Alterations in insulin action and contraction-mediated metabolism in myotubes derived from Roux-en-Y gastric bypass patients

Roux-en-Y gastric bypass (RYGB) surgery induces various metabolic benefits in severely obese (BMI> 40 kg/m2) individuals, including improved insulin action in peripheral tissues, most notably skeletal muscle, and remission of type 2 diabetes. Despite these improvements, the mechanism in which RYGB improves metabolism is unclear. To examine this, primary human skeletal muscle cells were isolated from muscle biopsies obtained from individuals prior to, 1-month, and 7-months following RYGB. Insulin-stimulated glycogen synthesis, an index of insulin action, improved in myotubes derived from subjects at 1-month following RYGB, which was sustained at 7-months post-surgery. The cellular mechanisms involved appear to consist of distinct acute and chronic components, with the acute response consisting of reduced muscle glycogen content and increased phosphorylation of ACC, and the chronic response associated with a physiological increase in PGC1[alpha] protein abundance. To further examine the combined role of RYGB surgery and muscle contraction on skeletal muscle metabolism, fully differentiated myotubes from RYGB patients were electrically stimulated to contract for 24-hours. Prior to surgery, myotubes were unresponsive to the benefits of muscle contraction to subsequently increase insulin action, suggesting exercise resistance in these cells. However, only 1-month following RYGB surgery, myotubes became responsive to muscle contraction, as indicated by enhanced insulin-stimulated glycogen synthesis and AS160 phosphorylation, as well as increased basal glucose oxidation. To explore whether the improvements in insulin action were due to an improved ability of cells to switch fuel preference, we examined in vitro metabolic flexibility in cells derived from RYGB patients. Utilizing several methods to examine in vitro metabolic flexibility, we were unable to detect major differences amongst the groups, suggesting that alterations in metabolic flexibility at the whole-body level following RYGB surgery are not retained in primary myotubes. The results from this study suggest RYGB surgery alters the inherent characteristics of skeletal muscle that invoke improved insulin action and exercise-responsiveness. While previous research suggest insulin action in skeletal muscle is improved once substantial weight loss is achieved, we show that, when utilizing a muscle-specific model, improvements in insulin action occur as early as 1-month following RYGB surgery. Furthermore, it appears that acute adaptations in skeletal muscle following RYGB surgery invoke a cellular environment that is more responsive to the additional benefits of muscle contraction. Collectively, the results of this study provide valuable mechanisms in which RYGB surgery and muscle contraction can improve insulin action in skeletal muscle

The Sensitivity of US Wildfire Occurrence to Pre-Season Soil Moisture Conditions Across Ecosystems

It is generally accepted that year-to-year variability in moisture conditions and drought are linked with increased wildfire occurrence. However, quantifying the sensitivity of wildfire to surface moisture state at seasonal lead-times has been challenging due to the absence of a long soil moisture record with the appropriate coverage and spatial resolution for continental-scale analysis. Here we apply model simulations of surface soil moisture that numerically assimilate observations from NASA's Gravity Recovery and Climate Experiment (GRACE) mission with the US Forest Service"TM"s historical Fire-Occurrence Database over the contiguous United States. We quantify the relationships between pre-fire-season soil moisture and subsequent-year wildfire occurrence by land-cover type and produce annual probable wildfire occurrence and burned area maps at 0.25-degree resolution. Cross-validated results generally indicate a higher occurrence of smaller fires when months preceding fire season are wet, while larger fires are more frequent when soils are dry. This result is consistent with the concept of increased fuel accumulation under wet conditions in the pre-season. These results demonstrate the fundamental strength of the relationship between soil moisture and fire activity at long lead-times and are indicative of that relationship's utility for the future development of national-scale predictive capability

Roux-en-Y Gastric Bypass Surgery Regulates Mitochondrial Dynamics Proteins in Primary Human Myotubes Derived from Severely Obese Humans

Mitochondrial dynamics including mitochondrial fission (e.g., Dynamin-related protein 1 (Drp1) and Fission 1 (Fis1)) and fusion (e.g., Mitofusin 2 (MFN 2)) regulates mitochondrial homeostasis. Defects in mitochondrial dynamics are suggested to contribute to skeletal muscle mitochondrial dysfunction and insulin resistance associated with severe obesity. Roux-en-Y gastric bypass (RYGB) surgery markedly improves metabolic health as indicated by enhanced substrate oxidation and insulin action in skeletal muscle. However, the underlying cellular mechanisms responsible for these are unclear and could possibly be due to the improvement of mitochondrial dynamics. PURPOSE: The purpose of this study was to determine whether RYGB surgery improves mitochondria dynamics proteins in primary human myotubes from severely obese humans. METHODS: Primary skeletal muscle cells were isolated from muscle biopsies obtained from six lean subjects (BMI = 23.4 ± 0.6 kg/m2) and six RYGB patients prior to, 1-month and 7-months after surgery (BMI = 50.2 ± 2.0, 43.2 ± 2.8 and 35.7 ± 2.2 kg/m2, respectively) and were differentiated to myotubes. On day 7 of differentiation, myotubes were harvested for further assessing the expressions of mitochondria dynamics proteins. RESULTS: Before surgery, Drp1Ser616 phosphorylation and Fis1 expression were significantly higher in myotubes derived from severely obese patients when compared to lean controls (41% and 26%, respectively, P \u3c 0.05). While there were no improvements at 1-month post-surgery, Drp1Ser616 phosphorylation and Fis1 expression were significantly decreased in myotubes from severely obese humans at 7-months post-surgery (Pre vs. 7-months post: 0.046 ± 0.004 vs. 0.035 ± 0.003; 0.023 ± 0.008 vs. 0.014 ± 0.003 AU; respectively, P \u3c 0.05), and not statistically different from lean controls. However, MFN2 expression did not change post-surgery in comparison to pre-surgery. CONCLUSION: These data suggest that RYGB surgery reduces obesity-induced rise in mitochondrial fission, but not fusion in primary human myotubes derived from severely obese humans

The Sensitivity of US Wildfire Occurrence to Pre-Season Soil Moisture Conditions Across Ecosystems

It is well accepted that drought and low moisture conditions are linked with increased wildfire occurrence. However, quantifying the sensitivity of wildfire to surface moisture state has been challenging due to a lack of soil moisture observations at an appropriate spatial scale. Here we apply model simulations of surface soil moisture that numerically assimilate observations from NASAs Gravity Recovery and Climate Experiment (GRACE) mission, combined in a predictive algorithm with the US Forest Services Fire-Occurrence Database. We estimate a relationship between historic surface moisture and wildfire occurrence to produce annual probable wildfire occurrence and burned area at 0.25-degree resolution for the contiguous United States by land-cover classification. Cross-validation indicates increased frequency of smaller fires when the months preceding fire season are wet, while larger fires are more frequent when soils are dry. This demonstrates that assimilated GRACE data holds information that could aid national-scale fire potential assessments for early decision-support

Mitochondria as a Target for Mitigating Sarcopenia

Sarcopenia is the loss of muscle mass, strength, and physical function that is characteristic of aging. The progression of sarcopenia is gradual but may be accelerated by periods of muscle loss during physical inactivity secondary to illness or injury. The loss of mobility and independence and increased comorbidities associated with sarcopenia represent a major healthcare challenge for older adults. Mitochondrial dysfunction and impaired proteostatic mechanisms are important contributors to the complex etiology of sarcopenia. As such, interventions that target improving mitochondrial function and proteostatic maintenance could mitigate or treat sarcopenia. Exercise is currently the only effective option to treat sarcopenia and does so, in part, by improving mitochondrial energetics and protein turnover. Exercise interventions also serve as a discovery tool to identify molecular targets for development of alternative therapies to treat sarcopenia. In summary, we review the evidence linking mitochondria and proteostatic maintenance to sarcopenia and discuss the therapeutic potential of interventions addressing these two factors to mitigate sarcopenia

A multi-instrument and multi-wavelength high angular resolution study of MWC614: quantum heated particles inside the disk cavity

High angular resolution observations of young stellar objects are required to study the inner astronomical units of protoplanetary disks in which the majority of planets form. As they evolve, gaps open up in the inner disk regions and the disks are fully dispersed within ~10 Myrs. MWC 614 is a pre-transitional object with a ~10au radius gap. We present a set of high angular resolution observations of this object including SPHERE/ZIMPOL polarimetric and coronagraphic images in the visible, KECK/NIRC2 near-infrared aperture masking observations and VLTI (AMBER, MIDI, and PIONIER) and CHARA (CLASSIC and CLIMB) long-baseline interferometry at infrared wavelengths. We find that all the observations are compatible with an inclined disk (i ~55deg at a position angle of ~20-30deg). The mid-infrared dataset confirms the disk inner rim to be at 12.3+/-0.4 au from the central star. We determined an upper mass limit of 0.34 Msun for a companion inside the cavity. Within the cavity, the near-infrared emission, usually associated with the dust sublimation region, is unusually extended (~10 au, 30 times larger than the theoretical sublimation radius) and indicates a high dust temperature (T~1800 K). As a possible result of companion-induced dust segregation, quantum heated dust grains could explain the extended near-infrared emission with this high temperature. Our observations confirm the peculiar state of this object where the inner disk has already been accreted onto the star exposing small particles inside the cavity to direct stellar radiation.Comment: 24 pages. Published in Ap

Distinct Adaptations of Mitochondrial Dynamics to Electrical Pulse Stimulation in Lean and Severely Obese Primary Myotubes

