Search

On UT 29 June 2015, the occultation by Pluto of a bright star (r′ = 11.9) was observed from the Stratospheric Observatory for Infrared Astronomy (SOFIA) and several ground-based stations in New Zealand and Australia. Pre-event astrometry allowed for an in-flight update to the SOFIA team with the result that SOFIA was deep within the central flash zone (~22 km from center). Analysis of the combined data leads to the result that Pluto's middle atmosphere is essentially unchanged from 2011 and 2013 (Person et al. 2013; Bosh et al. 2015); there has been no significant expansion or contraction of the atmosphere. Additionally, our multi-wavelength observations allow us to conclude that a haze component in the atmosphere is required to reproduce the light curves obtained. This haze scenario has implications for understanding the photochemistry of Pluto's atmosphere.

SOFIA HAWC+ polarimetry at $154~\micron$ is reported for the face-on galaxy M51 and the edge-on galaxy NGC 891. For M51, the polarization vectors generally follow the spiral pattern defined by the molecular gas distribution, the far-infrared (FIR) intensity contours, and other tracers of star formation. The fractional polarization is much lower in the FIR-bright central regions than in the outer regions, and we rule out loss of grain alignment and variations in magnetic field strength as causes. When compared with existing synchrotron observations, which sample different regions with different weighting, we find the net position angles are strongly correlated, the fractional polarizations are moderately correlated, but the polarized intensities are uncorrelated. We argue that the low fractional polarization in the central regions must be due to significant numbers of highly turbulent segments across the beam and along lines of sight in the beam in the central 3 kpc of M51. For NGC 891, the FIR polarization vectors within an intensity contour of 1500 $\rm{MJy~sr^{-1}}$ are oriented very close to the plane of the galaxy. The FIR polarimetry is probably sampling the magnetic field geometry in NGC 891 much deeper into the disk than is possible with NIR polarimetry and radio synchrotron measurements. In some locations in NGC 891 the FIR polarization is very low, suggesting we are preferentially viewing the magnetic field mostly along the line of sight, down the length of embedded spiral arms. There is tentative evidence for a vertical field in the polarized emission off the plane of the disk., Comment: AJ, Accepted, In Press

We report on polarimetric maps made with HAWC+/SOFIA toward Rho Oph A, the densest portion of the Rho Ophiuchi molecular complex. We employed HAWC+ bands C (89 $��$m) and D (154 $��$m). The slope of the polarization spectrum was investigated by defining the quantity R_DC = p_D/p_C, where p_C and p_D represent polarization degrees in bands C and D, respectively. We find a clear correlation between R_DC and the molecular hydrogen column density across the cloud. A positive slope (R_DC > 1) dominates the lower density and well illuminated portions of the cloud, that are heated by the high mass star Oph S1, whereas a transition to a negative slope (R_DC < 1) is observed toward the denser and less evenly illuminated cloud core. We interpret the trends as due to a combination of: (1) Warm grains at the cloud outskirts, which are efficiently aligned by the abundant exposure to radiation from Oph S1, as proposed in the radiative torques theory; and (2) Cold grains deep in the cloud core, which are poorly aligned due to shielding from external radiation. To assess this interpretation, we developed a very simple toy model using a spherically symmetric cloud core based on Herschel data, and verified that the predicted variation of R_DC is consistent with the observations. This result introduces a new method that can be used to probe the grain alignment efficiency in molecular clouds, based on the analysis of trends in the far-infrared polarization spectrum., Accepted by ApJ (July 18 2019)

We report the first detection of galactic spiral structure by means of thermal emission from magnetically aligned dust grains. Our 89 $��$m polarimetric imaging of NGC 1068 with the High-resolution Airborne Wideband Camera/Polarimeter (HAWC+) on NASA's Stratospheric Observatory for Infrared Astronomy (SOFIA) also sheds light on magnetic field structure in the vicinity of the galaxy's inner-bar and active galactic nucleus (AGN). We find correlations between the 89 $��$m magnetic field vectors and other tracers of spiral arms, and a symmetric polarization pattern as a function of the azimuthal angle arising from the projection and inclination of the disk field component in the plane of the sky. The observations can be fit with a logarithmic spiral model with pitch angle of $16.9^{+2.7}_{-2.8}$$^{\circ}$ and a disk inclination of $48\pm2^{\circ}$. We infer that the bulk of the interstellar medium from which the polarized dust emission originates is threaded by a magnetic field that closely follows the spiral arms. Inside the central starburst disk ($, 13 pages, 7 figures, Accepted for publication by ApJ

High-resolution Airborne Wide-band Camera (HAWC[Formula: see text]) is the facility far-infrared imager and polarimeter for SOFIA, NASA’s Stratospheric Observatory for Infrared Astronomy. It is designed to cover the portion of the infrared spectrum that is completely inaccessible to ground-based observatories and which is essential for studies of astronomical sources with temperatures between tens and hundreds of degrees Kelvin. Its ability to make polarimetric measurements of aligned dust grains provides a unique new capability for studying interstellar magnetic fields. HAWC[Formula: see text] began commissioning flights in April 2016 and was accepted as a facility instrument in early 2018. In this paper, we describe the instrument, its operational procedures, and its performance on the observatory.

