Lymphocytes require glucose uptake and metabolism for normal survival and function. The signals that regulate the expression and localization of glucose transporter 1 (Glut1) to allow glucose uptake ...in T cells are now beginning to be understood. Resting T cells require extracellular signals, such as cytokines, hormones, and growth factors, or low‐level TCR stimulation to take up adequate glucose to maintain housekeeping functions. In the absence of extrinsic signals, resting T cells internalize and degrade Glut1 and cannot maintain viability. Activated T cells have dramatically increased metabolic requirements to support the energy and biosynthetic needs necessary for growth, proliferation, and effector function. In particular, glucose metabolism and aerobic glycolysis fuel this demand. Therefore, activation of T cells causes a large increase in Glut1 expression and surface localization. If glucose uptake is limited, glycolytic flux decreases to a level that no longer sustains viability, and proapoptotic Bcl‐2 family members become activated, promoting cell death. However, excessive glucose uptake can promote hyperactive immune responses and possible immune pathology. Tight regulation of glucose uptake is required to maintain immune homeostasis, and understanding of these metabolic pathways may lead to therapeutic strategies to target some forms of cancer or autoimmunity.
ABSTRACT
The nebular He ii λ1640 emission line is observed in star-forming galaxies out to large distances and can be used to constrain the properties of sources of He+-ionizing photons. For this ...purpose, it is crucial to understand which are the main stellar sources of these photons. In some nearby metal-poor starburst galaxies, nebular He ii λ4686 (optical equivalent) is accompanied by a broad underlying component, which is generally attributed to formation in the winds of classical (He-burning) Wolf–Rayet stars, primarily of the WN subtype. In such cases, the origin of the nebular component has been proposed to be the escape of He+-ionizing photons from the winds of the WN stars, at least partially. We use archival long-slit observations obtained with Focal Reducer Low Dispersion Spectrograph (FORS1) on the Very Large Telescope to look for nebular He ii λ4686 emission south of the WN6h + WN6-7 close binary in HD 5980. We only find broad He ii λ4686 emission, as far as ∼7.6 pc from the binary. A comparison with observations obtained with Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope, at a similar orbital phase, shows that the FORS1 broad He ii emission is likely contamination from the multiple-star system HD 5980. We use models to show that no significant He+-ionizing flux is expected from the WN stars in HD 5980 and that when similar stars are present in a coeval stellar population, the O stars can be far greater emitters of He+-ionizing radiation.
We present an investigation of the relationship between giant molecular cloud (GMC) properties and the associated stellar clusters in the nearby flocculent galaxy NGC 7793. We combine the star ...cluster catalogue from the HST LEGUS (Legacy ExtraGalactic UV Survey) programme with the 15 pc resolution ALMA CO(2-1) observations. We find a strong spatial correlation between young star clusters and GMCs such that all clusters still associated with a GMC are younger than 11 Myr and display a median age of 2 Myr. The age distribution increases gradually as the cluster-GMC distance increases, with star clusters that are spatially unassociated with molecular gas exhibiting a median age of 7 Myr. Thus, star clusters are able to emerge from their natal clouds long before the time-scale required for clouds to disperse. To investigate if the hierarchy observed in the stellar components is inherited from the GMCs, we quantify the amount of clustering in the spatial distributions of the components and find that the star clusters have a fractal dimension slope of -0.35 +/- 0.03, significantly more clustered than the molecular cloud hierarchy with slope of -0.18 +/- 0.04 over the range 40-800 pc. We find, however, that the spatial clustering becomes comparable in strength for GMCs and star clusters with slopes of -0.44 +/- 0.03 and -0.45 +/- 0.06, respectively, when we compare massive (> 10(5) M-circle dot) GMCs to massive and young star clusters. This shows that massive star clusters trace the same hierarchy as their parent GMCs, under the assumption that the star formation efficiency is a few per cent.
Abstract
We report the large effort that is producing comprehensive high-level young star cluster (YSC) catalogs for a significant fraction of galaxies observed with the Legacy ExtraGalactic UV ...Survey (LEGUS)
Hubble
treasury program. We present the methodology developed to extract cluster positions, verify their genuine nature, produce multiband photometry (from NUV to NIR), and derive their physical properties via spectral energy distribution fitting analyses. We use the nearby spiral galaxy NGC 628 as a test case for demonstrating the impact that LEGUS will have on our understanding of the formation and evolution of YSCs and compact stellar associations within their host galaxy. Our analysis of the cluster luminosity function from the UV to the NIR finds a steepening at the bright end and at all wavelengths suggesting a dearth of luminous clusters. The cluster mass function of NGC 628 is consistent with a power-law distribution of slopes
and a truncation of a few times 10
5
. After their formation, YSCs and compact associations follow different evolutionary paths. YSCs survive for a longer time frame, confirming their being potentially bound systems. Associations disappear on timescales comparable to hierarchically organized star-forming regions, suggesting that they are expanding systems. We find mass-independent cluster disruption in the inner region of NGC 628, while in the outer part of the galaxy there is little or no disruption. We observe faster disruption rates for low mass (≤10
4
) clusters, suggesting that a mass-dependent component is necessary to fully describe the YSC disruption process in NGC 628.
ABSTRACT
The analysis of star cluster ages in tandem with the morphology of their H ii regions can provide insight into the processes that clear a cluster’s natal gas, as well as the accuracy of ...cluster ages and dust reddening derived from Spectral Energy Distribution (SED) fitting. We classify 3757 star clusters in 16 nearby galaxies according to their H α morphology (concentrated, partially exposed, no emission), using Hubble Space Telescope (HST) imaging from the Legacy ExtraGalactic Ultraviolet Survey (LEGUS). We find: (1) The mean SED ages of clusters with concentrated (1–2 Myr) and partially exposed H ii region morphologies (2–3 Myr) indicate a relatively early onset of gas clearing and a short (1–2 Myr) clearing time-scale. (2) The reddening of clusters can be overestimated due to the presence of red supergiants, which is a result of stochastic sampling of the IMF in low mass clusters. (3) The age-reddening degeneracy impacts the results of the SED fitting – out of 1408 clusters with M* ≥ 5000 M⊙, we find that at least 46 (3 per cent) have SED ages which appear significantly underestimated or overestimated based on H α and their environment, while the total percentage of poor age estimates is expected to be several times larger. (4) Lastly, we examine the dependence of the morphological classifications on spatial resolution. At HST resolution, our conclusions are robust to the distance range spanned by the sample (3–10 Mpc). However, analysis of ground-based H α images shows that compact and partially exposed morphologies frequently cannot be distinguished from each other.
ABSTRACT
The morphology of H ii regions around young star clusters provides insight into the time-scales and physical processes that clear a cluster’s natal gas. We study ∼700 young clusters (≤10 ...Myr) in three nearby spiral galaxies (NGC 7793, NGC 4395, and NGC 1313) using Hubble Space Telescope (HST) imaging from LEGUS (Legacy ExtraGalactic Ultraviolet Survey). Clusters are classified by their H α morphology (concentrated, partially exposed, no-emission) and whether they have neighbouring clusters (which could affect the clearing time-scales). Through visual inspection of the HST images, and analysis of ages, reddenings, and stellar masses from spectral energy distributions fitting, together with the (U− B), (V − I) colours, we find (1) the median ages indicate a progression from concentrated (∼3 Myr), to partially exposed (∼4 Myr), to no H α emission (>5 Myr), consistent with the expected temporal evolution of H ii regions and previous results. However, (2) similarities in the age distributions for clusters with concentrated and partially exposed H α morphologies imply a short time-scale for gas clearing (≲1 Myr). Also, (3) our cluster sample’s median mass is ∼1000 M⊙, and a significant fraction ($\sim 20{{\ \rm per\ cent}}$) contain one or more bright red sources (presumably supergiants), which can mimic reddening effects. Finally, (4) the median E(B − V) values for clusters with concentrated H α and those without H α emission appear to be more similar than expected (∼0.18 versus ∼0.14, respectively), but when accounting for stochastic effects, clusters without H α emission are less reddened. To mitigate stochastic effects, we experiment with synthesizing more massive clusters by stacking fluxes of clusters within each H α morphological class. Composite isolated clusters also reveal a colour and age progression for H α morphological classes, consistent with analysis of the individual clusters.
Abstract
The Legacy ExtraGalactic UV Survey (LEGUS) is a multiwavelength Cycle 21 Treasury program on the
Hubble Space Telescope
. It studied 50 nearby star-forming galaxies in 5 bands from the ...near-UV to the I-band, combining new Wide Field Camera 3 observations with archival Advanced Camera for Surveys data. LEGUS was designed to investigate how star formation occurs and develops on both small and large scales, and how it relates to the galactic environments. In this paper we present the photometric catalogs for all the apparently single stars identified in the 50 LEGUS galaxies. Photometric catalogs and mosaicked images for all filters are available for download. We present optical and near-UV color–magnitude diagrams for all the galaxies. For each galaxy we derived the distance from the tip of the red giant branch. We then used the NUV color–magnitude diagrams to identify stars more massive than 14
M
⊙
, and compared their number with the number of massive stars expected from the
GALEX
FUV luminosity. Our analysis shows that the fraction of massive stars forming in star clusters and stellar associations is about constant with the star formation rate. This lack of a relation suggests that the timescale for evaporation of unbound structures is comparable or longer than 10 Myr. At low star formation rates this translates to an excess of mass in clustered environments as compared to model predictions of cluster evolution, suggesting that a significant fraction of stars form in unbound systems.
Protein arginine methylation is a posttranslational modification critical for a variety of biological processes. Misregulation of protein arginine methyltransferases (PRMTs) has been linked to many ...pathological conditions. Most current PRMT inhibitors display limited specificity and selectivity, indiscriminately targeting many methyltransferase enzymes that use S-adenosyl-l-methionine as a cofactor. Here we report diamidine compounds for specific inhibition of PRMT1, the primary type I enzyme. Docking, molecular dynamics, and MM/PBSA analysis together with biochemical assays were conducted to understand the binding modes of these inhibitors and the molecular basis of selective inhibition for PRMT1. Our data suggest that 2,5-bis(4-amidinophenyl)furan (1, furamidine, DB75), one leading inhibitor, targets the enzyme active site and is primarily competitive with the substrate and noncompetitive toward the cofactor. Furthermore, cellular studies revealed that 1 is cell membrane permeable and effectively inhibits intracellular PRMT1 activity and blocks cell proliferation in leukemia cell lines with different genetic lesions.
Abstract
We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program ‘Legacy ExtraGalactic UV Survey’ (LEGUS). Cluster identification and photometry in this ...sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of −2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of ≈− 0.80 ± 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (<2σ) in the composite cluster mass function, and can rule out a truncation mass below ≈104.5M⊙ but cannot rule out the existence of a truncation at higher masses.
We test the predictions of spectral synthesis models based on seven different massive-star prescriptions against Legacy ExtraGalactic UV Survey (LEGUS) observations of eight young massive clusters in ...two local galaxies, NGC 1566 and NGC 5253, chosen because predictions of all seven models are available at the published galactic metallicities. The high angular resolution, extensive cluster inventory, and full near-ultraviolet to near-infrared photometric coverage make the LEGUS data set excellent for this study. We account for both stellar and nebular emission in the models and try two different prescriptions for attenuation by dust. From Bayesian fits of model libraries to the observations, we find remarkably low dispersion in the median E(B − V) (∼0.03 mag), stellar masses (∼104 M⊙), and ages (∼1 Myr) derived for individual clusters using different models, although maximum discrepancies in these quantities can reach 0.09 mag and factors of 2.8 and 2.5, respectively. This is for ranges in median properties of 0.05–0.54 mag, 1.8–10 × 104 M⊙, and 1.6–40 Myr spanned by the clusters in our sample. In terms of best fit, the observations are slightly better reproduced by models with interacting binaries and least well reproduced by models with single rotating stars. Our study provides a first quantitative estimate of the accuracies and uncertainties of the most recent spectral synthesis models of young stellar populations, demonstrates the good progress of models in fitting high-quality observations, and highlights the needs for a larger cluster sample and more extensive tests of the model parameter space.
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