Iron Overload and Diabetes Risk: A Shift From Glucose to Fatty Acid Oxidation and Increased Hepatic Glucose Production in a Mouse Model of Hereditary Hemochromatosis

OBJECTIVE Excess tissue iron levels are a risk factor for diabetes, but the mechanisms underlying the association are incompletely understood. We previously published that mice and humans with a form of hereditary iron overload, hemochromatosis, exhibit loss of beta-cell mass. This effect by itself is not sufficient, however, to fully explain the diabetes risk phenotype associated with all forms of iron overload. RESEARCH DESIGN AND METHODS We therefore examined glucose and fatty acid metabolism and hepatic glucose production in vivo and in vitro in a mouse model of hemochromatosis in which the gene most often mutated in the human disease, HFE, has been deleted (Hfe(-/-)). RESULTS Although Hfe(-/-) mice exhibit increased glucose uptake in skeletal muscle, glucose oxidation is decreased and the ratio of fatty acid to glucose oxidation is increased. On a high-fat diet, the Hfe(-/-) mice exhibit increased fatty acid oxidation and are hypermetabolic. The decreased glucose oxidation in skeletal muscle is due to decreased pyruvate dehydrogenase (PDH) enzyme activity related, in turn, to increased expression of PDH kinase 4 (pdk4). Increased substrate recycling to liver contributes to elevated hepatic glucose production in the Hfe(-/-) mice. CONCLUSIONS Increased hepatic glucose production and metabolic inflexibility, both of which are characteristics of type 2 diabetes, may contribute to the risk of diabetes with excessive tissue iron

The PuZZling Li-Rich Red Giant Associated With NGC 6819

A Li-rich red giant (RG) star (2M19411367+4003382) recently discovered in the direction of NGC 6819 belongs to the rare subset of Li-rich stars that have not yet evolved to the luminosity bump, an evolutionary stage where models predict Li can be replenished. The currently favored model to explain Li enhancement in first-ascent RGs like 2M19411367+4003382 requires deep mixing into the stellar interior. Testing this model requires a measurement of C-12/C-13, which is possible to obtain from Apache Point Observatory Galactic Evolution Experiment (APOGEE) spectra. However, the Li-rich star also has abnormal asteroseismic properties that call into question its membership in the cluster, even though its radial velocity and location on color-magnitude diagrams are consistent with membership. To address these puzzles, we have measured a wide array of abundances in the Li-rich star and three comparison stars using spectra taken as part of the APOGEE survey to determine the degree of stellar mixing, address the question of membership, and measure the surface gravity. We confirm that the Li-rich star is a RG with the same overall chemistry as the other cluster giants. However, its log g is significantly lower, consistent with the asteroseismology results and suggestive of a very low mass if the star is indeed a cluster member. Regardless of the cluster membership, the C-12/C-13 and C/N ratios of the Li-rich star are consistent with standard first dredge-up, indicating that Li dilution has already occurred, and inconsistent with internal Li enrichment scenarios that require deep mixing.National Science Foundation AST1109888NSF AST-1358862, AST 1109718, AST 1312863Alfred P. Sloan FoundationNational Science FoundationU.S. Department of Energy Office of ScienceUniversity of ArizonaBrazilian Participation GroupBrookhaven National LaboratoryCarnegie Mellon UniversityUniversity of FloridaFrench Participation GroupGerman Participation GroupHarvard UniversityInstituto de Astrofisica de CanariasMichigan State/NotreDame/JINA Participation GroupJohns Hopkins UniversityLawrence Berkeley National LaboratoryMax Planck Institute for AstrophysicsMax Planck Institute for Extraterrestrial PhysicsNew Mexico State UniversityNew York UniversityOhio State UniversityPennsylvania State UniversityUniversity of PortsmouthPrinceton UniversitySpanish Participation GroupUniversity of TokyoUniversity of UtahVanderbilt UniversityUniversity of VirginiaUniversity of WashingtonYale UniversityNational Aeronautics and Space AdministrationTwo Micron All Sky SurveyUniversity of MassachusettsInfrared Processing and Analysis Center/California Institute of TechnologyU.S. Government NAG W-2166Astronom

Can variation in standard metabolic rate explain context-dependent performance of farmed Atlantic salmon offspring?

Escaped farmed Atlantic salmon interbreed with wild Atlantic salmon, leaving offspring that often have lower success in nature than pure wild salmon. On top of this, presence of farmed salmon descendants can impair production of wild‐type recruits. We hypothesize that both these effects connect with farmed salmon having acquired higher standard metabolic rates (SMR, the energetic cost of self‐maintenance) during domestication. Fitness‐related advantages of phenotypic traits associated with both high SMR and farmed salmon (e.g., social dominance) depend on environmental conditions, such as food availability. We hypothesize that farmed offspring have an advantage at high food availability due to, for example, dominance behavior but suffer increased risks of starvation when food is scarce because this behavior is energy‐demanding. To test these hypotheses, we first compare embryo SMR of pure farmed, farmed‐wild hybrids and pure wild offspring. Next, we test early‐life performance (in terms of survival and growth) of hybrids relative to that of their wild half‐siblings, as well as their competitive abilities, in semi‐natural conditions of high and low food availability. Finally, we test how SMR affects early‐life performance at high and low food availability. We find inconclusive support for the hypothesis that domestication has induced increased SMR. Further, wild and hybrid juveniles had similar survival and growth in the semi‐natural streams. Yet, the presence of hybrids led to decreased survival of their wild half‐siblings. Contrary to our hypothesis about context‐dependency, these effects were not modified by food availability. However, wild juveniles with high SMR had decreased survival when food was scarce, but there was no such effect at high food availability. This study provides further proof that farmed salmon introgression may compromise the viability of wild salmon populations. We cannot, however, conclude that this is connected to alterations in the metabolic phenotype of farmed salmon

Somatostatin neuron contributions to cortical slow wave dysfunction in adult mice exposed to developmental ethanol

IntroductionTransitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology.MethodsSST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states.ResultsOptical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice.DiscussionTogether, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ

The First Extrasolar Planet Discovered with a New Generation High Throughput Doppler Instrument

We report the detection of the first extrasolar planet, ET-1 (HD 102195b), using the Exoplanet Tracker (ET), a new generation Doppler instrument. The planet orbits HD 102195, a young star with solar metallicity that may be part of the local association. The planet imparts radial velocity variability to the star with a semiamplitude of $63.4\pm2.0$ m s$^{-1}$ and a period of 4.11 days. The planetary minimum mass ($m \sin i$) is $0.488\pm0.015$ $M_J$.Comment: 42 pages, 11 figures and 5 tables, Accepted for publication in Ap

Kepler-730: A hot Jupiter system with a close-in, transiting, Earth-sized planet

Kepler-730 is a planetary system hosting a statistically validated hot Jupiter in a 6.49-day orbit and an additional transiting candidate in a 2.85-day orbit. We use spectroscopic radial velocities from the APOGEE-2N instrument, Robo-AO contrast curves, and Gaia distance estimates to statistically validate the planetary nature of the additional Earth-sized candidate. We perform astrophysical false positive probability calculations for the candidate using the available Kepler data and bolster the statistical validation by using radial velocity data to exclude a family of possible binary star solutions. Using a radius estimate for the primary star derived from stellar models, we compute radii of $1.100^{+0.047}_{-0.050}\ R_{Jup}$ and $0.140\pm0.012\ R_{Jup}$ ($1.57\pm0.13\ R_{\oplus}$) for Kepler-730b and Kepler-730c, respectively. Kepler-730 is only the second compact system hosting a hot Jupiter with an inner, transiting planet.Comment: 13 pages, 2 figures, 3 tables, published in ApJ

Relational Quantum Mechanics

I suggest that the common unease with taking quantum mechanics as a fundamental description of nature (the "measurement problem") could derive from the use of an incorrect notion, as the unease with the Lorentz transformations before Einstein derived from the notion of observer-independent time. I suggest that this incorrect notion is the notion of observer-independent state of a system (or observer-independent values of physical quantities). I reformulate the problem of the "interpretation of quantum mechanics" as the problem of deriving the formalism from a few simple physical postulates. I consider a reformulation of quantum mechanics in terms of information theory. All systems are assumed to be equivalent, there is no observer-observed distinction, and the theory describes only the information that systems have about each other; nevertheless, the theory is complete.Comment: Substantially revised version. LaTeX fil