This Week in Science

Science  13 Aug 2010:
Vol. 329, Issue 5993, pp. 723
  1. Designer Anti-HIV


      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.

    1. Peripheral Quality Control

        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.

      1. A Nova Source of Gamma Rays

          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.

        1. De-Twinning a Superconductor

            CREDIT: CHU ET AL.

            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 direction will be averaged over these orientations. Chu et al. (p. 824) were able to “de-twin” the compound Ba(Fe1−xCox)2As2, enabling unambiguous measurements of its normal-state resistivity along the in-plane lattice axes. Differences were observed in the resistivity values along the two axes, which suggests that the breaking of the symmetry of the lattice and electron subsystems occur simultaneously.

          1. Changes in the Rocks

              Changing sea level or major tectonic events, such as continental collisions, shift stratigraphic sequences by changing the depositional environment where certain rock types form. For example, a deep marine environment where limestone formation is favored may shift relatively quickly to a near-shore environment favoring sandstone formation because the relative sea level has dropped several meters. Petersen et al. (p. 827; see the Perspective by Müller), however, suggest that small-scale convection in the mantle may also induce appreciable changes in the sequence of sedimentary deposits. Using a modeling approach, they found that this is possible on a small scale (that is, just a few hundreds of kilometers) over variable time scales. Thus, while the co-occurrence of sedimentary deposit sequences at regional and global scales can allow sedimentary rocks to serve as markers of marine environments, it should be kept in mind that local changes in surface movements may also manifest themselves in the rock record.

            1. Nanoprobes of Cell Potential

                Direct electrical measurements of cell potentials usually face design compromises. Microelectrodes probe within the cytosol of cells but have a minimum size (hundreds of nanometers in width) for obtaining useful signals. Nanoscale field effect transistors (FETs) can have an active probe size of only tens of nanometers but generally allow only the outer cell potential to be measured. Tian et al. (p. 830) fabricated nanowires in which kinks could be introduced to create a sharp probe tip pointing away from the fabrication substrate. Coating the tip with a phospholipid bilayer allowed the probe to be inserted through the membranes of beating cardiac cells, where it could be used to follow temporal changes in cell potential.

              1. Carbon Cycle and Climate Change

                  As climate change accelerates, it is important to know the likely impact of climate change on the carbon cycle (see the Perspective by Reich). Gross primary production (GPP) is a measure of the amount of CO2 removed from the atmosphere every year to fuel photosynthesis. Beer et al. (p. 834, published online 5 July) used a combination of observation and calculation to estimate that the total GPP by terrestrial plants is around 122 billion tons per year; in comparison, burning fossil fuels emits about 7 billion tons annually. Thirty-two percent of this uptake occurs in tropical forests, and precipitation controls carbon uptake in more than 40% of vegetated land. The temperature sensitivity (Q10) of ecosystem respiratory processes is a key determinant of the interaction between climate and the carbon cycle. Mahecha et al. (p. 838, published online 5 July) now show that the Q10 of ecosystem respiration is invariant with respect to mean annual temperature, independent of the analyzed ecosystem type, with a global mean value for Q10 of 1.6. This level of temperature sensitivity suggests a less-pronounced climate sensitivity of the carbon cycle than assumed by recent climate models.

                1. A Gut Feeling

                    CREDIT: MANICASSAMY ET AL.

                    Special immune controls are necessary in the gut to prevent the immune system from reacting to the commensal microbiota and to food antigens. Dendritic cells (DCs) are important for maintaining gut tolerance because they help to keep T cells in an unresponsive state. However, in other environments, DCs activate T cells. What signals determine whether DCs induce T cell tolerance or activation? Manicassamy et al. (p. 849; see the Perspective by Mellman and Clausen) found that β-catenin–dependent signaling is required for maintaining DC-mediated gut tolerance in mice. Wnt ligands were expressed in the gut, and β-catenin signaling was activated in DCs in the small and large intestines but not in the spleen. When β-catenin was specifically deleted from DCs in mice, the frequency of regulatory T cells and anti-inflammatory cytokines was reduced, whereas the frequency of pro-inflammatory T helper 1 and T helper 17 cells and their associated cytokines was increased. Mice lacking β-catenin in dendritic cells also exhibited enhanced susceptibility in a mouse model of colitis.

                  1. Out of Africa

                      Kidney disease is more common in African Americans than in Americans of European descent, and genetics is likely to be a major contributing factor. Genovese et al. (p. 841, published online 15 July) now show that African Americans who carry specific sequence variants in a gene on chromosome 22 encoding apolipoprotein L-1 (APOL1) have an increased risk of developing hypertension-attributed end-stage kidney disease or focal segmental glomerulosclerosis. These variants are absent from European chromosomes. Among the functions ascribed to APOL1 is the ability to lyse and kill trypanosomes. Intriguingly, APOL1 derived from the risk alleles, but not the “wild-type” allele, killed Trypanosoma brucei rhodesiense, which causes African sleeping sickness.

                    1. Riboswitch Revealed

                        Short regulatory regions—riboswitches—are found in the messenger RNAs of many bacteria, plants, and fungi. They bind to small-molecule metabolites and, through switching between alternate RNA secondary structures, regulate the expression of the linked RNA. Lee et al. (p. 845) have identified a c-di-GMP (cyclic di-guanosyl-5′-monophosphate)–binding riboswitch in the bacterium Clostridium difficile that regulates the splicing of a group I self-splicing ribozyme. Binding of c-di-GMP to the riboswitch favors a conformation of the ribozyme that promotes splicing in the presence of guanosine triphosphate (as is typical for this class of ribozymes). Concomitantly, splicing promotes the formation of a ribosome binding site, thereby stimulating protein production from the downstream pathogenesis-related gene. This regulatory region may thus constitute a two-input gene-control system that reads the concentration of both GTP and c-di-GMP. Thus, not all group I self-splicing ribozymes represent selfish genetic elements.

                      1. Carrier Mobility in Topological Insulators

                          In addition to an energy gap, which is a characteristic of all band insulators, the electronic structure of the recently discovered three-dimensional topological insulators Bi2Te3 and Bi2Se3 contains a surface state with a Dirac-like dispersion. This state is predicted to be associated with high carrier mobility. However, the transport properties of the surface state are obscured by the bulk material and challenging to measure. Qu et al. (p. 821, published online 29 July) produced crystals of Bi2Te3 with the Fermi energy lying in the bulk gap and detected quantum oscillations whose magnetic field dependence reveals that they come from a two-dimensional Fermi surface. An anomaly in the Hall conductance originating from the surface state was also observed. The two measurements independently yield mutually consistent high electron mobilities.

                        1. Building a Network

                            The relation between the architecture of ecological networks and community stability is important to understand the assembly of complex communities. By combining a model approach and a meta-analysis of a large collection of ecological networks, Thébault and Fontaine (p. 853; see the Perspective by Bascompte) found that network architecture and stability fundamentally differed between trophic networks that involved herbivory and mutualistic networks that involved pollination. These findings have implications for the understanding of community structure, evolution, and response to perturbation.

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