LIGHT/HVEM/LTβR Interaction as a Target for the Modulation of the Allogeneic Immune Response in Transplantation

[EN] The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTβR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance. This review discusses how targeting the interaction of LIGHT with HVEM and/or LTbR using recombinant soluble decoy receptors or monoclonal antibodies may represent an innovative therapeutic intervention for the prevention and treatment of allograft rejection and promotion of donor-specific tolerance. © 2013 The American Society of Transplantation and the American Society of Transplant SurgeonsSIThis work has been supported by grants FIS reference # PI10/01039 from Ministry of Health and Department of Education from Junta of Castilla and Leon reference # LE007A10-2 (to JIRB), and by the Swiss National Science Foundation (to PS

Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation

[EN]Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were impli-cated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting proper-ties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic allore-sponses refractory to current immunosuppression.SIThis work has been supported by grant FIS PI# 1300029 (Fondo de Investigaciones Sanitarias, Ministry of Health, Spanish Government and co-funded by European Union ERDF/ESF, “Investing in your future”), LE093U13 and Unit of Excellence Research UIC #012 (Department of Education of the Regional Government, Junta de Castilla y Leon) and Gerencia Regional de Salud (BIO/01/15) to JIRB, and by Miguel Servet National Grant (Health National Organization Research) CP12/03063, CPII17/00002 and FIS PI16/00002 (Instituto de Salud Carlos III and co-funded by European Union ERDF/ESF, “Investing in your future”), and Gerencia Regional de Salud GRS963/A/2014, GRS1142/A/2015 and GRS 1505/A/2017 to M.L.R.G.This work has been partially funded by the National Network CIBER-ONC (oncology research) CB16/12/00480. P.S. is funded by grant 31003A-17-6256 of the Swiss National Science Foundation. We thank University of Leon for providing funding to cover publication expenses

Spanish Research Report for 2021

Spanish catch and effort information used in this Report is based on the preliminary logbook data contributed by the Spanish Administration. The logbooks information for 2021 was available haul by haul. Total effort of the Spanish fleet in 2021 was 1,170 fishing days. Table 1 presents the preliminary Spanish catches by species and Division in 2021 in NAFO Regulatory Area. These catch figures are preliminary, the final catches to carry out the NAFO assessments will be agreed by the NAFO Joint Commission-Scientific Council Catch Estimation Strategy Advisory Group (CESAG)

Spanish Research Report for 2020

within the National Program of collection, management and use of data in the fisheries sector and support for scientific advice regarding the Common Fisheries Policy.Spanish catch and effort information used in this Report is based on the preliminary logbook data contributed by the Spanish Administration. The logbooks information for 2020 was available haul by haul. Table 1 presents the preliminary Spanish catches by species and Division in 2020 in NAFO Regulatory Area. Total effort of the Spanish fleet in 2020 was 1,200 fishing days. In 2020, IEO scientific observers were on board 31 fishing days that it means 3 % of the Spanish total effort. All length, age and biological information presented in this paper is based on sampling carried out by IEO scientific observers. In 2020, 37 samples were taken with 4816 individuals of different species examined (Table 2).The collection of the data presented in this document has been funded by the European Union through the European Maritime and Fisheries Fund (EMFF)Versión del editor

Processing and mechanical properties of novel biodegradable poly-lactic acid/Zn 3D printed scaffolds for application in tissue regeneration

The feasibility to manufacture scaffolds of poly-lactic acid reinforced with Zn particles by fused filament fabrication is demonstrated for the first time. Filaments of 2.85 mm in diameter of PLA reinforced with different weight fractions of $\mu$m-sized Zn - 1 wt. \% Mg alloy particles (in the range 3.5 to 17.5 wt. \%) were manufactured by a double extrusion in method in which standard extrusion is followed by a precision extrusion in a filament-maker machine. Filaments with constant diameter, negligible porosity and a homogeneous reinforcement distribution were obtained for Zn weight fractions of up to 10.5\%. It was found that the presence of Zn particles led to limited changes in the physico-chemical properties of the PLA that did not affect the window temperature for 3D printing nor the melt flow index. Thus, porous scaffolds could be manufactured by fused filament fabrication at 190\textdegree C with poly-lactic acid/Zn composites containing 3.5 and 7 wt. \% of Zn and at 170\textdegree C when the Zn content was 10.5 wt. \% with excellent dimensional accuracy and mechanical properties

Submarine deltaic geometries linked to steep, mountainous drainage basins in the northern shelf of the Alboran Sea: Filling the gaps in the spectrum of deltaic deposition