We present observations of NGC 1068 covering the $19.7-53.0$ $\mu$m wavelength range using FORCAST and HAWC+ onboard SOFIA. Using these observations, high-angular resolution infrared (IR) and sub-mm observations, we find an observational turn-over of the torus emission in the $30-40$ $\mu$m wavelength range with a characteristic temperature of $70-100$ K. This component is clearly different from the diffuse extended emission in the narrow line and star formation regions at 10-100 $\mu$m within the central 700 pc. We compute $2.2-432$ $\mu$m 2D images using the best inferred \textsc{clumpy} torus model based on several nuclear spectral energy distribution (SED) coverages. We find that when $1-20$ $\mu$m SED is used, the inferred result gives a small torus size ($, Comment: 12 pages, 7 Figures, Accepted for publication in ApJ

We present Far-Infrared polarimetry observations of M82 at 53 and $154~\mu \rm{m}$ and NGC 253 at $89~\mu \rm{m}$, which were taken with HAWC+ in polarimetry mode on the Stratospheric Observatory for Infrared Astronomy (SOFIA). The polarization of M82 at $53~\mu \rm{m}$ clearly shows a magnetic field geometry perpendicular to the disk in the hot dust emission. For M82 the polarization at $154~\mu \rm{m}$ shows a combination of field geometry perpendicular to the disk in the nuclear region, but closer to parallel to the disk away from the nucleus. The fractional polarization at $53~\mu \rm{m}$ $(154~\mu \rm{m})$ ranges from 7% (3%) off nucleus to 0.5% (0.3%) near the nucleus. A simple interpretation of the observations of M82 invokes a massive polar outflow, dragging the field along, from a region $\sim 700$~pc in diameter that has entrained some of the gas and dust, creating a vertical field geometry seen mostly in the hotter $(53~\mu \rm{m})$ dust emission. This outflow sits within a larger disk with a more typical planar geometry that more strongly contributes to the cooler $(154~\mu \rm{m})$ dust emission. For NGC 253, the polarization at $89~\mu \rm{m}$ is dominated by a planar geometry in the tilted disk, with weak indication of a vertical geometry above and below the plane from the nucleus. The polarization observations of NGC 253 at $53~\mu \rm{m}$ were of insufficient S/N for detailed analysis., Comment: 6 Figures, 20 pages, ApJL accepted

We report new polarimetric and photometric maps of the massive star-forming region OMC-1 using the HAWC+ instrument on the Stratospheric Observatory for Infrared Astronomy (SOFIA). We present continuum polarimetric and photometric measurements of this region at 53, 89, 154, and 214 microns at angular resolutions of 5.1, 7.9, 14.0, and 18.7 arcseconds for the four bands, respectively. The photometric maps enable the computation of improved SEDs for the region. We find that at the longer wavelengths, the inferred magnetic field configuration matches the `hourglass' configuration seen in previous studies, indicating magnetically-regulated star formation. The field morphology differs at the shorter wavelengths. The magnetic field inferred at these wavelengths traces the bipolar structure of the explosive Becklin-Neugebauer (BN)/Kleinman-Low (KL) outflow emerging from OMC-1 behind the Orion Nebula. Using statistical methods to estimate the field strength in the region, we find that the explosion dominates the magnetic field near the center of the feature. Farther out, the magnetic field is close to energetic equilibrium with the ejecta and may be providing confinement to the explosion. The correlation between polarization fraction and the local polarization angle dispersion indicates that the depolarization as a function of unpolarized intensity is a result of intrinsic field geometry as opposed to decreases in grain alignment efficiency in denser regions., Comment: 28 pages, 14 figures, ApJ, accepted

The mammalian target of rapamycin (mTOR) plays an important role in cardiac development and function. Inhibition of mTOR by rapamycin has been shown to attenuate pathological cardiac hypertrophy and improve the function of aging heart, accompanied by an inhibition of the cardiac proteasome activity. The current study aimed to determine the potential mechanism(s) by which mTOR inhibition modulates cardiac proteasome. Inhibition of mTOR by rapamycin was found to reduce primarily the immunoproteasome in both H9c2 cells in vitro and mouse heart in vivo, without significant effect on the constitutive proteasome and protein ubiquitination. Concurrent with the reduction of the immunoproteasome, rapamycin reduced two important inflammatory response pathways, the NF-κB and Stat3 signaling. In addition, rapamycin attenuated the induction of the immunoproteasome in H9c2 cells by inflammatory cytokines, including INFγ and TNFα, by suppressing NF-κB signaling. These data indicate that rapamycin indirectly modulated immunoproteasome through the suppression of inflammatory response pathways. Lastly, the role of the immunoproteasome during the development of cardiac hypertrophy was investigated. Administration of a specific inhibitor of the immunoproteasome ONX 0914 attenuated isoproterenol-induced cardiac hypertrophy, suggesting that the immunoproteasome may be involved in the development of cardiac hypertrophy and therefore could be a therapeutic target. In conclusion, rapamycin inhibits the immunoproteasome through its effect on the inflammatory signaling pathways and the immunoproteasome could be a potential therapeutic target for pathological cardiac hypertrophy.

The benchmark exoplanet GJ 1214b is one of the best studied transiting planets in the transition zone between rocky Earth-sized planets and gas or ice giants. This class of super-Earth/mini-Neptune planets is unknown in our Solar System, yet is one of the most frequently detected classes of exoplanets. Understanding the transition from rocky to gaseous planets is a crucial step in the exploration of extrasolar planetary systems, in particular with regard to the potential habitability of this class of planets. GJ 1214b has already been studied in detail from various platforms at many different wavelengths. Our airborne observations with SOFIA add information in the Paschen-alpha cont. 1.9 micron infrared wavelength band, which is not accessible by any other current ground- or space-based instrument due to telluric absorption or limited spectral coverage. We used FLIPO and FPI+ on SOFIA to comprehensively analyse the transmission signal of the possible water-world GJ 1214b through photometric observations during transit in three optical and one infrared channels. We present four simultaneous light curves and corresponding transit depths in three optical and one infrared channel, which we compare to previous observations and state-of-the-art synthetic atmospheric models of GJ 1214b. The final precision in transit depth is between 1.5 and 2.5 times the theoretical photon noise limit, not sensitive enough to constrain the theoretical models any better than previous observations. This is the first exoplanet observation with SOFIA that uses its full set of instruments available to exoplanet spectrophotometry. Therefore we use these results to evaluate SOFIA's potential in this field and suggest future improvements., Comment: Accepted for publication in Astronomy and Astrophysics

