Copper-Catalyzed Regioselective Aminothiolation of Aromatic and Aliphatic Alkenes with N-Fluorobenzenesulfonimide and Thiols through Three-Component Radical Coupling

Copper-catalyzed regioselective aminothiolation of terminal and internal alkenes with N-fluorobenzenesulfonimide and thiols has been developed. The three-component reaction is promoted by the addition of dimethyl sulfide. In addition to aromatic alkenes, aliphatic alkenes are subjected to the reaction, affording various aminothiolation adducts as single regioisomers. The radical process is proposed by preliminary mechanistic studies, involving radical trap and radical clock experiments

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Aged gp78 knockout mice develop obesity and gp78 is unregulated upon ER stress.

<p>(<b>A</b>) Schematic of gp78-targeting strategy. The gp78 allele disrupted by the insertion of a gene trap vector (OmniBank Vector 76) in the first intron. Genomic DNA isolated from WT, heterozygous and homozygous was genotyped by PCR. Primer set including double reverse primers was designed for internal PCR quality. (<b>B</b>) Total RNA and lysates were prepared in embryo and adult liver and were analyzed in RT-PCR (Top), both lysates were immunoprecipitated with rabbit anti-gp78 antibodies (epitope: 524–537) and then immunoblotted with monoclonal anti-gp78 antibodies (epitope: 451–551) to identify gp78 protein (bottom). (<b>C</b>) Immunohistochemistry (IHC) of liver with monoclonal anti-gp78 antibody. Arrow indicates gp78 positive stain. PV, portal vein. Original image, x400. (<b>D</b>) Upregulation of gp78 in response to ER stress. Immortalized THLE-3 and cancerous HepG2 liver cells were treated with tunicamycin (1ug/ml) for 24 hrs. and lysates were immunoprecipitated with anti-gp78 antibody and immunoblotted. GRP78/BIP, a chaperon of UPR pathways. (<b>F</b>) Photography of abdomen of 1-year-old mice (left). Comparison of body weight of WT and gp78-KO mice at 3 months (n = 25), 6 months (n = 25), 12 months (n = 25) old (right). Asterisk indicates a significance determined by Student’s test (*, p < 0.05).</p

Gp78-KO mice spontaneously develop hepatic steatosis with inflammatory infiltrates.

<p>(<b>A</b>) Livers of 1-year-old gp78 KO mice, grown with normal diet were stained with H&E and visualized as indicated magnification. (a) Steatohepatitis shows swelling cytoplasm with lipid droplets (black arrow) and infiltrating cells. (b) Mild lipid droplets and infiltrating cells (Red arrow). (c) Infiltrate cells gather in the absence of lipid droplets. (<b>B</b>) Oil red stain. Arrow indicates lipid droplets. (<b>C</b>) Trichrome stain was preformed to identify blue colored collagen fibers. PV; portal vein, FL; fatty liver area. (<b>D</b>) Percentage of incidence including mild fatty liver, inflammation in 1-year-old KO mice (n = 25 mice per each group).</p

Gp78-KO mice with acute ER stress progresses to severe fatty liver through UPR-driving SREBP-1 activation.

<p>(<b>A</b>) 1mg/kg body weight of tunicamycin (TM) was intraperitoneally injected to 6 months-old gp78-KO mice. Body weight is represented after normalization to the starting weight as the meant ± SE (n = 3 per group). (<b>B</b>) Radish livers are brown colored after TM injection. Liver of gp78-KO at 11 days was not recovered. (<b>C</b>) Acute ER stress potentiates entire fatty liver of gp78-KO. H&E stain at 3 days after TM injection. Ballooned cells (b) are typically bigger size than WT hepatocytes (a). Cytoplasmic lipid droplets (arrow) (40x). (<b>D</b>) Prolonged fatty liver and fibrosis in gp78-KO. H&E, oil red and Trichrome stains at 11 days after TM injection. White ballooned cells (arrows) were maintained on H&E (200x). Frozen tissues were stained with oil-red O. Irregular fibrosis was extended from connective tissue of portal vein surrounding accumulated lipid droplets (white spots) at pinkish gp78-KO liver (100x). (<b>E</b>) Persistent SREBP-1 activation along with UPR up regulation is responsible for fatty liver of gp78-KO. TM-injected mice were scarified respectively (n = 3). Liver extracts at indicated days were subjected to immunoblots. GRP78, Glucose-Regulated Protein; PDI, Protein Disulfide Isomerase, SERBP; Sterol Regulatory Element Binding Transcription Factor; Insig, Insulin Induced Gene. (<b>F</b>) Chop-mediated apoptosis. Cell survival was analyzed with viable counting in gp78-KO mouse embryonic fibroblast (MEF) cells treated with TM (1μg/ml) as indicated times (top). Induction of UPR was analyzed in immunoblots and gp78 expression was visualized after its immunoprecipitation (bottom). Chop; ER stress-mediated apoptosis marker.</p