Mapping the Recent Star Formation History of the Disk of M51

Using data acquired as part of a unique Hubble Heritage imaging program of broadband colors of the interacting spiral system M51/NGC 5195, we have conducted a photometric study of the stellar associations across the entire disk of the galaxy in order to assess trends in size, luminosity, and local environment associated with recent star formation activity in the system. Starting with a sample of over 900 potential associations, we have produced color-magnitude and color-color diagrams for the 120 associations that were deemed to be single-aged. It has been found that main sequence turnoffs are not evident for the vast majority of the stellar associations in our set, potentially due to the overlap of isochronal tracks at the high mass end of the main sequence, and the limited depth of our images at the distance of M51. In order to obtain ages for more of our sample, we produced model spectral energy distributions (SEDs) to fit to the data from the GALEXEV simple stellar population (SSP) models of Bruzual and Charlot (2003). These SEDs can be used to determine age, size, mass, metallicity, and dust content of each association via a simple chi-squared minimization to each association's B, V, and I-band fluxes. The derived association properties are mapped as a function of location, and recent trends in star formation history of the galaxy are explored in light of these results. This work is the first phase in a program that will compare these stellar systems with their environments using ultraviolet data from GALEX and infrared data from Spitzer, and ultimately we plan to apply the same stellar population mapping methodology to other nearby face-on spiral galaxies.Comment: 13 pages, 3 figures, 1 table. Accepted to The Astronomical Journa

Using H-alpha Morphology and Surface Brightness Fluctuations to Age-Date Star Clusters in M83

We use new WFC3 observations of the nearby grand design spiral galaxy M83 to develop two independent methods for estimating the ages of young star clusters. The first method uses the physical extent and morphology of Halpha emission to estimate the ages of clusters younger than tau ~10 Myr. It is based on the simple premise that the gas in very young (tau < few Myr) clusters is largely coincident with the cluster stars, is in a small, ring-like structure surrounding the stars in slightly older clusters (e.g., tau ~5 Myr), and is in a larger ring-like bubble for still older clusters (i.e., ~5-10 Myr). The second method is based on an observed relation between pixel-to-pixel flux variations within clusters and their ages. This method relies on the fact that the brightest individual stars in a cluster are most prominent at ages around 10 Myr, and fall below the detection limit (i.e., M_V < -3.5) for ages older than about 100 Myr. These two methods are the basis for a new morphological classification system which can be used to estimate the ages of star clusters based on their appearance. We compare previous age estimates of clusters in M83 determined from fitting UBVI Halpha measurements using predictions from stellar evolutionary models with our new morphological categories and find good agreement at the ~95% level. The scatter within categories is ~0.1 dex in log tau for young clusters (10 Myr) clusters. A by-product of this study is the identification of 22 "single-star" HII regions in M83, with central stars having ages ~4 Myr.Comment: 33 pages, 10 figures, 3 tables; published in March Ap

The Luminosity, Mass, and Age Distributions of Compact Star Clusters in M83 Based on HST/WFC3 Observations

The newly installed Wide Field Camera 3 (WFC3) on the Hubble Space Telescope has been used to obtain multi-band images of the nearby spiral galaxy M83. These new observations are the deepest and highest resolution images ever taken of a grand-design spiral, particularly in the near ultraviolet, and allow us to better differentiate compact star clusters from individual stars and to measure the luminosities of even faint clusters in the U band. We find that the luminosity function for clusters outside of the very crowded starburst nucleus can be approximated by a power law, dN/dL \propto L^{alpha}, with alpha = -2.04 +/- 0.08, down to M_V ~ -5.5. We test the sensitivity of the luminosity function to different selection techniques, filters, binning, and aperture correction determinations, and find that none of these contribute significantly to uncertainties in alpha. We estimate ages and masses for the clusters by comparing their measured UBVI,Halpha colors with predictions from single stellar population models. The age distribution of the clusters can be approximated by a power-law, dN/dt propto t^{gamma}, with gamma=-0.9 +/- 0.2, for M > few x 10^3 Msun and t < 4x10^8 yr. This indicates that clusters are disrupted quickly, with ~80-90% disrupted each decade in age over this time. The mass function of clusters over the same M-t range is a power law, dN/dM propto M^{beta}, with beta=-1.94 +/- 0.16, and does not have bends or show curvature at either high or low masses. Therefore, we do not find evidence for a physical upper mass limit, M_C, or for the earlier disruption of lower mass clusters when compared with higher mass clusters, i.e. mass-dependent disruption. We briefly discuss these implications for the formation and disruption of the clusters.Comment: 36 pages, 13 figures, 1 table; accepted for publication in the Astrophysical Journa

Interaction of Oral Bacteria With Gingival Epithelial Cell Multilayers

Primary gingival epithelial cells were cultured in multilayers as a model for the study of interactions with oral bacteria associated with health and periodontal disease. Multilayers maintained at an air-liquid interface in low calcium medium displayed differentiation and cytokeratin properties characteristic of junctional epithelium. Multilayers were infected with fluorescently labeled Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum or Streptococcus gordonii, and bacterial association was determined by confocal microscopy and quantitative image analysis. P. gingivalis invaded intracellularly and spread cell to cell. A. actinomycetemcomitans and F. nucleatum remained extracellular and showed intercellular movement through the multilayer. S. gordonii remained extracellular and predominantly associated with the superficial cell layer. None of the bacterial species disrupted barrier function as measured by transepithelial electrical resistance. P. gingivalis did not elicit secretion of proinflammatory cytokines. However, A. actinomycetemcomitans and S. gordonii induced IL-1β, TNF-α, IL-6 and IL-8 secretion; and F. nucleatum stimulated production of IL-1β and TNF-α. A. actinomycetemcomitans, F. nucleatum and S. gordonii, but not P. gingivalis, increased levels of apoptosis after 24 h infection. The results indicate that the organisms with pathogenic potential were able to traverse the epithelium, while the commensal bacteria did not. In addition, distinct host responses characterized the interaction between the junctional epithelium and oral bacteria

The evidence base for emergency use authorizations for COVID-19 treatments : A rapid review

Background and Aims During the COVID-19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021). Methods A review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature. Results The number of clinical studies published pre-EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN-COV, bamlanivimab + etesevimab,sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post-EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN-COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab. Conclusion The number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced-based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic

Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression. Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers. Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic

Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response

Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n = 6), normoglycemic obese (n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg−1·min−1) or normal saline. Insulin, NEFA, SAT-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0-4 h ± SE, 41,992 ± 9,843 µmol·l−1·min−1 vs. 71,468 ± 13,605 with placebo, P = 0.039, 95% CI: 0.31-0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ± 0.4 vs 0.86 ± 0.1-fold with placebo, P = 0.043, 95% CI: 0.1-1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson, r = 0.56, P = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM

The antiangiogenic activity of naturally occurring and synthetic homoisoflavonoids from the Hyacinthaceae (sensu APGII)

Excessive blood vessel formation in the eye is implicated in wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes of blindness. Small molecule antiangiogenic drugs are strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown to have potent antiproliferative activities in endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Here, we tested the antiangiogenic activity of a group of naturally occurring homoisoflavonoids isolated from the family Hyacinthaceae and related synthetic compounds, chosen for synthesis based on structure–activity relationship observations. Several compounds showed interesting antiproliferative and antiangiogenic activities in vitro on retinal microvascular endothelial cells, a disease-relevant cell type, with the synthetic chromane, 46, showing the best activity (GI50 of 2.3 × 10–4 μM)

Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients: a maladaptive response

Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean ( n = 6), normoglycemic obese ( n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM ( n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg−1·min−1) or normal saline. Insulin, NEFA, SAT-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0–4 h ± SE, 41,992 ± 9,843 µmol·l−1·min−1 vs. 71,468 ± 13,605 with placebo, P = 0.039, 95% CI: 0.31–0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ± 0.4 vs 0.86 ± 0.1-fold with placebo, P = 0.043, 95% CI: 0.1–1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson, r = 0.56, P = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM. </jats:p