Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-'omic analysis of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a down-regulation in NRF2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment.

Does the Debris Disk around HD 32297 Contain Cometary Grains?

We present an adaptive optics imaging detection of the HD 32297 debris disk at L' (3.8 \microns) obtained with the LBTI/LMIRcam infrared instrument at the LBT. The disk is detected at signal-to-noise per resolution element ~ 3-7.5 from ~ 0.3-1.1" (30-120 AU). The disk at L' is bowed, as was seen at shorter wavelengths. This likely indicates the disk is not perfectly edge-on and contains highly forward scattering grains. Interior to ~ 50 AU, the surface brightness at L' rises sharply on both sides of the disk, which was also previously seen at Ks band. This evidence together points to the disk containing a second inner component located at $\lesssim$ 50 AU. Comparing the color of the outer (50 $< r$/AU $< 120$) portion of the disk at L' with archival HST/NICMOS images of the disk at 1-2 \microns allows us to test the recently proposed cometary grains model of Donaldson et al. 2013. We find that the model fails to match the disk's surface brightness and spectrum simultaneously (reduced chi-square = 17.9). When we modify the density distribution of the model disk, we obtain a better overall fit (reduced chi-square = 2.9). The best fit to all of the data is a pure water ice model (reduced chi-square = 1.06), but additional resolved imaging at 3.1 \microns is necessary to constrain how much (if any) water ice exists in the disk, which can then help refine the originally proposed cometary grains model.Comment: Accepted to ApJ January 13, 2014. 12 pages (emulateapj style), 9 figures, 1 tabl

Effect of proton irradiation followed by hindlimb unloading on bone in mature mice: A model of long-duration spaceflight

Bone loss associated with microgravity unloading is well documented; however, the effects of spaceflight-relevant types and doses of radiation on the skeletal system are not well defined. In addition, the combined effect of unloading and radiation has not received much attention. In the present study, we investigated the effect of proton irradiation followed by mechanical unloading via hindlimb suspension (HLS) in mice. Sixteen-week-old female C57BL/6 mice were either exposed to 1 Gy of protons or a sham irradiation procedure (n=30/group). One day later, half of the mice in each group were subjected to four weeks of HLS or normal loading conditions. Radiation treatment alone (IRR) resulted in approximately 20% loss of trabecular bone volume fraction (BV/TV) in the tibia and femur, with no effect in the cortical bone compartment. Conversely, unloading induced substantially greater loss of both trabecular bone (60–70% loss of BV/TV) and cortical bone (approximately 20% loss of cortical bone volume) in both the tibia and femur, with corresponding decreases in cortical bone strength. Histological analyses and serum chemistry data demonstrated increased levels of osteoclast-mediated bone resorption in unloaded mice, but not IRR. HLS+IRR mice generally experienced greater loss of trabecular bone volume fraction, connectivity density, and trabecular number than either unloading or irradiation alone. Although the duration of unloading may have masked certain effects, the skeletal response to irradiation and unloading appears to be additive for certain parameters. Appropriate modeling of the environmental challenges of long duration spaceflight will allow for a better understanding of the underlying mechanisms mediating spaceflight-associated bone loss and for the development of effective countermeasures

Dynamical Masses of Young Stars I:Discordant Model Ages of Upper Scorpius

We present the results of a long term orbit monitoring program, using sparse aperture masking observations taken with NIRC2 on the Keck-II telescope, of seven G to M-type members of the Upper Scorpius subgroup of the Sco-Cen OB association. We present astrometry and derived orbital elements of the binary systems we have monitored, and also determine the age, component masses, distance and reddening for each system using the orbital solutions and multi-band photometry, including Hubble Space Telescope photometry, and a Bayesian fitting procedure. We find that the models can be forced into agreement with any individual system by assuming an age, but that age is not consistent across the mass range of our sample. The G-type binary systems in our sample have model ages of ~11.5 Myr, which is consistent with the latest age estimates for Upper Scorpius, while the M-type binary systems have significantly younger model ages of ~7 Myr. Based on our fits, this age discrepancy in the models corresponds to a luminosity under-prediction of 0.8-0.15 dex, or equivalently an effective temperature over-prediction of 100-300 K for M-type stars at a given premain-sequence age. We also find that the M-type binary system RXJ 1550.0-2312 has an age (~16 Myr) and distance (~90 pc) indicating that it is either a nearby young binary system or a member of the Upper-Centaurus-Lupus subgroup with a 57% probability of membership.Comment: 16 pages, 8 figures, 9 tables, accepted for publication in Ap

THE RADIAL AND ROTATIONAL VELOCITIES OF PSO J318.5338-22.8603, A NEWLY CONFIRMED PLANETARY-MASS MEMBER OF THE β PICTORIS MOVING GROUP

