Background Corticotropin-releasing factor (CRF) mediates our body's overall responses to stress. The role of central CRF in stress-stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress-induced colonic motor and secretory responses. Methods Sprague-Dawley rats (adult, male) were subjected to 1-h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24h. CRF mRNA and peptide levels in the colon were quantified by real-time RT-PCR, enzyme immuno-assay and immunohistochemistry. Double-stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference-mediated inhibition of CRF mRNA expression. DsRNA for -globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1-h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance. Key Results Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS-induced increase in CRF expression, whereas CRF expression in dsControl-injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS-induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance. Conclusions & Inferences These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MAT alpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

High-pressure neutron powder diffraction, muon-spin rotation, and magnetization studies of the structural, magnetic, and the superconducting properties of the Ce-underdoped superconducting (SC) electron-doped cuprate system with the Nd2CuO4 (the so-called T') structure T'-Pr1.3-xLa0.7CexCuO4 with x = 0.1 are reported. Astrong reduction of the in-plane and out-of-plane lattice constants is observed under pressure. However, no indication of any pressure-induced phase transition from T' to the K2NiF4 (the so-called T) structure is observed up to the maximum applied pressure of p = 11 GPa. Large and nonlinear increase of the short-range magnetic order temperature T-so in T'-Pr1.3-xLa0.7CexCuO4 (x = 0.1) was observed under pressure. Simultaneous pressure causes a nonlinear decrease of the SC transition temperature T-c. All these experiments establish the short-range magnetic order as an intrinsic and competing phase in SC T'-Pr1.3-xLa0.7CexCuO4 (x = 0.1). The observed pressure effects may be interpreted in terms of the improved nesting conditions through the reduction of the in-plane and out-of-plane lattice constants upon hydrostatic pressure.

One challenge in studying high-temperature superconductivity (HTSC) stems from a lack of direct experimental evidence linking lattice inhomogeneity and superconductivity. Here, we apply synchrotron hard X-ray nanoimaging and small-angle scattering to reveal a novel micron-scaled ribbon phase in optimally doped Bi2Sr2CaCu2O8+delta (Bi-2212, with delta = 0.1). The morphology of the ribbon-like phase evolves simultaneously with the dome-shaped T-c behavior under pressure. X-ray absorption studies show that the increasing of T-c is associated with oxygen-hole redistribution in the CuO2 plan, while T-c starts to decrease with pressure when oxygen holes become immobile. Additional X-ray irradiation experiments reveal that nanoscaled short-range ordering of oxygen vacancies could further lower T-c which indicates that the optimal T-c is affected not only by an optimal morphology of the ribbon phase, but also an optimal distribution of oxygen vacancies. Our studies thereby provide for the first time compelling experimental evidence correlating the T-c with micron to nanoscale inhomogeneity.

The intertwined charge, spin, orbital, and lattice degrees of freedom could endow 5d compounds with exotic properties. Current interest is focused on electromagnetic interactions in these materials, whereas the important role of lattice geometry remains to be fully recognized. For this sake, we investigate pressure-induced phase transitions in the spin-orbit Mott insulator Sr3Ir2O7 with Raman, electrical resistance, and x-ray diffraction measurements. We reveal an interesting magnetic transition coinciding with a structural transition at 14.4 GPa, but without a concurrent insulator-metal transition. The conventional correlation between magnetic and Mott insulating states is thereby absent. The observed softening of the one-magnon mode can be explained by a reduced tetragonal distortion, while the actual magnetic transition is associated with tilting of the IrO6 octahedra. This work highlights the critical role of lattice frustration in determining the high-pressure phases of Sr3Ir2O7. The ability to control electromagnetic properties via manipulating the crystal structure with pressure promises a new way to explore new quantum states in spin-orbit Mott insulators.

Lineage-specific stem cells are critical for the production and maintenance of specific cell types and tissues in multicellular organisms. In Arabidopsis, the initiation and proliferation of stomatal lineage cells is controlled by the basic helix-loop-helix transcription factor SPEECHLESS (SPCH). SPCH-driven asymmetric and self-renewing divisions allow flexibility in stomatal production and overall organ growth. How SPCH directs stomatal lineage cell behaviors, however, is unclear. Here, we improved the chromatin immunoprecipitation (ChIP) assay and profiled the genome-wide targets of Arabidopsis SPCH in vivo. We found that SPCH controls key regulators of cell fate and asymmetric cell divisions and modulates responsiveness to peptide and phytohormone-mediated intercellular communication. Our results delineate the molecular pathways that regulate an essential adult stem cell lineage in plants.

The complicated story of the Cetus Stream (CS) is recently revealed by its newly discovered similar to 150 members with 6D kinematics from the cross-matched catalog of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) DR5 K giants and Gaia DR2. It exhibits a very diffuse structure at heliocentric distances between 20 and 50 kpc, extending over at least 100 degrees, and crossing the Galactic plane. Interestingly, The CS is dynamically linked to a massive globular cluster, NGC 5824. A suggestive scenario is that NGC 5824 was the nuclear star cluster of the dwarf progenitor of the CS. We explore this scenario by modeling the disruption process of a dwarf galaxy in the Milky Way potential, on the orbit of NGC 5824, using a suite of N-body simulations. Our results show that the simulated stream can marginally recover the main component of the CS, which is the densest part of the observed stream. Inspired by this mismatch, we use a dwarf progenitor following the representative orbit of the main component members, and find it can reproduce the general morphology of the CS. This gives us a more favorable scenario of the CS progenitor, in which NGC 5824 was not the core, but located off-center. Our fiducial model also predicts a vast extension of the CS in the South, surprisingly coincident with a newly discovered wide southern stream "Palca." Another more diffuse substructure, the Eridanus-Phoenix overdensity is also likely to be related to the CS progenitor.