Estudio de los mecanismos inmunopatológicos en lipodistrofias adquiridas de tipo parcial y generalizado

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 22-06-2018Esta tesis tiene embargado el acceso al texto completo hasta el 22-12-2019Las lipodistrofias son un conjunto heterogéneo de patologías ultra-raras (1:1.000.000) caracterizadas por el déficit específico de tejido adiposo en ausencia de deprivación nutricional o estado catabólico. La patogenia de las lipodistrofias adquiridas de tipo parcial (LPA o síndrome de Barraquer-Simons) y generalizado (LGA o síndrome de Lawrence), tiene un componente inmunológico, aunque el mecanismo se desconoce. Por un lado, la LPA se caracteriza por la desregulación de la vía alternativa del complemento, lo que ha llevado a proponer que ocurre una lisis del adipocito mediante un mecanismo dependiente del complemento. En la LGA, sin embargo, las evidencias apuntan a la destrucción del tejido adiposo debido a la existencia de anticuerpos dirigidos contra el tejido adiposo. Por ello, en este trabajo se planteó como objetivo principal la caracterización de los mecanismos inmunológicos implicados la patogenia de ambas lipodistrofias. Para conseguirlo se propuso: 1) profundizar en el estudio del perfil plasmático del complemento y la aparición de anticuerpos que producen la desregulación del mismo; y 2) analizar la presencia de anticuerpos específicos contra el tejido adiposo y caracterizarlos en caso de que existieran. Un 75% de los pacientes con LPA presentaron un descenso significativo de los niveles de C3. Además se midieron los niveles plasmáticos de C3adesArg, una potente adipoquina implicada en el metabolismo lipídico, encontrándose elevados. En todos los pacientes con alteraciones del complemento se detectaron anticuerpos relacionados con la desregulación del complemento, como factor nefrítico de C3 (C3NeF) o anticuerpos contra componentes y reguladores de la vía alternativa del complemento, como C3, factor B, properdina, factor H y factor I. Por otra parte, la oportunidad de estudiar la evolución del perfil del complemento en un paciente con LPA ha puesto de manifiesto su posible utilidad como biomarcador para el progreso de la lipodistrofia. En este trabajo se ha descrito un autoanticuerpo relacionado con la pérdida del tejido adiposo en pacientes con LGA. Este anticuerpo reconoce la proteína perilipina-1, muy presente el tejido adiposo blanco, y con un papel clave en el control de la vía lipolítica. Los estudios in vitro en adipocitos en cultivo han evidenciado que en presencia de estos anticuerpos se produce un incremento significativo de la lipólisis basal, tal y como le ocurre a los pacientes con lipodistrofia parcial familiar con mutaciones en esta proteín

Single Crystal Growth of Hybrid Lead Bromide Perovskites Using a Spin-Coating Method

[EN] Synthesis and studies of single crystals of hybrid perovskite are important for achieving a better understanding of the optoelectronic phenomena occurring in this material and for improving ongoing applications. Here, we report on the growth of micrometer-size single crystals of methylammonium lead bromide (MAPbBr3) using the spin coating deposition method on a quartz substrate. We studied the influence of the rotation speed and the use of three different additives N-cyclohexyl-2-pyrrolidone, dimethyl sulfoxide, and 4-tert-butylpyridine on the crystal size and shape. The introduction of an additive in the precursor solution is revealed to be very useful for obtaining crystals with well-defined geometries and for decreasing the amount of defects. In this way, high-quality single crystals that sustain optical resonating modes were obtained and characterized by transmittance and photoluminescence measurements.Financial support from the Spanish Ministry of Economy and Competitiveness (Severo Ochoa, SEV-2016-0683), Intramural CSIC project 201680I006, and Fundacion Ramon Areces (XVII Concurso Nacional para la adjudicacion de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia) is gratefully acknowledged. Financial support was also provided by the Spanish Ministry of Economy and Competitiveness (Mineco) of Spain (TEC2015-74405-JIN), MAT2015-69669-P, and regional government grant PrometeoII/2017/026.García-Aboal, R.; Fenollosa Esteve, R.; Ramiro Manzano, F.; Rodriguez, I.; Messeguer Rico, FJ.; Atienzar Corvillo, PE. (2018). Single Crystal Growth of Hybrid Lead Bromide Perovskites Using a Spin-Coating Method. ACS Omega. 3(5):5229-5236. https://doi.org/10.1021/acsomega.8b00447S522952363

