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Making the right catch

Jue, 08/17/2017 - 11:30

Breathing in the dark

Jue, 08/17/2017 - 11:30

A phenyl ring hops with a light step

Jue, 08/17/2017 - 11:30

Wired-up wash and go

Jue, 08/17/2017 - 11:30

Protection by a parasitic plant

Jue, 08/17/2017 - 11:30

Bugs and drugs: A work in progress

Jue, 08/17/2017 - 11:30

Human spit contains ancestral surprises

Jue, 08/17/2017 - 11:30

Comprehensive single-cell transcriptional profiling of a multicellular organism

Jue, 08/17/2017 - 11:30

To resolve cellular heterogeneity, we developed a combinatorial indexing strategy to profile the transcriptomes of single cells or nuclei, termed sci-RNA-seq (single-cell combinatorial indexing RNA sequencing). We applied sci-RNA-seq to profile nearly 50,000 cells from the nematode Caenorhabditis elegans at the L2 larval stage, which provided >50-fold "shotgun" cellular coverage of its somatic cell composition. From these data, we defined consensus expression profiles for 27 cell types and recovered rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. We integrated these profiles with whole-animal chromatin immunoprecipitation sequencing data to deconvolve the cell type–specific effects of transcription factors. The data generated by sci-RNA-seq constitute a powerful resource for nematode biology and foreshadow similar atlases for other organisms.

Preventing mussel adhesion using lubricant-infused materials

Jue, 08/17/2017 - 11:30

Mussels are opportunistic macrofouling organisms that can attach to most immersed solid surfaces, leading to serious economic and ecological consequences for the maritime and aquaculture industries. We demonstrate that lubricant-infused coatings exhibit very low preferential mussel attachment and ultralow adhesive strengths under both controlled laboratory conditions and in marine field studies. Detailed investigations across multiple length scales—from the molecular-scale characterization of deposited adhesive proteins to nanoscale contact mechanics to macroscale live observations—suggest that lubricant infusion considerably reduces fouling by deceiving the mechanosensing ability of mussels, deterring secretion of adhesive threads, and decreasing the molecular work of adhesion. Our study demonstrates that lubricant infusion represents an effective strategy to mitigate marine biofouling and provides insights into the physical mechanisms underlying adhesion prevention.

Two-dimensional sp2 carbon-conjugated covalent organic frameworks

Jue, 08/17/2017 - 11:30

We synthesized a two-dimensional (2D) crystalline covalent organic framework (sp2c-COF) that was designed to be fully -conjugated and constructed from all sp2 carbons by C=C condensation reactions of tetrakis(4-formylphenyl)pyrene and 1,4-phenylenediacetonitrile. The C=C linkages topologically connect pyrene knots at regular intervals into a 2D lattice with conjugations extended along both x and y directions and develop an eclipsed layer framework rather than the more conventionally obtained disordered structures. The sp2c-COF is a semiconductor with a discrete band gap of 1.9 electron volts and can be chemically oxidized to enhance conductivity by 12 orders of magnitude. The generated radicals are confined on the pyrene knots, enabling the formation of a paramagnetic carbon structure with high spin density. The sp2 carbon framework induces ferromagnetic phase transition to develop spin-spin coherence and align spins unidirectionally across the material.

A molecular spin-photovoltaic device

Jue, 08/17/2017 - 11:30

We fabricated a C60 fullerene–based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers.

An unusual white dwarf star may be a surviving remnant of a subluminous Type Ia supernova

Jue, 08/17/2017 - 11:30

Subluminous Type Ia supernovae, such as the Type Iax–class prototype SN 2002cx, are described by a variety of models such as the failed detonation and partial deflagration of an accreting carbon-oxygen white dwarf star or the explosion of an accreting, hybrid carbon-oxygen-neon core. These models predict that bound remnants survive such events with, according to some simulations, a high kick velocity. We report the discovery of a high proper motion, low-mass white dwarf (LP 40-365) that travels at a velocity greater than the Galactic escape velocity and whose peculiar atmosphere is dominated by intermediate-mass elements. Strong evidence indicates that this partially burnt remnant was ejected following a subluminous Type Ia supernova event. This supports the viability of single-degenerate supernova progenitors.

Zones, spots, and planetary-scale waves beating in brown dwarf atmospheres

Jue, 08/17/2017 - 11:30

Brown dwarfs are massive analogs of extrasolar giant planets and may host types of atmospheric circulation not seen in the solar system. We analyzed a long-term Spitzer Space Telescope infrared monitoring campaign of brown dwarfs to constrain cloud cover variations over a total of 192 rotations. The infrared brightness evolution is dominated by beat patterns caused by planetary-scale wave pairs and by a small number of bright spots. The beating waves have similar amplitudes but slightly different apparent periods because of differing velocities or directions. The power spectrum of intermediate-temperature brown dwarfs resembles that of Neptune, indicating the presence of zonal temperature and wind speed variations. Our findings explain three previously puzzling behaviors seen in brown dwarf brightness variations.

Conversion of object identity to object-general semantic value in the primate temporal cortex

Jue, 08/17/2017 - 11:30

At the final stage of the ventral visual stream, perirhinal neurons encode the identity of memorized objects through learning. However, it remains elusive whether and how object percepts alone, or concomitantly a nonphysical attribute of the objects ("learned"), are decoded from perirhinal activities. By combining monkey psychophysics with optogenetic and electrical stimulations, we found a focal spot of memory neurons where both stimulations led monkeys to preferentially judge presented objects as "already seen." In an adjacent fringe area, where neurons did not exhibit selective responses to the learned objects, electrical stimulation induced the opposite behavioral bias toward "never seen before," whereas optogenetic stimulation still induced bias toward "already seen." These results suggest that mnemonic judgment of objects emerges via the decoding of their nonphysical attributes encoded by perirhinal neurons.

Deriving genomic diagnoses without revealing patient genomes

Jue, 08/17/2017 - 11:30

Patient genomes are interpretable only in the context of other genomes; however, genome sharing enables discrimination. Thousands of monogenic diseases have yielded definitive genomic diagnoses and potential gene therapy targets. Here we show how to provide such diagnoses while preserving participant privacy through the use of secure multiparty computation. In multiple real scenarios (small patient cohorts, trio analysis, two-hospital collaboration), we used our methods to identify the causal variant and discover previously unrecognized disease genes and variants while keeping up to 99.7% of all participants’ most sensitive genomic information private.

A central neural circuit for itch sensation

Jue, 08/17/2017 - 11:30

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

Methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction

Jue, 08/17/2017 - 11:30

In methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)–[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B. Here, we present the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15-angstrom resolution. HdrB contains two noncubane [4Fe-4S] clusters composed of fused [3Fe-4S]-[2Fe-2S] units sharing 1 iron (Fe) and 1 sulfur (S), which were coordinated at the CCG motifs. Soaking experiments showed that the heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways.

Vinculin forms a directionally asymmetric catch bond with F-actin

Jue, 08/17/2017 - 11:30

Vinculin is an actin-binding protein thought to reinforce cell-cell and cell-matrix adhesions. However, how mechanical load affects the vinculin–F-actin bond is unclear. Using a single-molecule optical trap assay, we found that vinculin forms a force-dependent catch bond with F-actin through its tail domain, but with lifetimes that depend strongly on the direction of the applied force. Force toward the pointed (–) end of the actin filament resulted in a bond that was maximally stable at 8 piconewtons, with a mean lifetime (12 seconds) 10 times as long as the mean lifetime when force was applied toward the barbed (+) end. A computational model of lamellipodial actin dynamics suggests that the directionality of the vinculin–F-actin bond could establish long-range order in the actin cytoskeleton. The directional and force-stabilized binding of vinculin to F-actin may be a mechanism by which adhesion complexes maintain front-rear asymmetry in migrating cells.

ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice

Jue, 08/17/2017 - 11:30

Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.

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