Early-time Spitzer observations of the type II-Plateau supernova, 2004dj

We present mid-infrared observations with the Spitzer Space Telescope of the nearby type II-P supernova, SN 2004dj, at epochs of 89 to 129 days. We have obtained the first mid-IR spectra of any supernova apart from SN 1987A. A prominent [NiII] 6.64 micron line is observed, from which we deduce that the mass of stable nickel must be at least 2.2e10(-4) Msun. We also observe the red wing of the CO-fundamental band. We relate our findings to possible progenitors and favour an evolved star, most likely a red supergiant, with a probable initial mass between ~10 and 15 Msun.Comment: ApJ Letters (accepted

The Rise Times of High and Low Redshift Type Ia Supernovae are Consistent

We present a self-consistent comparison of the rise times for low- and high-redshift Type Ia supernovae. Following previous studies, the early light curve is modeled using a t-squared law, which is then mated with a modified Leibundgut template light curve. The best-fit t-squared law is determined for ensemble samples of low- and high-redshift supernovae by fitting simultaneously for all light curve parameters for all supernovae in each sample. Our method fully accounts for the non-negligible covariance amongst the light curve fitting parameters, which previous analyses have neglected. Contrary to Riess et al. (1999), we find fair to good agreement between the rise times of the low- and high-redshift Type Ia supernovae. The uncertainty in the rise time of the high-redshift Type Ia supernovae is presently quite large (roughly +/- 1.2 days statistical), making any search for evidence of evolution based on a comparison of rise times premature. Furthermore, systematic effects on rise time determinations from the high-redshift observations, due to the form of the late-time light curve and the manner in which the light curves of these supernovae were sampled, can bias the high-redshift rise time determinations by up to +3.6/-1.9 days under extreme situations. The peak brightnesses - used for cosmology - do not suffer any significant bias, nor any significant increase in uncertainty.Comment: 18 pages, 4 figures, Accepted for publication in the Astronomical Journal. Also available at http://www.lbl.gov/~nugent/papers.html Typos were corrected and a few sentences were added for improved clarit

On the Spectroscopic Diversity of Type Ia Supernovae

A comparison of the ratio of the depths of two absorption features in the spectra of TypeIa supernovae (SNe Ia) near the time of maximum brightness with the blueshift of the deep red Si II absorption feature 10 days after maximum shows that the spectroscopic diversity of SNe Ia is multi-dimensional. There is a substantial range of blueshifts at a given value of the depth ratio. We also find that the spectra of a sample of SNe Ia obtained a week before maximum brightness can be arranged in a ``blueshift sequence'' that mimics the time evolution of the pre-maximum-light spectra of an individual SN Ia, the well observed SN 1994D. Within the context of current SN Ia explosion models, we suggest that some of the SNe Ia in our sample were delayed-detonations while others were plain deflagrations.Comment: accepted for publication in ApJ

Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass

Aims/hypothesis: Pancreatic beta cells secrete insulin to maintain glucose homeostasis, and beta cell failure is a hallmark of type 2 diabetes. Glucose triggers insulin secretion in beta cells via oxidative mitochondrial pathways. However, it also feeds mitochondrial anaplerotic pathways, driving citrate export and cytosolic malonyl-CoA production by the acetyl-CoA carboxylase 1 (ACC1) enzyme. This pathway has been proposed as an alternative glucose-sensing mechanism, supported mainly by in vitro data. Here, we sought to address the role of the beta cell ACC1-coupled pathway in insulin secretion and glucose homeostasis in vivo. Methods: Acaca, encoding ACC1 (the principal ACC isoform in islets), was deleted in beta cells of mice using the Cre/loxP system. Acaca floxed mice were crossed with Ins2cre mice (βACC1KO; life-long beta cell gene deletion) or Pdx1creER mice (tmx-βACC1KO; inducible gene deletion in adult beta cells). Beta cell function was assessed using in vivo metabolic physiology and ex vivo islet experiments. Beta cell mass was analysed using histological techniques. Results: βACC1KO and tmx-βACC1KO mice were glucose intolerant and had defective insulin secretion in vivo. Isolated islet studies identified impaired insulin secretion from beta cells, independent of changes in the abundance of neutral lipids previously implicated as amplification signals. Pancreatic morphometry unexpectedly revealed reduced beta cell size in βACC1KO mice but not in tmx-βACC1KO mice, with decreased levels of proteins involved in the mechanistic target of rapamycin kinase (mTOR)-dependent protein translation pathway underpinning this effect. Conclusions/interpretation: Our study demonstrates that the beta cell ACC1-coupled pathway is critical for insulin secretion in vivo and ex vivo and that it is indispensable for glucose homeostasis. We further reveal a role for ACC1 in controlling beta cell growth prior to adulthood.</p

Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis

The early mechanisms regulating progression towards beta cell failure in type 1 diabetes (T1D) are poorly understood, but it is generally acknowledged that genetic and environmental components are involved. The metabolomic phenotype is sensitive to minor variations in both, and accordingly reflects changes that may lead to the development of T1D. We used two different extraction methods in combination with both liquid- and gas chromatographic techniques coupled to mass spectrometry to profile the metabolites in a transgenic non-diabetes prone C57BL/6 mouse expressing CD154 under the control of the rat insulin promoter (RIP) crossed into the immuno-deficient recombination-activating gene (RAG) knockout (−/−) C57BL/6 mouse, resembling the early stages of human T1D. We hypothesized that alterations in the metabolomic phenotype would characterize the early pathogenesis of T1D, thus metabolomic profiling could provide new insight to the development of T1D. Comparison of the metabolome of the RIP CD154 × RAG(−/−) mice to RAG(−/−) mice and C57BL/6 mice revealed alterations of >100 different lipids and metabolites in serum. Low lysophosphatidylcholine levels, accumulation of ceramides as well as methionine deficits were detected in the pre-type 1 diabetic mice. Additionally higher lysophosphatidylinositol levels and low phosphatidylglycerol levels where novel findings in the pre-type 1 diabetic mice. These observations suggest that metabolomic disturbances precede the onset of T1D. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-015-0889-1) contains supplementary material, which is available to authorized users

