Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome

BACKGROUND Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a d-chiro-inositol–containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of d-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. METHODS We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of d-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation. RESULTS In the 22 women given d-chiro-inositol, the mean (±SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417±11,572 to 5158±6714 μU per milliliter per minute (81±69 to 31±40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1±0.8 to 0.5±0.5 ng per deciliter (38±28 to 17±17 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women\u27s diastolic and systolic blood pressure decreased by 4 mm Hg (Pchiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P\u3c0.001). CONCLUSIONS d-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations

Low CCR7-Mediated Migration of Human Monocyte Derived Dendritic Cells in Response to Human Respiratory Syncytial Virus and Human Metapneumovirus

Human respiratory syncytial virus (HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC) is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to lymphatic tissue contributes to reduced adaptive responses to these viruses

Progress with the Prime Focus Spectrograph for the Subaru Telescope: a massively multiplexed optical and near-infrared fiber spectrograph

The Prime Focus Spectrograph (PFS) is an optical/near-infrared multi-fiber spectrograph with 2394 science fibers, which are distributed in 1.3 degree diameter field of view at Subaru 8.2-meter telescope. The simultaneous wide wavelength coverage from 0.38 um to 1.26 um, with the resolving power of 3000, strengthens its ability to target three main survey programs: cosmology, Galactic archaeology, and galaxy/AGN evolution. A medium resolution mode with resolving power of 5000 for 0.71 um to 0.89 um also will be available by simply exchanging dispersers. PFS takes the role for the spectroscopic part of the Subaru Measurement of Images and Redshifts project, while Hyper Suprime-Cam works on the imaging part. To transform the telescope plus WFC focal ratio, a 3-mm thick broad-band coated glass-molded microlens is glued to each fiber tip. A higher transmission fiber is selected for the longest part of cable system, while one with a better FRD performance is selected for the fiber-positioner and fiber-slit components, given the more frequent fiber movements and tightly curved structure. Each Fiber positioner consists of two stages of piezo-electric rotary motors. Its engineering model has been produced and tested. Fiber positioning will be performed iteratively by taking an image of artificially back-illuminated fibers with the Metrology camera located in the Cassegrain container. The camera is carefully designed so that fiber position measurements are unaffected by small amounts of high special-frequency inaccuracies in WFC lens surface shapes. Target light carried through the fiber system reaches one of four identical fast-Schmidt spectrograph modules, each with three arms. Prototype VPH gratings have been optically tested. CCD production is complete, with standard fully-depleted CCDs for red arms and more-challenging thinner fully-depleted CCDs with blue-optimized coating for blue arms.Comment: 14 pages, 12 figures, submitted to "Ground-based and Airborne Instrumentation for Astronomy V, Suzanne K. Ramsay, Ian S. McLean, Hideki Takami, Editors, Proc. SPIE 9147 (2014)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure