RR Lyrae Variables in the Local Group Dwarf Galaxy NGC 147

We investigate the RR Lyrae population in NGC 147, a dwarf satellite galaxy of M31 (Andromeda). We used both Thuan-Gunn g-band ground-based photometry from the literature and Hubble Space Telescope Wide Field Planetary Camera 2 archival data in the F555W and F814W passbands to investigate the pulsation properties of RR Lyrae variable candidates in NGC 147. These datasets represent the two extreme cases often found in RR Lyrae studies with respect to the phase coverage of the observations and the quality of the photometric measurements. Extensive artificial variable star tests for both cases were performed. We conclude that neither dataset is sufficient to confidently determine the pulsation properties of the NGC 147 RR Lyraes. Thus, while we can assert that NGC 147 contains RR Lyrae variables, and therefore a population older than ~10 Gyr, it is not possible at this time to use the pulsation properties of these RR Lyraes to study other aspects of this old population. Our results provide a good reference for gauging the completeness of RR Lyrae variable detection in future studies.Comment: Accepted for publication in The Astrophysical Journa

Data on the effects of low iron diet on serum lipid profile in HCV transgenic mouse model

Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presented original data have not been published elsewhere

RR Lyrae Variables in Two Fields in the Spheroid of M31

We present Hubble Space Telescope observations taken with the Advanced Camera for Surveys Wide Field Channel of two fields near M32—between 4 and 6 kpc from the center of M31. The data cover a time baseline sufficient for the identification and characterization of 681 RR Lyrae variables of which 555 are ab-type and 126 are c-type. The mean magnitude of these stars is = 25.29 ± 0.05, where the uncertainty combines both the random and systematic errors. The location of the stars in the Bailey diagram and the ratio of c-type RR Lyraes to all types are both closer to RR Lyraes in Oosterhoff type I globular clusters in the Milky Way as compared with Oosterhoff II clusters. The mean periods of the ab-type and c-type RR Lyraes are = 0.557 ± 0.003 and = 0.327 ± 0.003, respectively, where the uncertainties in each case represent the standard error of the mean. When the periods and amplitudes of the ab-type RR Lyraes in our sample are interpreted in terms of metallicity, we find the metallicity distribution function to be indistinguishable from a Gaussian with a peak at = –1.50 ± 0.02, where the quoted uncertainty is the standard error of the mean. Using a relation between RR Lyrae luminosity and metallicity along with a reddening of E(B – V) = 0.08 ± 0.03, we find a distance modulus of (m – M)_0 = 24.46 ± 0.11 for M31. We examine the radial metallicity gradient in the environs of M31 using published values for the bulge and halo of M31 as well as the abundances of its dwarf spheroidal companions and globular clusters. In this context, we conclude that the RR Lyraes in our two fields are more likely to be halo objects rather than associated with the bulge or disk of M31, in spite of the fact that they are located at 4-6 kpc in projected distance from the center

SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation.Conclusions: Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation. © 2014 Montaldo et al.; licensee BioMed Central Ltd

Hepatitis C virus production requires apolipoprotein A-I and affects its association with nascent low-density lipoproteins

Background/aims The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of viral particles. However, the details of how HCV interacts with and influences the metabolism of the host lipoproteins are not well understood. A study was undertaken to investigate whether HCV directly affects the protein composition of host circulating lipoproteins. Methods A proteomic analysis of circulating very low-, low- and high-density lipoproteins (VLDL, LDL and HDL), isolated from either in-treatment naive HCV-infected patients or healthy donors (HD), was performed using two-dimensional gel electrophoresis and tandem mass spectrometry (MALDI-TOF/TOF). The results obtained were further investigated using in vitro models of HCV infection and replication. Results A decreased level of apolipoprotein A-I (apoA-I) was found in the LDL fractions of HCV-infected patients. This result was confirmed by western blot and ELISA analysis. HCV cellular models (JFH1 HCV cell culture system (HCVcc) and HCV subgenomic replicons) showed that the decreased apoA-I/LDL association originates from hepatic biogenesis rather than lipoprotein catabolism occurring in the circulation, and is not due to a downregulation of the apoA-I protein concentration. The sole non-structural viral proteins were sufficient to impair the apoA-I/LDL association. Functional evidence was obtained for involvement of apoA-I in the viral life cycle such as RNA replication and virion production. The specific siRNA-mediated downregulation of apoA-I led to a reduction in both HCV RNA and viral particle levels in culture. Conclusions This study shows that HCV induces lipoprotein structural modification and that its replication and production are linked to the host lipoprotein metabolism, suggesting apoA-I as a new possible target for antiviral therapy