Spitzer measurements of atomic and molecular abundances in the Type IIP SN 2005af

We present results based on Spitzer Space Telescope mid-infrared (3.6-30 micron) observations of the nearby IIP supernova 2005af. We report the first ever detection of the SiO molecule in a Type IIP supernova. Together with the detection of the CO fundamental, this is an exciting finding as it may signal the onset of dust condensation in the ejecta. From a wealth of fine-structure lines we provide abundance estimates for stable Ni, Ar, and Ne which, via spectral synthesis, may be used to constrain nucleosynthesis models.Comment: ApJ Letters (accepted

Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months

INTRODUCTION: The identification of metabolomic dysregulation appears promising for the prediction of type 1 diabetes and may also reveal metabolic pathways leading to beta-cell destruction. Recent studies indicate that regulation of multiple phospholipids precede the presence of autoantigens in the development of type 1 diabetes. OBJECTIVES: We hypothesize that lipid biomarkers in plasma from children with recent onset type 1 diabetes will reflect their remaining beta-cell function and predict future changes in beta-cell function. METHODS: We performed targeted lipidomic profiling by electrospray ionization tandem mass spectrometry to acquire comparative measures of 354 lipid species covering 25 lipid classes and subclasses in plasma samples from 123 patients < 17 years of age followed prospectively at 1, 3, 6 and 12 months after diagnosis. Lipidomic profiles were analysed using liner regression to investigate the relationship between plasma lipids and meal stimulated C-peptide levels at each time point. P-values were corrected for multiple comparisons by the method of Benjamini and Hochberg. RESULTS: Linear regression analysis showed that the relative levels of cholesteryl ester, diacylglycerol and triacylglycerol at 1 month were associated to the change in c-peptide levels from 1 to 6 months (corrected p-values of 4.06E-03, 1.72E-02 and 1.72E02, respectively). Medium chain saturated and monounsaturated fatty acids were the major constituents of the di- and triacylglycerol species suggesting a link with increased lipogenesis. CONCLUSION: These observations support the hypothesis of lipid disturbances as explanatory factors for residual beta-cell function in children with new onset type 1 diabetes

Analysis of the Flux and Polarization Spectra of the Type Ia Supernova SN 2001el: Exploring the Geometry of the High-velocity Ejecta

SN 2001el is the first normal Type Ia supernova to show a strong, intrinsic polarization signal. In addition, during the epochs prior to maximum light, the CaII IR triplet absorption is seen distinctly and separately at both normal photospheric velocities and at very high velocities. The high-velocity triplet absorption is highly polarized, with a different polarization angle than the rest of the spectrum. The unique observation allows us to construct a relatively detailed picture of the layered geometrical structure of the supernova ejecta: in our interpretation, the ejecta layers near the photosphere (v \approx 10,000 km/s) obey a near axial symmetry, while a detached, high-velocity structure (v \approx 18,000-25,000 km/s) with high CaII line opacity deviates from the photospheric axisymmetry. By partially obscuring the underlying photosphere, the high-velocity structure causes a more incomplete cancellation of the polarization of the photospheric light, and so gives rise to the polarization peak and rotated polarization angle of the high-velocity IR triplet feature. In an effort to constrain the ejecta geometry, we develop a technique for calculating 3-D synthetic polarization spectra and use it to generate polarization profiles for several parameterized configurations. In particular, we examine the case where the inner ejecta layers are ellipsoidal and the outer, high-velocity structure is one of four possibilities: a spherical shell, an ellipsoidal shell, a clumped shell, or a toroid. The synthetic spectra rule out the spherical shell model, disfavor a toroid, and find a best fit with the clumped shell. We show further that different geometries can be more clearly discriminated if observations are obtained from several different lines of sight.Comment: 14 pages (emulateapj5) plus 18 figures, accepted by The Astrophysical Journa

Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids

<p>Abstract</p> <p>Background</p> <p>Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake.</p> <p>Methods</p> <p>Mice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated: a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [¹⁴C]cholesterol and [³H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS.</p> <p>Results</p> <p>Both PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, <it>P </it>< 0.05). Hepatic accumulation of intragastrically-administered [¹⁴C]cholesterol was significantly less (-30% to -60%, <it>P </it>< 0.05) and fecal excretion of [¹⁴C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, <it>P </it>< 0.05). Liver cholesterol and triglyceride levels were positively correlated with hepatic accumulation of intragastrically-administered [¹⁴C]cholesterol (<it>P </it>< 0.001) and negatively correlated with fecal excretion of [¹⁴C]cholesterol (<it>P </it>< 0.05). Increased PL and ceramide levels in the diet of mice supplemented with milk PL were associated with significantly higher levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and ceramide, specifically, phosphatidylcholine (-21%, <it>P </it>< 0.05) and monohexosylceramide (-33%, <it>P </it>< 0.01).</p> <p>Conclusion</p> <p>These results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.</p

Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.

HIV infection has a profound effect on "bystander" cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected with ΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities