INTERFERÓN: MECANISMOS BIOQUÍMICOS DE FORMACIÓN Y ACCION

The group of proteins known as interferons is now one of the most important fields of research in Biology. This review summarizes our present knowledge about the biochemical mechanisms of synthesis and action of interferons. Discovered by Isaacs and Lindenmann as agents of vira1 interference, today it is known that they are produced by most of vertebrates in response to a lot of appropiate stimuli. Here we discuss the classification of interferons, the human genes in which the information for their production and for the protein machinery involved in their response is contained, the biochemical mechanisms of the interferon production in cues treated by an inductor, and those developed in the surrounding cells when interferon is secreted. We conclude with the expression of therapeutic use of interferon and the existence of similar proteins in vegetal species.El grupo.de proteínas conocido con el nombre de interferón constituye actualmente uno de los campos de investigación más fecundo de la Biología. El presente es un texto de revisión sobre los mecanismos bioquímicos de su síntesis y acción. Descubiertos por lsaacs y Lindenmann como agentes de interferencia vírica, se sabe que los interferones son producidos por la mayoría de los vertebrados en respuesta a una serie de estímulos apropiados. Aquí se revisa la clasificación de los interferones, los genes humanos que contienen la información tanto para su producción como para la de las proteínas que constituyen el sistema de respuesta, y los mecanismos bioquímicos por los que una célula tratada con un inductor produce el interferón, así como los que desencadenan éste, cuando es segregado, en las células del entorno. Tras una mención al empleo terapéutico de los interferones, se concluye abordando la posibilidad de existencia de fitointerferones

Influencia de temperatura y luz sobre la toxicidad del DNBP en postemergencia en trigo (Triticum vulgare L.).

