Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo

AbstractUterine implantation is a critical element of mammalian reproduction and is a tightly and highly coordinated event. An intricate and reciprocal uterine-embryo dialog exists to synchronize uterine receptivity with the concomitant activation of the blastocyst, maximizing implantation success. While a number of pathways involved in regulating uterine receptivity have been identified in the mouse, less is understood about blastocyst activation, the process by which the trophectoderm (TE) receives extrinsic cues that initiate new characteristics essential for implantation. Amino acids (AA) have been found to regulate blastocyst activation and TE motility in vitro. In particular, we find that arginine and leucine alone are necessary and sufficient to induce TE motility. Both arginine and leucine act individually and additively to propagate signals that are dependent on the activity of the mammalian target of rapamycin complex 1 (mTORC1). The activities of the well-established downstream targets of mTORC1, p70S6K and 4EBP, do not correlate with trophoblast motility, suggesting that an independent-rapamycin-sensitive pathway operates to induce trophoblast motility, or that other, parallel amino acid-dependent pathways are also involved. We find that endogenous uterine factors act to induce mTORC1 activation and trophoblast motility at a specific time during pregnancy, and that this uterine signal is later than the previously defined signal that induces the attachment reaction. In vivo matured blastocysts exhibit competence to respond to an 8-hour AA stimulus by activating mTOR and subsequently undergoing trophoblast outgrowth by the morning of day 4.5 of pregnancy, but not on day 3.5. By the late afternoon of day 4.5, the embryos no longer require any exposure to AA to undergo trophoblast outgrowth in vitro, demonstrating the existence and timing of an equivalent in vivo signal. These results suggest that there are two separate uterine signals regulating implantation, one that primes the embryo for the attachment reaction and another that activates mTOR and initiates invasive behavior

The color signature of the transit of HD 209458: Discrepancies between stellar atmospheric models and observations

Exoplanetary transits produce a double-horned color signature that is distinct from both binaries and blends and can thus be used to separate exoplanets from false positives in transit searches. Color photometry with precision sufficient to detect this signal in transits of HD 209458 is available in the literature. Analysis of these observations reveals that, while the signature does exhibit the expected shape, it is significantly stronger than PHOENIX atmospheric models predict.Comment: 4 pages, 3 figures, accepted to A&

The Signal Transducer and Activator of Transcription 1 (STAT1) Inhibits Mitochondrial Biogenesis in Liver and Fatty Acid Oxidation in Adipocytes

The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a master regulator of mitochondrial biogenesis. STAT1 binds to the PGC1α promoter in fed mice but not in fasted animals, suggesting that STAT1 inhibited transcription of PGC1α. Since STAT1-/-mice utilized more lipids we examined white adipose tissue (WAT) stores. Contrary to expectations, fasted STAT1-/- mice did not lose lipid from WAT. β-adrenergic stimulation of glycerol release from isolated STAT1-/- WAT was decreased, while activation of hormone sensitive lipase was not changed. These findings suggest that STAT1-/- adipose tissue does not release glycerol and that free fatty acids (FFA) re-esterify back to triglycerides, thus maintaining fat mass in fasted STAT1-/- mice

Probing the atmosphere of the bulge G5III star OGLE-2002-BUL-069 by analysis of microlense H alpha line

We discuss high-resolution, time-resolved spectra of the caustic exit of the binary microlensing event OGLE 2002-BUL-69 obtained with UVES on the VLT. The source star is a G5III giant in the Galactic Bulge. During such events, the source star is highly magnified, and a strong differential magnification around the caustic resolves its surface. Using an appropriate model stellar atmosphere generated by the NextGEN code we obtained a model light curve for the caustic exit and compared it with a dense set of photometric observations obtained by the PLANET microlensing follow up network. We further compared predicted variations in the H alpha equivalent width with those measured from our spectra. While the model and observations agree in the gross features, there are discrepancies suggesting shortcomings in the model, particularly for the H alpha line core, where we have detected amplified emission from the stellar chromosphere as the source star's trailing limb exited the caustic. This achievement became possible by the provision of the OGLE-III Early Warning System, a network of small telescopes capable of nearly-continuous round-the-clock photometric monitoring, on-line data reduction, daily near-real-time modelling in order to predict caustic crossing parameters, and a fast and efficient response of a 8m-class telescope to a ``Target-Of-Opportunity'' observation request.Comment: 4 pages Latex, 3 figures, accepted for publication to astronomy and astrophysics letter

Limb-darkening measurements for a cool red giant in microlensing event OGLE 2004-BLG-482

Aims: We present a detailed analysis of OGLE 2004-BLG-482, a relatively high-magnification single-lens microlensing event which exhibits clear extended-source effects. These events are relatively rare, but they potentially contain unique information on the stellar atmosphere properties of their source star, as shown in this study. Methods: Our dense photometric coverage of the overall light curve and a proper microlensing modelling allow us to derive measurements of the OGLE 2004-BLG-482 source star's linear limb-darkening coefficients in three bands, including standard Johnson-Cousins I and R, as well as in a broad clear filter. In particular, we discuss in detail the problems of multi-band and multi-site modelling on the expected precision of our results. We also obtained high-resolution UVES spectra as part of a ToO programme at ESO VLT from which we derive the source star's precise fundamental parameters. Results: From the high-resolution UVES spectra, we find that OGLE 2004-BLG-482's source star is a red giant of MK type a bit later than M3, with Teff = 3667 +/- 150 K, log g = 2.1 +/- 1.0 and an assumed solar metallicity. This is confirmed by an OGLE calibrated colour-magnitude diagram. We then obtain from a detailed microlensing modelling of the light curve linear limb-darkening coefficients that we compare to model-atmosphere predictions available in the literature, and find a very good agreement for the I and R bands. In addition, we perform a similar analysis using an alternative description of limb darkening based on a principal component analysis of ATLAS limb-darkening profiles, and also find a very good agreement between measurements and model predictions.Comment: Accepted in A&

Resolving Stellar Atmospheres I: The H alpha line and comparisons to microlensing observations

We present work on H alpha spectral line characteristics in PHOENIX stellar model atmospheres and their comparison to microlensing observations. We examine in detail the H alpha equivalent width (EW) and the line shape characteristics for effective temperatures of 4500K< Teff < 5600K where H alpha is a strong spectral feature. We find that H alpha EW in models calculated under the assumption of local thermodynamic equilibrium (LTE) is up to 15% smaller than in models without this assumption, non-LTE models (NLTE) and that line shapes vary significantly for the two model types. A comparison with available high quality microlensing data, capable of tracing H alpha absorption across the face of one G5III giant, shows that the LTE model that fits the EW best is about 100K hotter than and the best-fitting NLTE model has a similar Teff as predicted by the spectral type analysis of the observed star but agree within the uncertainties of the observationally derived temperature. Neither LTE nor NLTE models fit the line shape well. We suspect unmodelled chromospheric emission. Line shape diagnostics suggest lower gravities than derived for the star and are unacceptable low in the case of the LTE models. We show that EW alone is insufficient for comparison to stellar model atmospheres, but combined with a new shape parameter we define is promising. In stellar parameter ranges where the H alpha line is strong, a NLTE approach of modeling stellar atmospheres is not only beneficial but mandatory.Comment: 11 pages, 9 figures, accepted to Astronomy & Astrophysic