that promoted clearance of defective proteins from the plasma membrane. This peripheral quality-control step will also need to be overcome to increase the effectiveness of strategies to overcome protein misfolding disorders.
Novae are thermonuclear explosions that occur at the surface of a white dwarf when material is pulled onto it from a companion star in a binary system. They are different from supernovae because the explosion does not completely destroy the white dwarf. Novae have not been widely considered as high-energy gamma-ray sources. Using the Fermi Large Area Telescope, Abdo et al. (p. 817) now report the detection of a nova explosion in gamma rays. The observations provide evidence for the acceleration to relativistic energies of particles in the shock wave following the explosion.
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Insight into the mechanism of electrical transport in a solid can often be gained by measuring its resistivity along different spatial directions. However, iron-based superconductors form numerous twin boundaries where two different orientations of a crystal meet, and so the measured resistivity along any in-plane
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