Breaking the Habit: The Peculiar 2016 Eruption of the Unique Recurrent Nova M31N 2008-12a

Since its discovery in 2008, the Andromeda galaxy nova M31N 2008-12a has been observed in eruption every single year. This unprecedented frequency indicates an extreme object, with a massive white dwarf and a high accretion rate, which is the most promising candidate for the single-degenerate progenitor of a Type Ia supernova known to date. The previous three eruptions of M31N 2008-12a have displayed remarkably homogeneous multiwavelength properties: (i) from a faint peak, the optical light curve declined rapidly by two magnitudes in less than two days, (ii) early spectra showed initial high velocities that slowed down significantly within days and displayed clear He/N lines throughout, and (iii) the supersoft X-ray source (SSS) phase of the nova began extremely early, six days after eruption, and only lasted for about two weeks. In contrast, the peculiar 2016 eruption was clearly different. Here we report (i) the considerable delay in the 2016 eruption date, (ii) the significantly shorter SSS phase, and (iii) the brighter optical peak magnitude (with a hitherto unobserved cusp shape). Early theoretical models suggest that these three different effects can be consistently understood as caused by a lower quiescence mass accretion rate. The corresponding higher ignition mass caused a brighter peak in the free–free emission model. The less massive accretion disk experienced greater disruption, consequently delaying the re-establishment of effective accretion. Without the early refueling, the SSS phase was shortened. Observing the next few eruptions will determine whether the properties of the 2016 outburst make it a genuine outlier in the evolution of M31N 2008-12a

Breaking the Habit: The Peculiar 2016 Eruption of the Unique Recurrent Nova M31N 2008-12a

Since its discovery in 2008, the Andromeda galaxy nova M31N 2008-12a has been observed in eruption every single year. This unprecedented frequency indicates an extreme object, with a massive white dwarf and a high accretion rate, which is the most promising candidate for the single-degenerate progenitor of a Type Ia supernova known to date. The previous three eruptions of M31N 2008-12a have displayed remarkably homogeneous multiwavelength properties: (i) from a faint peak, the optical light curve declined rapidly by two magnitudes in less than two days, (ii) early spectra showed initial high velocities that slowed down significantly within days and displayed clear He/N lines throughout, and (iii) the supersoft X-ray source (SSS) phase of the nova began extremely early, six days after eruption, and only lasted for about two weeks. In contrast, the peculiar 2016 eruption was clearly different. Here we report (i) the considerable delay in the 2016 eruption date, (ii) the significantly shorter SSS phase, and (iii) the brighter optical peak magnitude (with a hitherto unobserved cusp shape). Early theoretical models suggest that these three different effects can be consistently understood as caused by a lower quiescence mass accretion rate. The corresponding higher ignition mass caused a brighter peak in the free–free emission model. The less massive accretion disk experienced greater disruption, consequently delaying the re-establishment of effective accretion. Without the early refueling, the SSS phase was shortened. Observing the next few eruptions will determine whether the properties of the 2016 outburst make it a genuine outlier in the evolution of M31N 2008-12a

AT 2016dah and AT 2017fyp: the first classical novae discovered within a tidal stream

AT2016dah and AT2017fyp are fairly typical Andromeda Galaxy (M31) classical novae. AT2016dah is an almost text book example of a 'very fast' declining, yet uncommon, Fe II'b' (broad-lined) nova, discovered during the rise to peak optical luminosity, and decaying with a smooth broken power-law light curve. AT2017fyp is classed as a 'fast' nova, unusually for M31, its early decline spectrum simultaneously shows properties of both Fe II and He/N spectral types - a 'hybrid'. Similarly, the light curve of AT2017fyp has a broken power-law decline but exhibits an extended flat-topped maximum. Both novae were followed in the UV and X-ray by the Neil Gehrels Swift Observatory, but no X-ray source was detected for either nova. The pair were followed photometrically and spectroscopically into their nebular phases. The progenitor systems were not visible in archival optical data, implying that the mass donors are main sequence stars. What makes AT2016dah and AT2017fyp particularly interesting is their position with respect to M31. The pair are close on the sky but are located far from the centre of M31, lying almost along the semi-minor axis of their host. Radial velocity measurements and simulations of the M31 nova population leads to the conclusion that both novae are members of the Andromeda Giant Stellar Stream (GSS). We find the probability of at least two M31 novae appearing coincident with the GSS by chance is ~1%. Therefore, we claim that these novae arose from the GSS progenitor, not M31 - the first confirmed novae discovered in a tidal steam

Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

AT2016dah and AT2017fyp: the first classical novae discovered within a tidal stream

AT 2016dah and AT 2017fyp are fairly typical Andromeda galaxy (M 31) classical novae. AT 2016dah is an almost text book example of a 'very fast' declining, yet uncommon, Fe II'b' (broad-lined) nova, discovered during the rise to peak optical luminosity, and decaying with a smooth broken power-law light curve. AT 2017fyp is classed as a 'fast' nova, unusually for M31, its early decline spectrum simultaneously shows properties of both Fe II and He/N spectral types - a 'hybrid'. Similarly, the light curve of AT 2017fyp has a broken power-law decline but exhibits an extended flat-topped maximum. Both novae were followed in the UV and X-ray by the Neil Gehrels Swift Observatory, but no X-ray source was detected for either nova. The pair were followed photometrically and spectroscopically into their nebular phases. The progenitor systems were not visible in archival optical data, implying that the mass donors are main-sequence stars. What makes AT 2016dah and AT 2017fyp particularly interesting is their position with respect to M31. The pair are close on the sky but are located far from the centre ofM31, lying almost along the semiminor axis of their host. Radial velocity measurements and simulations of the M31 nova population leads to the conclusion that both novae are members of the Andromeda Giant Stellar Stream (GSS). We find the probability of at least two M31 novae appearing coincident with the GSS by chance is similar to 1 per cent. Therefore, we claim that these novae arose from the GSS progenitor, not M31 - the first confirmed novae discovered in a tidal steam

Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques

BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques

PPARα downregulates airway inflammation induced by lipopolysaccharide in the mouse

BACKGROUND: Inflammation is a hallmark of acute lung injury and chronic airway diseases. In chronic airway diseases, it is associated with profound tissue remodeling. Peroxisome proliferator-activated receptor-α (PPARα) is a ligand-activated transcription factor, that belongs to the nuclear receptor family. Agonists for PPARα have been recently shown to reduce lipopolysaccharide (LPS)- and cytokine-induced secretion of matrix metalloproteinase-9 (MMP-9) in human monocytes and rat mesangial cells, suggesting that PPARα may play a beneficial role in inflammation and tissue remodeling. METHODS: We have investigated the role of PPARα in a mouse model of LPS-induced airway inflammation characterized by neutrophil and macrophage infiltration, by production of the chemoattractants, tumor necrosis factor-α (TNF-α), keratinocyte derived-chemokine (KC), macrophage inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1), and by increased MMP-2 and MMP-9 activity in bronchoalveolar lavage fluid (BALF). The role of PPARα in this model was studied using both PPARα-deficient mice and mice treated with the PPARα activator, fenofibrate. RESULTS: Upon intranasal exposure to LPS, PPARα(-/- )mice exhibited greater neutrophil and macrophage number in BALF, as well as increased levels of TNF-α, KC, MIP-2 and MCP-1, when compared to PPARα(+/+ )mice. PPARα(-/- )mice also displayed enhanced MMP-9 activity. Conversely, fenofibrate (0.15 to 15 mg/day) dose-dependently reduced the increase in neutrophil and macrophage number induced by LPS in wild-type mice. In animals treated with 15 mg/day fenofibrate, this effect was associated with a reduction in TNF-α, KC, MIP-2 and MCP-1 levels, as well as in MMP-2 and MMP-9 activity. PPARα(-/- )mice treated with 15 mg/day fenofibrate failed to exhibit decreased airway inflammatory cell infiltrate, demonstrating that PPARα mediates the anti-inflammatory effect of fenofibrate. CONCLUSION: Using both genetic and pharmacological approaches, our data clearly show that PPARα downregulates cell infiltration, chemoattractant production and enhanced MMP activity triggered by LPS in mouse lung. This suggests that PPARα activation may have a beneficial effect in acute or chronic inflammatory airway disorders involving neutrophils and macrophages

Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

BACKGROUND: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPARα or PPARγ ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPARα or PPARγ antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPARα and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPARα and PPARγ enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPARα and PPARγ agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPARγ agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. CONCLUSIONS: PPARα/γ and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired

Vanin-1 Pantetheinase Drives Smooth Muscle Cell Activation in Post-Arterial Injury Neointimal Hyperplasia

The pantetheinase vanin-1 generates cysteamine, which inhibits reduced glutathione (GSH) synthesis. Vanin-1 promotes inflammation and tissue injury partly by inducing oxidative stress, and partly by peroxisome proliferator-activated receptor gamma (PPARγ) expression. Vascular smooth muscle cells (SMCs) contribute to neointimal hyperplasia in response to injury, by multiple mechanisms including modulation of oxidative stress and PPARγ. Therefore, we tested the hypothesis that vanin-1 drives SMC activation and neointimal hyperplasia. We studied reactive oxygen species (ROS) generation and functional responses to platelet-derived growth factor (PDGF) and the pro-oxidant diamide in cultured mouse aortic SMCs, and also assessed neointima formation after carotid artery ligation in vanin-1 deficiency. Vnn1−/− SMCs demonstrated decreased oxidative stress, proliferation, migration, and matrix metalloproteinase 9 (MMP-9) activity in response to PDGF and/or diamide, with the effects on proliferation linked, in these studies, to both increased GSH levels and PPARγ expression. Vnn1−/− mice displayed markedly decreased neointima formation in response to carotid artery ligation, including decreased intima:media ratio and cross-sectional area of the neointima. We conclude that vanin-1, via dual modulation of GSH and PPARγ, critically regulates the activation of cultured SMCs and development of neointimal hyperplasia in response to carotid artery ligation. Vanin-1 is a novel potential therapeutic target for neointimal hyperplasia following revascularization