Immediate effects of dasatinib on the migration and redistribution of naïve and memory lymphocytes associated with lymphocytosis in chronic myeloid leukemia patients

Introduction: Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib. Patients, Materials and Methods: Peripheral blood samples from CML patients treated with second-line dasatinib were collected before and 2 h after the first dasatinib intake, and follow-up samples from the same patients 3 and 6 months after the start of therapy. The migratory capacity and phenotype of lymphocytes and differential blood counts before and after drug intake were compared for all study time-points. Results: We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naïve CD45RA+ and central memory CD45RO+ T-cells. Similarly, naïve B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte counts remained unchanged after taking the drug. Discussion: We, therefore, conclude that lymphocytosis induced by dasatinib reflects a pronounced redistribution of naïve and memory populations of all lymphocyte subsets including CD4+ and CD8+ T-cells and B-cells

Science requirement document (SRD) for the European Solar Telescope (EST) (2nd edition, December 2019)

The European Solar Telescope (EST) is a research infrastructure for solar physics. It is planned to be an on-axis solar telescope with an aperture of 4 m and equipped with an innovative suite of spectro-polarimetric and imaging post-focus instrumentation. The EST project was initiated and is driven by EAST, the European Association for Solar Telescopes. EAST was founded in 2006 as an association of 14 European countries. Today, as of December 2019, EAST consists of 26 European research institutes from 18 European countries. The Preliminary Design Phase of EST was accomplished between 2008 and 2011. During this phase, in 2010, the first version of the EST Science Requirement Document (SRD) was published. After EST became a project on the ESFRI roadmap 2016, the preparatory phase started. The goal of the preparatory phase is to accomplish a final design for the telescope and the legal governance structure of EST. A major milestone on this path is to revisit and update the Science Requirement Document (SRD). The EST Science Advisory Group (SAG) has been constituted by EAST and the Board of the PRE-EST EU project in November 2017 and has been charged with the task of providing with a final statement on the science requirements for EST. Based on the conceptual design, the SRD update takes into account recent technical and scientific developments, to ensure that EST provides significant advancement beyond the current state-of-the-art. The present update of the EST SRD has been developed and discussed during a series of EST SAG meetings. The SRD develops the top-level science objectives of EST into individual science cases. Identifying critical science requirements is one of its main goals. Those requirements will define the capabilities of EST and the post-focus instrument suite. The technical requirements for the final design of EST will be derived from the SRD

J-PLUS: The javalambre photometric local universe survey

ABSTRACT: TheJavalambrePhotometric Local UniverseSurvey (J-PLUS )isanongoing 12-band photometricopticalsurvey, observingthousands of squaredegrees of theNorthernHemispherefromthededicated JAST/T80 telescope at the Observatorio Astrofísico de Javalambre (OAJ). The T80Cam is a camera with a field of view of 2 deg2 mountedon a telescopewith a diameter of 83 cm, and isequippedwith a uniquesystem of filtersspanningtheentireopticalrange (3500–10 000 Å). Thisfiltersystemis a combination of broad-, medium-, and narrow-band filters, optimallydesigned to extracttherest-framespectralfeatures (the 3700–4000 Å Balmer break region, Hδ, Ca H+K, the G band, and the Mg b and Ca triplets) that are key to characterizingstellartypes and delivering a low-resolutionphotospectrumforeach pixel of theobservedsky. With a typicaldepth of AB ∼21.25 mag per band, thisfilter set thusallowsforanunbiased and accuratecharacterization of thestellarpopulation in our Galaxy, itprovidesanunprecedented 2D photospectralinformationforall resolved galaxies in the local Universe, as well as accuratephoto-z estimates (at the δ z/(1 + z)∼0.005–0.03 precisionlevel) formoderatelybright (up to r ∼ 20 mag) extragalacticsources. Whilesomenarrow-band filters are designedforthestudy of particular emissionfeatures ([O II]/λ3727, Hα/λ6563) up to z < 0.017, theyalsoprovidewell-definedwindowsfortheanalysis of otheremissionlines at higherredshifts. As a result, J-PLUS has thepotential to contribute to a widerange of fields in Astrophysics, both in thenearbyUniverse (MilkyWaystructure, globular clusters, 2D IFU-likestudies, stellarpopulations of nearby and moderate-redshiftgalaxies, clusters of galaxies) and at highredshifts (emission-line galaxies at z ≈ 0.77, 2.2, and 4.4, quasi-stellarobjects, etc.). Withthispaper, wereleasethefirst∼1000 deg2 of J-PLUS data, containingabout 4.3 millionstars and 3.0 milliongalaxies at r <  21mag. With a goal of 8500 deg2 forthe total J-PLUS footprint, thesenumbers are expected to rise to about 35 millionstars and 24 milliongalaxiesbytheend of thesurvey.Funding for the J-PLUS Project has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel, the Spanish Ministry of Economy and Competitiveness (MINECO; under grants AYA2017-86274-P, AYA2016-77846-P, AYA2016-77237-C3-1-P, AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, AGAUR grant SGR-661/2017, and ICTS-2009-14), and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685

Capa de fibras nerviosas en ojos glaucomatosos. Estudio realizado mediante OCT y su comparación con el campo visual

To investigate the retinal nerve fiber layer (RNFL) thickness in glaucomatous eyes using Optical Coherence Tomography (OCT). To compare the RNFL thickness with visual field damage (Humphrey field analyzer). MATERIAL AND METHODS: The mean RNFL thickness in glaucomatous eyes (n = 80) was compared with age-matched normal eyes (n = 40). Three circular scans were obtained for each eye using OCT (3.4 mm diameter). In each eye, average RNFL, 4 quadrants and 12 meridians were calculated and compared. The superior-inferior asymmetry of RNFL was studied. The average RNFL thickness was compared with mean deviation (MD) and mean standard deviation (MSD) of SITA 24-2 visual field program. RESULTS: Mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes (p<0.001). The RNFL thickness was decrease in the 4 quadrants and 11 of 12 meridians studied in glaucomatous eyes (p<0.05). The superior-inferior asymmetry showed a significant difference in RNFL thickness at 30 degrees central meridian (p<0.05). Mean RNFL thickness was significantly associated with DM and DSM of visual field (p<0.001) in glaucomatous eyes. CONCLUSIONS: OCT revealed significant quantitative differences in RNFL thickness between glaucomatous and normal eyes. OCT showed a considerable measurements overlap between glaucomatous and normal eyes, which can limit the sensitivity and specificity of this instrumen

Capa de fibras nerviosas en ojos glaucomatosos. Estudio realizado mediante OCT y su comparación con el campo visual

To investigate the retinal nerve fiber layer (RNFL) thickness in glaucomatous eyes using Optical Coherence Tomography (OCT). To compare the RNFL thickness with visual field damage (Humphrey field analyzer). MATERIAL AND METHODS: The mean RNFL thickness in glaucomatous eyes (n = 80) was compared with age-matched normal eyes (n = 40). Three circular scans were obtained for each eye using OCT (3.4 mm diameter). In each eye, average RNFL, 4 quadrants and 12 meridians were calculated and compared. The superior-inferior asymmetry of RNFL was studied. The average RNFL thickness was compared with mean deviation (MD) and mean standard deviation (MSD) of SITA 24-2 visual field program. RESULTS: Mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes (p<0.001). The RNFL thickness was decrease in the 4 quadrants and 11 of 12 meridians studied in glaucomatous eyes (p<0.05). The superior-inferior asymmetry showed a significant difference in RNFL thickness at 30 degrees central meridian (p<0.05). Mean RNFL thickness was significantly associated with DM and DSM of visual field (p<0.001) in glaucomatous eyes. CONCLUSIONS: OCT revealed significant quantitative differences in RNFL thickness between glaucomatous and normal eyes. OCT showed a considerable measurements overlap between glaucomatous and normal eyes, which can limit the sensitivity and specificity of this instrumen

Melatonin as an apoptotis antagonist

The pineal hormone melatonin (Mel), in addition to having a well-established role as a regulator of circadian rhythms, modulates nonneural compartments by acting on specific plasma membrane receptors (MT1/MT2) present in many different cell types. Mel plays immunomodulatory roles and is an oncostatic and antiproliferative agent; this led to the widespread belief that Mel may induce or potentiate apoptosis on tumor cells, even though no clear indications have been presented so far. Here we report that Mel is not apoptogenic on U937 human monocytic cells, which are known to possess MT1 receptors at the times (up to 48 h) and doses (up to 1 mM) tested. Mel does not even potentiate apoptosis, but instead, significantly reduces apoptosis induced by both cell-damaging agents (intrinsic pathway) and physiological means (extrinsic pathway). The doses required for the antiapoptotic effect (>or=100 microM) are apparently not compatible with receptor stimulation (receptor affinity<1 nM). However, receptor involvement cannot be ruled out, because we discovered that the actual Mel concentration active on cells was lower than the nominal one because of sequestration by fetal calf serum (FCS). Accordingly, in FCS-free conditions, Mel doses required for a significant antiapoptotic effect are much lower