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Quantum control of molecular collisions at 1 kelvin

Jue, 10/19/2017 - 11:22

Measurement of vector correlations in molecular scattering is an indispensable tool for mapping out interaction potentials. In a coexpanded supersonic beam, we have studied the rotationally inelastic process wherein deuterium hydride (HD) (v = 1, j = 2) collides with molecular deuterium (D2) to form HD (v = 1, j = 1), where v and j are the vibrational and rotational quantum numbers, respectively. HD (v = 1, j = 2) was prepared by Stark-induced adiabatic Raman passage, with its bond axis aligned preferentially parallel or perpendicular to the lab-fixed relative velocity. The coexpansion brought the collision temperature down to 1 kelvin, restricting scattering to s and p partial waves. Scattering angular distributions showed a dramatic stereodynamic preference (~3:1) for perpendicular versus parallel alignment. The four-vector correlation measured between the initial and final velocities and the initial and final rotational angular momentum vectors of HD provides insight into the strong anisotropic forces present in the collision process.

Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation

Jue, 10/19/2017 - 11:22

Intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease. However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize in the gut. These Klebsiella strains are resistant to multiple antibiotics, tend to colonize when the intestinal microbiota is dysbiotic, and elicit a severe gut inflammation in the context of a genetically susceptible host. Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.

Recent natural selection causes adaptive evolution of an avian polygenic trait

Jue, 10/19/2017 - 11:22

We used extensive data from a long-term study of great tits (Parus major) in the United Kingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirm that these genes, especially the collagen gene COL4A5, explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.

Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus

Jue, 10/19/2017 - 11:22

Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces.

Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl synthase

Jue, 10/19/2017 - 11:22

Lipoyl synthase (LipA) catalyzes the last step in the biosynthesis of the lipoyl cofactor, which is the attachment of two sulfhydryl groups to C6 and C8 of a pendant octanoyl chain. The appended sulfur atoms derive from an auxiliary [4Fe-4S] cluster on the protein that is degraded during turnover, limiting LipA to one turnover in vitro. We found that the Escherichia coli iron-sulfur (Fe-S) cluster carrier protein NfuA efficiently reconstitutes the auxiliary cluster during LipA catalysis in a step that is not rate-limiting. We also found evidence for a second pathway for cluster regeneration involving the E. coli protein IscU. These results show that enzymes that degrade their Fe-S clusters as a sulfur source can nonetheless act catalytically. Our results also explain why patients with NFU1 gene deletions exhibit phenotypes that are indicative of lipoyl cofactor deficiencies.

Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling

Jue, 10/19/2017 - 11:22

The LAMTOR [late endosomal and lysosomal adaptor and MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) activator] complex, also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain–folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag guanosine triphosphatases (GTPases) associated with the pentamer through their carboxyl-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the effect of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.

D4 dopamine receptor high-resolution structures enable the discovery of selective agonists

Jue, 10/19/2017 - 11:22

Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D4 dopamine receptor. The ability to efficiently exploit structure for specific probe discovery—rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists—testifies to the power of structure-based approaches.

Taxon-restricted genes at the origin of a novel trait allowing access to a new environment

Jue, 10/19/2017 - 11:22

Taxon-restricted genes make up a considerable proportion of genomes, yet their contribution to phenotypic evolution is poorly understood. We combined gene expression with functional and behavioral assays to study the origin and adaptive value of an evolutionary innovation exclusive to the water strider genus Rhagovelia: the propelling fan. We discovered that two taxon-restricted genes, which we named geisha and mother-of-geisha, specifically control fan development. geisha originated through a duplication event at the base of the Rhagovelia lineage, and both duplicates acquired a novel expression in a specific cell population prefiguring fan development. These gene duplicates played a central role in Rhagovelia’s adaptation to a new physical environment, demonstrating that the evolution of taxon-restricted genes can contribute directly to evolutionary novelties that allow access to unexploited ecological niches.

New Products

Jue, 10/19/2017 - 11:22

From patients to partners

Jue, 10/19/2017 - 11:22

Ultraslow waves on the nanoscale

Jue, 10/19/2017 - 11:22

There has recently been a surge of interest in the physics and applications of broadband ultraslow waves in nanoscale structures operating below the diffraction limit. They range from light waves or surface plasmons in nanoplasmonic devices to sound waves in acoustic-metamaterial waveguides, as well as fermions and phonon polaritons in graphene and van der Waals crystals and heterostructures. We review the underlying physics of these structures, which upend traditional wave-slowing approaches based on resonances or on periodic configurations above the diffraction limit. Light can now be tightly focused on the nanoscale at intensities up to ~1000 times larger than the output of incumbent near-field scanning optical microscopes, while exhibiting greatly boosted density of states and strong wave-matter interactions. We elucidate the general methodology by which broadband and, simultaneously, large wave decelerations, well below the diffraction limit, can be obtained in the above interdisciplinary fields. We also highlight a range of applications for renewable energy, biosensing, quantum optics, high-density magnetic data storage, and nanoscale chemical mapping.

Natural polyreactive IgA antibodies coat the intestinal microbiota

Jue, 10/19/2017 - 11:22

Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse, but defined, subset of microbiota. These antibodies arose at low frequencies among naïve B cells and were selected into the IgA repertoire upon recirculation in Peyer’s patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, although some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.

Comment on "Persistent effects of pre-Columbian plant domestication on Amazonian forest composition"

Jue, 10/19/2017 - 11:22

Levis et al. (Research Articles, 3 March 2017, p. 925) concluded that pre-Columbian tree domestication has shaped present-day Amazonian forest composition. The study, however, downplays five centuries of human influence following European arrival to the Americas. We show that the effects of post-Columbian activities in Amazonia are likely to have played a larger role than pre-Columbian ones in shaping the observed floristic patterns.

Response to Comment on "Persistent effects of pre-Columbian plant domestication on Amazonian forest composition"

Jue, 10/19/2017 - 11:22

McMichael et al. state that we overlooked the effects of post-Columbian human activities in shaping current floristic patterns in Amazonian forests. We formally show that post-Columbian human influences on Amazonian forests are indeed important, but they have played a smaller role when compared to the persistent effects of pre-Columbian human activities on current forest composition.

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