PSO J318.5338$-$22.8603 is an extremely-red planetary-mass object that has been identified as a candidate member of the $\beta$ Pictoris moving group based on its spatial position and tangential velocity. We present a high resolution $K$-band spectrum of PSO J318.5338$-$22.8603. Using a forward-modeling Markov Chain Monte Carlo approach, we report the first measurement of the radial velocity and $v$ sin($i$) of PSO J318.5$-$22, $-$6.0$^{+0.8}_{-1.1}$ km s$^{-1}$ and 17.5$^{+2.3}_{-2.8}$ km s$^{-1}$, respectively. We calculate the space velocity and position of PSO J318.5$-$22 and confirm that it is a member of the $\beta$ Pictoris moving group. Adopting an age of 23$\pm$3 Myr for PSO J318.5$-$22, we determine a mass of $8.3\pm0.5$ $M_{\rm{Jup}}$ and effective temperature of $1127^{+24}_{-26}$ K using evolutionary models. PSO J318.5338$-$22.8603 is intermediate in mass and temperature to the directly-imaged planets $\beta$ Pictoris b and 51 Eridani b, making it an important benchmark object in the sequence of planetary-mass members of the $\beta$ Pictoris moving group. Combining our $v$ sin($i$) measurement with recent photometric variability data, we constrain the inclination of PSO J318.5$-$22 to $>29^{\circ}$ and its rotational period to 5-10.2 hours. The equatorial velocity of PSO J318.5$-$22 indicates that its rotation is consistent with an extrapolation of the velocity-mass relationship for solar system planets.Comment: 8 pages, 5 figures, 2 tables, ApJ accepte

Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space

Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer–related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA’s Space Shuttle Program, exploration of space will undoubtedly continue

On the binary frequency of the lowest mass members of the pleiades with hubble space telescope wide field camera 3

E. V. Garcia, et al., “On the Binary Frequency of the Lowest mass Members of the Pleiades with Hubble Space Telescope Wide Field Camera 3”, The Astrophysical Journal, Vol. 804(1), May 2015. © 2015. The American Astronomical Society.We present the results of a Hubble Space Telescope Wide Field Camera 3 (WFC3) imaging survey of 11 of the lowest mass brown dwarfs in the Pleiades known (25-40 MJup). These objects represent the predecessors to T dwarfs in the field. Using a semi-empirical binary point-spread function (PSF)-fitting technique, we are able to probe to 0.″ 03 (0.75 pixel), better than 2x the WFC3/UVIS diffraction limit. We did not find any companions to our targets. From extensive testing of our PSF-fitting method on simulated binaries, we compute detection limits which rule out companions to our targets with mass ratios of 0.7 and separations 4 AU. Thus, our survey is the first to attain the high angular resolution needed to resolve brown dwarf binaries in the Pleiades at separations that are most common in the field population. We constrain the binary frequency over this range of separation and mass ratio of 25-40 MJup Pleiades brown dwarfs to bePeer reviewe

Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization.

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well

Spaceflight Activates Lipotoxic Pathways in Mouse Liver

Spaceflight affects numerous organ systems in the body, leading to metabolic dysfunction that may have long-term consequences. Microgravity-induced alterations in liver metabolism, particularly with respect to lipids, remain largely unexplored. Here we utilize a novel systems biology approach, combining metabolomics and transcriptomics with advanced Raman microscopy, to investigate altered hepatic lipid metabolism in mice following short duration spaceflight. Mice flown aboard Space Transportation System -135, the last Shuttle mission, lose weight but redistribute lipids, particularly to the liver. Intriguingly, spaceflight mice lose retinol from lipid droplets. Both mRNA and metabolite changes suggest the retinol loss is linked to activation of PPARα-mediated pathways and potentially to hepatic stellate cell activation, both of which may be coincident with increased bile acids and early signs of liver injury. Although the 13-day flight duration is too short for frank fibrosis to develop, the retinol loss plus changes in markers of extracellular matrix remodeling raise the concern that longer duration exposure to the space environment may result in progressive liver damage, increasing the risk for nonalcoholic fatty liver disease

A nearby m star with three transiting super-earths discovered by k2

I. J. M. Crossfied, “A Nearby M Star with Three Transiting Super-Earths Discovered by K2”, The Astrophysical Journal, Vol 804(1), April 2015. © 2015. The American Astronomical Society.Small, cool planets represent the typical end-products of planetary formation. Studying the architectures of these systems, measuring planet masses and radii, and observing these planets' atmospheres during transit directly informs theories of planet assembly, migration, and evolution. Here we report the discovery of three small planets orbiting a bright (Ks = 8.6 mag) M0 dwarf using data collected as part of K2, the new ecliptic survey using the re-purposed Kepler spacecraft. Stellar spectroscopy and K2 photometry indicate that the system hosts three transiting planets with radii 1.5-2.1 , straddling the transition region between rocky and increasingly volatile-dominated compositions. With orbital periods of 10-45 days the planets receive just 1.5-10x the flux incident on Earth, making these some of the coolest small planets known orbiting a nearby star; planet d is located near the inner edge of the system's habitable zone. The bright, low-mass star makes this system an excellent laboratory to determine the planets' masses via Doppler spectroscopy and to constrain their atmospheric compositions via transit spectroscopy. This discovery demonstrates the ability of K2 and future space-based transit searches to find many fascinating objects of interest.Peer reviewe