Our recent study in a mouse model of familial-Amyotrophic Lateral Sclerosis (f-ALS) revealed that muscle proteins are equally sensitive to misfolding as spinal cord proteins despite the presence of low mutant CuZn-superoxide dismutase, which is considered to be the key toxic element for initiation and progression of f-ALS. More importantly, we observed differential level of heat shock proteins (Hsp's) between skeletal muscle and spinal cord tissues prior to the onset and during disease progression; spinal cord maintains significantly higher level of Hsp's compared to skeletal muscle. In this study, we report two important observations; (i) muscle cells (but not neuronal cells) are extremely vulnerable to protein misfolding and cell death during challenge with oxidative stress and (ii) muscle cells fail to mount Hsp's during challenge unlike neuronal cells. These two findings can possibly explain why muscle atrophy precedes the death of motor neurons in f-ALS mice.

The 'oxidative stress theory of aging' predicts that aging is primarily regulated by progressive accumulation of oxidized macromolecules that cause deleterious effects to cellular homeostasis and induces a decline in physiological function. However, our reports on the detection of higher level of oxidized protein carbonyls in the soluble cellular fractions of long-living rodent naked-mole rats (NMRs, lifespan ~30yrs) compared to short-lived mice (lifespan ~3.5yrs) apparently contradicts a key tenet of the oxidative theory. As oxidation often inactivates enzyme function and induces higher-order soluble oligomers, we performed a comprehensive study to measure global protein carbonyl level in different tissues of age-matched NMRs and mice to determine if the traditional concept of oxidation mediated impairment of function and induction of higher-order structures of proteins are upheld in the NMRs. We made three intriguing observations with NMRs proteins: (1) protein carbonyl is significantly elevated across different tissues despite of its exceptional longevity, (2) enzyme function is restored despite of experiencing higher level of protein carbonylation, and (3) enzymes show lesser sensitivity to form higher-order non-reducible oligomers compared to short-living mouse proteins in response to oxidative stress. These observations were made based on the global analysis of protein carbonyl and identification of two heavily carbonylated proteins in the kidney, triosephosphate isomerase (TPI) and cytosolic peroxiredoxin (Prdx1). These un-expected intriguing observations thus strongly suggest that oxidative modification may not be the only criteria for impairment of protein and enzyme function; cellular environment is likely be the critical determining factor in this process and may be the underlying mechanism for exceptional longevity of NMR.

Effective stray light control is a key requirement for wide dynamic range performance of scientific optical and infrared systems. SOFIA now has over 325 mission flights including extended southern hemisphere deployments; science campaigns using 7 different instrument configurations have been completed. The research observations accomplished on these missions indicate that the telescope and cavity designs are effective at suppressing stray light. Stray light performance impacts, such as optical surface contamination, from cavity environment conditions during mission flight cycles and while on-ground, have proved to be particularly benign. When compared with earlier estimates, far fewer large optics re-coatings are now anticipated, providing greater facility efficiency.

Aging is associated with a decline in peripheral nerve function of both motor and sensory nerves. The decline in function of peripheral sensorimotor nerves with aging has been linked to sarcopenia, the age-related decline in muscle mass and function that significantly compromises the quality of life in older humans. In this study, we report a significant increase in oxidized fatty acids and insoluble protein carbonyls in sciatic nerves of aged C57BL/6 male mice (28-30mo) that exhibit a profound decline in motor nerve function and degenerative changes in both axon and myelin structure, compared to young mice (6-8mo). Our data further suggests that this age-related loss of function of peripheral motor nerves is likely precipitated by changes in mechanisms that protect and/or repair oxidative damage. We predict that interventions that target these mechanisms may protect against age-related decline in peripheral sensorimotor nerve function and likely improve the debilitating outcome of sarcopenia in older humans.

著者人数: 87名, Accepted: 2011-02-08, 資料番号: SA1004099000

The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. Both ER selective agonists significantly increased the mitochondrial respiratory control ratio and cytochrome oxidase (COX) activity relative to vehicle. Western blots of purified whole brain mitochondria detected ERα and, to a greater extent, ERβ localisation. Pre-treatment with DPN, an ERβ agonist, significantly increased ERβ association with mitochondria. In the hippocampus, DPN activated mitochondrial DNA-encoded COX I expression, whereas PPT was ineffective, indicating that mechanistically ERβ, and not ERα, activated mitochondrial transcriptional machinery. Both selective ER agonists increased protein expression of nuclear DNA-encoded COX IV, suggesting that activation of ERβ or ERα is sufficient. Selective ER agonists up-regulated a panel of bioenergetic enzymes and antioxidant defence proteins. Up-regulated proteins included pyruvate dehydrogenase, ATP synthase, manganese superoxide dismutase and peroxiredoxin V. In vitro, whole cell metabolism was assessed in live primary cultured hippocampal neurones and mixed glia. The results of analyses conducted in vitro were consistent with data obtained in vivo. Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERα and ERβ is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails can be tailored to improve brain mitochondrial endpoints.

