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1 Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation 2018-10-13             

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The 26S proteasome is the primary eukaryotic degradation machine and thus critically involved in numerous cellular processes. The hetero-hexameric ATPase motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core, while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-EM structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26S proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination, and how ATP-binding, hydrolysis, and phosphate-release events are coordinated within the AAA+ motor to induce conformational changes and propel the substrate through the central pore.

2 Controlled crack propagation for atomic precision handling of wafer-scale two-dimensional materials 2018-10-13             

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Although flakes of two-dimensional (2D) heterostructures at micrometer scale can be formed with adhesive-tape methods, isolation of 2D flakes into monolayers is extremely time-consuming as it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits the high-throughput production of multiple monolayers of wafer-scale (5 centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of h-BN, WS2, WSe2, MoS2, and MoSe2 monolayers was verified by photoluminescence (PL) response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.

3 Methylammonium-free, high-performance and stable perovskite solar cells on a planar architecture 2018-10-13             

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Currently, perovskite solar cells (PSCs) with high performances >20% contain Br, causing a suboptimal bandgap, and the thermally unstable methylammonium (MA) molecule. Avoiding Br and especially MA can, therefore, result in more optimal bandgaps and stable perovskites. We show that inorganic cation tuning, using Rb and Cs, enables highly crystalline formamidinium-based perovskites without Br or MA. On a conventional, planar device architecture, using polymeric interlayers at the electron and hole transporting interface, we demonstrate an efficiency of 20.35% (stabilized), one of the highest for MA-free perovskites, with a drastically improved stability reached without the stabilizing influence of mesoporous interlayers. The perovskite is not heated beyond 100°C. Going MA-free is a new direction for perovskites that are inherently stable and compatible with tandems or flexible substrates which are the main routes commercializing PSCs.

4 In vivo modeling of human neuron dynamics and Down syndrome 2018-10-13             

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Harnessing the potential of human stem cells for modelling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. Here, we show that human iPSC–derived cortical neurons transplanted in the adult mouse cortex consistently organized in large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Finally, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modelling of cortical development, physiology, and pathogenesis.

5 Identity inference of genomic data using long-range familial searches 2018-10-13             

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Consumer genomics databases have reached the scale of millions of individuals. Recently, law enforcement authorities have exploited some of these databases to identify suspects via distant familial relatives. Using genomic data of 1.28 million individuals tested with consumer genomics, we investigated the power of this technique. We project that about 60% of the searches for individuals of European-descent will result in a third cousin or closer match, which can allow their identification using demographic identifiers. Moreover, the technique could implicate nearly any US-individual of European-descent in the near future. We demonstrate that the technique can also identify research participants of a public sequencing project. Based on these results, we propose a potential mitigation strategy and policy implications to human subject research.

6 Observation of the topological Anderson insulator in disordered atomic wires 2018-10-13             

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Topology and disorder have a rich combined influence on quantum transport. In order to probe their interplay, we synthesized one-dimensional chiral symmetric wires with controllable disorder via spectroscopic Hamiltonian engineering, based on the laser-driven coupling of discrete momentum states of ultracold atoms. Measuring the bulk evolution of a topological indicator following a sudden quench, we observed the topological Anderson insulator phase, in which added disorder drives the band structure of a wire from topologically trivial to non-trivial. In addition, we observed the robustness of topologically non-trivial wires to weak disorder and measured the transition to a trivial phase in the presence of strong disorder. Atomic interactions in this quantum simulation platform may enable realizations of strongly interacting topological fluids.

7 Structural basis of the nucleosome transition during RNA polymerase II passage 2018-10-06             

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Genomic DNA forms chromatin, in which the nucleosome is the repeating unit. The mechanism by which RNA polymerase II (RNAPII) transcribes the nucleosomal DNA remains unclear. Here we report the cryo–electron microscopy structures of RNAPII-nucleosome complexes, in which RNAPII pauses at the superhelical locations, SHL(-6), SHL(-5), SHL(-2), and SHL(-1), of the nucleosome. RNAPII pauses at the major histone-DNA contact sites, and the nucleosome interactions with the RNAPII subunits stabilize the pause. These structures reveal snapshots of nucleosomal transcription, where RNAPII gradually tears DNA from the histone surface, while preserving the histone octamer. Interestingly, the nucleosomes in the SHL(-1) complexes are bound to a "foreign" DNA segment, which might explain the histone transfer mechanism. These results provide the foundations for understanding chromatin transcription and epigenetic regulation.

8 An autoimmune disease variant of IgG1 modulates B cell activation and differentiation 2018-10-06             

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The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here, we identify a variant of human IgG1 (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog G390R knock-in mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies. This enhanced production of antibodies is also observed in hapten-immunized G390R mice, as well as in influenza-vaccinated human G396R homozygous carriers. This variant potentiates the phosphorylation of IgG1 immunoglobulin tail tyrosine (ITT) motif. This, in turn, alters the availability of phospho-ITT to trigger longer Grb2 dwell times in immunological synapses, leading to hyper-Grb2-Btk signaling upon antigen binding. Thus, the hIgG1-G396R variant is important for both lupus pathogenesis and antibody responses after vaccination.

9 Reversible self-assembly of superstructured networks 2018-10-06             

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Soft structures in nature such as protein assemblies can organize reversibly into functional and often hierarchical architectures through noncovalent interactions. Molecularly encoding this dynamic capability in synthetic materials has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of neural cells in contact with these materials.

10 Hierarchically porous polymer coatings for highly efficient passive daytime radiative cooling 2018-09-29             

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Passive daytime radiative cooling (PDRC) involves spontaneously cooling a surface by reflecting sunlight and radiating heat to the cold outer space. Current PDRC designs are promising alternatives to electrical cooling, but are either inefficient or have limited applicability. We present a simple, inexpensive and scalable phase-inversion-based method for fabricating hierarchically porous poly(vinylidene fluoride-co-hexafluoropropene) (P(VdF-HFP)HP) coatings with excellent PDRC capability. High, substrate-independent hemispherical solar reflectances (0.96 ± 0.03) and long-wave infrared (LWIR) emittances (0.97 ± 0.02) allow for sub-ambient temperature drops of ~6°C and cooling powers of ~96 W m–2 under solar intensities of 890 and 750 W m–2 respectively. The performance equals or surpasses those of state-of-the-art PDRC designs, while the technique offers a paint-like simplicity.

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