Trigo-Triticum aestiv

High-pressure study of ScVO4 by Raman scattering and ab initio calculations

We report results of experimental and theoretical lattice-dynamics studies on scandium orthovanadate up to 35 GPa. Raman-active modes of the low-pressure zircon phase are measured up to 8.2 GPa, where the onset of an irreversible zircon-to-scheelite phase transition is detected. Raman-active modes in the scheelite structure are observed up to 16.5 GPa. Beyond 18.2 GPa we detected a gradual splitting of the Eg modes of the scheelite phase, indicating the onset of a second phase transition. Raman symmetries, frequencies, and pressure coefficients in the three phases of ScVO4 are discussed in the light of ab initio lattice-dynamics calculations that support the experimental results. The results on all the three phases of ScVO4 are compared with those previously reported for related orthovanadates.We acknowledge the financial support of the Spanish MCYT under Grants No. MAT2007-65990-C03-01/03, No. MAT2010-21270-C04-01/03/04, and No. CSD2007-00045, and the computation time provided by the Red Espanola de Supercomputacion and the supercomputer Atlante. F.J.M. acknowledges also financial support from "Vicerrectorado de Innovacion y Desarrollo de la UPV" (No. PAID-05-2009 through Project No. UPV2010-0096). Some of the authors are members of the MALTA Consolider Team.Panchal, V.; Manjón Herrera, FJ.; Errandonea, D.; Rodriguez-Hernandez, P.; López-Solano, J.; Muñoz, A.; Achary, S.... (2011). High-pressure study of ScVO4 by Raman scattering and ab initio calculations. Physical Review B. 83(6):641111-1-64111-10. https://doi.org/10.1103/PhysRevB.83.064111S641111-164111-10836Shafi, S. P., Kotyk, M. W., Cranswick, L. M. D., Michaelis, V. K., Kroeker, S., & Bieringer, M. (2009). In Situ Powder X-ray Diffraction, Synthesis, and Magnetic Properties of the Defect Zircon Structure ScVO4−x. Inorganic Chemistry, 48(22), 10553-10559. doi:10.1021/ic900927jMullica, D. F., Sappenfield, E. L., Abraham, M. M., Chakoumakos, B. C., & Boatner, L. A. (1996). Structural investigations of several LnVO4 compounds. Inorganica Chimica Acta, 248(1), 85-88. doi:10.1016/0020-1693(95)04971-1Errandonea, D., & Manjón, F. J. (2008). Pressure effects on the structural and electronic properties of ABX4 scintillating crystals. Progress in Materials Science, 53(4), 711-773. doi:10.1016/j.pmatsci.2008.02.001Aldred, A. T. (1984). Cell volumes of APO4, AVO4, and ANbO4 compounds, where A = Sc, Y, La–Lu. Acta Crystallographica Section B Structural Science, 40(6), 569-574. doi:10.1107/s0108768184002718Errandonea, D., Lacomba-Perales, R., Ruiz-Fuertes, J., Segura, A., Achary, S. N., & Tyagi, A. K. (2009). High-pressure structural investigation of several zircon-type orthovanadates. Physical Review B, 79(18). doi:10.1103/physrevb.79.184104López-Solano, J., Rodríguez-Hernández, P., & Muñoz, A. (2009). Ab initiostudy of high-pressure structural properties of the LuVO4and ScVO4zircon-type orthovanadates. High Pressure Research, 29(4), 582-586. doi:10.1080/08957950903417444Manjón, F. J., Rodríguez-Hernández, P., Muñoz, A., Romero, A. H., Errandonea, D., & Syassen, K. (2010). Lattice dynamics ofYVO4at high pressures. Physical Review B, 81(7). doi:10.1103/physrevb.81.075202Wang, X., Loa, I., Syassen, K., Hanfland, M., & Ferrand, B. (2004). Structural properties of the zircon- and scheelite-type phases ofYVO4at high pressure. Physical Review B, 70(6). doi:10.1103/physrevb.70.064109Klotz, S., Chervin, J.-C., Munsch, P., & Le Marchand, G. (2009). Hydrostatic limits of 11 pressure transmitting media. Journal of Physics D: Applied Physics, 42(7), 075413. doi:10.1088/0022-3727/42/7/075413Errandonea, D., Meng, Y., Somayazulu, M., & Häusermann, D. (2005). 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Physical Review Letters, 77(18), 3865-3868. doi:10.1103/physrevlett.77.3865Mujica, A., Rubio, A., Muñoz, A., & Needs, R. J. (2003). High-pressure phases of group-IV, III–V, and II–VI compounds. Reviews of Modern Physics, 75(3), 863-912. doi:10.1103/revmodphys.75.863Guedes, I., Hirano, Y., Grimsditch, M., Wakabayashi, N., Loong, C.-K., & Boatner, L. A. (2001). Raman study of phonon modes in ErVO4 single crystals. Journal of Applied Physics, 90(4), 1843-1846. doi:10.1063/1.1384858Garg, A. B., Rao, R., Sakuntala, T., Wani, B. N., & Vijayakumar, V. (2009). Phase stability of YbVO4 under pressure: In situ x-ray and Raman spectroscopic investigations. Journal of Applied Physics, 106(6), 063513. doi:10.1063/1.3223327Santos, C. C., Silva, E. N., Ayala, A. P., Guedes, I., Pizani, P. S., Loong, C.-K., & Boatner, L. A. (2007). Raman investigations of rare earth orthovanadates. Journal of Applied Physics, 101(5), 053511. doi:10.1063/1.2437676Zhang, F. X., Wang, J. W., Lang, M., Zhang, J. 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Lattice dynamics study of scheelite tungstates under high pressure I.BaWO4. Physical Review B, 74(14). doi:10.1103/physrevb.74.144111Manjon, F. J., Errandonea, D., Garro, N., Pellicer-Porres, J., López-Solano, J., Rodríguez-Hernández, P., … Muñoz, A. (2006). Lattice dynamics study of scheelite tungstates under high pressure II.PbWO4. Physical Review B, 74(14). doi:10.1103/physrevb.74.144112Panchal, V., Garg, N., & Sharma, S. M. (2006). Raman and x-ray diffraction investigations on BaMoO4under high pressures. Journal of Physics: Condensed Matter, 18(16), 3917-3929. doi:10.1088/0953-8984/18/16/002Hardcastle, F. D., & Wachs, I. E. (1991). Determination of vanadium-oxygen bond distances and bond orders by Raman spectroscopy. The Journal of Physical Chemistry, 95(13), 5031-5041. doi:10.1021/j100166a025Brown, I. D., & Wu, K. K. (1976). Empirical parameters for calculating cation–oxygen bond valences. Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, 32(7), 1957-1959. doi:10.1107/s0567740876006869Lacomba-Perales, R., Martinez-García, D., Errandonea, D., Le Godec, Y., Philippe, J., Le Marchand, G., … López-Solano, J. (2010). Experimental and theoretical investigation of the stability of the monoclinicBaWO4-II phase at high pressure and high temperature. Physical Review B, 81(14). doi:10.1103/physrevb.81.144117Tschauner, O., Errandonea, D., & Serghiou, G. (2006). Possible superlattice formation in high-temperature treated carbonaceous MgB2 at elevated pressure. Physica B: Condensed Matter, 371(1), 88-94. doi:10.1016/j.physb.2005.09.042Errandonea, D., Kumar, R. S., Ma, X., & Tu, C. (2008). High-pressure X-ray diffraction study of SrMoO4 and pressure-induced structural changes. Journal of Solid State Chemistry, 181(2), 355-364. doi:10.1016/j.jssc.2007.12.010Errandonea, D., Santamaria-Perez, D., Grover, V., Achary, S. N., & Tyagi, A. K. (2010). High-pressure x-ray diffraction study of bulk and nanocrystalline PbMoO4. Journal of Applied Physics, 108(7), 073518. doi:10.1063/1.3493048Errandonea, D., Santamaria-Perez, D., Bondarenko, T., & Khyzhun, O. (2010). New high-pressure phase of HfTiO4 and ZrTiO4 ceramics. Materials Research Bulletin, 45(11), 1732-1735. doi:10.1016/j.materresbull.2010.06.061Marqués, M., Flórez, M., Recio, J. M., Gerward, L., & Olsen, J. S. (2006). Structure and stability ofZrSiO4under hydrostatic pressure. Physical Review B, 74(1). doi:10.1103/physrevb.74.014104Lacomba-Perales, R., Errandonea, D., Meng, Y., & Bettinelli, M. (2010). High-pressure stability and compressibility ofAPO4(A=La, Nd, Eu, Gd, Er, and Y) orthophosphates: An x-ray diffraction study using synchrotron radiation. Physical Review B, 81(6). doi:10.1103/physrevb.81.064113Long, Y. W., Zhang, W. W., Yang, L. X., Yu, Y., Yu, R. C., Ding, S., … Jin, C. Q. (2005). 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The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate

Different types of graft-versus-host disease prophylaxis have been proposed in the setting of reduced intensity and non-myeloablative allogeneic stem cell transplantation. An alternative combination with sirolimus and tacrolimus has recently been tested although comparative studies against the classical combination of a calcineurin inhibitor and mycophenolate mofetil or methotrexate are lacking. We describe the results of a prospective, multicenter trial using sirolimus + tacrolimus as immunoprophylaxis, and compare this approach with our previous experience using cyclosporine + mycophenolate in the setting of unrelated donor transplantation setting after reduced-intensity conditioning. Forty-five patients received cyclosporine + mycophenolate between 2002 and mid-2007, while the subsequent 50 patients, who were transplanted from late 2007, were given sirolimus + tacrolimus. No significant differences were observed in terms of hematopoietic recovery or acute graft-versus-host disease overall, although gastrointestinal acute graft-versus-host disease grade ≥2 was more common in the cyclosporine + mycophenolate group (55% versus 21%, respectively, P=0.003). The 1-year cumulative incidence of chronic graftversus-host disease was 50% versus 90% for the patients treated with the sirolimus- versus cyclosporine-based regimen, respectively (P<0.001), while the incidence of extensive chronic disease was 27% versus 49%, respectively (P=0.043). The 2-year non-relapse mortality rate was 18% versus 38% for patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively (P=0.02). The event-free survival and overall survival at 2 years were 53% versus 29% (P=0.028) and 70% versus 45% (P=0.018) among patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively. In conclusion, in the setting of reduced intensity transplantation from an unrelated donor, promising results can be achieved with the combination of sirolimus + tacrolimus, due to a lower risk of chronic graft-versus-host disease and non-relapse mortality, which translates into better event-free and over all survival rates, in comparison with those achieved with cyclosporine + mycophenolate

Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regression analysis of a randomized, open-label study in Latin American patients with rheumatoid arthritis

Background: Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. Methods: Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score  28.5 kg/m2 (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. Conclusions In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy

Microplastic pollution in sublittoral coastal sediments of a North Atlantic island: The case of La Palma (Canary Islands, Spain)

In this work, the microplastic content of sediments collected in July 2020 between 5 and 7 m depth was studied in four locations of La Palma island (Canary Islands, Spain). At each sampling location, three samples were taken parallel to the shoreline. The microplastic content in each sampling corer was studied every 2.5 cm depth after digestion with a H2O2 solution followed by flotation in a saturated NaCl solution. Visualization of the final filtrates under a stereomicroscope revealed that all the sediment samples evaluated contained mostly microfibers (98.3%) which were mainly white/colorless (86.0%) and blue (9.8%), with an average length of 2423 ± 2235 (SD) mm and an average concentration of 2682 ± 827 items per kg of dry weight, being the total number of items found 1,019. Fourier Transform Infrared microscopy analysis of 13.9% (n = 139) of the microfibers also showed that they were mainly cellulosic (81.3%). No significant differences were found between the depths of the sediment. However, significant differences were found between the number of fibers from the sampling sites at the east and west of the island. Such variability could be driven by the winds and ocean mesoscale dynamics in the area. This study confirms the wide distribution of microfibers in sediments from an oceanic island like La Palma, providing their first report in marine sediments of the Canary Islands.En prensa3,20

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

COPPADIS Study Group.[Introduction] We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.[Methods] The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.[Results] Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).[Conclusions] Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.This work was supported by the Alzheimer Forschung Initiative e.V. (AFI International Training Grant to MJG), the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576, PI20/00613], the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], the Fundación Alicia Koplowitz and the Fundación “Curemos el Parkinson” (https://www.curemoselparkinson.org). MJG is supported by the “Miguel Servet” program [CP19/00031], MALE by the University of Seville [USE-20046-J], JFM by the “Sara Borrell” program [CD13/00229] and VI-PPIT-US from the University of Seville [USE-18817-A], SJ by the “Acción B-Clínicos-Investigadores” program [B-0007-2019], and DMG by the “Río Hortega” program [CM18/00142].Peer reviewe

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease

Altres ajuts: acord transformatiu CRUE-CSICBackground and purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. Methods: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. Results: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (β = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. Conclusion: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge

NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system

Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10−10). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28null compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression