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- HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Science 2014 Dec 12; 346(6215):1380-3.
Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.
- Electron microscopy. Ultrastable gold substrates for electron cryomicroscopy. [Journal Article, Research Support, Non-U.S. Gov't]
- Science 2014 Dec 12; 346(6215):1377-80.
Despite recent advances, the structures of many proteins cannot be determined by electron cryomicroscopy because the individual proteins move during irradiation. This blurs the images so that they cannot be aligned with each other to calculate a three-dimensional density. Much of this movement stems from instabilities in the carbon substrates used to support frozen samples in the microscope. Here we demonstrate a gold specimen support that nearly eliminates substrate motion during irradiation. This increases the subnanometer image contrast such that α helices of individual proteins are resolved. With this improvement, we determine the structure of apoferritin, a smooth octahedral shell of α-helical subunits that is particularly difficult to solve by electron microscopy. This advance in substrate design will enable the solution of currently intractable protein structures.
- Systems biology. Accurate information transmission through dynamic biochemical signaling networks. [Journal Article, Research Support, N.I.H., Extramural]
- Science 2014 Dec 12; 346(6215):1370-3.
Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation--that is, dynamics--to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2+)), and nuclear factor kappa-B (NF-κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.
- Political science. When contact changes minds: an experiment on transmission of support for gay equality. [Journal Article, Research Support, Non-U.S. Gov't]
- Science 2014 Dec 12; 346(6215):1366-9.
Can a single conversation change minds on divisive social issues, such as same-sex marriage? A randomized placebo-controlled trial assessed whether gay (n = 22) or straight (n = 19) messengers were effective at encouraging voters (n = 972) to support same-sex marriage and whether attitude change persisted and spread to others in voters' social networks. The results, measured by an unrelated panel survey, show that both gay and straight canvassers produced large effects initially, but only gay canvassers' effects persisted in 3-week, 6-week, and 9-month follow-ups. We also find strong evidence of within-household transmission of opinion change, but only in the wake of conversations with gay canvassers. Contact with gay canvassers further caused substantial change in the ratings of gay men and lesbians more generally. These large, persistent, and contagious effects were confirmed by a follow-up experiment. Contact with minorities coupled with discussion of issues pertinent to them is capable of producing a cascade of opinion change.
- Nutritional immunity. Escape from bacterial iron piracy through rapid evolution of transferrin. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Science 2014 Dec 12; 346(6215):1362-6.
Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.
- Pollinator declines. Extinctions of aculeate pollinators in Britain and the role of large-scale agricultural changes. [Journal Article]
- Science 2014 Dec 12; 346(6215):1360-2.
Pollinators are fundamental to maintaining both biodiversity and agricultural productivity, but habitat destruction, loss of flower resources, and increased use of pesticides are causing declines in their abundance and diversity. Using historical records, we assessed the rate of extinction of bee and flower-visiting wasp species in Britain from the mid-19th century to the present. The most rapid phase of extinction appears to be related to changes in agricultural policy and practice beginning in the 1920s, before the agricultural intensification prompted by the Second World War, often cited as the most important driver of biodiversity loss in Britain. Slowing of the extinction rate from the 1960s onward may be due to prior loss of the most sensitive species and/or effective conservation programs.
- Membranes. Metal-organic framework nanosheets as building blocks for molecular sieving membranes. [Journal Article, Research Support, Non-U.S. Gov't]
- Science 2014 Dec 12; 346(6215):1356-9.
Layered metal-organic frameworks would be a diverse source of crystalline sheets with nanometer thickness for molecular sieving if they could be exfoliated, but there is a challenge in retaining the morphological and structural integrity. We report the preparation of 1-nanometer-thick sheets with large lateral area and high crystallinity from layered MOFs. They are used as building blocks for ultrathin molecular sieve membranes, which achieve hydrogen gas (H2) permeance of up to several thousand gas permeation units (GPUs) with H2/CO2 selectivity greater than 200. We found an unusual proportional relationship between H2 permeance and H2 selectivity for the membranes, and achieved a simultaneous increase in both permeance and selectivity by suppressing lamellar stacking of the nanosheets.
- Nanolithography. Large-scale nanoshaping of ultrasmooth 3D crystalline metallic structures. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2014 Dec 12; 346(6215):1352-6.
We report a low-cost, high-throughput benchtop method that enables thin layers of metal to be shaped with nanoscale precision by generating ultrahigh-strain-rate deformations. Laser shock imprinting can create three-dimensional crystalline metallic structures as small as 10 nanometers with ultrasmooth surfaces at ambient conditions. This technique enables the successful fabrications of large-area, uniform nanopatterns with aspect ratios as high as 5 for plasmonic and sensing applications, as well as mechanically strengthened nanostructures and metal-graphene hybrid nanodevices.
- Ultrafast dynamics. Attosecond band-gap dynamics in silicon. [Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2014 Dec 12; 346(6215):1348-52.
Electron transfer from valence to conduction band states in semiconductors is the basis of modern electronics. Here, attosecond extreme ultraviolet (XUV) spectroscopy is used to resolve this process in silicon in real time. Electrons injected into the conduction band by few-cycle laser pulses alter the silicon XUV absorption spectrum in sharp steps synchronized with the laser electric field oscillations. The observed ~450-attosecond step rise time provides an upper limit for the carrier-induced band-gap reduction and the electron-electron scattering time in the conduction band. This electronic response is separated from the subsequent band-gap modifications due to lattice motion, which occurs on a time scale of 60 ± 10 femtoseconds, characteristic of the fastest optical phonon. Quantum dynamical simulations interpret the carrier injection step as light-field-induced electron tunneling.
- Solid state theory. Quantum spin Hall effect in two-dimensional transition metal dichalcogenides. [Journal Article, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2014 Dec 12; 346(6215):1344-7.
Quantum spin Hall (QSH) effect materials feature edge states that are topologically protected from backscattering. However, the small band gap in materials that have been identified as QSH insulators limits applications. We use first-principles calculations to predict a class of large-gap QSH insulators in two-dimensional transition metal dichalcogenides with 1T' structure, namely, 1T'-MX2 with M = (tungsten or molybdenum) and X = (tellurium, selenium, or sulfur). A structural distortion causes an intrinsic band inversion between chalcogenide-p and metal-d bands. Additionally, spin-orbit coupling opens a gap that is tunable by vertical electric field and strain. We propose a topological field effect transistor made of van der Waals heterostructures of 1T'-MX2 and two-dimensional dielectric layers that can be rapidly switched off by electric field through a topological phase transition instead of carrier depletion.