Erythropoietin production by fetal mouse liver cells in response to hypoxia and adenylate cyclase stimulation

This study was done to investigate aspects of control of extrarenal erythropoietin (Ep) production. To this end we studied the effects of three stimuli of renal Ep production in the adult, i.e. hypoxia, cobalt, and activation of adenylate cyclase on Ep generation by cultured fetal mouse liver cells. The fetal liver was taken as a model for extrarenal Ep production because this organ is considered the predominant site of extrarenal Ep production. We found that Ep production by the cells increased as the oxygen concentration was decreased in the incubation atmosphere from 20% to 1%. Cobalt (10(-4)-10(-5) M) had no effect on Ep production. Activation of adenylate cyclase by forskolin (10(-5) M) or isoproterenol (10(-5) M) greatly enhanced Ep production. These findings indicate that the Ep-stimulating effect of cobalt is specific for the kidney. However, oxygen depletion and activation of adenylate cyclase seem to be more general stimuli in Ep-producing cells. Furthermore we found that Ep production in hypoxia correlated with lactate formation in the cultured liver cells. This finding suggests that Ep production in fetal livers under hypoxic conditions parallels the shift from aerobic to anaerobic cellular energy metabolism

Hydrodynamical simulations of a compact source scenario for G2

The origin of the dense gas cloud G2 discovered in the Galactic Center (Gillessen et al. 2012) is still a debated puzzle. G2 might be a diffuse cloud or the result of an outflow from an invisible star embedded in it. We present here detailed simulations of the evolution of winds on G2's orbit. We find that the hydrodynamic interaction with the hot atmosphere present in the Galactic Center and the extreme gravitational field of the supermassive black hole must be taken in account when modeling such a source scenario. We find that the hydrodynamic interaction with the hot atmosphere present in the Galactic Center and the extreme gravitational field of the supermassive black hole must be taken in account when modeling such a source scenario. We also find that in this scenario most of the Br\gamma\ luminosity is expected to come from the highly filamentary densest shocked wind material. G2's observational properties can be used to constrain the properties of the outflow and our best model has a mass outflow rate of Mdot,w=8.8 x 10^{-8} Msun/yr and a wind velocity of vw = 50 km/s. These values are compatible with those of a young TTauri star wind, as already suggested by Scoville & Burkert (2013).Comment: 4 pages, 3 figures; Proceeding of the IAU 303: "The GC: Feeding and Feedback in a Normal Galactic Nucleus" / September 30 - October 4, 2013, Santa Fe, New Mexico (USA

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3D AMR hydrosimulations of a compact source scenario for the Galactic Centre cloud G2

The nature of the gaseous and dusty cloud G2 in the Galactic Centre is still under debate. We present three-dimensional hydrodynamical adaptive mesh refinement (AMR) simulations of G2, modeled as an outflow from a "compact source" moving on the observed orbit. The construction of mock position-velocity (PV) diagrams enables a direct comparison with observations and allow us to conclude that the observational properties of the gaseous component of G2 could be matched by a massive ($\dot{M}_\mathrm{w}=5\times 10^{-7} \;M_{\odot} \mathrm{yr^{-1}}$) and slow ($50 \;\mathrm{km \;s^{-1}}$) outflow, as observed for T Tauri stars. In order for this to be true, only the material at larger ($>100 \;\mathrm{AU}$) distances from the source must be actually emitting, otherwise G2 would appear too compact compared to the observed PV diagrams. On the other hand, the presence of a central dusty source might be able to explain the compactness of G2's dust component. In the present scenario, 5-10 years after pericentre the compact source should decouple from the previously ejected material, due to the hydrodynamic interaction of the latter with the surrounding hot and dense atmosphere. In this case, a new outflow should form, ahead of the previous one, which would be the smoking gun evidence for an outflow scenario.Comment: resubmitted to MNRAS after referee report, 16 pages, 11 figure

Infrared interferometry to spatially and spectrally resolve jets in X-ray binaries

Infrared interferometry is a new frontier for precision ground based observing, with new instrumentation achieving milliarcsecond (mas) spatial resolutions for faint sources, along with astrometry on the order of 10 microarcseconds. This technique has already led to breakthroughs in the observations of the supermassive black hole at the Galactic centre and its orbiting stars, AGN, and exo-planets, and can be employed for studying X-ray binaries (XRBs), microquasars in particular. Beyond constraining the orbital parameters of the system using the centroid wobble and spatially resolving jet discrete ejections on mas scales, we also propose a novel method to discern between the various components contributing to the infrared bands: accretion disk, jets and companion star. We demonstrate that the GRAVITY instrument on the Very Large Telescope Interferometer (VLTI) should be able to detect a centroid shift in a number of sources, opening a new avenue of exploration for the myriad of transients expected to be discovered in the coming decade of radio all-sky surveys. We also present the first proof-of-concept GRAVITY observation of a low-mass X-ray binary transient, MAXI J1820+070, to search for extended jets on mas scales. We place the tightest constraints yet via direct imaging on the size of the infrared emitting region of the compact jet in a hard state XRB.Comment: 12 Pages, 3 figures, accepted for publication in MNRA