Fluid shear stress is intimately linked with vascular oxidative stress and atherosclerosis. We posited that atherogenic oscillatory shear stress (OSS) induced mitochondrial superoxide (mtO2•−) production via NADPH oxidase and c-Jun NH2-terminal kinase (JNK-1 and JNK-2) signaling. In bovine aortic endothelial cells, OSS (±3 dyn/cm2) induced JNK activation, which peaked at 1 h, accompanied by an increase in fluorescein isothiocyanate-conjugated JNK fluorescent and MitoSOX Red (specific for mtO2•− production) intensities. Pretreatment with apocynin (NADPH oxidase inhibitor) or N-acetyl cysteine (antioxidant) significantly attenuated OSS-induced JNK activation. Apocynin further reduced OSS-mediated dihydroethidium and MitoSOX Red intensities specific for cytosolic O2•− and mtO2•− production, respectively. As a corollary, transfecting bovine aortic endothelial cells with JNK siRNA (siJNK) and pretreating with SP600125 (JNK inhibitor) significantly attenuated OSS-mediated mtO2•− production. Immunohistochemistry on explants of human coronary arteries further revealed prominent phosphorylated JNK staining in OSS-exposed regions. These findings indicate that OSS induces mtO2•− production via NADPH oxidase and JNK activation relevant for vascular oxidative stress. Antioxid. Redox Signal. 15, 1379–1388.

A 'critical window of opportunity' has been proposed for the efficacy of ovarian hormone intervention in peri- and post-menopausal women. We sought to address this hypothesis using a long-term ovariectomized non-human primate (NHP) model, the cynomolgus macaque (Macaca fascicularis). In these studies, we assessed the ability of 17β-estradiol and equol to regulate markers of hippocampal bioenergetic capacity. Results indicated that 17β-estradiol treatment significantly increased expression of mitochondrial respiratory chain proteins complex-I and -III in the hippocampus when compared to non-hormone-treated animals. Expression of the TCA cycle protein succinate dehydrogenase α was decreased in animals treated with equol compared to those treated with 17β-estradiol. There were no significant effects of either 17β-estradiol or equol treatment on glycolytic protein expression in the hippocampus, nor were there significant effects of treatment on expression levels of antioxidant enzymes. Similarly, 17β-estradiol and equol treatment had no effect on mitochondrial fission and fusion protein expression. In summary, findings indicate that while 17β-estradiol induced a significant increase in several proteins, the overall profile of bioenergetic system proteins was neutral to slightly positively responsive. The profile of responses with the ERβ-preferring molecule equol was consistent with overall nonresponsiveness. Collectively, the data indicate that long-term ovariectomy is associated with a decline in response to estrogens and estrogen-like compounds. By extension, the data are consistent with a primary tenet of the critical window hypothesis, i.e., that the brains of post-menopausal women ultimately lose their ability to respond positively to estrogenic stimulation.

Estrogen therapy can promote cognitive function if initiated within a 'critical window' during the menopausal transition. However, in the absence of a progestogen, estrogens increase endometrial cancer risk which has spurred research into developing estrogenic alternatives that have the beneficial effects of estrogen but which are clinically safer. Soy protein is rich in isoflavones, which are a class of potential estrogenic alternatives. We sought to determine the effects of two diets, one with casein-lactalbumin as the main protein source and the other with soy protein containing isoflavones, on protein markers of hippocampal bioenergetic capacity in adult female cynomolgus macaques (Macaca fascicularis). Further, we assessed the effects of dietary soy isoflavones before or after ovariectomy. Animals receiving soy diet premenopausally then casein/lactalbumin post-ovariectomy had higher relative hippocampal content of glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and pyruvate dehydrogenase subunit e1α. Post-ovariectomy consumption of soy was associated with higher succinate dehydrogenase α levels and lower levels of isocitrate dehydrogenase, both proteins involved in the tricarboxylic acid cycle, significantly decreased expression of the antioxidant enzyme peroxiredoxin-V, and a non-significant trend towards decreased manganese superoxide dismutase expression. None of the diet paradigms significantly affected expression levels of oxidative phosphorylation enzyme complexes, or of mitochondrial fission and fusion proteins. Together, these data suggest that long-term soy diet produces minimal effects on hippocampal expression of proteins involved in bioenergetics, but that switching between a diet containing primarily animal protein and one containing soy isoflavones before and after menopause may result in complex effects on brain chemistry.

Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherogenesis. Superoxide anion (O2(-.)) reacts with nitric oxide (.NO) at a rapid diffusion-limited rate to form peroxynitrite (O2(-.) + .NO-->ONOO(-)). Immunohistostaining of human coronary arterial bifurcations or curvatures, where OSS develops, revealed the presence of nitrotyrosine staining, a fingerprint of peroxynitrite; whereas in straight segments, where PSS occurs, nitrotyrosine was absent. We examined vascular nitrative stress in models of oscillatory (OSS) and pulsatile shear stress (PSS). Bovine aortic endothelial cells (BAEC) were exposed to fluid shear stress that simulates arterial blood flow: (1) PSS at a mean shear stress (tau(ave)) of 23 dyn cm(-2) and a temporal gradient (partial differential(tau)/partial differential(t)) at 71 dyn cm(-2) s(-1), and (2) OSS at tau(ave) = 0.02 dyn cm(- 2) and partial differential(tau)/partial differential(t) = +/- 3.0 dyn cm(-2) s(-1) at a frequency of 1 Hz. OSS significantly up-regulated one of the NADPH oxidase subunits (NOx4) expression accompanied with an increase in O2(-.) production. In contrast, PSS up-regulated eNOS expression accompanied with .NO production (total NO(2)(-) and NO(3)(-)). To demonstrate that O2(-.) and .NO are implicated in ONOO(-) formation, we added low-density lipoprotein cholesterol (LDL) to the medium in which BAEC were exposed to the above flow conditions. The medium was analyzed for LDL apo-B-100 nitrotyrosine by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS). OSS induced higher levels of 3-nitrotyrosine, dityrosine, and o-hydroxyphenylalanine compared with PSS. In the presence of ONOO(-), specific apo-B-100 tyrosine residues underwent nitration in the alpha and beta helices: alpha-1 (Tyr(144)), alpha-2 (Tyr(2524)), beta-2 (Tyr(3295)), alpha-3 (Tyr(4116)), and beta-2 (Tyr(4211)). Hence, the characteristics of shear stress in the arterial bifurcations influenced the relative production of O2(-.) and .NO with an implication for ONOO(-) formation as evidenced by LDL protein nitration.

