Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair

Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair. SIGNIFICANCE STATEMENT Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury

High Energy Electron Confinement in a Magnetic Cusp Configuration

We report experimental results validating the concept that plasma confinement is enhanced in a magnetic cusp configuration when beta (plasma pressure/magnetic field pressure) is order of unity. This enhancement is required for a fusion power reactor based on cusp confinement to be feasible. The magnetic cusp configuration possesses a critical advantage: the plasma is stable to large scale perturbations. However, early work indicated that plasma loss rates in a reactor based on a cusp configuration were too large for net power production. Grad and others theorized that at high beta a sharp boundary would form between the plasma and the magnetic field, leading to substantially smaller loss rates. The current experiment validates this theoretical conjecture for the first time and represents critical progress toward the Polywell fusion concept which combines a high beta cusp configuration with an electrostatic fusion for a compact, economical, power-producing nuclear fusion reactor.Comment: 12 pages, figures included. 5 movies in Ancillary file

Whole genome sequencing-based mapping and candidate identification of mutations from fixed zebrafish tissue

As forward genetic screens in zebrafish become more common, the number of mutants that cannot be identified by gross morphology or through transgenic approaches, such as many nervous system defects, has also increased. Screening for these difficult-to-visualize phenotypes demands techniques such as whole-mount in situ hybridization (WISH) or antibody staining, which require tissue fixation. To date, fixed tissue has not been amenable for generating libraries for whole genome sequencing (WGS). Here, we describe a method for using genomic DNA from fixed tissue and a bioinformatics suite for WGS-based mapping of zebrafish mutants. We tested our protocol using two known zebrafish mutant alleles, gpr126st49 and egr2bfh227, both of which cause myelin defects. As further proof of concept we mapped a novel mutation, stl64, identified in a zebrafish WISH screen for myelination defects. We linked stl64 to chromosome 1 and identified a candidate nonsense mutation in the F-box and WD repeat domain containing 7 (fbxw7) gene. Importantly, stl64 mutants phenocopy previously described fbxw7vu56 mutants, and knockdown of fbxw7 in wild-type animals produced similar defects, demonstrating that stl64 disrupts fbxw7. Together, these data show that our mapping protocol can map and identify causative lesions in mutant screens that require tissue fixation for phenotypic analysis

On Random Field Induced Ordering in the Classical XY Model

Consider the classical XY model in a weak random external field pointing along the $Y$ axis with strength $\epsilon$. We study the behavior of this model as the range of the interaction is varied. We prove that in any dimension $d \geq 2$ and for all $\epsilon$ sufficiently small, there is a range $L=L(\epsilon)$ so that whenever the inverse temperature $\beta$ is larger than some $\beta(\epsilon)$, there is strong residual ordering along the $X$ direction.Comment: 30 page

Set1/COMPASS repels heterochromatin invasion at euchromatic sites by disrupting Suv39/Clr4 activity and nucleosome stability.

Protection of euchromatin from invasion by gene-repressive heterochromatin is critical for cellular health and viability. In addition to constitutive loci such as pericentromeres and subtelomeres, heterochromatin can be found interspersed in gene-rich euchromatin, where it regulates gene expression pertinent to cell fate. While heterochromatin and euchromatin are globally poised for mutual antagonism, the mechanisms underlying precise spatial encoding of heterochromatin containment within euchromatic sites remain opaque. We investigated ectopic heterochromatin invasion by manipulating the fission yeast mating type locus boundary using a single-cell spreading reporter system. We found that heterochromatin repulsion is locally encoded by Set1/COMPASS on certain actively transcribed genes and that this protective role is most prominent at heterochromatin islands, small domains interspersed in euchromatin that regulate cell fate specifiers. Sensitivity to invasion by heterochromatin, surprisingly, is not dependent on Set1 altering overall gene expression levels. Rather, the gene-protective effect is strictly dependent on Set1's catalytic activity. H3K4 methylation, the Set1 product, antagonizes spreading in two ways: directly inhibiting catalysis by Suv39/Clr4 and locally disrupting nucleosome stability. Taken together, these results describe a mechanism for spatial encoding of euchromatic signals that repel heterochromatin invasion

Fish, Coral, and Sponge Assemblages Associated With Altiphotic and Mesophotic Reefs Along the Guánica Biosphere Reserve Continental Shelf Edge, Southwest Puerto Rico