A comprehensive analysis of small deltaic environments linked to short, mountainous, and seasonal fluvial systems in the northern shelf of the Alboran Sea was undertaken in order to define the controlling parameters of the geomorphological variability. The database includes multibeam and backscatter imagery, surficial sediment samples, and high-resolution seismic profiles. Additionally, geomorphological and hydrodynamic modeling and statistical analysis (principal component and cluster analysis) of hydrological and physiographic variables were performed.Most of the studied deltaic systems have high-gradient, coarse-grained deposits with preferential development of the submarine portions to the detriment of the deltaic plains. The geomorphological analysis identified three basic types of plan-viewdistributions according to the length-to-width ratios: elongate, linguoid and lobate. Cross-slope profiles evidence dominant concave-upward geometries, fewer occurrences of planar geometries, and no sigmoid profiles. Sediment depocenters are extremely thick in proximal locations, but thin out rapidly seawards. The geometric distribution patterns of the deltaic systems are characterized by a predictable pattern in plan-view according to the type of fluvial system, ranging from a relatively large river to ephemeral creeks. Prevailing concave and secondary planar profiles support strong sediment progradation in the submarine realmand lowsediment retention in the emerged deltaic environment. Two different types of systems are distinguished: (1) larger rivers,where deltaic deposition is largely controlled by basin dimensions, ultimately dictating themagnitude of water and sediment discharges; and (2) smaller rivers and creeks,where deltaic geometries are related to the basin slopes. The influence of hydrodynamic variables on defining the submarine deltaic geometry has been observed in the case of concave-upward geometries, where geomorphological boundaries are defined by medium- and high-energy wave conditions.Versión del editor2,520

Spanish Research Report for 2019

Spanish catch and effort information used in this Report is based on the preliminary logbook data contributed by the Spanish Administration. The logbooks information for 2019 was available haul by haul. Table 1 presents the preliminary Spanish catches by species and Division in 2019 in NAFO Regulatory Area. Total effort of the Spanish fleet in 2019 was 1,272 fishing days. In 2019, IEO scientific observers were on board 257 fishing days that it means 20 % of the Spanish total effort. All length, age and biological information presented in this paper is based on sampling carried out by IEO scientific observers. In 2019, 376 samples were taken with 45,831 individuals of different species examined (Table 2)

Episodios de construcción de un delta mediterráneo: Cambio climático y modificaciones antropogénicas en el delta del río Adra

The evolutionary stages of the submarine delta off the Adra River are investigated in this study, under the context of climatic fluctuations entangled with increasing human activities and interventions in the drainage basins and adjacent shores during the Middle to Late Holocene. To achieve that goal, we used an extensive database comprising a set of bathymetric data covering different time slices, a dense grid of high-resolution seismic data and several sediment cores collected in the two submarine lobes of the Adra River delta. Two main evolutionary phases can be identified. The first one extended through most of the construction history and was mediated by major climatic events at the Mediterranean scale; this phase included three major progradational events occurring during the Mid Holocene, the Roman time and the Little Ice Age. The most recent phase is strongly determined by human modifications of the fluvial channels, and resulted in a drastic transformation of the submarine sedimentary environment.Versión del edito

Selective Reagent Ion Mass Spectrometric Investigations of the Nitroanilines

This paper presents an investigation of proton and charge transfer reactions to 2-, 3- and 4-nitroanilines (C6H6N2O2) involving the reagent ions H3O+·(H2O)n (n=0, 1 and 2) and O2+, respectively, as a function of reduced electric field (60-240 Td), using Selective Reagent Ion-Time-of-Flight-Mass Spectrometry (SRI-ToF-MS). To aid in the interpretation of the H3O+·(H2O)n experimental data, the proton affinities and gas-phase basicities for the three nitroaniline isomers have been determined using density functional theory. These calculations show that proton transfer from both the H3O+ and H3O+·H2O reagent ions to the nitroanilines will be exoergic and hence efficient, with the reactions proceeding at the collisional rate. For proton transfer from H3O+ to the NO2 sites, the exoergicities are 171 kJ mol-1 (1.8 eV), 147 kJ mol-1 (1.5 eV) and 194 kJ mol-1 (2.0 eV) for 2-, 3- and 4-nitroanilines, respectively. Electron transfer from all three of the nitroanilines is also significantly exothermic by approximately 4 eV. Although a substantial transfer of energy occurs during the ion/molecule reactions, the processes are found to predominantly proceed via non-dissociative pathways over a large reduced electric field range. Only at relatively high reduced electric fields (>180 Td) is dissociative proton and charge transfer observed. Differences in fragment product ions and their intensities provide a means to distinguish the isomers, with proton transfer distinguishing 2-nitroaniline (2-NA) from 3- and 4-NA, and charge transfer distinguishing 4-NA from 2- and 3-NA, thereby providing a means to enhance selectivity using SRI-ToF-MS.(VLID)4826158Version of recor