ABSTRACT miRNAs (miRs), or small approximately 22-nucleotide-long single-stranded noncoding RNA molecules, interact with 3′ untranslated regions of target mRNAs, leading to inhibition of protein production. miR-214 is often dysregulated in various cancers, which governs both tumorigenic and tumor suppressive functions. This review focuses on the current knowledge of miR-214 switching in diverse forms of cancer either by its upregulation or downregulation and sheds light on the mechanism of its tumorigenic and suppressive roles. This article describes known targets and signaling pathways that impact tumorigenesis and tumor suppression and summarizes all information available on circulating levels of miR-214 to address whether miR-214 may function as a potential biomarker and therapy for cancer patients in the future.

Protein oxidation and misfolding have been considered as key players for progression of aging and etiology of various pathological conditions. However, few attempts have been made to develop sensitive and reproducible assays to quantify the changes in protein oxidation and alteration in structure. Here we describe three distinct fluorescence-based assays to quantify changes in protein oxidation, namely carbonylation and disulfides and alteration in protein surface hydrophobicity as a reporter for protein conformation. These techniques will provide investigators the opportunity to address important biological questions in their experimental models.

We use a modified version of MOOG to generate large grids of synthetic spectra in an attempt to derive quantitative abundances for three CVs (GK Per, RU Peg, and SS Cyg) by comparing the models to moderate resolution (R $\sim$ 25,000) $K$-band spectra obtained with NIRSPEC on Keck. For each of the three systems we find solar, or slightly sub-solar values for [Fe/H], but significant deficits of carbon: for SS Cyg we find [C/Fe] = $-$0.50, for RU Peg [C/Fe] = $-$0.75, and for GK Per [C/Fe] = $-$1.00. We show that it is possible to use lower resolution (R $\sim$ 2,000) spectra to quantify carbon deficits. We examine realistic veiling scenarios and find that emission from H I or CO cannot reproduce the observations., Comment: Accepted in the Astronomical Journal

Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated NO production was mitigated by the NO synthase inhibitor N(G)-nitro- l -argenine methyl ester. The rates of O2− production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2− production (n = 4, p donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.

Cancer incidence and/or mortality among individuals varies with diet, socio-culture, ethnicity, race, gender, and age. Similarly, environmental temperature modulates many biological functions. To study the effect of environment temperature on cancer incidence, the US population was selected. Because, county-wise cancer incidence rate data of various anatomical site–specific cancers and different races/ethnicities for both males and females are available. Moreover, the differences amongst the aforementioned factors among individuals are much less, as compared to the world population. Statistical analysis showed a negative correlation between the average annual temperature and cancer incidence rate at all anatomical sites and individually for 13 types (out of 16 types) of anatomical site–specific cancer incidence rates (e.g. uterine, bladder, thyroid, breast, esophagus, ovary, melanoma, non-Hodgkin lymphoma, leukemia, brain, pancreas, etc.) for females. Further analysis found a similar inverse trend in all races/ethnicities of the female population but not in all male races/ethnicities or anatomical site–specific cancers. Moreover, the majority of the counties having the top-most cancer incidence rate in females are located above the latitude 36.5°N. These findings indicate that living in a cold county in the United States might have a higher risk of cancer irrespective of cancer type (except cervical and liver) and races/ethnicities for females but not in all such cases for the male population.

We present a status report and early commissioning results for FLITECAM, the 1-5 micron imager and spectrometer for SOFIA (the Stratospheric Observatory for Infrared Astronomy). In February 2014 we completed six flights with FLITECAM mounted in the FLIPO configuration, a co-mounting of FLITECAM and HIPO (High-speed Imaging Photometer for Occultations; PI Edward W. Dunham, Lowell Observatory). During these flights, the FLITECAM modes from ~1-4 μm were characterized. Since observatory verification flights in 2011, several improvements have been made to the FLITECAM system, including the elimination of a light leak in the FLITECAM filter wheel enclosure, and updates to the observing software. We discuss both the improvements to the FLITECAM system and the results from the commissioning flights, including updated sensitivity measurements. Finally, we discuss the utility of FLITECAM in the FLIPO configuration for targeting exoplanet transits.

Twenty-one randomly selected clones from a turkey (Meleagris gallopavo) pituitary complementary DNA (cDNA) library were sequenced to develop expressed sequence tags (ESTs) for this economically important avian species whose genome is among the least understood. Primers specific for the ESTs were used to produce amplicons from the genomic DNA of turkey, chicken (Gallus gallus), guinea fowl (Numidia meleagris), pigeon (Columba domestica), and quail (Corturnix japonica). The amplicons were sequenced and analyzed for sequence variation within- and similarity among-species and with GenBank database sequences. The proportion of shared bases between the turkey sequence and the consensus sequence from each of the other species ranged from 72% to 93% between turkey and pigeon and quail and between turkey and chicken, respectively. The total number of single nucleotide polymorphisms (SNPs) observed ranged from 3 in quail to 18 in chicken out of 4898 and 5265 bases analyzed, respectively. The most frequent nucleotide variation observed was a C-->T transition. Linkage analysis of one such SNP in the backcross progeny of the East Lansing reference DNA panel, localized TUS0005, the chicken sequence derived from primers specific for turkey TUT2E EST, to chromosome 4. The ESTs reported, as well as the SNPs may provide a useful resource for ongoing efforts to develop high utility genome maps for the turkey and chicken. The primers described can also be used as a tool in future investigations directed at further understanding the biology of the guinea fowl, pigeon and quail and their relatedness to the turkey.