Groove-assisted solution growth of lead bromide perovskite aligned nanowires: a simple method towards photoluminescent materials with guiding light properties

[EN] High refractive index nanowires are very attractive because of their waveguiding properties and their multiple applications. In this sense, metal halide perovskites, an emerging and appealing optoelectronic material, have also been tailored into nanowire structures. Here, we present an easy, low-cost and versatile method that has made possible to achieve nanowires of controlled and uniform width. The method has been applied here to all-inorganic and hybrid lead bromide perovskite (CsPbBr3 and CH3NH3PbBr3 respectively) materials. The procedure is based on the spin coating of precursor solutions, at room temperature, on a PDMS replica of the periodic grooves and lands of commercially available Compact Disc (CD) or Digital Versatile Disc (DVD) polycarbonate plates. The method can be applied for the synthesis of other material nanowires before being transferred onto other substrates. The obtained CsPbBr3 and CH3NH3PbBr3 nanowires exhibit high photoluminescence and guiding light properties along the material.The authors would like to gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness (MIMECO) (Severo Ochoa (SEV-2016-0683), MAT2015-69669-P projects) and Generalitat Valenciana (Prometeo II/2017/026 Excellency project). P. A. acknowledges the Fundacion Ramon Areces (XVII Concurso Nacional para la adjudicacion de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia) for its funding. F. R.-M. thanks the financial contribution of the Spanish Ministry of Economy and Competitiveness (MIMECO) through the program for young researchers support (TEC 2015 2015-74405-JIN). Finally, IR also thanks the Electron Microscopy Service of the Universitat Politecnica de Valencia for their support in FESEM image acquisition and FIB milling, as well as Ana Moreno for her help in template preparation.Rodriguez, I.; Fenollosa Esteve, R.; Ramiro Manzano, F.; García-Aboal, R.; Atienzar Corvillo, PE.; Meseguer Rico, FJ. (2019). Groove-assisted solution growth of lead bromide perovskite aligned nanowires: a simple method towards photoluminescent materials with guiding light properties. Materials Chemistry Frontiers. 3(9):1754-1760. https://doi.org/10.1039/c9qm00210cS1754176039Semiconductor nanowires: From next-generation Electronics to Sustainable Energy , ed. W. Lu and J. Xiang , RSC Smart Materials Series, 2015Semiconductor Nanowires, Materials, Synthesis, Characterization and Applications , ed. J. Arbiol and Q. Xiong , Woodhead Publishing , 2015Peng, K.-Q., Wang, X., Li, L., Hu, Y., & Lee, S.-T. (2013). Silicon nanowires for advanced energy conversion and storage. 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Nano Letters, 16(12), 7974-7981. doi:10.1021/acs.nanolett.6b04297Park, K., Lee, J. W., Kim, J. D., Han, N. S., Jang, D. M., Jeong, S., … Song, J. K. (2016). Light–Matter Interactions in Cesium Lead Halide Perovskite Nanowire Lasers. The Journal of Physical Chemistry Letters, 7(18), 3703-3710. doi:10.1021/acs.jpclett.6b01821Chen, J., Fu, Y., Samad, L., Dang, L., Zhao, Y., Shen, S., … Jin, S. (2016). Vapor-Phase Epitaxial Growth of Aligned Nanowire Networks of Cesium Lead Halide Perovskites (CsPbX3, X = Cl, Br, I). Nano Letters, 17(1), 460-466. doi:10.1021/acs.nanolett.6b04450Zhou, H., Yuan, S., Wang, X., Xu, T., Wang, X., Li, H., … Pan, A. (2016). Vapor Growth and Tunable Lasing of Band Gap Engineered Cesium Lead Halide Perovskite Micro/Nanorods with Triangular Cross Section. ACS Nano, 11(2), 1189-1195. doi:10.1021/acsnano.6b07374Wang, X., Zhou, H., Yuan, S., Zheng, W., Jiang, Y., Zhuang, X., … Pan, A. (2017). Cesium lead halide perovskite triangular nanorods as high-gain medium and effective cavities for multiphoton-pumped lasing. Nano Research, 10(10), 3385-3395. doi:10.1007/s12274-017-1551-1Oksenberg, E., Sanders, E., Popovitz-Biro, R., Houben, L., & Joselevich, E. (2017). Surface-Guided CsPbBr3 Perovskite Nanowires on Flat and Faceted Sapphire with Size-Dependent Photoluminescence and Fast Photoconductive Response. Nano Letters, 18(1), 424-433. doi:10.1021/acs.nanolett.7b04310Chen, J., Luo, Z., Fu, Y., Wang, X., Czech, K. J., Shen, S., … Jin, S. (2019). Tin(IV)-Tolerant Vapor-Phase Growth and Photophysical Properties of Aligned Cesium Tin Halide Perovskite (CsSnX3; X = Br, I) Nanowires. ACS Energy Letters, 4(5), 1045-1052. doi:10.1021/acsenergylett.9b00543Eaton, S. W., Lai, M., Gibson, N. A., Wong, A. B., Dou, L., Ma, J., … Yang, P. (2016). Lasing in robust cesium lead halide perovskite nanowires. Proceedings of the National Academy of Sciences, 113(8), 1993-1998. doi:10.1073/pnas.1600789113Tavakoli, M. M., Waleed, A., Gu, L., Zhang, D., Tavakoli, R., Lei, B., … Fan, Z. (2017). A non-catalytic vapor growth regime for organohalide perovskite nanowires using anodic aluminum oxide templates. Nanoscale, 9(18), 5828-5834. doi:10.1039/c7nr00444cIm, J.-H., Luo, J., Franckevičius, M., Pellet, N., Gao, P., Moehl, T., … Park, N.-G. (2015). Nanowire Perovskite Solar Cell. Nano Letters, 15(3), 2120-2126. doi:10.1021/acs.nanolett.5b00046Wong, A. B., Lai, M., Eaton, S. W., Yu, Y., Lin, E., Dou, L., … Yang, P. (2015). Growth and Anion Exchange Conversion of CH3NH3PbX3 Nanorod Arrays for Light-Emitting Diodes. Nano Letters, 15(8), 5519-5524. doi:10.1021/acs.nanolett.5b02082Deng, H., Dong, D., Qiao, K., Bu, L., Li, B., Yang, D., … Song, H. (2015). Growth, patterning and alignment of organolead iodide perovskite nanowires for optoelectronic devices. 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Autoantibodies against perilipin 1 as a cause of acquired generalized lipodystrophy

