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- Compartmentalization of GABAergic inhibition by dendritic spines. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Science 2013 May 10; 340(6133):759-62.
γ-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca(2+)) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca(2+) signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling.
- Emergence of individuality in genetically identical mice. [Journal Article, Research Support, Non-U.S. Gov't]
- Science 2013 May 10; 340(6133):756-9.
Brain plasticity as a neurobiological reflection of individuality is difficult to capture in animal models. Inspired by behavioral-genetic investigations of human monozygotic twins reared together, we obtained dense longitudinal activity data on 40 inbred mice living in one large enriched environment. The exploratory activity of the mice diverged over time, resulting in increasing individual differences with advancing age. Individual differences in cumulative roaming entropy, indicating the active coverage of territory, correlated positively with individual differences in adult hippocampal neurogenesis. Our results show that factors unfolding or emerging during development contribute to individual differences in structural brain plasticity and behavior. The paradigm introduced here serves as an animal model for identifying mechanisms of plasticity underlying nonshared environmental contributions to individual differences in behavior.
- Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. [Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2013 May 10; 340(6133):751-6.
Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.
- Wolbachia invades Anopheles stephensi populations and induces refractoriness to Plasmodium infection. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Science 2013 May 10; 340(6133):748-51.
Wolbachia is a maternally transmitted symbiotic bacterium of insects that has been proposed as a potential agent for the control of insect-transmitted diseases. One of the major limitations preventing the development of Wolbachia for malaria control has been the inability to establish inherited infections of Wolbachia in anopheline mosquitoes. Here, we report the establishment of a stable Wolbachia infection in an important malaria vector, Anopheles stephensi. In A. stephensi, Wolbachia strain wAlbB displays both perfect maternal transmission and the ability to induce high levels of cytoplasmic incompatibility. Seeding of naturally uninfected A. stephensi populations with infected females repeatedly resulted in Wolbachia invasion of laboratory mosquito populations. Furthermore, wAlbB conferred resistance in the mosquito to the human malaria parasite Plasmodium falciparum.
- Robust circadian oscillations in growing cyanobacteria require transcriptional feedback. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Science 2013 May 10; 340(6133):737-40.
The remarkably stable circadian oscillations of single cyanobacteria enable a population of growing cells to maintain synchrony for weeks. The cyanobacterial pacemaker is a posttranslational regulation (PTR) circuit that generates circadian oscillations in the phosphorylation state of the clock protein KaiC. Layered on top of the PTR is transcriptional-translational feedback regulation (TTR), common to all circadian systems, consisting of a negative feedback loop in which KaiC regulates its own production. We found that the PTR circuit is sufficient to generate oscillations in growing cyanobacteria. However, in the absence of TTR, individual oscillators were less stable and synchrony was not maintained in a population of cells. Experimentally constrained mathematical modeling reproduced sustained oscillations in the PTR circuit alone and demonstrated the importance of TTR for oscillator synchrony.
- Networks of bZIP protein-protein interactions diversified over a billion years of evolution. [Journal Article, Research Support, N.I.H., Extramural]
- Science 2013 May 10; 340(6133):730-4.
Differences in biomolecular sequence and function underlie dramatic ranges of appearance and behavior among species. We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species. The metazoan bZIP interactomes have broadly similar structures, but there has been extensive rewiring of connections compared to the last common ancestor, and each species network is highly distinct. Many metazoan bZIP orthologs and paralogs have strikingly different interaction specificities, and some differences arise from minor sequence changes. Our data show that a shifting landscape of biochemical functions related to signaling and gene expression contributes to species diversity.
- Enhanced role of transition metal ion catalysis during in-cloud oxidation of SO2. [Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2013 May 10; 340(6133):727-30.
Global sulfate production plays a key role in aerosol radiative forcing; more than half of this production occurs in clouds. We found that sulfur dioxide oxidation catalyzed by natural transition metal ions is the dominant in-cloud oxidation pathway. The pathway was observed to occur primarily on coarse mineral dust, so the sulfate produced will have a short lifetime and little direct or indirect climatic effect. Taking this into account will lead to large changes in estimates of the magnitude and spatial distribution of aerosol forcing. Therefore, this oxidation pathway-which is currently included in only one of the 12 major global climate models-will have a significant impact on assessments of current and future climate.
- Spin-optical metamaterial route to spin-controlled photonics. [Journal Article, Research Support, Non-U.S. Gov't]
- Science 2013 May 10; 340(6133):724-6.
Spin optics provides a route to control light, whereby the photon helicity (spin angular momentum) degeneracy is removed due to a geometric gradient onto a metasurface. The alliance of spin optics and metamaterials offers the dispersion engineering of a structured matter in a polarization helicity-dependent manner. We show that polarization-controlled optical modes of metamaterials arise where the spatial inversion symmetry is violated. The emerged spin-split dispersion of spontaneous emission originates from the spin-orbit interaction of light, generating a selection rule based on symmetry restrictions in a spin-optical metamaterial. The inversion asymmetric metasurface is obtained via anisotropic optical antenna patterns. This type of metamaterial provides a route for spin-controlled nanophotonic applications based on the design of the metasurface symmetry properties.
- Multiscale modeling of membrane rearrangement, drainage, and rupture in evolving foams. [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 2013 May 10; 340(6133):720-4.
Modeling the physics of foams and foamlike materials, such as soapy froths, fire retardants, and lightweight crash-absorbent structures, presents challenges, because of the vastly different time and space scales involved. By separating and coupling these disparate scales, we have designed a multiscale framework to model dry foam dynamics. This leads to a predictive and flexible computational methodology linking, with a few simplifying assumptions, foam drainage, rupture, and topological rearrangement, to coupled interface-fluid motion under surface tension, gravity, and incompressible fluid dynamics. Our computed results match theoretical analyses and experimentally observed physical effects, including thin-film drainage and interference, and are used to study bubble rupture cascades and macroscopic rearrangement. The developed multiscale model allows quantitative computation of complex foam evolution phenomena.
- Lorentz meets Fano in spectral line shapes: a universal phase and its laser control. [Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Science 2013 May 10; 340(6133):716-20.
Symmetric Lorentzian and asymmetric Fano line shapes are fundamental spectroscopic signatures that quantify the structural and dynamical properties of nuclei, atoms, molecules, and solids. This study introduces a universal temporal-phase formalism, mapping the Fano asymmetry parameter q to a phase φ of the time-dependent dipole response function. The formalism is confirmed experimentally by laser-transforming Fano absorption lines of autoionizing helium into Lorentzian lines after attosecond-pulsed excitation. We also demonstrate the inverse, the transformation of a naturally Lorentzian line into a Fano profile. A further application of this formalism uses quantum-phase control to amplify extreme-ultraviolet light resonantly interacting with He atoms. The quantum phase of excited states and its response to interactions can thus be extracted from line-shape analysis, with applications in many branches of spectroscopy.