Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.

Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, and its free radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of cancer and chronic infection. Previous studies have documented the effects of PGE2 on the various CD4+ T cell functions, but little is known about its impact on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating virally infected and tumor cells. Here we provide the first demonstration of the dramatic effects of PGE2 on the progression of human CD8+ T cells toward replicative senescence, a terminal dysfunctional state associated multiple pathologies during aging and chronic HIV-1 infection. Our data show that exposure of chronically activated CD8+ T cells to physiological levels of PGE2 and iso-PGE2 promotes accelerated acquisition of markers of senescence, including loss of CD28 expression, increased expression of p16 cell cycle inhibitor, reduced telomerase activity, telomere shortening and diminished production of key cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher levels of reactive oxygen species, suggesting that the resultant oxidative stress may have further enhanced telomere loss. Interestingly, we observed that even chronic activation per se resulted in increased CD8+ T cell production of PGE2, mediated by higher COX-2 activity, thus inducing a negative feedback loop that further inhibits effector function. Collectively, our data suggest that the elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1 infection, may accelerate progression of CD8+ T cells towards replicative senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a strategy to counteract this effect

Evidence of oxidative stress in young and aged DJ-1-deficient mice

AbstractLoss of DJ-1 function contributes to pathogenesis in Parkinson’s disease. Here, we investigate the impact of aging and DJ-1 deficiency in transgenic mice. Ventral midbrain from young DJ-1-deficient mice revealed no change in 4-hydroxy-2-nonenal (4-HNE), but HSP60, HSP40 and striatal dopamine turnover were significantly elevated compared to wildtype. In aged mice, the chaperone response observed in wildtype animals was absent from DJ-1-deficient transgenics, and nigral 4-HNE immunoreactivity was enhanced. These changes were concomitant with increased striatal dopamine levels and uptake. Thus, increased oxidants and diminished protein quality control may contribute to nigral oxidative damage with aging in the model

Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults

STUDY OBJECTIVES: Multiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildly impaired older adults. METHODS: Two hundred ninety-three participants were monitored at home for up to six nights with scEEG, actigraphy, and sleep diaries. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were calculated using each of these methods. In 109 of the 293 participants, the ratio of cerebrospinal fluid concentrations of phosphorylated tau (p-tau) and amyloid-β-42 (Aβ42) was used as a biomarker for AD pathology. RESULTS: Agreement was highest for TST across instruments, especially in cognitively normal older adults. Overall, scEEG and actigraphy appeared to have greater agreement for multiple sleep parameters than for scEEG and diary or actigraphy and diary. Levels of agreement between scEEG and actigraphy overall decreased in mildly impaired participants and those with biomarker evidence of AD pathology, especially for measurements of TST. CONCLUSIONS: Caution should be exercised when comparing scEEG and actigraphy in individuals with mild cognitive impairment or with AD pathology. Sleep diaries may capture different aspects of sleep compared to scEEG and actigraphy. Additional studies comparing different methods of measuring sleep-wake activity in older adults are necessary to allow for comparison between studies using different methods

Annihilation vs. Decay: Constraining dark matter properties from a gamma-ray detection

Most proposed dark matter candidates are stable and are produced thermally in the early Universe. However, there is also the possibility of unstable (but long-lived) dark matter, produced thermally or otherwise. We propose a strategy to distinguish between dark matter annihilation and/or decay in the case that a clear signal is detected in gamma-ray observations of Milky Way dwarf spheroidal galaxies with gamma-ray experiments. The sole measurement of the energy spectrum of an indirect signal would render the discrimination between these cases impossible. We show that by examining the dependence of the intensity and energy spectrum on the angular distribution of the emission, the origin could be identified as decay, annihilation, or both. In addition, once the type of signal is established, we show how these measurements could help to extract information about the dark matter properties, including mass, annihilation cross section, lifetime, dominant annihilation and decay channels, and the presence of substructure. Although an application of the approach presented here would likely be feasible with current experiments only for very optimistic dark matter scenarios, the improved sensitivity of upcoming experiments could enable this technique to be used to study a wider range of dark matter models.Comment: 29 pp, 8 figs; replaced to match published version (minor changes and some new references

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201