On the Ca2 + binding and conformational change in EF-hand domains: Experimental evidence of Ca2 +-saturated intermediates of N-domain of calmodulin

Double mutation of Q41L and K75I in the N-domain of calmodulin (N-Cam) stabilizes the closed form of N-Cam such that binding of Ca2 + in solution no longer triggers a conformational change to the open form, and its Ca2 + binding affinity decreases dramatically. To further investigate the solvation effects on the structure, Ca2 + binding affinity and conformational dynamics of this N-Cam double mutant in the Ca2 + saturated state, we solved its X-ray structure. Surprisingly, the structure revealed an open conformation of the domain which contradicts its closed conformation in solution. Here we provide evidence that crystallization conditions were responsible for this Ca2 +-saturated domain open conformation in the crystal. Importantly, we demonstrate that the presence of the crystallization co-precipitant and alcohols were able to induce a progressive opening of the closed form of this domain, in Ca2 + saturated state, in solution. However, in the Ca2 + depleted state, addition of alcohols was unable to induce any opening of this domain in solution. In addition, in the Ca2 + saturated state, the molecular dynamics simulations show that while N-Cam can populate the open and closed conformation, the N-Cam double mutant exclusively populates the closed conformation. Our results provide experimental evidence of intermediate conformations of Ca2 +-saturated N-Cam in solution. We propose that conformational change of Ca2 + sensor EF-hand domains depends on solvation energetics, Ca2 + binding to promote the full open form, Ca2 + depleted state conformational dynamics, and the chemical properties of the molecules nearby key residues such as those at positions 41 and 75 in N-Cam

The interferometric baselines and GRAVITY astrometric error budget

GRAVITY is a new generation beam combination instrument for the VLTI. Its goal is to achieve microarsecond astrometric accuracy between objects separated by a few arcsec. This $10^6$ accuracy on astrometric measurements is the most important challenge of the instrument, and careful error budget have been paramount during the technical design of the instrument. In this poster, we will focus on baselines induced errors, which is part of a larger error budget.Comment: SPIE Meeting 2014 -- Montrea

The Post-Pericenter Evolution of the Galactic Center Source G2

In early 2014 the fast-moving near-infrared source G2 reached its closest approach to the supermassive black hole Sgr A* in the Galactic Center. We report on the evolution of the ionized gaseous component and the dusty component of G2 immediately after this event, revealed by new observations obtained in 2015 and 2016 with the SINFONI integral field spectrograph and the NACO imager at the ESO VLT. The spatially resolved dynamics of the Br$\gamma$ line emission can be accounted for by the ballistic motion and tidal shearing of a test-particle cloud that has followed a highly eccentric Keplerian orbit around the black hole for the last 12 years. The non-detection of a drag force or any strong hydrodynamic interaction with the hot gas in the inner accretion zone limits the ambient density to less than a few 10$^3$ cm$^{-3}$ at the distance of closest approach (1500 $R_s$), assuming G2 is a spherical cloud moving through a stationary and homogeneous atmosphere. The dust continuum emission is unresolved in L'-band, but stays consistent with the location of the Br$\gamma$ emission. The total luminosity of the Br$\gamma$ and L' emission has remained constant to within the measurement uncertainty. The nature and origin of G2 are likely related to that of the precursor source G1, since their orbital evolution is similar, though not identical. Both object are also likely related to a trailing tail structure, which is continuously connected to G2 over a large range in position and radial velocity.Comment: 17 pages, 12 figures; accepted for publication in Ap

GRAVITY: the Calibration Unit

We present in this paper the design and characterisation of a new sub-system of the VLTI 2nd generation instrument GRAVITY: the Calibration Unit. The Calibration Unit provides all functions to test and calibrate the beam combiner instrument: it creates two artificial stars on four beams, and dispose of four delay lines with an internal metrology. It also includes artificial stars for the tip-tilt and pupil guiding systems, as well as four metrology pick-up diodes, for tests and calibration of the corresponding sub-systems. The calibration unit also hosts the reference targets to align GRAVITY to the VLTI, and the safety shutters to avoid the metrology light to propagate in the VLTI-lab. We present the results of the characterisation and validtion of these differrent sub-units.Comment: 12 pages, 11 figures. Proceeding of SPIE 9146 "Optical and Infrared Interferometry IV