The benthic and fish communities of the central portion of the Guánica, Puerto Rico shelf edge were studied to determine species abundance, distributions and species overlap between two depth stratifications, 20 and 45 m, at eight sites. A total of 67 fish species belonging to 21 families were identified. Similar species richness estimates were observed between depths, though fish assemblage composition differed significantly, with observable changes in feeding guild contributions of herbivore and omnivore (20 m) to a deeper assemblage composed of piscivores and planktivores (45 m). Coral assemblages consisted of 31 species at 20 m and 11 species at 45 m, accounting for 17.0% (±1.76 SE) and 2.6% (±0.89 SE) benthic cover for the altiphotic and mesophotic surveys, respectively. The altiphotic and mesophotic coral reef communities support different scleractinian coral assemblages with minimal species overlap. Altiphotic surveys of sponges yielded a higher species richness than mesophotic, with 60 and 54 species respectively, and an overall total of 71 species identified from both depths, with 45 species overlapping (63.0%). The percent cover of sponges surveyed at altiphotic reefs accounted for 9.0% (±1.04 SE), while the percent cover of sponges surveyed at mesophotic reefs was 14.0% (±1.96 SE). Our data show fish, coral, and sponge assemblages are differentiated between 20 and 45 m along the Guánica shelf edge offshore of the Guánica Biosphere Reserve. This study represents the first observations for species distributions of adjacent altiphotic and mesophotic coral reef habitats along the Guánica shelf edge, as well as provides an annotated species list of the local sponge fauna. Combined, these results highlight the need for continued environmental stewardship and conservation in the area

Multiwavelength Variations of 3C 454.3 during the November 2010 to January 2011 Outburst

We present multiwavelength data of the blazar 3C 454.3 obtained during an extremely bright outburst from November 2010 through January 2011. These include flux density measurements with the Herschel Space Observatory at five submillimeter-wave and far-infrared bands, the Fermi Large Area Telescope at gamma-ray energies, Swift at X-ray, ultraviolet (UV), and optical frequencies, and the Submillimeter Array at 1.3 mm. From this dataset, we form a series of 52 spectral energy distributions (SEDs) spanning nearly two months that are unprecedented in time coverage and breadth of frequency. Discrete correlation anlaysis of the millimeter, far-infrared, and gamma-ray light curves show that the variations were essentially simultaneous, indicative of co-spatiality of the emission, at these wavebands. In contrast, differences in short-term fluctuations at various wavelengths imply the presence of inhomegeneities in physical conditions across the source. We locate the site of the outburst in the parsec-scale core, whose flux density as measured on 7 mm Very Long Baseline Array images increased by 70 percent during the first five weeks of the outburst. Based on these considerations and guided by the SEDs, we propose a model in which turbulent plasma crosses a conical standing shock in the parsec-scale region of the jet. Here, the high-energy emission in the model is produced by inverse Compton scattering of seed photons supplied by either nonthermal radiation from a Mach disk, thermal emission from hot dust, or (for X-rays) synchrotron radiation from plasma that crosses the standing shock. For the two dates on which we fitted the model SED to the data, the model corresponds very well to the observations at all bands except at X-ray energies, where the spectrum is flatter than observed.Comment: Accepted for publication in Astrophysical Journal. 82 pages, 13 figure

Visible‐light‐controlled oxidation of glucose using titania‐supported silver photocatalysts

The visible‐light‐mediated photo‐catalytic selective valorisation of glucose using TiO2‐supported Ag nanoparticles is shown for the first time. The optimisation of the catalyst composition, substrate‐to‐catalyst ratio and reaction medium proved that a near total suppression of the mineralisation pathway could be achieved with a selectivity to partial oxidation products and small‐chain monosaccharides as high as 98 %. The primary products were determined to be gluconic acid, arabinose, erythrose, glyceraldehyde and formic acid. Under UVA light, the selectivity to organics decreases because of the production of CO2 from mineralisation. A reaction mechanism is proposed based on an α‐scission process combined with the Ruff degradation reaction, which explains the presence of the oxidation products, the smaller carbohydrates and formic acid. X‐ray photoelectron spectroscopy, UV/Vis spectroscopy and microscopy studies showed the presence of plasmonic 4 nm particles of silver that were oxidised to silver oxide over the course of the reaction, and recycling studies revealed that this was not detrimental to activity