Missing hard states and regular outbursts: the puzzling case of the black hole candidate 4U 1630-472

4U 1630-472 is a recurrent X-ray transient classified as a black-hole candidate from its spectral and timing properties. One of the peculiarities of this source is the presence of regular outbursts with a recurrence period between 600 and 730 d that has been observed since the discovery of the source in 1969. We report on a comparative study on the spectral and timing behaviour of three consecutive outbursts occurred in 2006, 2008 and 2010. We analysed all the data collected by the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) and the Rossi X-ray timing Explorer (RXTE) during these three years of activity. We show that, in spite of having a similar spectral and timing behaviour in the energy range between 3 and 30 keV, these three outbursts show pronounced differences above 30 keV. In fact, the 2010 outburst extends at high energies without any detectable cut-off until 150-200 keV, while the two previous outbursts that occurred in 2006 and 2008 are not detected at all above 30 keV. Thus, in spite of a very similar accretion disk evolution, these three outbursts exhibit totally different characteristics of the Compton electron corona, showing a softening in their evolution rarely observed before in a low mass X-ray binary hosting a black hole. We argue the possibility that the unknown perturbation that causes the outbursts to be equally spaced in time could be at the origin of this particular behaviour. Finally we describe several possible scenarios that could explain the regularity of the outbursts, identifying the most plausible, such as a third body orbiting around the binary system.Comment: April 2015: accepted for publication in MNRAS. May 2015: in pres

Missing hard states and regular outbursts: the puzzling case of the black hole candidate 4U 1630-472

4U 1630-472 is a recurrent X-ray transient classified as a black hole candidate from its spectral and timing properties. One of the peculiarities of this source is the presence of regular outbursts with a recurrence period between 600 and 730d that has been observed since the discovery of the source in 1969. We report on a comparative study of the spectral and timing behaviour of three consecutive outbursts that occurred in 2006, 2008 and 2010. We have analysed all the data collected by INTEGRAL and the Rossi X-ray Timing Explorer (RXTE) during these three years of activity. We show that, in spite of having a similar spectral and timing behaviour in the energy range between 3 and 30keV, these three outbursts show pronounced differences above 30keV. In fact, the 2010 outburst extends at high energies without any detectable cut-off until 150-200keV, while the two previous outbursts that occurred in 2006 and 2008 are not detected at all above 30keV. Thus, in spite of a very similar accretion disc evolution, these three outbursts exhibit totally different characteristics of the Compton electron corona, showing a softening in their evolution rarely observed before in a low-mass X-ray binary hosting a black hole. We argue the possibility that the unknown perturbation that causes the outbursts to be equally spaced in time could be at the origin of this particular behaviour. Finally, we describe several possible scenarios that could explain the regularity of the outbursts, identifying the most plausible, such as a third body orbiting around the binary syste

Effect of chicken bone extracts on metabolic and mitochondrial functions of K562 cell line

Background: Tetracyclines’ use in intensive animal farming has raised some concerns regarding the biosafety for humans. Increasing evidences have revealed the presence of these drugs in processed animal by-products, such as bone, throughout the food chain. A potential off-target of tetracyclines is the bacterial-like mitochondrial translational machinery, thereby causing proteostatic alterations in mitochondrial DNA-encoded components of the oxidative phosphorylation system. Methods: The Seahorse methodology, confocal microscopy imaging of mitochondrial potential and reactive oxygen species, and q-RT-PCR analysis of the expression of genes involved in mitochondrial biogenesis and mitophagy were carried out on human lymphoblast derived K562 cell line challenged with bone powder derived from chicken treated with or without oxytetracycline and pure oxytetracycline. Results: A complex dose-dependent profile was attained with a low dosage of bone powder extracts causing a metabolic adaptation hallmarked by stimulation of the mitochondrial respiration and enhanced expression of mitochondriogenic factors in particular in cells challenged with oxytetracycline-free bone extract. Conversely, a higher dosage of bone powder extracts, regardless of their source, caused a progressive inhibition of mitochondrial respiration and glycolysis, ultimately leading to cell death. No significant effects of the pure oxytetracycline were observed. Conclusion: Bone powder, regardless of chicken treatment, contains and releases factors/chemicals responsible for the observed effects on energy metabolism. Quantitative differential effects appear to depend on biochemical alterations in the bone matrix caused by antibiotics rather than antibiotics themselves

The peculiar 2011 outburst of the black hole candidate IGR J17091−3624, a GRS 1915+105-like source?

We report on the long-term monitoring campaign of the black hole candidate IGR J17091−3624 performed with INTEGRAL and Swift during the peculiar outburst started on 2011 January. We have studied the two-month spectral evolution of the source in detail. Unlike the previous outbursts, the initial transition from the hard to the soft state in 2011 was not followed by the standard spectral evolution expected for a transient black hole binary. IGR J17091−3624 showed pseudo-periodic flare-like events in the light curve, closely resembling those observed from GRS 1915+105. We find evidence that these phenomena are due to the same physical instability process ascribed to GRS 1915+105. Finally, we speculate that the faintness of IGR J17091−3624 could be not only due to the high distance of the source but also due to the high inclination angle of the syste

Unveiling metabolic vulnerability and plasticity of human osteosarcoma stem and differentiated cells to improve cancer therapy

Defining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. To this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. The results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. All together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy

Ultrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke

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Deferasirox drives ROS-mediated differentiation and induces interferon-stimulated gene expression in human healthy haematopoietic stem/progenitor cells and in leukemia cells

Background: Administration of the iron chelator deferasirox (DFX) in transfusion-dependent patients occasionally results in haematopoiesis recovery by a mechanism remaining elusive. This study aimed to investigate at a molecular level a general mechanism underlying DFX beneficial effects on haematopoiesis, both in healthy and pathological conditions. Methods: Human healthy haematopoietic stem/progenitor cells (HS/PCs) and three leukemia cell lines were treated with DFX. N-Acetyl cysteine (NAC) and fludarabine were added as antioxidant and STAT1 inhibitor, respectively. In vitro colony-forming assays were assessed both in healthy and in leukemia cells. Intracellular and mitochondrial reactive oxygen species (ROS) as well as mitochondrial content were assessed by cytofluorimetric and confocal microscopy analysis; mtDNA was assessed by qRT-PCR. Differentiation markers were monitored by cytofluorimetric analysis. Gene expression analysis (GEA) was performed on healthy HS/PCs, and differently expressed genes were validated in healthy and leukemia cells by qRT-PCR. STAT1 expression and phosphorylation were assessed by Western blotting. Data were compared by an unpaired Student t test or one-way ANOVA. Results: DFX, at clinically relevant concentrations, increased the clonogenic capacity of healthy human CD34+ HS/PCs to form erythroid colonies. Extension of this analysis to human-derived leukemia cell lines Kasumi-1, K562 and HL60 confirmed DFX capacity to upregulate the expression of specific markers of haematopoietic commitment. Notably, the abovementioned DFX-induced effects are all prevented by the antioxidant NAC and accompanied with overproduction of mitochondria-generated reactive oxygen species (ROS) and increase of mitochondrial content and mtDNA copy number. GEA unveiled upregulation of genes linked to interferon (IFN) signalling and tracked back to hyper-phosphorylation of STAT1. Treatment of leukemic cell lines with NAC prevented the DFX-mediated phosphorylation of STAT1 as well as the expression of the IFN-stimulated genes. However, STAT1 inhibition by fludarabine was not sufficient to affect differentiation processes in leukemic cell lines. Conclusions: These findings suggest a significant involvement of redox signalling as a major regulator of multiple DFX-orchestrated events promoting differentiation in healthy and tumour cells. The understanding of molecular mechanisms underlying the haematological response by DFX would enable to predict patient's ability to respond to the drug, to extend treatment to other patients or to anticipate the treatment, regardless of the iron overload

The 3rd IBIS/ISGRI soft gamma-ray survey catalog

In this paper we report on the third soft gamma-ray source catalog obtained with the IBIS/ISGRI gamma-ray imager on board the INTEGRAL satellite. The scientific dataset is based on more than 40 Ms of high quality observations performed during the first three and a half years of Core Program and public IBIS/ISGRI observations. Compared to previous IBIS/ISGRI surveys, this catalog includes a substantially increased coverage of extragalactic fields, and comprises more than 400 high-energy sources detected in the energy range 17-100 keV, including both transients and faint persistent objects which can only be revealed with longer exposure times.Comment: Accepted for publication in ApJ Suppl.; 11 pages; 4 figures Minor changes to conten

Hematopoietic Stem/Progenitor Cells Express Functional Mitochondrial Energy-Dependent Cystic Fibrosis Transmembrane Conductance Regulator

Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine. Cystic fibrosis (CF) is one of the diseases whose hope of cure relies on the successful application of cell-based gene therapy. This study was aimed at characterizing murine HSPCs on the basis of their bioenergetic competence and CF transmembrane conductance regulator (CFTR) expression. Positively immunoselected Sca-1(+) HSPCs encompassed 2 populations distinguished by their different size, Sca-1 expression and mitochondrial content. The smaller were the cells, the higher was Sca-1 expression and the lower was the intracellular density of functional mitochondria. Reverse transcription-polymerase chain reaction and western blotting revealed that HSPCs expressed CFTR mRNA and protein, which was also functional, as assessed by spectrofluorimetric and patch-clamp techniques. Inhibition of mitochondrial oxidative phosphorylation by oligomycin resulted in a 70% decrease of both the intracelluar adenosine triphosphate content and CFTR-mediated channel activity. Finally, HSPCs with lower Sca-1 expression and higher mitochondrial content displayed higher CFTR levels. Our findings identify 2 subpopulations in HSPCs and unveil a so-far unappreciated relationship between bioenergetic metabolism and CFTR in HSPC biology