Icy bodies may have delivered the oceans to the early Earth, yet little is known about water in the ice-dominated regions of extrasolar planet-forming disks. The Heterodyne Instrument for the ...Far-Infrared on board the Herschel Space Observatory has detected emission lines from both spin isomers of cold water vapor from the disk around the young star TW Hydrae. This water vapor likely originates from ice-coated solids near the disk surface, hinting at a water ice reservoir equivalent to several thousand Earth oceans in mass. The water's ortho-to-para ratio falls well below that of solar system comets, suggesting that comets contain heterogeneous ice mixtures collected across the entire solar nebula during the early stages of planetary birth.
Protein aggregates and damaged organelles are tagged with ubiquitin chains to trigger selective autophagy. To initiate mitophagy, the ubiquitin kinase PINK1 phosphorylates ubiquitin to activate the ...ubiquitin ligase parkin, which builds ubiquitin chains on mitochondrial outer membrane proteins, where they act to recruit autophagy receptors. Using genome editing to knockout five autophagy receptors in HeLa cells, here we show that two receptors previously linked to xenophagy, NDP52 and optineurin, are the primary receptors for PINK1- and parkin-mediated mitophagy. PINK1 recruits NDP52 and optineurin, but not p62, to mitochondria to activate mitophagy directly, independently of parkin. Once recruited to mitochondria, NDP52 and optineurin recruit the autophagy factors ULK1, DFCP1 and WIPI1 to focal spots proximal to mitochondria, revealing a function for these autophagy receptors upstream of LC3. This supports a new model in which PINK1-generated phospho-ubiquitin serves as the autophagy signal on mitochondria, and parkin then acts to amplify this signal. This work also suggests direct and broader roles for ubiquitin phosphorylation in other autophagy pathways.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given ...its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post Processing of the Society for Cardiovascular MR (SCMR). The aim of the task force is to recommend requirements and standards for image interpretation and post processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate.
PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective autophagy of damaged mitochondria. However, it has been unclear how PINK1 activates and recruits Parkin to mitochondria. ...Although PINK1 phosphorylates Parkin, other PINK1 substrates appear to activate Parkin, as the mutation of all serine and threonine residues conserved between Drosophila and human, including Parkin S65, did not wholly impair Parkin translocation to mitochondria. Using mass spectrometry, we discovered that endogenous PINK1 phosphorylated ubiquitin at serine 65, homologous to the site phosphorylated by PINK1 in Parkin's ubiquitin-like domain. Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. In cells, the phosphomimetic ubiquitin mutant S65D bound and activated Parkin. Furthermore, expression of ubiquitin S65A, a mutant that cannot be phosphorylated by PINK1, inhibited Parkin translocation to damaged mitochondria. These results explain a feed-forward mechanism of PINK1-mediated initiation of Parkin E3 ligase activity.
We have undertaken a new ground-based monitoring campaign to improve the estimates of the mass of the central black hole in NGC 4151. We measure the lag time of the broad Hb line response compared to ...the optical continuum at 5100 AA and find a lag of 6.6 super(+1.1-0.8) days. We combine our data with the recent reanalysis of UV emission lines by Metzroth and coworkers to calculate a weighted mean of the black hole mass, M sub(BH) = (4.57 super(+0.57-0.47)) x 10 super(7) M sub( ). The absolute calibration of the black hole mass is based on normalization of the AGN black hole mass-stellar velocity dispersion (M sub(BH)-s sub(*)) relationship to that of quiescent galaxies by Onken and coworkers. The scatter in the M sub(BH)-s sub(*) relationship suggests that reverberation-mapping-based mass measurements are typically uncertain by a factor of 3-4.
In vivo toxicity of poly(propyleneimine) dendrimers Ziemba, Barbara; Janaszewska, Anna; Ciepluch, Karol ...
Journal of biomedical materials research. Part A,
November 2011, Letnik:
99A, Številka:
2
Journal Article
COPD has been perceived as being a disease of older men. However, >7 million women are estimated to live with COPD in the USA alone. Despite a growing body of literature suggesting an increasing ...burden of COPD in women, the evidence is limited.
To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.
A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken. Gender-specific prevalence estimates were abstracted from relevant studies. Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected. A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.
Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval CrI: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women. Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%). Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.
We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review. These results will increase awareness of COPD as a critical woman's health issue.
Japan and China did not begin to emerge as unified political entities until the nineteenth century. Yet scholars and politicians persistently refer to "Japan" and "China" in discussions of earlier ...periods, as if the modern nation-state had long been established in these regions. Joshua Fogel here brings together essays by eight renowned East Asian scholars to demonstrate why this oversight distorts our historical analysis and understanding of both countries. The nation-states of Japan and China developed much later and, indeed, far less uniformly than usually conveyed in popular myth and political culture. Moreover, the false depiction of an earlier national identity not only alters the factual record; it serves the contemporary engines of nationalist mythology and propaganda.
This interdisciplinary volume asks deceptively simple questions: When did "Japan" and "China" become Japan and China? When and why do inhabitants begin to define their identity and interests nationally rather than locally? Identifying the role of mitigating factors from disease and travel abroad to the subtleties of political language and aesthetic sensibility, the answers provided in these diverse and insightful essays are appropriately complex. By setting aside Western notions of the nation-state, the contributors approach each region on its own terms, while the thematic organization of the book provides a unique lens through which to view the challenges common to understanding both Japan and China. This highly readable collection will be important to scholars both inside and beyond the field of East Asian studies.
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