Titan Mare Explorer (TiME): first in situ exploration of an extraterrestrial sea

The lakes and seas of Titan are a sink of products of photolysis in the atmosphere, and a crucial component in Titan's active methane cycle. In situ exploration of the seas is necessary to understand their intriguing prebiotic organic chemistry

Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products

BACKGROUND: Atherosclerosis is an inflammatory disease in which a perpetuated activation of NFkappaB via the RAGE (receptor for advanced glycation end products)-MAPK signalling pathway may play an important pathogenetic role. As recently S100 proteins have been identified as ligands of RAGE, we sought to determine the effects of the proinflammatory heterodimer of S100A8/S100A9 on the RAGE-NFkappaB mediated induction of proinflammatory gene expression. METHODS: Human umbilical vein endothelial cells (HUVEC) were preincubated for 72 h with AGE-albumin or unmodified albumin for control, whereas AGE-albumin induction resulted in an upregulation of RAGE. Following this preactivation, cells were stimulated for 48 h with heterodimeric human recombinant S100A8/S100A9. RESULTS: Heterodimeric S100A8/S100A9 enhanced secretion of IL-6, ICAM-1, VCAM-1 and MCP1 in AGE-albumin pretreated HUVEC in a dose dependent manner. These effects could not be detected after stimulation with the homodimeric proteins S100A8, S100A9, S100A1 and S100B. The effects of heterodimeric S100A8/S100A9 were reduced by inhibition of the MAP-kinase pathways ERK1/2 and p38 by PD 98059 and SB 203580, respectively. CONCLUSION: The heterodimeric S100A8/S100A9 might therefore play a hitherto unknown role in triggering atherosclerosis in diabetes and renal failure, pathophysiological entities associated with a high AGE burden. Thus, blocking heterodimeric S100A8/S100A9 might represent a novel therapeutic modality in treating atherosclerosis

The global surface roughness of 25143 Itokawa

Surface roughness is an important metric in understanding how the geologic history of an asteroid affects its small-scale topography and it provides an additional means to quantitatively compare one asteroid with another. In this study, we report the first detailed global surface roughness maps of 25143 Itokawa at horizontal scales from 8--32~m. Comparison of the spatial distribution of the surface roughness of Itokawa with 433 Eros, the other asteroid for which this kind of analysis has been possible, indicates that the two asteroids are dominated by different geologic processes. On Itokawa, the surface roughness reflects the results of down-slope activity that moves fine grained material into geopotential lows and leaves large blocks in geopotential highs. On 433 Eros, the surface roughness is controlled by geologically-recent large impact craters. In addition, large longitudinal spatial variations of surface roughness could impact the role of YORP on Itokawa

MP3 - A meteorology and physical properties package to explore air-sea interaction on Titan

The exchange of mass, heat and momentum at the air:sea interface are profound influences on the terrestrial environment, affecting the intensity of hurricanes, the size of waves and lake-effect precipitation. Titan presents us with an opportunity to study these processes in a novel physical context, with a different sea, atmosphere and gravity. The MP3 instrument, under development for the proposed Discovery mission TiME (Titan Mare Explorer [1,2]) is an integrated suite of small, simple sensors that combines the function of traditional meteorology packages with liquid physical properties and depth-sounding : these latter functions follow the concept of - and indeed use spare elements from - the Huygens Surface Science Package (SSP,[3]). However, unlike Huygens’ brief and dynamic 3 hours of measurement, in TiME’s 6-Titan-day (96 Earth day) nominal mission enabled by radioisotope power, MP3 will have an unprecedented long-term measurement opportunity in one of the most evocative environments in the solar system, Titan’s sea Ligeia Mare

Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response

This is the publisher's version, also available electronically from http://www.jci.org/articles/view/18704While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation