Infrared Period-Luminosity Relations of Evolved Variable Stars in the Large Magellanic Cloud

We combine variability information from the MAssive Compact Halo Objects (MACHO) survey of the Large Magellanic Cloud (LMC) with infrared photometry from the Spitzer Space Telescope Surveying the Agents of a Galaxy's Evolution (SAGE) survey to create a dataset of ~30 000 variable red sources. We photometrically classify these sources as being on the first ascent of the Red Giant Branch (RGB), or as being in one of three stages along the Asymptotic Giant Branch (AGB): oxygen-rich, carbon-rich, or highly reddened with indeterminate chemistry ("extreme" AGB candidates). We present linear period-luminosity relationships for these sources using 8 separate infrared bands (J, H, K, 3.6, 4.5, 5.8, 8.0, and 24 micron) as proxies for the luminosity. We find that the wavelength dependence of the slope of the period-luminosity relationship is different for different photometrically determined classes of AGB stars. Stars photometrically classified as O-rich show the least variation of slope with wavelength, while dust enshrouded extreme AGB stars show a pronounced trend toward steeper slopes with increasing wavelength. We find that O-rich AGB stars pulsating in the fundamental mode obey a period-magnitude relation with a slope of -3.41 +/- 0.04 when magnitude is measured in the 3.6 micron band, in contrast to C-rich AGB stars, which obey a relation of slope -3.77 +/- 0.05

Molecular hydrogen emission in the interstellar medium of the Large Magellanic Cloud

We present the detection and analysis of molecular hydrogen emission toward ten interstellar regions in the Large Magellanic Cloud. We examined low-resolution infrared spectral maps of twelve regions obtained with the Spitzer infrared spectrograph (IRS). The pure rotational 0--0 transitions of H$_2$ at 28.2 and 17.1${\,\rm \mu m}$ are detected in the IRS spectra for ten regions. The higher level transitions are mostly upper limit measurements except for three regions, where a 3$\sigma$ detection threshold is achieved for lines at 12.2 and 8.6${\,\rm \mu m}$. The excitation diagrams of the detected H$_2$ transitions are used to determine the warm H$_2$ gas column density and temperature. The single-temperature fits through the lower transition lines give temperatures in the range $86-137\,{\rm K}$. The bulk of the excited H$_2$ gas is found at these temperatures and contributes $\sim$5-17% to the total gas mass. We find a tight correlation of the H$_2$ surface brightness with polycyclic aromatic hydrocarbon and total infrared emission, which is a clear indication of photo-electric heating in photodissociation regions. We find the excitation of H$_2$ by this process is equally efficient in both atomic and molecular dominated regions. We also present the correlation of the warm H$_2$ physical conditions with dust properties. The warm H$_2$ mass fraction and excitation temperature show positive correlations with the average starlight intensity, again supporting H$_2$ excitation in photodissociation regions.Comment: Accepted for publication in MNRA

TgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite Toxoplasma gondii

New drugs to control infection with the protozoan parasite Toxoplasma gondii are needed as current treatments exert toxic side effects on patients. Approaches to develop novel compounds for drug development include screening of compound libraries and targeted inhibition of essential cellular pathways. We identified two distinct compounds that display inhibitory activity against the parasite's replicative stage: F3215-0002, which we previously identified during a compound library screen, and I-BET151, an inhibitor of bromodomains, the "reader" module of acetylated lysines. In independent studies, we sought to determine the targets of these two compounds using forward genetics, generating resistant mutants and identifying the determinants of resistance with comparative genome sequencing. Despite the dissimilarity of the two compounds, we recovered resistant mutants with nonsynonymous mutations in the same domain of the same gene, TGGT1_254250, which we found encodes a protein that localizes to the parasite mitochondrion (designated TgPRELID after the name of said domain). We found that mutants selected with one compound were cross resistant to the other compound, suggesting a common mechanism of resistance. To further support our hypothesis that TgPRELID mutations facilitate resistance to both I-BET151 and F3215-0002, CRISPR (clustered regularly interspaced short palindromic repeat)/CAS9-mediated mutation of TgPRELID directly led to increased F3215-0002 resistance. Finally, all resistance mutations clustered in the same subdomain of TgPRELID. These findings suggest that TgPRELID may encode a multidrug resistance factor or that I-BET151 and F3215-0002 have the same target(s) despite their distinct chemical structures. IMPORTANCE We report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite Toxoplasma gondii. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the development of new therapies for toxoplasmosis and other related parasitic diseases

