资源环境科技发展态势分析平台

Monitoring cells of the mouse presomitic mesoderm using the Achilles reporter fused to HES7 sheds light on the mechanisms that underpin synchronous oscillations in the expression of clock genes between neighbouring cells.

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules(1). Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins(2). Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors(3,4). These receptors have pivotal roles in shaping host innate immune responses(1,5). However, the effect of this host-microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3(+) regulatory T (T-reg) cells expressing the transcription factor ROR gamma. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T-reg cell population. Restoration of the intestinal BA pool increases colonic ROR gamma(+) T-reg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.

The size-dependent and shape-dependent characteristics that distinguish nanoscale materials from bulk solids arise from constraining the dimensionality of an inorganic structure(1-3). As a consequence, many studies have focused on rationally shaping these materials to influence and enhance their optical, electronic, magnetic and catalytic properties(4-6). Although a select number of stable clusters can typically be synthesized within the nanoscale regime for a specific composition, isolating clusters of a predetermined size and shape remains a challenge, especially for those derived from two-dimensional materials. Here we realize a multidentate coordination environment in a metal-organic framework to stabilize discrete inorganic clusters within a porous crystalline support. We show confined growth of atomically defined nickel(ii) bromide, nickel(ii) chloride, cobalt(ii) chloride and iron(ii) chloride sheets through the peripheral coordination of six chelating bipyridine linkers. Notably, confinement within the framework defines the structure and composition of these sheets and facilitates their precise characterization by crystallography. Each metal(ii) halide sheet represents a fragment excised from a single layer of the bulk solid structure, and structures obtained at different precursor loadings enable observation of successive stages of sheet assembly. Finally, the isolated sheets exhibit magnetic behaviours distinct from those of the bulk metal halides, including the isolation of ferromagnetically coupled large-spin ground states through the elimination of long-range, interlayer magnetic ordering. Overall, these results demonstrate that the pore environment of a metal-organic framework can be designed to afford precise control over the size, structure and spatial arrangement of inorganic clusters.

The beta(1)-adrenoceptor (beta(1)AR) is a G-protein-coupled receptor (GPCR) that couples(1)to the heterotrimeric G protein G(s). G-protein-mediated signalling is terminated by phosphorylation of the C terminus of the receptor by GPCR kinases (GRKs) and by coupling of beta-arrestin 1 (beta arr1, also known as arrestin 2), which displaces G(s)and induces signalling through the MAP kinase pathway(2). The ability of synthetic agonists to induce signalling preferentially through either G proteins or arrestins-known as biased agonism(3)-is important in drug development, because the therapeutic effect may arise from only one signalling cascade, whereas the other pathway may mediate undesirable side effects(4). To understand the molecular basis for arrestin coupling, here we determined the cryo-electron microscopy structure of the beta(1)AR-beta arr1 complex in lipid nanodiscs bound to the biased agonist formoterol(5), and the crystal structure of formoterol-bound beta(1)AR coupled to the G-protein-mimetic nanobody(6)Nb80. beta arr1 couples to beta(1)AR in a manner distinct to that(7)of G(s)coupling to beta(2)AR-the finger loop of beta arr1 occupies a narrower cleft on the intracellular surface, and is closer to transmembrane helix H7 of the receptor when compared with the C-terminal alpha 5 helix of G(s). The conformation of the finger loop in beta arr1 is different from that adopted by the finger loop of visual arrestin when it couples to rhodopsin(8). beta(1)AR coupled to beta arr1 shows considerable differences in structure compared with beta(1)AR coupled to Nb80, including an inward movement of extracellular loop 3 and the cytoplasmic ends of H5 and H6. We observe weakened interactions between formoterol and two serine residues in H5 at the orthosteric binding site of beta(1)AR, and find that formoterol has a lower affinity for the beta(1)AR-beta arr1 complex than for the beta(1)AR-G(s)complex. The structural differences between these complexes of beta(1)AR provide a foundation for the design of small molecules that could bias signalling in the beta-adrenoceptors.

A cryo-electron microscopy structure of the beta 1-adrenoceptor coupled to beta-arrestin 1 and activated by the biased agonist formoterol, as well as the crystal structure of a related formoterol-bound adrenoreceptor, provide insights into biased signalling in these systems.

Conventional information processors convert information between different physical carriers for processing, storage and transmission. It seems plausible that quantum information will also be held by different physical carriers in applications such as tests of fundamental physics, quantum enhanced sensors and quantum information processing. Quantum controlled molecules, in particular, could transduce quantum information across a wide range of quantum bit (qubit) frequencies-from a few kilohertz for transitions within the same rotational manifold(1), a few gigahertz for hyperfine transitions, a few terahertz for rotational transitions, to hundreds of terahertz for fundamental and overtone vibrational and electronic transitions-possibly all within the same molecule. Here we demonstrate entanglement between the rotational states of a (CaH+)-Ca-40 molecular ion and the internal states of a Ca-40(+) atomic ion(2). We extend methods used in quantum logic spectroscopy(1,3) for pure-state initialization, laser manipulation and state readout of the molecular ion. The quantum coherence of the Coulomb coupled motion between the atomic and molecular ions enables subsequent entangling manipulations. The qubit addressed in the molecule has a frequency of either 13.4 kilohertz(1) or 855 gigahertz(3), highlighting the versatility of molecular qubits. Our work demonstrates how molecules can transduce quantum information between qubits with different frequencies to enable hybrid quantum systems. We anticipate that our method of quantum control and measurement of molecules will find applications in quantum information science, quantum sensors, fundamental and applied physics, and controlled quantum chemistry.

Quantum entanglement is realized between rotational levels of a molecular ion with energy differences spanning several orders of magnitude and long-lived internal states of a single atomic ion.