AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia  through  the so-called  oxygen-dependent  metabolic  regulation,  which  involves  the competitive  binding  of  deoxyhemoglobin  and  glycolytic  enzymes  to  the  N-terminal  cytosolic domain  of  band  3.  This  mechanism  promotes  the  accumulation  of  2,3-DPG,  stabilizing  the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the  Bohr  effect.  Despite  in  vitro  studies,  in  vivo adaptations  to  hypoxia  have  not  yet  been completely elucidated. Within  the  framework  of  the AltitudeOmics  study,  erythrocytes  were  collected  from  21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following  reascent  after  7days  at 1525m.  UHPLC-MS  metabolomics  results  were  correlated  to physiological and athletic performance parameters. Immediate  metabolic  adaptations  were  noted as early as a few hours from ascending  to >5000m, and maintained for 16 days at high altitude.  Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory

Demystifying an unidentified EGRET source by VHE gamma-ray observations

In a novel approach in observational high-energy gamma-ray astronomy, observations carried out by imaging atmospheric Cherenkov telescopes provide necessary templates to pinpoint the nature of intriguing, yet unidentified EGRET gamma-ray sources. Using GeV-photons detected by CGRO EGRET and taking advantage of high spatial resolution images from H.E.S.S. observations, we were able to shed new light on the EGRET observed gamma-ray emission in the Kookaburra complex, whose previous coverage in the literature is somewhat contradictory. 3EGJ1420-6038 very likely accounts for two GeV gamma-ray sources (E>1 GeV), both in positional coincidence with the recently reported pulsar wind nebulae (PWN) by HESS in the Kookaburra/Rabbit complex. PWN associations at VHE energies, supported by accumulating evidence from observations in the radio and X-ray band, are indicative for the PSR/plerionic origin of spatially coincident, but still unidentified Galactic gamma-ray sources from EGRET. This not only supports the already suggested connection between variable, but unidentified low-latitude gamma-ray sources with pulsar wind nebulae (3EGJ1420-6038 has been suggested as PWN candidate previoulsy), it also documents the ability of resolving apparently confused EGRET sources by connecting the GeV emission as measured from a large-aperture space-based gamma-ray instrument with narrow field-of-view but superior spatial resolution observations by ground-based atmospheric Cherenkov telescopes, a very promising identification technique for achieving convincing individual source identifications in the era of GLAST-LAT.Comment: 4 pages, 5 figures, Accepted for publication in Astrophysics and Space Science, Proc. of "The Multi-Messenger Approach to High-Energy Gamma-ray Sources (Third Workshop on the Nature of Unidentified High-Energy Sources)", Barcelona, July 4-7, 2006, one typo correcte