The Spatial Distribution of Dust and Stellar Emission of the Magellanic Clouds

We study the emission by dust and stars in the Large and Small Magellanic Clouds, a pair of low-metallicity nearby galaxies, as traced by their spatially resolved spectral energy distributions (SEDs). This project combines Herschel Space Observatory PACS and SPIRE far-infrared photometry with other data at infrared and optical wavelengths. We build maps of dust and stellar luminosity and mass of both Magellanic Clouds, and analyze the spatial distribution of dust/stellar luminosity and mass ratios. These ratios vary considerably throughout the galaxies, generally between the range $0.01\leq L_{\rm dust}/L_\ast\leq 0.6$ and $10^{-4}\leq M_{\rm dust}/M_\ast\leq 4\times10^{-3}$. We observe that the dust/stellar ratios depend on the interstellar medium (ISM) environment, such as the distance from currently or previously star-forming regions, and on the intensity of the interstellar radiation field (ISRF). In addition, we construct star formation rate (SFR) maps, and find that the SFR is correlated with the dust/stellar luminosity and dust temperature in both galaxies, demonstrating the relation between star formation, dust emission and heating, though these correlations exhibit substantial scatter.Comment: 15 pages, 18 figures; ApJ, in press; version published in the journal will have higher-resolution figure

Impacts of Diet and Exercise on Maternal Gut Microbiota Are Transferred to Offspring

Background: It is well established that maternal exercise during pregnancy improves metabolic outcomes associated with obesity in mothers and offspring, however, its effects on the gut microbiota of both mother and offspring, are unknown. Here, we investigated whether wheel running exercise prior to and during pregnancy and prolonged feeding of an obesogenic diet were associated with changes in the gut microbiomes of Sprague-Dawley rat dams and their offspring. Female rats were fed either chow or obesogenic diet, and half of each diet group were given access to a running wheel 10 days before mating until delivery, while others remained sedentary. 16S rRNA gene amplicon sequencing was used to assess gut microbial communities in dams and their male and female offspring around the time of weaning.Results: Statistical analyses at the operational taxonomic unit (OTU) level revealed that maternal obesogenic diet decreased gut microbial alpha diversity and altered abundances of bacterial taxa previously associated with obesity such as Bacteroides and Blautia in dams, and their offspring of both sexes. Distance based linear modeling revealed that the relative abundances of Bacteroides OTUs were associated with adiposity measures in both dams and offspring. We identified no marked effects of maternal exercise on the gut microbiota of obesogenic diet dams or their offspring. In contrast, maternal exercise decreased gut microbial alpha diversity and altered the abundance of 88 microbial taxa in offspring of control dams. Thirty of these taxa were altered in a similar direction in offspring of sedentary obesogenic vs. control diet dams. In particular, the relative abundances of Oscillibacter OTUs were decreased in offspring of both exercised control dams and sedentary obesogenic diet dams, and associated with blood glucose concentrations and adiposity measures. Analyses of predicted bacterial metabolic pathways inferred decreased indole alkaloid biosynthesis in offspring of both obesogenic diet and exercised control dams.Conclusions: Our data suggest that maternal exercise prior to and during pregnancy resulted in gut dysbiosis in offspring of control dams. Importantly, alterations in the maternal gut microbiota by obesogenic diet or obesity were transferred to their offspring

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Dusty Stellar Birth and Death in the Metal-Poor Galaxy NGC 6822

The nearby ($\sim$500 kpc) metal-poor ([Fe/H] $\approx$ -1.2; $Z$ $\approx$ 30% $Z_{\odot}$) star-forming galaxy NGC 6822 has a metallicity similar to systems at the epoch of peak star formation. Through identification and study of dusty and dust-producing stars, it is therefore a useful laboratory to shed light on the dust life cycle in the early Universe. We present a catalog of sources combining near- and mid-IR photometry from the United Kingdom Infrared Telescope (UKIRT; $J$, $H$, and $K$) and the $Spitzer$ $Space$ $Telescope$ (IRAC 3.6, 4.5, 5.8, and 8.0 $\mu$m and MIPS 24 $\mu$m). This catalog is employed to identify dusty and evolved stars in NGC 6822 utilizing three color-magnitude diagrams (CMDs). With diagnostic CMDs covering a wavelength range spanning the near- and mid-IR, we develop color cuts using kernel density estimate (KDE) techniques to identify dust-producing evolved stars, including red supergiant (RSG) and thermally-pulsing asymptotic giant branch (TP-AGB) star candidates. In total, we report 1,292 RSG candidates, 1,050 oxygen-rich AGB star candidates, and 560 carbon-rich AGB star candidates with high confidence in NGC 6822. Our analysis of the AGB stars suggests a robust population inhabiting the central stellar bar of the galaxy, with a measured global stellar metallicity of [Fe/H] = -1.286 $\pm$ 0.095, consistent with previous studies. In addition, we identify 277 young stellar object (YSO) candidates. The detection of a large number of YSO candidates within a centrally-located, compact cluster reveals the existence of an embedded, high-mass star-formation region that has eluded previous detailed study. Spitzer I appears to be younger and more active than the other prominent star-forming regions in the galaxy.Comment: Accepted for publication in The Astrophysical Journal; 27 pages, 13 figures, 12 tables (master catalog will be available from publisher