Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

HS 2325+8205 - an ideal laboratory for accretion disk physics

We identify HS 2325+8205 as an eclipsing, frequently outbursting dwarf nova with an orbital period of 279.841731(5) min. Spectroscopic observations are used to derive the radial velocity curve of the secondary star from absorption features and also from the H-alpha emission lines, originating from the accretion disc, yielding K_secondary = K_abs = 237 +- 28 km/s and K_emn = 145 +- 9 km/s respectively. The distance to the system is calculated to be 400 (+200, -140) pc. A photometric monitoring campaign reveals an outburst recurrence time of 12-14 d, The combination of magnitude range (17-14 mag), high declination, eclipsing nature and frequency of outbursts makes HS 2325+8205 the ideal system for "real-time" studies of the accretion disc evolution and behavior in dwarf nova outbursts.Comment: 20 pages, 7 figures. Accepted for Publications of the Astronomical Society of the Pacifi

IPHAS J062746.41+014811.3: a deeply eclipsing intermediate polar

We present time-resolved photometry of a cataclysmic variable discovered in the Isaac Newton Telescope Photometric Halpha Survey of the northern galactic plane, IPHAS J062746.41+014811.3 and classify the system as the fourth deeply eclipsing intermediate polar known with an orbital period of Porb=8.16 h, and spin period of Pspin=2210 s. The system shows mild variations of its brightness, that appear to be accompanied by a change in the amplitude of the spin modulation at optical wavelengths, and a change in the morphology of the eclipse profile. The inferred magnetic moment of the white dwarf is mu_wd = 6-7 x 10^33 Gcm^3, and in this case IPHAS J0627 will either evolve into a short-period EX Hya-like intermediate polar with a large Pspin\Porb ratio, or, perhaps more likely, into a synchronised polar. Swift observations show that the system is an ultraviolet and X-ray source, with a hard X-ray spectrum that is consistent with those seen in other intermediate polars. The ultraviolet light curve shows orbital modulation and an eclipse, while the low signal-to-noise ratio X-ray light curve does not show a significant modulation on the spin period. The measured X-ray flux is about an order of magnitude lower than would be expected from scaling by the optical fluxes of well-known X-ray selected intermediate polars.Comment: 34 pages, 9 figures, accepted for publication in Ap

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

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. II: The Second Year (2009-2010)

As an extension of the project in Kato et al. (2009, arXiv:0905.1757), we collected times of superhump maxima for 61 SU UMa-type dwarf novae mainly observed during the 2009-2010 season. The newly obtained data confirmed the basic findings reported in Kato et al. (2009): the presence of stages A-C, as well as the predominance of positive period derivatives during stage B in systems with superhump periods shorter than 0.07 d. There was a systematic difference in period derivatives for systems with superhump periods longer than 0.075 d between this study and Kato et al. (2009). We suggest that this difference is possibly caused by the relative lack of frequently outbursting SU UMa-type dwarf novae in this period regime in the present study. We recorded a strong beat phenomenon during the 2009 superoutburst of IY UMa. The close correlation between the beat period and superhump period suggests that the changing angular velocity of the apsidal motion of the elliptical disk is responsible for the variation of superhump periods. We also described three new WZ Sge-type objects with established early superhumps and one with likely early superhumps. We also suggest that two systems, VX For and EL UMa, are WZ Sge-type dwarf novae with multiple rebrightenings. The O-C variation in OT J213806.6+261957 suggests that the frequent absence of rebrightenings in very short-Porb objects can be a result of sustained superoutburst plateau at the epoch when usual SU UMa-type dwarf novae return to quiescence preceding a rebrightening. We also present a formulation for a variety of Bayesian extension to traditional period analyses.Comment: 63 pages, 77 figures, 1 appendix, Accepted for publication in PASJ, data correctio

SDSS J162520.29+120308.7 – a new SU Ursae Majoris star in the period gap

We report results of an extensive world-wide observing campaign devoted to the recently discovered dwarf nova SDSS J162520.29+120308.7 (SDSS J1625). The data were obtained during the July 2010 eruption of the star and in August and September 2010 when the object was in quiescence. During the July 2010 superoutburst, SDSS J1625 clearly displayed superhumps with a mean period of Psh = 0.095942(17) days (138.16 ± 0.02 min) and a maximum amplitude reaching almost 0.4 mag. The superhump period was not stable, decreasing very rapidly at a rate of ˙P = −1.63(14) × 10−3 at the beginning of the superoutburst and increasing at a rate of ˙P = 2.81(20) × 10−4 in the middle phase. At the end of the superoutburst, it stabilized around the value of Psh = 0.09531(5) day. During the first twelve hours of the superoutburst, a low-amplitude double wave modulation was observed whose properties are almost identical to early superhumps observed in WZ Sge stars. The period of early superhumps, the period of modulations observed temporarily in quiescence, and the period derived from radial velocity variations are the same within measurement errors, allowing us to estimate the most probable orbital period of the binary to be Porb = 0.09111(15) days (131.20 ± 0.22 min). This value clearly indicates that SDSS J1625 is another dwarf nova in the period gap. Knowledge of the orbital and superhump periods allows us to estimate the mass ratio of the system to be q ≈ 0.25. This high value poses serious problems for both the thermal and tidal instability (TTI) model describing the behaviour of dwarf novae and for some models explaining the origin of early superhumps

Fingolimod Treatment Modulates PPARγ and CD36 Gene Expression in Women with Multiple Sclerosis

Fingolimod is an oral immunomodulatory drug used in the treatment of multiple sclerosis (MS) that may change lipid metabolism. Peroxisome proliferator-activated receptors (PPAR) are transcription factors that regulate lipoprotein metabolism and immune functions and have been implicated in the pathophysiology of MS. CD36 is a scavenger receptor whose transcription is PPAR regulated. The objective of this study was to evaluate whether fingolimod treatment modifies PPAR and CD36 gene expression as part of its action mechanisms. Serum lipoprotein profiles and PPAR and CD36 gene expression levels in peripheral leukocytes were analysed in 17 female MS patients before and at 6 and 12 months after fingolimod treatment initiation. Clinical data during the follow-up period of treatment were obtained. We found that fingolimod treatment increased HDL-Cholesterol and Apolipoprotein E levels and leukocyte PPARγ and CD36 gene expression. No correlations were found between lipid levels and variations in PPARγ and CD36 gene expression. PPARγ and CD36 variations were significantly correlated during therapy and in patients free of relapse and stable disease. Our results suggest that PPARγ and CD36-mediated processes may contribute to the mechanisms of action of fingolimod in MS. Further studies are required to explore the relation of the PPARγ/CD36 pathway to the clinical efficacy of the drug and its involvement in the pathogenesis of the disease.info:eu-repo/semantics/publishedVersio

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients