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The 1918 flu, 100 years later

2018-01-18T10:23:14-08:00




News at a glance

2018-01-18T10:23:14-08:00




Newborn exoplanet eyed for moons and rings

2018-01-18T10:23:14-08:00







Tamed immune reaction aids pregnancy

2018-01-18T10:23:14-08:00










Are algorithms good judges?

2018-01-18T10:23:14-08:00




The believer

2018-01-18T10:23:14-08:00




Assessing nature's contributions to people

2018-01-18T10:23:14-08:00




The art of manufacturing molecules

2018-01-18T10:23:14-08:00




Quantum liquids get thin

2018-01-18T10:23:14-08:00




A bacterial coat that is not pure cotton

2018-01-18T10:23:14-08:00




Taking down defenses to improve vaccines

2018-01-18T10:23:14-08:00




Remote control of nanoscale devices

2018-01-18T10:23:14-08:00




Ben Barres (1954-2017)

2018-01-18T10:23:14-08:00




Quarks, culture, combogenesis

2018-01-18T10:23:14-08:00




Enrico Fermi, flaws and all

2018-01-18T10:23:14-08:00







Vaccine mandates in France will save lives

2018-01-18T10:23:14-08:00




Have your momos and eat them, too

2018-01-18T10:23:14-08:00




Data-driven refugee assignment

2018-01-18T10:23:14-08:00




Lymphatics limp along after MRSA

2018-01-18T10:23:14-08:00




Electrically driving a DNA arm

2018-01-18T10:23:14-08:00







Avoiding interferon avoidance

2018-01-18T10:23:14-08:00




Making dilute quantum droplets

2018-01-18T10:23:14-08:00




Recognizing centromere by kinetochore

2018-01-18T10:23:14-08:00




Seismicity curbed by lowering volume

2018-01-18T10:23:14-08:00




Algorithms fail to improve predictions

2018-01-18T10:23:15-08:00




A plastic plan for organic synthesis

2018-01-18T10:23:15-08:00







Watching single molecules in motion

2018-01-18T10:23:15-08:00




Boosting chiral nanoparticle responses

2018-01-18T10:23:15-08:00




A global map of soil bacteria

2018-01-18T10:23:15-08:00




Substrate recognition by Dicer elucidated

2018-01-18T10:23:15-08:00




A naturally modified cellulose

2018-01-18T10:23:15-08:00




Processing microRNAs for blood vessels

2018-01-18T10:23:15-08:00




Regeneration circuits in the thymus

2018-01-18T10:23:15-08:00




How hunting affects brown bear populations

2018-01-18T10:23:15-08:00




Going dry in the Pacific Northwest

2018-01-18T10:23:15-08:00




Time-out for mRNAs in the nucleus

2018-01-18T10:23:15-08:00




Serious damage by soluble tau

2018-01-18T10:23:15-08:00




Lighting up riboswitching

2018-01-18T10:23:15-08:00




The value of scaffolds

2018-01-18T10:23:15-08:00




Social skills to pay the bills

2018-01-18T10:23:15-08:00




Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design

2018-01-18T10:23:15-08:00

In conventional attenuated viral vaccines, immunogenicity is often suboptimal. Here we present a systematic approach for vaccine development that eliminates interferon (IFN)–modulating functions genome-wide while maintaining virus replication fitness. We applied a quantitative high-throughput genomics system to influenza A virus that simultaneously measured the replication fitness and IFN sensitivity of mutations across the entire genome. By incorporating eight IFN-sensitive mutations, we generated a hyper–interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. Our approach, which attenuates the virus and promotes immune responses concurrently, is broadly applicable for vaccine development against other pathogens.




A self-assembled nanoscale robotic arm controlled by electric fields

2018-01-18T10:23:15-08:00

The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer–by–55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.




Quantum liquid droplets in a mixture of Bose-Einstein condensates

2018-01-18T10:23:15-08:00

Quantum droplets are small clusters of atoms self-bound by the balance of attractive and repulsive forces. Here, we report on the observation of droplets solely stabilized by contact interactions in a mixture of two Bose-Einstein condensates. We demonstrate that they are several orders of magnitude more dilute than liquid helium by directly measuring their size and density via in situ imaging. We show that the droplets are stablized against collapse by quantum fluctuations and that they require a minimum atom number to be stable. Below that number, quantum pressure drives a liquid-to-gas transition that we map out as a function of interaction strength. These ultradilute isotropic liquids remain weakly interacting and constitute an ideal platform to benchmark quantum many-body theories.




Hydraulic fracturing volume is associated with induced earthquake productivity in the Duvernay play

2018-01-18T10:23:15-08:00

A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (104 to 105 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index–modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.




Chiromagnetic nanoparticles and gels

2018-01-18T10:23:15-08:00

Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.




Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals

2018-01-18T10:23:15-08:00

Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the -aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.




A global atlas of the dominant bacteria found in soil

2018-01-18T10:23:15-08:00

The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a "most wanted" list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.




Improving refugee integration through data-driven algorithmic assignment

2018-01-18T10:23:15-08:00

Developed democracies are settling an increased number of refugees, many of whom face challenges integrating into host societies. We developed a flexible data-driven algorithm that assigns refugees across resettlement locations to improve integration outcomes. The algorithm uses a combination of supervised machine learning and optimal matching to discover and leverage synergies between refugee characteristics and resettlement sites. The algorithm was tested on historical registry data from two countries with different assignment regimes and refugee populations, the United States and Switzerland. Our approach led to gains of roughly 40 to 70%, on average, in refugees’ employment outcomes relative to current assignment practices. This approach can provide governments with a practical and cost-efficient policy tool that can be immediately implemented within existing institutional structures.




Dicer uses distinct modules for recognizing dsRNA termini

2018-01-18T10:23:15-08:00

Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo–electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate–dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers.




Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose

2018-01-18T10:23:15-08:00

Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that Escherichia coli produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway. The bcsEFG operon is present in many bacteria, including Salmonella species, that also produce the modified cellulose. The discovery of phosphoethanolamine cellulose and the genetic and molecular basis for its production offers opportunities to modulate its production in bacteria and inspires efforts to biosynthetically engineer alternatively modified cellulosic materials.




Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

2018-01-18T10:23:15-08:00

Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo–electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.




Multiplexed gene synthesis in emulsions for exploring protein functional landscapes

2018-01-18T10:23:15-08:00

Improving our ability to construct and functionally characterize DNA sequences would broadly accelerate progress in biology. Here, we introduce DropSynth, a scalable, low-cost method to build thousands of defined gene-length constructs in a pooled (multiplexed) manner. DropSynth uses a library of barcoded beads that pull down the oligonucleotides necessary for a gene’s assembly, which are then processed and assembled in water-in-oil emulsions. We used DropSynth to successfully build more than 7000 synthetic genes that encode phylogenetically diverse homologs of two essential genes in Escherichia coli. We tested the ability of phosphopantetheine adenylyltransferase homologs to complement a knockout E. coli strain in multiplex, revealing core functional motifs and reasons underlying homolog incompatibility. DropSynth coupled with multiplexed functional assays allows us to rationally explore sequence-function relationships at an unprecedented scale.




New Products

2018-01-18T10:23:15-08:00




AAAS 2018 Annual Meeting Program

2018-01-18T10:23:15-08:00




From parade ground to PI

2018-01-18T10:23:15-08:00




Toward dynamic structural biology: Two decades of single-molecule Förster resonance energy transfer

2018-01-18T10:23:15-08:00

Classical structural biology can only provide static snapshots of biomacromolecules. Single-molecule Förster resonance energy transfer (smFRET) paved the way for studying dynamics in macromolecular structures under biologically relevant conditions. Since its first implementation in 1996, smFRET experiments have confirmed previously hypothesized mechanisms and provided new insights into many fundamental biological processes, such as DNA maintenance and repair, transcription, translation, and membrane transport. We review 22 years of contributions of smFRET to our understanding of basic mechanisms in biochemistry, molecular biology, and structural biology. Additionally, building on current state-of-the-art implementations of smFRET, we highlight possible future directions for smFRET in applications such as biosensing, high-throughput screening, and molecular diagnostics.




Membrane protein insertion through a mitochondrial {beta}-barrel gate

2018-01-18T10:23:15-08:00

The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop, and inserts into the lateral gate by β-signal exchange. Transport through the Omp85-channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of β-barrel proteins.