Influence of Cognitive Orientation and Attentional Focus on Pain Perception

Background. Recently, a growing interest has emerged in the role of attention and hypervigilance in the experience of pain. Shifting attention away from pain seems likely to reduce the perception of pain itself. Objectives. The present study has been designed to test the following overall hypotheses: (1) disposition to catastrophize, self-efficacy perceived in pain resistance (task self-efficacy), previous experiences concerning the tolerance of physical pain, and degree of impulsiveness are significant predictors of the decision to abandon a painful test such as the cold pressor test (CPT); (2) the manipulation of the attentive focus (internal or external) can influence the level of perceived pain. Methods. Effects of the manipulation of attentional focus (internal and external) on pain perception and response of trial abandonment were evaluated in a sample of university students (n = 246) subjected to the cold pressor test. Results. A significant effect (p < 0.05) was found through a test–retest comparison on the final level of perceived pain among subjects who had received instruction to externalize the focus of their attention (mixed factorial analysis of variance), but no significance was observed with respect to the decision to abandon the experiment. A general explanatory model of the abandonment behavior demonstrating overall good fit measurements was tested too. Conclusion. The abandonment of tests has been shown to be predicted mainly by catastrophic attitude. Attentive impulsiveness showed a further positive effect on catastrophic attitude. Perceived self-efficacy in the tolerance of pain limited learned helplessness, which in turn positively influenced catastrophizing

The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α

The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase chain reaction. HNF4α recruitment on promoters of both mesenchymal and EMT regulator genes was determined by way of electrophoretic mobility shift assay and chromatin immunoprecipitation. The effect of HNF4α depletion was assessed in silenced cells and in the context of the whole liver of HNF4 knockout animals. Our results identified key EMT regulators and mesenchymal genes as new targets of HNF4α. HNF4α, in cooperation with its target HNF1α, directly inhibits transcription of the EMT master regulatory genes Snail, Slug, and HMGA2 and of several mesenchymal markers. HNF4α-mediated repression of EMT genes induces MET in hepatomas, and its silencing triggers the mesenchymal program in differentiated hepatocytes both in cell culture and in the whole liver. Conclusion: The pivotal role of HNF4α in the induction and maintenance of hepatocyte differentiation should also be ascribed to its capacity to continuously repress the mesenchymal program; thus, both HNF4α activator and repressor functions are necessary for the identity of hepatocytes. Copyright © 2011 American Association for the Study of Liver Diseases

The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4\uce\ub1

The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4\uce\ub1 (HNF4\uce\ub1) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase chain reaction. HNF4\uce\ub1 recruitment on promoters of both mesenchymal and EMT regulator genes was determined by way of electrophoretic mobility shift assay and chromatin immunoprecipitation. The effect of HNF4\uce\ub1 depletion was assessed in silenced cells and in the context of the whole liver of HNF4 knockout animals. Our results identified key EMT regulators and mesenchymal genes as new targets of HNF4\uce\ub1. HNF4\uce\ub1, in cooperation with its target HNF1\uce\ub1, directly inhibits transcription of the EMT master regulatory genes Snail, Slug, and HMGA2 and of several mesenchymal markers. HNF4\uce\ub1-mediated repression of EMT genes induces MET in hepatomas, and its silencing triggers the mesenchymal program in differentiated hepatocytes both in cell culture and in the whole liver. Conclusion: The pivotal role of HNF4\uce\ub1 in the induction and maintenance of hepatocyte differentiation should also be ascribed to its capacity to continuously repress the mesenchymal program; thus, both HNF4\uce\ub1 activator and repressor functions are necessary for the identity of hepatocytes. Copyright \uc2\ua9 2011 American Association for the Study of Liver Diseases

The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation

Lamin A is a component of the nuclear matrix that also controls proliferation by largely unknown mechanisms. NF-Y is a ubiquitous protein involved in cell proliferation composed of three subunits (-YA -YB -YC) all required for the DNA binding and transactivation activity. To get clues on new NF-Y partner(s) we performed a mass spectrometry screening of proteins that co-precipitate with the regulatory subunit of the complex, NF-YA. By this screening we identified lamin A as a novel putative NF-Y interactor. Co-immunoprecipitation experiments and confocal analysis confirmed the interaction between the two endogenous proteins. Interestingly, this association occurs on euchromatin regions, too. ChIP experiments demonstrate lamin A enrichment in several promoter regions of cell cycle related genes in a NF-Y dependent manner. Gain and loss of function experiments reveal that lamin A counteracts NF-Y transcriptional activity. Taking advantage of a recently generated transgenic reporter mouse, called MITO-Luc, in which an NF-Y–dependent promoter controls luciferase expression, we demonstrate that lamin A counteracts NF-Y transcriptional activity not only in culture cells but also in living animals. Altogether, our data demonstrate the occurrence of lamin A/NF-Y interaction and suggest a possible role of this protein complex in regulation of NF-Y function in cell proliferatio