BACKGROUND: Skeletal muscle from lean and obese subjects elicit differential adaptations in response to exercise/muscle contractions. In order to determine whether obesity alters the adaptations in mitochondrial dynamics in response to exercise/muscle contractions and whether any of these distinct adaptations are linked to alterations in insulin sensitivity, we compared the effects of electrical pulse stimulation (EPS) on mitochondrial network structure and regulatory proteins in mitochondrial dynamics in myotubes from lean humans and humans with severe obesity and evaluated the correlations between these regulatory proteins and insulin signaling. METHODS: Myotubes from human skeletal muscle cells obtained from lean humans (BMI 23.8 ± 1.67 kg/m(2)) and humans with severer obesity (45.5 ± 2.26 kg/m(2)) (n=8/group) were electrically stimulated for 24 hours. Four-hours after EPS, mitochondrial network structure, protein markers of insulin signaling and mitochondrial dynamics were assessed. RESULTS: EPS enhanced insulin-stimulated Akt(Ser473) phosphorylation, reduced the number of non-networked individual mitochondria and increased the mitochondrial network size in both groups (P<0.05). Mitochondrial fusion marker mitofusin 2 was significantly increased in myotubes from the lean subjects (P<0.05), but reduced in subjects with severe obesity (P<0.05). In contrast, fission marker dynamin-related protein 1 (Drp1(Ser616)) was reduced in myotubes from subjects with severe obesity (P<0.05), but remained unchanged in lean subjects. Reductions in Drp(Ser616) phosphorylation were correlated with improvements in insulin-stimulated Akt(Ser473) phosphorylation following EPS (r = −0.679, P = 0.004). CONCLUSION: Our data demonstrated that EPS induces more fused mitochondrial networks, which are associated with differential adaptations in mitochondrial dynamic processes in myotubes from lean humans and human with severe obesity. It also suggests that improved insulin signaling following muscle contractions may be linked to the reduction in Drp1 activity

KELT-6b: A P~7.9 d Hot Saturn Transiting a Metal-Poor Star with a Long-Period Companion

We report the discovery of KELT-6b, a mildly-inflated Saturn-mass planet transiting a metal-poor host. The initial transit signal was identified in KELT-North survey data, and the planetary nature of the occulter was established using a combination of follow-up photometry, high-resolution imaging, high-resolution spectroscopy, and precise radial velocity measurements. The fiducial model from a global analysis including constraints from isochrones indicates that the V=10.38 host star (BD+31 2447) is a mildly evolved, late-F star with T_eff=6102 \pm 43 K, log(g_*)=4.07_{-0.07}^{+0.04} and [Fe/H]=-0.28 \pm 0.04, with an inferred mass M_*=1.09 \pm 0.04 M_sun and radius R_star=1.58_{-0.09}^{+0.16} R_sun. The planetary companion has mass M_P=0.43 \pm 0.05 M_J, radius R_P=1.19_{-0.08}^{+0.13} R_J, surface gravity log(g_P)=2.86_{-0.08}^{+0.06}, and density rho_P=0.31_{-0.08}^{+0.07} g~cm^{-3}. The planet is on an orbit with semimajor axis a=0.079 \pm 0.001 AU and eccentricity e=0.22_{-0.10}^{+0.12}, which is roughly consistent with circular, and has ephemeris of T_c(BJD_TDB)=2456347.79679 \pm 0.00036 and P=7.845631 \pm 0.000046 d. Equally plausible fits that employ empirical constraints on the host star parameters rather than isochrones yield a larger planet mass and radius by ~4-7%. KELT-6b has surface gravity and incident flux similar to HD209458b, but orbits a host that is more metal poor than HD209458 by ~0.3 dex. Thus, the KELT-6 system offers an opportunity to perform a comparative measurement of two similar planets in similar environments around stars of very different metallicities. The precise radial velocity data also reveal an acceleration indicative of a longer-period third body in the system, although the companion is not detected in Keck adaptive optics images.Comment: Published in AJ, 17 pages, 15 figures, 6 table

First Light LBT AO Images of HR 8799 bcde at 1.65 and 3.3 Microns: New Discrepancies between Young Planets and Old Brown Dwarfs

As the only directly imaged multiple planet system, HR 8799 provides a unique opportunity to study the physical properties of several planets in parallel. In this paper, we image all four of the HR 8799 planets at H-band and 3.3 microns with the new LBT adaptive optics system, PISCES, and LBTI/LMIRCam. Our images offer an unprecedented view of the system, allowing us to obtain H and 3.3$ micron photometry of the innermost planet (for the first time) and put strong upper-limits on the presence of a hypothetical fifth companion. We find that all four planets are unexpectedly bright at 3.3 microns compared to the equilibrium chemistry models used for field brown dwarfs, which predict that planets should be faint at 3.3 microns due to CH4 opacity. We attempt to model the planets with thick-cloudy, non-equilibrium chemistry atmospheres, but find that removing CH4 to fit the 3.3 micron photometry increases the predicted L' (3.8 microns) flux enough that it is inconsistent with observations. In an effort to fit the SED of the HR 8799 planets, we construct mixtures of cloudy atmospheres, which are intended to represent planets covered by clouds of varying opacity. In this scenario, regions with low opacity look hot and bright, while regions with high opacity look faint, similar to the patchy cloud structures on Jupiter and L/T transition brown-dwarfs. Our mixed cloud models reproduce all of the available data, but self-consistent models are still necessary to demonstrate their viability.Comment: Accepted to Ap