Excess nutrient uptake leads to obesity, insulin resistance, and type 2 diabetes. Mammalian target of the rapamycin (mTOR), a major component of the nutrient-sensing pathway also regulates mitochondrial oxidative function. Rapamycin, a pharmacological inhibitor of mTOR, causes glucose intolerance and inhibits mitochondrial oxidative function. While a number of studies have focused on the effect of rapamycin on control wild-type mice, ours is the first to study the effect of rapamycin on mitochondrial gene expression and insulin sensitivity in the db/db mouse, a model of diabetic dyslipidemia. Female db/+ and db/db mice were fed ad libitum a rapamycin-containing diet or a control diet for 6 months, starting at two months of age. Body weight, fat mass, lean mass and food intake were measured monthly. Effect of rapamycin or control diet on markers of adipogenesis, fatty acid oxidation and mitochondrial biogenesis in the gonadal white adipose tissue (WAT) as well as different serum parameters were assessed. Whole body insulin sensitivity was measured by insulin tolerance test. Rapamycin feeding to db/db mice decreased body weight (58%) and fat mass (33%), elevated markers of fatty acid oxidation and mitochondrial biogenesis in WAT, reduced circulating non-esterified free fatty acids (NEFA), elevated circulating adiponectin and improved insulin sensitivity, compared to control diet fed db/db mice. These data demonstrate that rapamycin exhibits an anti-obesity effect and improves whole body insulin sensitivity in db/db mice and suggest an unexpected effect of simultaneous inhibition mTOR and leptin signaling in mice.

Protein misfolding is considered to be a potential contributing factor for motor neuron and muscle loss in diseases like Amyotrophic lateral sclerosis (ALS). Several independent studies have demonstrated using over-expressed mutated Cu/Zn-superoxide dismutase (mSOD1) transgenic mouse models which mimic familial ALS (f-ALS), that both muscle and motor neurons undergo degeneration during disease progression. However, it is unknown whether protein conformation of skeletal muscle and spinal cord is equally or differentially affected by mSOD1-induced toxicity. It is also unclear whether heat shock proteins (Hsp′s) differentially modulate skeletal muscle and spinal cord protein structure during ALS disease progression. We report three intriguing observations utilizing the f-ALS mouse model and cell-free in vitro system; (i) muscle proteins are equally sensitive to misfolding as spinal cord proteins despite the presence of low level of soluble and absence of insoluble G93A protein aggregate, unlike in spinal cord, (ii) Hsp′s levels are lower in muscle compared to spinal cord at any stage of the disease, and (iii) G93ASOD1 enzyme-induced toxicity selectively affects muscle protein conformation over spinal cord proteins. Together, these findings strongly suggest that differential chaperone levels between skeletal muscle and spinal cord may be a critical determinant for G93A-induced protein misfolding in ALS.

Skeletal muscle atrophy is a debilitating outcome of a number of chronic diseases and conditions associated with loss of muscle innervation by motor neurons, such as aging and neurodegenerative diseases. We previously reported that denervation-induced loss of muscle mass is associated with activation of cytosolic phospholipase A2 (cPLA2), the rate-limiting step for the release of arachidonic acid from membrane phospholipids, which then acts as a substrate for metabolic pathways that generate bioactive lipid mediators. In this study, we asked whether 5- and 12/15-lipoxygenase (LO) lipid metabolic pathways downstream of cPLA2 mediate denervation-induced muscle atrophy in mice. Both 5- and 12/15-LO were activated in response to surgical denervation; however, 12/15-LO activity was increased ~2.5-fold versus an ~1.5-fold increase in activity of 5-LO. Genetic and pharmacological inhibition of 12/15-LO (but not 5-LO) significantly protected against denervation-induced muscle atrophy, suggesting a selective role for the 12/15-LO pathway in neurogenic muscle atrophy. The activation of the 12/15-LO pathway (but not 5-LO) during muscle atrophy increased NADPH oxidase activity, protein ubiquitination, and ubiquitin-proteasome-mediated proteolytic degradation. In conclusion, this study reveals a novel pathway for neurogenic muscle atrophy and suggests that 12/15-LO may be a potential therapeutic target in diseases associated with loss of innervation and muscle atrophy.

The Lunar CRater Observation and Sensing Satellite (LCROSS) mission was designed to search for evidence of water in a permanently shadowed region near the lunar south pole. An instrumented Shepherding Spacecraft followed a kinetic impactor and provided--from a nadir perspective--the only images of the debris plume. With independent observations of the visible debris plume from a more oblique view, the angles and velocities of the ejecta from this unique cratering experiment are better constrained. Here we report the first visible observations of the LCROSS ejecta plume from Earth, thereby ascertaining the morphology of the plume to contain a minimum of two separate components, placing limits on ejecta velocities at multiple angles, and permitting an independent estimate of the illuminated ejecta mass. Our mass estimate implies that the lunar volatile inventory in the Cabeus permanently shadowed region includes a water concentration of 6.3±1.6% by mass.

Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus.

Aging is a complex process that affects every major system at the molecular, cellular and organ levels. Although the exact cause of aging is unknown, there is significant evidence that oxidative stress plays a major role in the aging process. The basis of the oxidative stress hypothesis is that aging occurs as a result of an imbalance between oxidants and antioxidants, which leads to the accrual of damaged proteins, lipids and DNA macromolecules with age. Age-dependent increases in protein oxidation and aggregates, lipofuscin, and DNA mutations contribute to age-related pathologies. Many transgenic/knockout mouse models over expressing or deficient in key antioxidant enzymes have been generated to examine the effect of oxidative stress on aging and age-related diseases. Based on currently reported lifespan studies using mice with altered antioxidant defense, there is little evidence that oxidative stress plays a role in determining lifespan. However, mice deficient in antioxidant enzymes are often more susceptible to age-related disease while mice overexpressing antioxidant enzymes often have an increase in the amount of time spent without disease, i.e., healthspan. Thus, by understanding the mechanisms that affect healthy aging, we may discover potential therapeutic targets to extend human healthspan.

[1] We observed the Lunar Crater Observation and Sensing Satellite (LCROSS) lunar impact on 9 October 2009 using three telescope and instrument combinations in southern New Mexico: the Agile camera with a V filter on the Astrophysical Research Consortium 3.5 m telescope at Apache Point Observatory (APO), a StellaCam video camera with an R filter on the New Mexico State University (NMSU) 1 m telescope at APO, and a Goodrich near-IR (J and H band) video camera on the NMSU 0.6 m telescope at Tortugas Mountain Observatory. The three data sets were analyzed to search for evidence of the debris plume that rose above the Cabeus crater shortly after the LCROSS impact. Although we saw no evidence of the plume in any of our data sets, we constrained its surface brightness through analysis of our photometrically calibrated data. The minimum surface brightness that we could have detected in our Agile data was 9.69 magnitudes arc sec−2, which is 177 times fainter than the brightest part of the foreground ridge of Cabeus. In our near-IR data, our minimum detectable surface brightness was 8.58 magnitudes arc sec−2, which is 370 times fainter than the brightest part of the foreground ridge in the J and H bands. The debris plume was detected by the LCROSS shepherding spacecraft and the Diviner radiometer on the Lunar Reconnaissance Orbiter. Given the plume radiance observed by LCROSS, we cannot distinguish between a conical or cylindrical plume geometry because when seen from Earth, both are below our detection thresholds.

Previously, we demonstrated that reproductive senescence was associated with mitochondrial deficits comparable to those of female triple-transgenic Alzheimer's mice (3xTgAD). Herein, we investigated the impact of chronic ovarian hormone deprivation and 17β-estradiol (E2) replacement on mitochondrial function in nontransgenic (nonTg) and 3xTgAD female mouse brain. Depletion of ovarian hormones by ovariectomy (OVX) in nontransgenic mice significantly decreased brain bioenergetics, and induced mitochondrial dysfunction and oxidative stress. In 3xTgAD mice, OVX significantly exacerbated mitochondrial dysfunction and induced mitochondrial β-amyloid and β-amyloid (Aβ)-binding-alcohol-dehydrogenase (ABAD) expression. Treatment with E2 at OVX prevented OVX-induced mitochondrial deficits, sustained mitochondrial bioenergetic function, decreased oxidative stress, and prevented mitochondrial β-amyloid and ABAD accumulation. In vitro, E2 increased maximal mitochondrial respiration in neurons and basal and maximal respiration in glia. Collectively, these data demonstrate that ovarian hormone loss induced a mitochondrial phenotype comparable to a transgenic female model of Alzheimer's disease (AD), which was prevented by E2. These findings provide a plausible mechanism for increased risk of Alzheimer's disease in premenopausally oophorectomized women while also suggesting a therapeutic strategy for prevention.

We present K-band spectroscopy of short period, "sub-gap" cataclysmic variable (CV) systems obtained using ISAAC on the VLT. We show the infrared spectra (IR) for nine systems below the 2-3 hour period gap: V2051 Oph, V436 Cen, EX Hya, VW Hyi, Z Cha, WX Hyi, V893 Sco, RZ Leo, and TY PsA. We are able to clearly detect the secondary star in all but WX Hyi, V893 Sco, and TY PsA. We present the first direct detection of the secondary stars of V2051 Oph, V436 Cen, and determine new spectral classifications for EX Hya, VW Hyi, Z Cha, and RZ Leo. We find that the CO band strengths of all but Z Cha appear normal for their spectral types, in contrast to their longer period cousins above the period gap. This brings the total number of CVs and pre-CVs with moderate resolution (R >~ 1500) IR spectroscopy to sixty-one systems: nineteen pre-CVs, thirty-one non-magnetic systems, and eleven magnetic or partially magnetic systems. We discuss the trends seen in the IR abundance patterns thus far, and highlight a potential link between anomalous abundances seen in the IR with the C IV/N V anomaly seen in the ultraviolet. We present a compilation of all systems with sufficient resolution IR observations to assess the CO band strengths, and, by proxy, obtain an estimate on the C abundance on the secondary star., 44 pages, 8 figures, 4 tables. Accepted for publication to ApJ

Mitochondrial dysfunction has been proposed to play a pivotal role in neurodegenerative diseases, including Alzheimer's disease (AD). To address whether mitochondrial dysfunction precedes the development of AD pathology, we conducted mitochondrial functional analyses in female triple transgenic Alzheimer's mice (3xTg-AD) and age-matched nontransgenic (nonTg). Mitochondrial dysfunction in the 3xTg-AD brain was evidenced by decreased mitochondrial respiration and decreased pyruvate dehydrogenase (PDH) protein level and activity as early as 3 months of age. 3xTg-AD mice also exhibited increased oxidative stress as manifested by increased hydrogen peroxide production and lipid peroxidation. Mitochondrial amyloid beta (Aβ) level in the 3xTg-AD mice was significantly increased at 9 months and temporally correlated with increased level of Aβ binding to alcohol dehydrogenase (ABAD). Embryonic neurons derived from 3xTg-AD mouse hippocampus exhibited significantly decreased mitochondrial respiration and increased glycolysis. Results of these analyses indicate that compromised mitochondrial function is evident in embryonic hippocampal neurons, continues unabated in females throughout the reproductive period, and is exacerbated during reproductive senescence. In nontransgenic control mice, oxidative stress was coincident with reproductive senescence and accompanied by a significant decline in mitochondrial function. Reproductive senescence in the 3xTg-AD mouse brain markedly exacerbated mitochondrial dysfunction. Collectively, the data indicate significant mitochondrial dysfunction occurs early in AD pathogenesis in a female AD mouse model. Mitochondrial dysfunction provides a plausible mechanistic rationale for the hypometabolism in brain that precedes AD diagnosis and suggests therapeutic targets for prevention of AD.

This study evaluated the effect of ageing on brain mitochondrial function mediated through protein post-translational modifications. Neuronal nitric oxide synthase increased with age and this led to a discreet pattern of nitration of mitochondrial proteins. LC/MS/MS analyses identified the nitrated mitochondrial proteins as succinyl-CoA-transferase and F1-ATPase; the latter was nitrated at Tyr269, suggesting deficient ADP binding to the active site. Activities of succinyl-CoA-transferase, F1-ATPase and cytochrome oxidase decreased with age. The decreased activity of the latter cannot be ascribed to protein modifications and is most likely due to a decreased expression and assembly of complex IV. Mitochondrial protein post-translational modifications were associated with a moderately impaired mitochondrial function, as indicated by the decreased respiratory control ratios as a function of age and by the release of mitochondrial cytochrome c to the cytosol, thus supporting the amplification of apoptotic cascades. Fil: Lam, Philip Y.. University of Southern California; Estados Unidos Fil: Yin, Fei. University of Southern California; Estados Unidos Fil: Hamilton, Ryan T.. University of Southern California; Estados Unidos Fil: Boveris, Alberto Antonio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Cadenas, Enrique. University of Southern California; Estados Unidos

Oxidatively- or enzymatically-modified low-density lipoprotein (LDL) is intimately involved in the initiation and progression of atherosclerosis. The in vivo modified LDL is electro-negative (LDL(-)) and consists of peroxidized lipid and unfolded apoB-100 protein. This study was aimed at establishing specific protein modifications and conformational changes in LDL(-) assessed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) and circular dichroism analyses, respectively. The functional significance of these chemical modifications and structural changes were validated with binding and uptake experiments to- and by bovine aortic endothelial cells (BAEC). The plasma LDL(-) fraction showed increased nitrotyrosine and lipid peroxide content as well as a greater cysteine oxidation as compared with native- and total-LDL. LC/MS/MS analyses of LDL(-) revealed specific modifications in the apoB-100 moiety, largely involving nitration of tyrosines in the alpha-helical structures and beta(2) sheet as well as cysteine oxidation to cysteic acid in beta(1) sheet. Circular dichroism analyses showed that the alpha-helical content of LDL(-) was substantially lower ( approximately 25%) than that of native LDL ( approximately 90%); conversely, LDL(-) showed greater content of beta-sheet and random coil structure, in agreement with unfolding of the protein. These results were mimicked by treatment of LDL subfractions with peroxynitrite (ONOO(-)) or SIN-1: similar amino acid modifications as well as conformational changes (loss of alpha-helical structure and gain in beta-sheet structure) were observed. Both LDL(-) and ONOO(-)-treated LDL showed a statistically significant increase in binding and uptake to- and by BAEC compared to native LDL. We further found that most binding and uptake in control-LDL was through LDL-R with minimal oxLDL-R-dependent uptake. ONOO(-)-treated LDL was significantly bound and endocytosed by LOX-1, CD36, and SR-A with minimal contribution from LDL-R. It is suggested that lipid peroxidation and protein nitration may account for the mechanisms leading to apoB-100 protein unfolding and consequential increase in modified LDL binding and uptake to and by endothelial cells that is dependent on oxLDL scavenger receptors.

The ovarian hormones progesterone and estrogen have well-established neurotrophic and neuroprotective effects supporting both reproductive function and cognitive health. More recently, it has been recognized that these steroids also regulate metabolic functions sustaining the energetic demands of this neuronal activation. Underlying this metabolic control is an interpretation of signals from diverse environmental sources integrated by receptor-mediated responses converging upon mitochondrial function. In this study, to determine the effects of progesterone (P4) and 17β-estradiol (E2) on metabolic control via mitochondrial function, ovariectomized rats were treated with P4, E2, or E2 plus P4, and whole-brain mitochondria were isolated for functional assessment. Brain mitochondria from hormone-treated rats displayed enhanced functional efficiency and increased metabolic rates. The hormone-treated mitochondria exhibited increased respiratory function coupled to increased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). This increased respiratory activity was coupled with a decreased rate of reactive oxygen leak and reduced lipid peroxidation representing a systematic enhancement of brain mitochondrial efficiency. As such, ovarian hormone replacement induces mitochondrial alterations in the central nervous system supporting efficient and balanced bioenergetics reducing oxidative stress and attenuating endogenous oxidative damage.

The prototype nova-like variable VY Sculptoris was observed by the IUE during four different optical brightness states of the system. The FUV flux level from the highest state to the lowest state declines by a factor of 28. We have carried out model accretion disk and white dwarf atmosphere fitting to the spectra. The corresponding accretion rates range from $\dot{M}= 8 \times 10^{-9}$M$_{\sun}$ yr$^{-1}$ at the highest FUV flux level down to $\dot{M}= 1.9\times 10^{-10}$M$_{\sun}$ yr$^{-1}$ at the lowest flux level. We report tentative evidence for the detection of the underlying white dwarf with $T_{\rm eff} = 45,000$K in the spectrum with the lowest flux level., Accepted for publication in the PASP (to appear in February, 2008 issue)