Plasmodium falciparum glutamate dehydrogenase a is dispensable and not a drug target during erythrocytic development

<p>Background: Plasmodium falciparum contains three genes encoding potential glutamate dehydrogenases. The protein encoded by gdha has previously been biochemically and structurally characterized. It was suggested that it is important for the supply of reducing equivalents during intra-erythrocytic development of Plasmodium and, therefore, a suitable drug target.</p> <p>Methods: The gene encoding the NADP(H)-dependent GDHa has been disrupted by reverse genetics in P. falciparum and the effect on the antioxidant and metabolic capacities of the resulting mutant parasites was investigated.</p> <p>Results: No growth defect under low and elevated oxygen tension, no up-or down-regulation of a number of antioxidant and NADP(H)-generating proteins or mRNAs and no increased levels of GSH were detected in the D10(Delta gdha) parasite lines. Further, the fate of the carbon skeleton of [(13)C] labelled glutamine was assessed by metabolomic studies, revealing no differences in the labelling of a-ketoglutarate and other TCA pathway intermediates between wild type and mutant parasites.</p> <p>Conclusions: First, the data support the conclusion that D10(Delta gdha) parasites are not experiencing enhanced oxidative stress and that GDHa function may not be the provision of NADP(H) for reductive reactions. Second, the results imply that the cytosolic, NADP(H)-dependent GDHa protein is not involved in the oxidative deamination of glutamate but that the protein may play a role in ammonia assimilation as has been described for other NADP(H)dependent GDH from plants and fungi. The lack of an obvious phenotype in the absence of GDHa may point to a regulatory role of the protein providing glutamate (as nitrogen storage molecule) in situations where the parasites experience a limiting supply of carbon sources and, therefore, under in vitro conditions the enzyme is unlikely to be of significant importance. The data imply that the protein is not a suitable target for future drug development against intra-erythrocytic parasite development.</p&gt

NGC 1866: First Spectroscopic Detection of Fast Rotating Stars in a Young LMC Cluster

High-resolution spectroscopic observations were taken of 29 extended main sequence turn-off (eMSTO) stars in the young ($\sim$200 Myr) LMC cluster, NGC 1866 using the Michigan/Magellan Fiber System and MSpec spectrograph on the Magellan-Clay 6.5-m telescope. These spectra reveal the first direct detection of rapidly rotating stars whose presence has only been inferred from photometric studies. The eMSTO stars exhibit H-alpha emission (indicative of Be-star decretion disks), others have shallow broad H-alpha absorption (consistent with rotation $\gtrsim$150 km s$^{-1}$), or deep H-alpha core absorption signaling lower rotation velocities ($\lesssim$150 km s$^{-1}$ ). The spectra appear consistent with two populations of stars - one rapidly rotating, and the other, younger and slowly rotating.Comment: 9 pages, 4 figures, Accepted for publication in ApJ Letter

A Chemical Composition Survey of the Iron-Complex Globular Cluster NGC 6273 (M 19)

Recent observations have shown that a growing number of the most massive Galactic globular clusters contain multiple populations of stars with different [Fe/H] and neutron-capture element abundances. NGC 6273 has only recently been recognized as a member of this "iron-complex" cluster class, and we provide here a chemical and kinematic analysis of > 300 red giant branch (RGB) and asymptotic giant branch (AGB) member stars using high resolution spectra obtained with the Magellan-M2FS and VLT-FLAMES instruments. Multiple lines of evidence indicate that NGC 6273 possesses an intrinsic metallicity spread that ranges from about [Fe/H] = -2 to -1 dex, and may include at least three populations with different [Fe/H] values. The three populations identified here contain separate first (Na/Al-poor) and second (Na/Al-rich) generation stars, but a Mg-Al anti-correlation may only be present in stars with [Fe/H] > -1.65. The strong correlation between [La/Eu] and [Fe/H] suggests that the s-process must have dominated the heavy element enrichment at higher metallicities. A small group of stars with low [alpha/Fe] is identified and may have been accreted from a former surrounding field star population. The cluster's large abundance variations are coupled with a complex, extended, and multimodal blue horizontal branch (HB). The HB morphology and chemical abundances suggest that NGC 6273 may have an origin that is similar to omega Cen and M 54.Comment: Accepted for Publication in The Astrophysical Journal; 50 pages; 18 figures; 8 tables; higher resolution figures are available upon request or in the published journal articl

Exploring the Chemical Composition and Double Horizontal Branch of the Bulge Globular Cluster NGC 6569

Photometric and spectroscopic analyses have shown that the Galactic bulge cluster Terzan 5 hosts several populations with different metallicities and ages that manifest as a double red horizontal branch (HB). A recent investigation of the massive bulge cluster NGC 6569 revealed a similar, though less extended, HB luminosity split, but little is known about the cluster's detailed chemical composition. Therefore, we have used high-resolution spectra from the Magellan-M2FS and VLT-FLAMES spectrographs to investigate the chemical compositions and radial velocity distributions of red giant branch and HB stars in NGC 6569. We found the cluster to have a mean heliocentric radial velocity of -48.8 km/s (sigma = 5.3 km/s; 148 stars) and a mean [Fe/H] =-0.87 dex (19 stars), but the cluster's 0.05 dex [Fe/H] dispersion precludes a significant metallicity spread. NGC 6569 exhibits light- and heavy-element distributions that are common among old bulge/inner Galaxy globular clusters, including clear (anti)correlations between [O/Fe], [Na/Fe], and [Al/Fe]. The light-element data suggest that NGC 6569 may be composed of at least two distinct populations, and the cluster's low mean [La/Eu] = -0.11 dex indicates significant pollution with r-process material. We confirm that both HBs contain cluster members, but metallicity and light-element variations are largely ruled out as sources for the luminosity difference. However, He mass fraction differences as small as delta Y ~ 0.02 cannot be ruled out and may be sufficient to reproduce the double HB.Comment: 72 pages, 14 figures, 8 tables; published in The Astronomical Journal; electronic versions of all tables are available in the published versio

AGB Sodium Abundances in the Globular Cluster 47 Tucanae (NGC 104)

A recent analysis comparing the [Na/Fe] distributions of red giant branch (RGB) and asymptotic giant branch (AGB) stars in the Galactic globular cluster NGC 6752 found that the ratio of Na-poor to Na-rich stars changes from 30:70 on the RGB to 100:0 on the AGB. The surprising paucity of Na-rich stars on the AGB in NGC 6752 warrants additional investigations to determine if the failure of a significant fraction of stars to ascend the AGB is an attribute common to all globular clusters. Therefore, we present radial velocities, [Fe/H], and [Na/Fe] abundances for 35 AGB stars in the Galactic globular cluster 47 Tucanae (47 Tuc; NGC 104), and compare the AGB [Na/Fe] distribution with a similar RGB sample published previously. The abundances and velocities were derived from high resolution spectra obtained with the Michigan/Magellan Fiber System (M2FS) and MSpec spectrograph on the Magellan-Clay 6.5m telescope. We find the average heliocentric radial velocity and [Fe/H] values to be =-18.56 km s^-1 (sigma=10.21 km s^-1) and =-0.68 (sigma=0.08), respectively, in agreement with previous literature estimates. The average [Na/Fe] abundance is 0.12 dex lower in the 47 Tuc AGB sample compared to the RGB sample, and the ratio of Na-poor to Na-rich stars is 63:37 on the AGB and 45:55 on the RGB. However, in contrast to NGC 6752, the two 47 Tuc populations have nearly identical [Na/Fe] dispersion and interquartile range values. The data presented here suggest that only a small fraction <20% of Na-rich stars in 47 Tuc may fail to ascend the AGB. Regardless of the cause for the lower average [Na/Fe] abundance in AGB stars, we find that Na-poor stars and at least some Na-rich stars in 47 Tuc evolve through the early AGB phase. [abridged]Comment: Accepted for publication in the Astronomical Journal; 15 pages; 8 figures; 4 table

Magellan/M2FS Spectroscopy of Galaxy Clusters: Stellar Population Model and Application to Abell 267

We report the results of a pilot program to use the Magellan/M2FS spectrograph to survey the galactic populations and internal kinematics of galaxy clusters. For this initial study, we present spectroscopic measurements for $223$ quiescent galaxies observed along the line of sight to the galaxy cluster Abell 267 ($z\sim0.23$). We develop a Bayesian method for modeling the integrated light from each galaxy as a simple stellar population, with free parameters that specify redshift ($v_\mathrm{los}/c$) and characteristic age, metallicity ($\mathrm{[Fe/H]}$), alpha-abundance ($[\alpha/\mathrm{Fe}]$), and internal velocity dispersion ($\sigma_\mathrm{int}$) for individual galaxies. Parameter estimates derived from our 1.5-hour observation of A267 have median random errors of $\sigma_{v_\mathrm{los}}=20\ \mathrm{km\ s^{-1}}$, $\sigma_{\mathrm{Age}}=1.2\ \mathrm{Gyr}$, $\sigma_{\mathrm{[Fe/H]}}=0.11\ \mathrm{dex}$,$\sigma_{[\alpha/\mathrm{Fe}]}=0.07\ \mathrm{dex}$, and$\sigma_{\sigma_\mathrm{int}}=20\ \mathrm{km\ s^{-1}}$. In a companion paper, we use these results to model the structure and internal kinematics of A267.Comment: 16 pages, 11 figures, accepted for publication in The Astronomical Journa

Dark matter annihilation and decay profiles for the Reticulum II dwarf spheroidal galaxy

The dwarf spheroidal galaxies (dSph) of the Milky Way are among the most attractive targets for indirect searches of dark matter. In this work, we reconstruct the dark matter annihilation (J-factor) and decay profiles for the newly discovered dSph Reticulum II. Using an optimized spherical Jeans analysis of kinematic data obtained from the Michigan/Magellan Fiber System (M2FS), we find Reticulum II's J-factor to be among the largest of any Milky Way dSph. We have checked the robustness of this result against several ingredients of the analysis. Unless it suffers from tidal disruption or significant inflation of its velocity dispersion from binary stars, Reticulum II may provide a unique window on dark matter particle properties.Comment: 5 pages, 4 figures. Match the ApJL accepted versio

Photometry and spectroscopy of faint candidate spectrophotometric standard DA white dwarfs

We present precise photometry and spectroscopy for 23 candidate spectrophotometric standard white dwarfs. The selected stars are distributed in the Northern hemisphere and around the celestial equators and are all fainter than r ~ 16.5 mag. This network of stars, when established as standards, together with the three Hubble Space Telescope primary CALSPEC white dwarfs, will provide a set of spectrophotometric standards to directly calibrate data products to better than 1%. These new faint standard white dwarfs will have enough signal-to-noise ratio in future deep photometric surveys and facilities to be measured accurately while still avoiding saturation in such surveys. They will also fall within the dynamic range of large telescopes and their instruments for the foreseeable future. This paper discusses the provenance of the observational data for our candidate standard stars. The comparison with models, reconciliation with reddening, and the consequent derivation of the full spectral energy density distributions for each of them is reserved for a subsequent paper.Comment: 31 pages, 17 figures, 10 tables, ApJ in press (accepted on December 23rd, 2018