Spectroscopic observations of ices around embedded young stellar objects in the Large Magellanic Cloud with AKARI

The aim of this study is to understand the chemical conditions of ices around embedded young stellar objects (YSOs) in the metal-poor Large Magellanic Cloud (LMC). We performed near-infrared (2.5-5 micron) spectroscopic observations toward 12 massive embedded YSOs and their candidates in the LMC using the Infrared Camera (IRC) onboard AKARI. We estimated the column densities of the H2O, CO2, and CO ices based on their 3.05, 4.27, and 4.67 micron absorption features, and we investigated the correlation between ice abundances and physical properties of YSOs.The ice absorption features of H2O, CO2, 13CO2, CO, CH3OH, and possibly XCN are detected in the spectra. In addition, hydrogen recombination lines and PAH emission bands are detected toward the majority of the targets. The derived typical CO2/H2O ice ratio of our samples (~0.36 +- 0.09) is greater than that of Galactic massive YSOs (~0.17 +- 0.03), while the CO/H2O ice ratio is comparable. It is shown that the CO2 ice abundance does not correlate with the observed characteristics of YSOs; the strength of hydrogen recombination line and the total luminosity. Likewise, clear no correlation is seen between the CO ice abundance and YSO characteristics, but it is suggested that the CO ice abundance of luminous samples is significantly lower than in other samples.The systematic difference in the CO2 ice abundance around the LMC's massive YSOs, which was suggested by previous studies, is confirmed with the new near-infrared data. We suggest that the strong ultraviolet radiation field and/or the high dust temperature in the LMC are responsible for the observed high abundance of the CO2 ice. It is suggested that the internal stellar radiation does not play an important role in the evolution of the CO2 ice around a massive YSO, while more volatile molecules like CO are susceptible to the effect of the stellar radiation.Comment: 12 pages, 8 figures, 5 tables, accepted for Astronomy & Astrophysics journa

C2D Spitzer-IRS spectra of disks around T Tauri stars: I. Silicate emission and grain growth

Infrared ~5--35 um spectra for 40 solar-mass T Tauri stars and 7 intermediate-mass Herbig Ae stars with circumstellar disks were obtained using the Spitzer Space Telescope as part of the c2d IRS survey. This work complements prior spectroscopic studies of silicate infrared emission from disks, which were focused on intermediate-mass stars, with observations of solar-mass stars limited primarily to the 10 um region. The observed 10 and 20 um silicate feature strengths/shapes are consistent with source-to-source variations in grain size. A large fraction of the features are weak and flat, consistent with um-sized grains indicating fast grain growth (from 0.1--1.0 um in radius). In addition, approximately half of the T Tauri star spectra show crystalline silicate features near 28 and 33 um indicating significant processing when compared to interstellar grains. A few sources show large 10-to-20 um ratios and require even larger grains emitting at 20 um than at 10 um. This size difference may arise from the difference in the depth into the disk probed by the two silicate emission bands in disks where dust settling has occurred. The 10 um feature strength vs. shape trend is not correlated with age or Halpha equivalent width, suggesting that some amount of turbulent mixing and regeneration of small grains is occurring. The strength vs. shape trend is related to spectral type, however, with M stars showing significantly flatter 10 um features (larger grain sizes) than A/B stars. The connection between spectral type and grain size is interpreted in terms of the variation in the silicate emission radius as a function of stellar luminosity, but could also be indicative of other spectral-type dependent factors (e.g, X-rays, UV radiation, stellar/disk winds, etc.).Comment: 17 pages, 13 figures, accepted for publication by ApJ, formatted with emulateapj using revtex4 v4.

