Unveiling optical signatures of outflows in accreting white dwarfs

Accreting white dwarfs are known to show signatures of wind-type outflows in the ultraviolet. At optical wavelengths, however, wind detections have only been reported for a few sources. We present GTC-10.4m optical spectroscopy of four accreting white dwarfs (BZ Cam, V751 Cyg, MV Lyr, and V425 Cas) observed during luminous epochs, when their optical emission is expected to be dominated by the accretion disc. We focused the analysis on four emission lines: H$\alpha$ and He I $\lambda$5876, $\lambda$6678, $\lambda$7065. Line profiles are complex and variable on short (minutes) and long (days to weeks) time scales, with transient absorption and emission components. Among them, we detect strong blue-shifted absorptions at $\gtrsim 1000$ km s$^{-1}$. These high-velocity components, present only in the blue wing of the emission lines, are observed in all four sources and could be associated with accretion disc winds. For MV Lyr and V425 Cas, these would represent the first detection of optical outflows in these objects, while in the case of BZ Cam and V751 Cyg, the presence of outflows has been previously reported. This study suggests that, in addition to ultraviolet winds, optical outflows might be also common in accreting white dwarfs. We discuss the observational properties of these winds and their possible similarity to those detected in accreting black holes and neutrons stars.Comment: Accepted for publication in A&

Optical and near-infrared spectroscopy of the black hole transient 4U 1543-47 during its 2021 ultra-luminous state

We present simultaneous optical and near-infrared spectra obtained during the 2021 outburst of the black hole transient 4U 1543-47. The X-ray hardness-intensity diagram and the comparison with similar systems reveal a luminous outburst, probably reaching the Eddington luminosity, as well as a long-lasting excursion to the so-called ultra-luminous state. VLT/X-shooter spectra were taken in two epochs 14 days apart during the early and brightest part of the outburst, while the source was in this ultra-luminous accretion state. The data show strong H and HeI emission lines, as well as high-excitation HeII and OIII transitions. Most lines are single-peaked in both spectra, except for the OIII lines that exhibit evident double-peaked profiles during the second epoch. The Balmer lines are embedded in broad absorption wings that we believe are mainly produced by the contribution of the A2V donor to the optical flux, which we estimate to be in the range of 11 to 14 per cent in the $r$ band during our observations. Although no conspicuous outflow features are found, we observe some wind-related line profiles, particularly in the near-infrared. Such lines include broad emission line wings and skewed red profiles, suggesting the presence of a cold (i.e. low ionisation) outflow with similar observational properties to those found in other low-inclination black hole transients.Comment: Accepted for publication in A&

A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome

ETV6/TEL is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners of which 16 have been cloned. Fluorescence in situ hybridization (FISH) analysis in a patient with myelodysplastic syndrome (MDS) revealed a t(1;12)(p36;p13) involving ETV6, with the breakpoint in this gene between exon 2 and exon 3. We report here the cloning of a novel ETV6 partner located on 1p36.1, involved in the t(1;12). 3' RACE-PCR from RNA identified a novel sequence fused to exon 2 of ETV6. Database searches localized this sequence in a bacterial artificial chromosome (BAC) mapped to 1p36 by fingerprint analysis. This result was confirmed by FISH using this BAC as probe. 5' and 3' RACE experiments with primers from this novel sequence were carried out on RNA from a healthy donor and identified a novel full-length mRNA, which we named MDS2 (myelodysplastic syndrome 2). RT-PCR experiments were performed on a panel of human cDNAs to analyze the expression pattern of this gene and they revealed four splicing variants. RT-PCR analysis showed that ETV6-MDS2, but not the reciprocal MDS2-ETV6 fusion transcript, was expressed in the bone marrow of the patient. The product of the ETV6-MDS2 fusion transcript predicts a short ETV6 protein containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking both the PTN and the DNA-binding domains. Possible mechanisms to account for the development of MDS in this patient are discussed

Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis

Purpose and Experimental Design: The stem cell factor/ KIT receptor loop may represent a novel target for molecular- based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWSFLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5–20 M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC50, 12–15 M). However, imatinib administered alone at doses close to IC50 for growth inhibition (10 M) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 M) was able to increase the antitumor in vitro effect of doxorubicin (DXR)and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15–20 and 15–36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. Conclusions: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor

Metástasis ganglionares de osteosarcomas

En este artículo presentamos dos pa cientes con osteosarcoma osteoblástico de tercio distal de fémur que cursaron con afectación ganglionar loco - regional. En el primer caso, el paciente presentó dos metástasis ganglionares en re gión inguinal y pél vica dos años después del diagnóstico del tumor pri mario. Actualmente tres meses después de la linfadenectomía se encuentra libre de enfermedad. En el segundo caso, durante el estudio de extensión del tu mor primario, se observaron imá genes nodulares de alta densidad en zona inguinal derecha, que corres pondieron a metástasis del tumor primari

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38 6% and were serious in 30 0%. AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only 2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of 33 5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Discovery of optical outflows and inflows in the black hole candidate GRS 1716-249

We present optical spectroscopy obtained with the GTC, VLT and SALT telescopes during the decline of the 2016-2017 outburst of the black hole candidate GRS 1716-249 (Nova Oph 1993). Our 18-epoch data set spans 6 months and reveals that the observational properties of the main emission lines are very variable, even on time scales of a few hours. Several epochs are characterised by P-Cyg (as well as flat-top and asymmetric) profiles in the H$\alpha$, H$\beta$ and He II ($\lambda$4686) emission lines, implying the presence of an accretion disc wind, which is likely hot and dense. The wind's terminal velocity ($\sim$2000 km s$^{-1}$) is similar to that observed in other black hole X-ray transients. These lines also show transient and sharp red-shifted absorptions, taking the form of inverted P-Cyg profiles. We argue that these profiles can be explained by the presence of infalling material at $\sim$1300 km s$^{-1}$. We propose a failed wind scenario to explain this inflow and discuss other alternatives, such as obscuration produced by an accretion-related structure (e.g. the gas stream) in a high inclination system.Comment: Published in MNRAS main journa

Role of Klotho and AGE/RAGE-Wnt/β-catenin signalling pathway on the development of cardiac and renal fibrosis in diabetes

Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, markers of fibrosis (collagen deposition, fibronectin, TGF-β1, and Wnt/β-catenin pathway), hypertrophy of the kidney and/or heart were analysed. At the end of study, diabetic rats showed higher levels of urinary sKlotho, AGEs and sRAGE and lower serum sKlotho compared with controls without differences in the renal Klotho expression. A significant positive correlation was found between urinary sKlotho and AGEs and urinary albumin/creatinine ratio (uACR). Fibrosis and RAGE levels were significantly higher in the heart without differences in the kidney of diabetic rats compared to controls. The results also suggest the increase in sKlotho and sRAGE excretion may be due to polyuria in the diabetic rats