Nuclear basket protein ZC3HC1 and its yeast homolog Pml39p feature an evolutionary conserved bimodular construction essential for initial binding to NPC-anchored homologs of scaffold protein TPR

Proteins ZC3HC1 and TPR are construction elements of the nuclear pore complex (NPC)-attached nuclear basket (NB). NB-location of ZC3HC1 depends on TPR already occurring NPC-anchored, whereas additional TPR polypeptides are appended to the NB by ZC3HC1. The current study examined the molecular properties of ZC3HC1 that enable it to bind to the NB and TPR. We report the identification and definition of a nuclear basket-interaction domain (NuBaID) of HsZC3HC1 comprising two similarly built modules, both essential for the binding to the NB’s NPC-anchored HsTPR. Furthermore, we describe such a bimodular construction as evolutionarily conserved and exemplify the kinship of HsZC3HC1 by the NB- and DdTPR-interacting homolog of Dictyostelium discoideum and by characterizing protein Pml39 as the ZC3HC1 homolog in Saccharomyces cerevisiae. Among several properties shared by the different species’ homologs, we unveil the integrity of the bimodular NuBaID of ScPml39p as being essential for binding to the yeast’s NBs and its TPR homologs ScMlp1p and ScMlp2p, and we further present Pml39p as enabling interlinkage of Mlp1p subpopulations. In addition to phyla-specific features, we delineate the three species’ common NuBaID as the characterizing structural entity of a one-of-a-kind protein found not in all but likely most taxa of the eukaryotic realm

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Transport limits in defect-engineered LaAlO3/SrTiO3 bilayers

The electrical properties of the metallic interface in LaAlO3/SrTiO3 (LAO/STO) bilayers are investigated with focus on the role of cationic defects in thin film STO. Systematic growth-control of the STO thin film cation stoichiometry (defect-engineering) yields a relation between cationic defects in the STO layer and electronic properties of the bilayer-interface. Hall measurements reveal a stoichiometry-effect primarily on the electron mobility. The results indicate an enhancement of scattering processes in as-grown non-stoichiometric samples indicating an increased density of defects. Furthermore, we discuss the thermodynamic processes and defect-exchange reactions at the LAO/STO-bilayer interface determined in high temperature equilibrium. By quenching defined defect states from high temperature equilibrium, we finally connect equilibrium thermodynamics with room temperature transport. The results are consistent with the defect-chemistry model suggested for LAO/STO interfaces. Moreover, they reveal an additional healing process of extended defects in thin film STO

Biomimetic Planar Polymer Membranes Decorated with Enzymes as Functional Surfaces

Functional surfaces were generated by a combination of enzymes with polymer membranes composed of an amphiphilic, asymmetric block copolymer poly(ethyleneglycol)-block-poly(γ-methyl-ε-caprolactone)-block-poly[(2-dimethylamino)ethylmethacrylate]. First, polymer films formed at the air–water interface were transferred in different sequences onto silica solid support using the Langmuir–Blodgett technique, generating homogeneous monolayers and bilayers. A detailed characterization of these films provided insight into their properties (film thickness, wettability, topography, and roughness). On the basis of these findings, the most promising membranes were selected for enzyme attachment. Functional surfaces were then generated by the adsorption of two model enzymes that can convert phenol and its derivatives (laccase and tyrosinase), well known as high-risk pollutants of drinking and natural water. Both enzymes preserved their activity upon immobilization with respect to their substrates. Depending on the properties of the polymer films, different degrees of enzymatic activity were observed: bilayers provided the best conditions in terms of both overall stability and enzymatic activity. The interaction between amphiphilic triblock copolymer films and enzymes is exploited to engineer “active surfaces” with specific functionalities and high efficacy resulting from the intrinsic activity of the biomolecules that is preserved by an appropriate synthetic environment

Revue bibliographique sur les techniques mises en œuvre pour le traitement des sols pollués par les isomères et les résidus de l’hexachlorocyclohexane (HCH)

This paper presents the treatment techniques of contaminated soils by hexachlorocyclohexane (HCH) isomers. The most available techniques are presented: thermal treatment (incineration and thermal desorption), extraction, physicochemical treatments (Gas Phase Chemical Reduction, base catalysed decomposition, solvated electrons deshalogenation), biological treatments and stabilization table presenting the techniques, their application possibilities, their development state and the costs is given. Ce travail bibliographique fait le point sur les dernières techniques de traitement de sols pollués par des pesticides organochlorés et plus particulièrement par des isomères ou des résidus d’isomères de l’hexachlorocyclohexane (HCH). Les techniques les plus utilisées sont présentées : traitements thermiques (incinération, désorption thermique), extraction, traitements physico-chimiques (réduction chimique en phase gazeuse, décomposition catalytique en milieu basique, déshalogénation par électrons solvatés), traitements biologiques et stabilisation. Un tableau récapitulatif permettant de juger les différentes techniques, leur champ d’application, leur stade de développement et les coûts de mise en œuvre est donné

MINSTED nanoscopy enters the Ångström localization range

We report all-optical, room-temperature localization of fluorophores with precision in the Ångström range. These precisions are attained in a STED microscope, by encircling the fluorophore with the low-intensity edge of the STED donut beam, while constantly increasing the absolute donut power. Individual fluorophores bound to a DNA strand are localized with σ = 4.7 Å, corresponding to a fraction of the fluorophore size, with only 2,000 detected photons. MINSTED fluorescence nanoscopy with single-digit nanometer resolution is exemplified by imaging nuclear pore complexes and the distribution of nuclear lamin in mammalian cells labeled by transient DNA hybridization. Since our experiments yield a localization precision σ = 2.3 Å, estimated for 10,000 detected photons, we anticipate that MINSTED will open up entirely new areas of application in the study of macromolecular complexes in cells

Polymer-templated mesoporous lithium titanate microspheres for high-performance lithium batteries

The spinel Li4Ti5O12 (LTO) is a promising lithium ion battery anode material with the potential to supplement graphite as an industry standard, but its low electrical conductivity and Li–ion diffusivity need to be overcome. Here, mesoporous LTO microspheres with carbon-coatings were formed by phase separation of a homopolymer from microphase-separated block copolymers of varying molar masses containing sol–gel precursors. Upon heating the composite underwent a sol–gel condensation reaction followed by the eventual pyrolysis of the polymer templates. The optimised mesoporous LTO microspheres demonstrated an excellent electrochemical performance with an excellent specific discharge capacity of 164 mA h g−1, 95% of which was retained after 1000 cycles at a C-rate of 10

Optical Imaging of Large Gyroid Grains in Block Copolymer Templates by Confined Crystallization.

Block copolymer (BCP) self-assembly is a promising route to manufacture functional nanomaterials for applications from nanolithography to optical metamaterials. Self-assembled cubic morphologies cannot, however, be conveniently optically characterized in the lab due to their structural isotropy. Here, the aligned crystallization behavior of a semicrystalline-amorphous polyisoprene-b-polystyrene-b-poly(ethylene oxide) (ISO) triblock terpolymer was utilized to visualize the grain structure of the cubic microphase-separated morphology. Upon quenching from a solvent swollen state, ISO first self-assembles into an alternating gyroid morphology, in the confinement of which the PEO crystallizes preferentially along the least tortuous pathways of the single gyroid morphology with grain sizes of hundreds of micrometers. Strikingly, the resulting anisotropic alignment of PEO crystallites gives rise to a unique optical birefringence of the alternating gyroid domains, which allows imaging of the self-assembled grain structure by optical microscopy alone. This study provides insight into polymer crystallization within a tortuous three-dimensional network and establishes a useful method for the optical visualization of cubic BCP morphologies that serve as functional nanomaterial templates.This research was supported through the Swiss National Science Foundation through grant numbers 163220 (U.S.) and 168223 (B.D.W.), the National Center of Competence in Research Bio-Inspired Materials (U.S., B.D.W, I.G.), the Adolphe Merkle Foundation (B.D.W., U.S., I.G.), the Engineering and Physical Sciences Research Council through the Cambridge NanoDTC EP/G037221/1, EP/L027151/1, EP/N016920/1, and EP/G060649/1 (R.D., J.A.D., J.J.B.), and ERC LINASS 320503 (J.J.B.). This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 706329/cOMPoSe (I.G.). Y.G. and U.W. thank the National Science Foundation (DMR-1409105) for financial support. Part of the work was conducted at beamline D1 at the Cornell High Energy Synchrotron Source (CHESS); CHESS is supported by the NSF and NIH/NIGMS via NSF award DMR-1332208. We also thank Diamond Light Source for access to beamline I22 (SM13448) that contributed to the results presented here

Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19. However, their production in mammalian cells is not scalable to meet the global demand. Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS-CoV-2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X-ray and cryo-EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune-escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low-picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold-promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape-mutations

How AI Systems Challenge the Conditions of Moral Agency?

The article explores the effects increasing automation has on our conceptions of human agency. We conceptualize the central features of human agency as ableness, intentionality, and rationality and define responsibility as a central feature of moral agency. We discuss suggestions in favor of holding AI systems moral agents for their functions but join those who refute this view. We consider the possibility of assigning moral agency to automated AI systems in settings of machine-human cooperation but come to the conclusion that AI systems are not genuine participants in joint action and cannot be held morally responsible. Philosophical issues notwithstanding, the functions of AI systems change human agency as they affect our goal setting and pursuing by influencing our conceptions of the attainable. Recommendation algorithms on news sites, social media platforms, and in search engines modify our possibilities to receive accurate and comprehensive information, hence influencing our decision making. Sophisticated AI systems replace human workforce even in such demanding fields as medical surgery, language translation, visual arts, and composing music. Being second to a machine in an increasing number of fields of expertise will affect how human beings regard their own abilities. We need a deeper understanding of how technological progress takes place and how it is intertwined with economic and political realities. Moral responsibility remains a human characteristic. It is our duty to develop AI to serve morally good ends and purposes. Protecting and strengthening the conditions of human agency in any AI environment is part of this task.Peer reviewe