资源环境科技发展态势分析平台

A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.

The cryo-electron microscopy structure of human thyroglobulin reveals that proximity, flexibility and solvent exposure are key characteristics of its hormonogenic tyrosine pairs, and provides a framework for understanding the formation of thyroid hormones.

Thyroglobulin (TG) is the protein precursor of thyroid hormones, which are essential for growth, development and the control of metabolism in vertebrates(1,2). Hormone synthesis from TG occurs in the thyroid gland via the iodination and coupling of pairs of tyrosines, and is completed by TG proteolysis(3). Tyrosine proximity within TG is thought to enable the coupling reaction but hormonogenic tyrosines have not been clearly identified, and the lack of a three-dimensional structure of TG has prevented mechanistic understanding(4). Here we present the structure of full-length human thyroglobulin at a resolution of approximately 3.5 angstrom, determined by cryo-electron microscopy. We identified all of the hormonogenic tyrosine pairs in the structure, and verified them using site-directed mutagenesis and in vitro hormone-production assays using human TG expressed in HEK293T cells. Our analysis revealed that the proximity, flexibility and solvent exposure of the tyrosines are the key characteristics of hormonogenic sites. We transferred the reaction sites from TG to an engineered tyrosine donor-acceptor pair in the unrelated bacterial maltose-binding protein (MBP), which yielded hormone production with an efficiency comparable to that of TG. Our study provides a framework to further understand the production and regulation of thyroid hormones.

Prussian blue analogues (PBAs) are a diverse family of microporous inorganic solids, known for their gas storage ability(1), metal-ion immobilization(2), proton conduction(3), and stimuli-dependent magnetic(4,5), electronic(6) and optical(7) properties. This family of materials includes the double-metal cyanide catalysts(8,9) and the hexacyanoferrate/ hexacyanomanganate battery materials(10,11). Central to the various physical properties of PBAs is their ability to reversibly transport mass, a process enabled by structural vacancies. Conventionally presumed to be random(12,13), vacancy arrangements are crucial because they control micropore-network characteristics, and hence the diffusivity and adsorption profiles(14,15). The long-standing obstacle to characterizing the vacancy networks of PBAs is the inaccessibility of single crystals(16). Here we report the growth of single crystals of various PBAs and the measurement and interpretation of their X-ray diffuse scattering patterns. We identify a diversity of non-random vacancy arrangements that is hidden from conventional crystallographic powder analysis. Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry. The hidden phase boundaries that emerge demarcate vacancynetwork polymorphs with very different micropore characteristics. Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiency.

The impact of topological defects associated with grain boundaries (GB defects) on the electrical, optical, magnetic, mechanical and chemical properties of nanocrystalline materials(1,2) is well known. However, elucidating this influence experimentally is difficult because grains typically exhibit a large range of sizes, shapes and random relative orientations(3-5). Here we demonstrate that precise control of the heteroepitaxy of colloidal polyhedral nanocrystals enables ordered grain growth and can thereby produce material samples with uniform GB defects. We illustrate our approach with a multigrain nanocrystal comprising a Co3O4 nanocube core that carries a Mn3O4 shell on each facet. The individual shells are symmetry-related interconnected grains(6), and the large geometric misfit between adjacent tetragonal Mn3O4 grains results in tilt boundaries at the sharp edges of the Co3O4 nanocube core that join via disclinations. We identify four design principles that govern the production of these highly ordered multigrain nanostructures. First, the shape of the substrate nanocrystal must guide the crystallographic orientation of the overgrowth phase(7). Second, the size of the substrate must be smaller than the characteristic distance between the dislocations. Third, the incompatible symmetry between the overgrowth phase and the substrate increases the geometric misfit strain between the grains. Fourth, for GB formation under near-equilibrium conditions, the surface energy of the shell needs to be balanced by the increasing elastic energy through ligand passivation(8-10). With these principles, we can produce a range of multigrain nanocrystals containing distinct GB defects.