Long term AMPK activation limits obesity induced muscle atrophy

The aim of this study was to identify obesity-induced alterations in regulatory mechanisms of skeletal muscle mass and how they would be altered with long term (8 weeks) AMPK-agonist treatment. 8 week old male, lean (L) wild type [body weight (BW) = 26.9 g] and ob/ob (O) [BW = 46.2 g] mice were fed an AMP kinase (AMPK) activator, beta-GPA (F), mixed at a 1% concentration within their food or normal chow as control (C) for 8 weeks. Following an overnight (12 hr) fast, all mice were sacrificed and the gastrocnemius complex was excised for analysis. Muscle mass was lower in the OC mice (121.08 +/- 9.3 mg) versus LC (158.4 +/- 5.6 mg). This corresponded with decreases in raptor associated with mTOR. Following treatment, western analysis of OF muscle lysates displayed increased AMPK and acetyl-CoA carboxylase phosphorylation compared with LC and OC mice. OC mice displayed higher activation of mammalian Target of Rapamycin (mTOR)-regulated signaling (S6K1, 4E-BP1, and GSK3), which was reciprocally altered after 8 weeks of beta-GPA feeding. These data show that long term (8 week) AMPK-agonist treatment can augment obesity-induced alterations in regulatory mechanisms of skeletal muscle mass through the normalization to lean levels of mTOR signaling

The Apparently Decaying Orbit of WASP-12

We present new transit and occultation times for the hot Jupiter WASP-12b. The data are compatible with a constant period derivative: $\dot{P}=-29 \pm 3$ ms yr$^{-1}$ and $P/\dot{P}= 3.2$ Myr. However, it is difficult to tell whether we have observed orbital decay, or a portion of a 14-year apsidal precession cycle. If interpreted as decay, the star's tidal quality parameter $Q_\star$ is about $2\times 10^5$. If interpreted as precession, the planet's Love number is $0.44\pm 0.10$. Orbital decay appears to be the more parsimonious model: it is favored by $\Delta\chi^2=5.5$ despite having two fewer free parameters than the precession model. The decay model implies that WASP-12 was discovered within the final $\sim$0.2% of its existence, which is an unlikely coincidence but harmonizes with independent evidence that the planet is nearing disruption. Precession does not invoke any temporal coincidence, but does require some mechanism to maintain an eccentricity of $\approx$0.002 in the face of rapid tidal circularization. To distinguish unequivocally between decay and precession will probably require a few more years of monitoring. Particularly helpful will be occultation timing in 2019 and thereafter.Comment: 10 pages [AAS journals, in press, note added in proof

Long‐lived Snell dwarf mice display increased proteostatic mechanisms that are not dependent on decreased mTORC1 activity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111144/1/acel12329.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111144/2/acel12329-sup-0001-SuppInfo.pd

Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle.

Deterioration of neuromuscular junction (NMJ) integrity and function is causal to muscle atrophy and frailty, ultimately hindering quality of life and increasing the risk of death. In particular, NMJ is vulnerable to ischemia reperfusion (IR) injury when blood flow is restricted followed by restoration. However, little is known about the underlying mechanism(s) and hence the lack of effective interventions. New evidence suggests that mitochondrial oxidative stress plays a causal role in IR injury, which can be precluded by enhancing mitochondrial protein S-nitrosation (SNO). To elucidate the role of IR and mitochondrial protein SNO in skeletal muscle, we utilized a clinically relevant model and showed that IR resulted in significant muscle and motor nerve injuries with evidence of elevated muscle creatine kinase in the serum, denervation at NMJ, myofiber degeneration and regeneration, as well as muscle atrophy. Interestingly, we observed that neuromuscular transmission improved prior to muscle recovery, suggesting the importance of the motor nerve in muscle functional recovery. Injection of a mitochondria-targeted S-nitrosation enhancing agent, MitoSNO, into ischemic muscle prior to reperfusion reduced mitochondrial oxidative stress in the motor nerve and NMJ, attenuated denervation at NMJ, and resulted in accelerated functional recovery of the muscle. These findings demonstrate that enhancing mitochondrial protein SNO protects against IR-induced denervation at NMJ in skeletal muscle and accelerates functional regeneration. This could be an efficacious intervention for protecting neuromuscular injury under the condition of IR and other related pathological conditions

Exploring the Optical Transient Sky with the Palomar Transient Factory

The Palomar Transient Factory (PTF) is a wide-field experiment designed to investigate the optical transient and variable sky on time scales from minutes to years. PTF uses the CFH12k mosaic camera, with a field of view of 7.9 deg^2 and a plate scale of 1 asec/pixel, mounted on the the Palomar Observatory 48-inch Samuel Oschin Telescope. The PTF operation strategy is devised to probe the existing gaps in the transient phase space and to search for theoretically predicted, but not yet detected, phenomena, such as fallback supernovae, macronovae, .Ia supernovae and the orphan afterglows of gamma-ray bursts. PTF will also discover many new members of known source classes, from cataclysmic variables in their various avatars to supernovae and active galactic nuclei, and will provide important insights into understanding galactic dynamics (through RR Lyrae stars) and the Solar system (asteroids and near-Earth objects). The lessons that can be learned from PTF will be essential for the preparation of future large synoptic sky surveys like the Large Synoptic Survey Telescope. In this paper we present the scientific motivation for PTF and describe in detail the goals and expectations for this experiment.Comment: 15 pages, 6 figures, submitted to PAS

Mitochondrial plasticity supports proliferative outgrowth and invasion of ovarian cancer spheroids during adhesion

BackgroundOvarian cancer cells aggregate during or after exfoliation from the primary tumor to form threedimensional spheroids. Spheroid formation provides a survival advantage during peritoneal dissemination in nutrient and oxygen-depleted conditions which is accompanied by a suppressed metabolic phenotype and fragmented mitochondria. Upon arrival to their metastatic sites, spheroids adhere to peritoneal organs and transition to a more epithelial phenotype to support outgrowth and invasion. In this study, we investigated the plasticity of mitochondrial morphology, dynamics, and function upon adhesion.MethodsUsing our slow-developing (MOSE-L) and fast-developing (MOSE-LTICv) ovarian cancer models, we mimicked adhesion and reoxygenation conditions by plating the spheroids onto tissue culture dishes and changing culture conditions from hypoxia and low glucose to normoxia with high glucose levels after adhesion. We used Western Blot, microscopy and Seahorse analyses to determine the plasticity of mitochondrial morphology and functions upon adhesion, and the impact on proliferation and invasion capacities.ResultsIndependent of culture conditions, all spheroids adhered to and began to grow onto the culture plates. While the bulk of the spheroid was unresponsive, the mitochondrial morphology in the outgrowing cells was indistinguishable from cells growing in monolayers, indicating that mitochondrial fragmentation in spheroids was indeed reversible. This was accompanied by an increase in regulators of mitobiogenesis, PGC1a, mitochondrial mass, and respiration. Reoxygenation increased migration and invasion in both cell types but only the MOSE-L responded with increased proliferation to reoxygenation. The highly aggressive phenotype of the MOSE-LTICv was characterized by a relative independence of oxygen and the preservation of higher levels of proliferation, migration and invasion even in limiting culture conditions but a higher reliance on mitophagy. Further, the outgrowth in these aggressive cells relies mostly on proliferation while the MOSE-L cells both utilize proliferation and migration to achieve outgrowth. Suppression of proliferation with cycloheximide impeded aggregation, reduced outgrowth and invasion via repression of MMP2 expression and the flattening of the spheroids.DiscussionOur studies indicate that the fragmentation of the mitochondria is reversible upon adhesion. The identification of regulatory signaling molecules and pathways of these key phenotypic alterations that occur during primary adhesion and invasion is critical for the identification of druggable targets for therapeutic intervention to prevent aggressive metastatic disease

TESS Discovery of a Transiting Super-Earth in the π\pi Mensae System

We report the detection of a transiting planet around $\pi$ Mensae (HD 39091), using data from the Transiting Exoplanet Survey Satellite (TESS). The solar-type host star is unusually bright (V=5.7) and was already known to host a Jovian planet on a highly eccentric, 5.7-year orbit. The newly discovered planet has a size of $2.04\pm 0.05$ $R_\oplus$ and an orbital period of 6.27 days. Radial-velocity data from the HARPS and AAT/UCLES archives also displays a 6.27-day periodicity, confirming the existence of the planet and leading to a mass determination of $4.82\pm 0.85$ $M_\oplus$. The star's proximity and brightness will facilitate further investigations, such as atmospheric spectroscopy, asteroseismology, the Rossiter--McLaughlin effect, astrometry, and direct imaging.Comment: Accepted for publication ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase. The discovery light curve is included in a table inside the arxiv submissio

Open science in archaeology

No abstract available

The Science Case for an Extended Spitzer Mission

Although the final observations of the Spitzer Warm Mission are currently scheduled for March 2019, it can continue operations through the end of the decade with no loss of photometric precision. As we will show, there is a strong science case for extending the current Warm Mission to December 2020. Spitzer has already made major impacts in the fields of exoplanets (including microlensing events), characterizing near Earth objects, enhancing our knowledge of nearby stars and brown dwarfs, understanding the properties and structure of our Milky Way galaxy, and deep wide-field extragalactic surveys to study galaxy birth and evolution. By extending Spitzer through 2020, it can continue to make ground-breaking discoveries in those fields, and provide crucial support to the NASA flagship missions JWST and WFIRST, as well as the upcoming TESS mission, and it will complement ground-based observations by LSST and the new large telescopes of the next decade. This scientific program addresses NASA's Science Mission Directive's objectives in astrophysics, which include discovering how the universe works, exploring how it began and evolved, and searching for life on planets around other stars.Comment: 75 pages. See page 3 for Table of Contents and page 4 for Executive Summar