The impact and challenges of implementing CTCA according to the 2019 ESC guidelines on chronic coronary syndromes:a survey and projection of CTCA services in the Netherlands

BACKGROUND: The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands. METHODS AND RESULTS: A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variation considering CTCA indications, CTCA equipment and acquisition and reporting standards. To fully implement the new ESC guideline, our model suggests that 70,000 additional CTCA-examinations would have to be performed in the Netherlands. CONCLUSIONS: Despite high national CTCA-services coverage in the Netherlands, a substantial increase in CTCA capacity is expected to be able to implement the 2019 ESC-CCS recommendations on the use of CTCA. Furthermore, the results of this survey highlight the importance to address variations in image acquisition and to standardise the interpretation and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment

Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations

The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls. B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP

Defective Lipid Droplet-Lysosome Interaction Causes Fatty Liver Disease as Evidenced by Human Mutations in TMEM199 and CCDC115

BACKGROUND &amp; AIMS: Recently, novel inborn errors of metabolism were identified because of mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models, and a mouse model.METHODS AND RESULTS: Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very low density lipoprotein range. HepG2 hepatoma cells, in which the expression of TMEM199 and CCDC115 was silenced, and induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells from patients with TMEM199 mutations showed markedly increased secretion of apolipoprotein B (apoB) compared with controls. A mouse model for TMEM199 deficiency with a CRISPR/Cas9-mediated knock-in of the human A7E mutation had marked hepatic steatosis on chow diet. Plasma N-glycans were hypogalactosylated, consistent with the patient phenotype, but no clear plasma lipid abnormalities were observed in the mouse model. In the siTMEM199 and siCCDC115 HepG2 hepatocyte models, increased numbers and size of lipid droplets were observed, including abnormally large lipid droplets, which colocalized with lysosomes. Excessive de novo lipogenesis, failing oxidative capacity, and elevated lipid uptake were not observed. Further investigation of lysosomal function revealed impaired acidification combined with impaired autophagic capacity.CONCLUSIONS: Our data suggest that the hyperchole-sterolemia in TMEM199 and CCDC115 deficiency is due to increased secretion of apoB-containing particles. This may in turn be secondary to the hepatic steatosis observed in these patients as well as in the mouse model. Mechanistically, we observed impaired lysosomal function characterized by reduced acidification, autophagy, and increased lysosomal lipid accumulation. These findings could explain the hepatic steatosis seen in patients and highlight the importance of lipophagy in fatty liver disease. Because this pathway remains understudied and its regulation is largely untargeted, further exploration of this pathway may offer novel strategies for therapeutic interventions to reduce lipotoxicity in fatty liver disease.</p

From Molecular Cores to Planet-forming Disks: A SIRTF Legacy Program

Crucial steps in the formation of stars and planets can be studied only at mid-infrared to far-infrared wavelengths, where SIRTF provides an unprecedented improvement in sensitivity. We will use all three SIRTF instruments (IRAC, MIPS, and IRS) to observe sources that span the evolutionary sequence from molecular cores to protoplanetary disks, encompassing a wide range of cloud masses, stellar masses, and star-forming environments. In addition to targeting about 150 known compact cores, we will survey with IRAC and MIPS (3.6 to 70 micron) the entire areas of five of the nearest large molecular clouds for new candidate protostars and substellar objects as faint as 0.001 solar luminosities. We will also observe with IRAC and MIPS about 190 systems likely to be in the early stages of planetary system formation(ages up to about 10 Myr), probing the evolution of the circumstellar dust, the raw material for planetary cores. Candidate planet-forming disks as small as 0.1 lunar masses will be detectable. Spectroscopy with IRS of new objects found in the surveys and of a select group of known objects will add vital information on the changing chemical and physical conditions in the disks and envelopes. The resulting data products will include catalogs of thousands of previously unknown sources, multiwavelength maps of about 20 square degrees of molecular clouds, photometry of about 190 known young stars, spectra of at least 170 sources, ancillary data from ground-based telescopes, and new tools for analysis and modeling. These products will constitute the foundations for many follow-up studies with ground-based telescopes, as well as with SIRTF itself and other space missions such as SIM, JWST, Herschel, and TPF.Comment: (22 pages, 10 figures, PASP in press

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs