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- Gavriilidis, GI, et al.
(author)
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Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia
- 2021
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:3, s. 692-700
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Journal article (peer-reviewed)abstract
- The inflammatory cytokine Stem Cell Factor (SCF, ligand of c-kit receptor) has been implicated as a pro-oncogenic driver and an adverse prognosticator in several human cancers. Increased SCF levels have recently been reported in a small series of patients with chronic lymphocytic leukemia (CLL), however its precise role in CLL pathophysiology remains elusive. In this study, CLL cells were found to predominantly express the membrane isoform of SCF that is known to elicit a more robust activation of the c-kit receptor. SCF was significantly overexpressed in CLL cells compared to healthy tonsillar B cells whilst it correlated with adverse-prognostic biomarkers, shorter time-to-first treatment and shorter overall survival. Activation of immune receptors and long-term cell-cell interactions with the mesenchymal stroma led to an elevation of SCF primarily in adverse-prognostic CLL cases. On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels. Interestingly, SCF significantly correlated with mitochondrial dynamics and HIF-1α which have previously been linked with clinical aggressiveness in CLL. SCF was able to elicit direct biological effects in CLL cells affecting redox homeostasis and cell proliferation. Overall, the aberrantly expressed SCF in CLL cells emerges as a key response regulator to microenvironmental stimuli whilst correlating with poor prognosis. On these grounds, specific targeting of this inflammatory molecule could serve as a novel therapeutic approach in CLL.
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- Maharana, S., et al.
(author)
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Bright-Moon sky as a wide-field linear Polarimetric flat source for calibration
- 2023
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
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Journal article (peer-reviewed)abstract
- Context. Next-generation wide-field optical polarimeters such as Wide-Area Linear Optical Polarimeters (WALOPs) have a field of view (FoV) of tens of arcminutes. Wide-field polarimetric flat sources are essential to the efficient and accurate calibration of these instruments. However, no established wide-field polarimetric standard or flat sources exist at present. Aims. This study tests the feasibility of using the polarized sky patches of the size of around 10 × 10 arcminutes2, at a distance of up to 20 from the Moon, on bright-Moon nights as a wide-field linear polarimetric flat source. Methods. We observed 19 patches of the sky adjacent to the bright-Moon with the RoboPol instrument in the SDSS-r broadband filter. These patches were observed on five nights within two days of the full-Moon across two RoboPol observing seasons. Results. We find that for 18 of the 19 patches, the uniformity in the measured normalized Stokes parameters q and u is within 0.2%, with 12 patches exhibiting uniformity within 0.07% or better for both q and u simultaneously, making them reliable and stable wide-field linear polarization flats. Conclusions. We demonstrate that the sky on bright-Moon nights is an excellent wide-field linear polarization flat source. Various combinations of the normalized Stokes parameters q and u can be obtained by choosing suitable locations of the sky patch with respect to the Moon.
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- Pelgrims, V., et al.
(author)
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The first degree-scale starlight-polarization-based tomography map of the magnetized interstellar medium
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Journal article (peer-reviewed)abstract
- We present the first degree-scale tomography map of the dusty magnetized interstellar medium (ISM) from stellar polarimetry and distance measurements. We used the RoboPol polarimeter at Skinakas Observatory to conduct a survey of the polarization of starlight in a region of the sky of about four square degrees. We propose a Bayesian method to decompose the stellar-polarization source field along the distance to invert the three-dimensional (3D) volume occupied by the observed stars. We used this method to obtain the first 3D map of the dusty magnetized ISM. Specifically, we produced a tomography map of the orientation of the plane-of-sky component of the magnetic field threading the diffuse, dusty regions responsible for the stellar polarization. For the targeted region centered on Galactic coordinates (l, b) (103.3, 22.3), we identified several ISM clouds. Most of the lines of sight intersect more than one cloud. A very nearby component was detected in the foreground of a dominant component from which most of the polarization signal comes and which we identified as being an intersection of the wall of the Local Bubble and the Cepheus Flare. Farther clouds, with a distance of up to 2 kpc, were similarly detected. Some of them likely correspond to intermediate-velocity clouds seen in H I spectra in this region of the sky. We found that the orientation of the plane-of-sky component of the magnetic field changes along distance for most of the lines of sight. Our study demonstrates that starlight polarization data coupled to distance measures have the power to reveal the great complexity of the dusty magnetized ISM in 3D and, in particular, to provide local measurements of the plane-of-sky component of the magnetic field in dusty regions. This demonstrates that the inversion of large data volumes, as expected from the PASIPHAE survey, will provide the necessary means to move forward in the modeling of the Galactic magnetic field and of the dusty magnetized ISM as a contaminant in observations of the cosmic microwave background polarization.
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- Georgakis, Spiros, et al.
(author)
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NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE
- 2021
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In: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:21
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Journal article (peer-reviewed)abstract
- IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33-decorated NETs that stimulate robust IFN-α synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. IL33-silenced neutrophil-like cells cultured under lupus-inducing conditions generated NETs with diminished interferogenic effect. Importantly, NETs derived from patients with SLE are enriched in mature bioactive isoforms of IL-33 processed by the neutrophil proteases elastase and cathepsin G. Pharmacological inhibition of these proteases neutralized IL-33-dependent IFN-α production elicited by NETs. We believe these data demonstrate a novel role for cleaved IL-33 alarmin decorating NETs in human SLE, linking neutrophil activation, type I IFN production, and end-organ inflammation, with skin pathology mirroring that observed in the kidneys.
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