A place to die for: apoptosis in cancer and infection, Capri 2002

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Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity

During macroautophagy, conjugation of ATG12 to ATG5 is essential for LC3 lipidation and autophagosome formation. Additionally, ATG12 has ATG5-independent functions in diverse processes including mitochondrial fusion and mitochondrial-dependent apoptosis. In this study, we investigated the regulation of free ATG12. In stark contrast to the stable ATG12–ATG5 conjugate, we find that free ATG12 is highly unstable and rapidly degraded in a proteasome-dependent manner. Surprisingly, ATG12, itself a ubiquitin-like protein, is directly ubiquitinated and this promotes its proteasomal degradation. As a functional consequence of its turnover, accumulation of free ATG12 contributes to proteasome inhibitor-mediated apoptosis, a finding that may be clinically important given the use of proteasome inhibitors as anticancer agents. Collectively, our results reveal a novel interconnection between autophagy, proteasome activity, and cell death mediated by the ubiquitin-like properties of ATG12

RIPK3 restricts viral pathogenesis via cell death-independent neuroinflammation

Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3(-/-) mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS

Marco Polo: near Earth object sample return mission

Marco Polo is a joint European-Japanese mission of sample return from a Near Earth Object. The Marco Polo proposal was submitted to ESA on July 2007 in the framework of the Cosmic Vision 2015-2025 context, and on October 2007 passed the first evaluation process. The primary objectives of this mission is to visit a primitive NEO, belonging to a class that cannot be related to known meteorite types, to characterize it at multiple scales, and to bring samples back to Earth. Marco Polo will give us the first opportunity for detailed laboratory study of the most primitive materials that formed the planets. This will allow us to improve our knowledge on the processes which governed the origin and early evolution of the Solar System, and possibly of the life on Earth

Phobos DTM and Coordinate Refinement for Phobos-Grunt Mission Support.

Images obtained by the High Resolution Stereo Camera (HRSC) during recent Phobos flybys were used to study the proposed new landing site area of the Russian Phobos-Grunt mission, scheduled for launch in 2011 [1]. From the stereo images (resolution of up to 4.4 m/pixel), a digital terrain model (DTM) with a lateral resolution of 100 m per pixel and a relative point accuracy of ±15 m, was determined. Images and DTM were registered to the established Phobos control point network [7]. A map of the landing site area was produced enabling mission planers and scientists to extract accurate body-fixed coordinates of features in the Phobos Grunt landing site area

Perceptions of Electoral Fairness and Voter Turnout

Previous research has established a link between turnout and the extent to which voters are faced with a “meaningful” partisan choice in elections; this study extends the logic of this argument to perceptions of the “meaningfulness” of electoral conduct. It hypothesizes that perceptions of electoral integrity are positively related to turnout. The empirical analysis to test this hypothesis is based on aggregate-level data from 31 countries, combined with survey results from Module 1 of the Comparative Study of Electoral Systems survey project, which includes new and established democracies. Multilevel modeling is employed to control for a variety of individual- and election-level variables that have been found in previous research to influence turnout. The results of the analysis show that perceptions of electoral integrity are indeed positively associated with propensity to vote. </jats:p

Marco Polo: A near Earth object sample return mission

From Introduction: MARCO POLO is a joint European-Japanese sample return mission to a Near-Earth Object. In late 2007 this mission was selected by ESA, in the framework of COSMIC VISION 2015-2025, for an assessment scheduled to last until mid 2009. This Euro-Asian mission will go to a primitive Near-Earth Object (NEO), such as a C or D type asteroid. The spacecraft will rendezvous with the object, and over an extended period scientifically characterize it at multiple scales and bring samples back to Earth for detailed scientific investigation

Orbital evolution of P\v{r}\'{i}bram and Neuschwanstein

The orbital evolution of the two meteorites P\v{r}\'{i}bram and Neuschwanstein on almost identical orbits and also several thousand clones were studied in the framework of the N-body problem for 5000 years into the past. The meteorites moved on very similar orbits during the whole investigated interval. We have also searched for photographic meteors and asteroids moving on similar orbits. There were 5 meteors found in the IAU MDC database and 6 NEAs with currently similar orbits to P\v{r}\'{i}bram and Neuschwanstein. However, only one meteor 161E1 and one asteroid 2002 QG46 had a similar orbital evolution over the last 2000 years.Comment: 7 pages, 2 figures, 3 table