Acquired generalized lipodystrophy (AGL) is a rare condition characterized by an altered distribution of adipose tissue and predisposition to develop hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia. Diagnosis of AGL is based on the observation of generalized fat loss, autoimmunity and lack of family history of lipodystrophy. The pathogenic mechanism of fat destruction remains unknown but evidences suggest an autoimmune origin. Anti-adipocyte antibodies have been previously reported in patients with AGL, although their involvement in the pathogenesis has been poorly studied and the autoantibody target/s remain/s to be identified. Using a combination of immunochemical and cellular studies, we investigated the presence of anti-adipocyte autoantibodies in patients with AGL, acquired partial lipodystrophy, localized lipoatrophy due to intradermic insulin injections or systemic lupus erythematosus. Moreover, the impact of anti-adipocyte autoantibodies from AGL patients was assessed in cultured mouse preadipocytes. Following this approach, we identified anti-perilipin 1 IgG autoantibodies in the serum of patients with autoimmune variety-AGL, but in no other lipodystrophies tested. These autoantibodies altered the ability of perilipin 1 to regulate lipolysis in cultured preadipocytes causing abnormal, significantly elevated basal lipolysis. Our data provide strong support for the conclusion that perilipin 1 autoantibodies are a cause of generalized lipodystrophy in these patientsFC, ML-T, AL-L, and SG were supported by grants PI15- 00255 from Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad) and Fondos FEDER, Complemento II-CM network (B2017/BMD3673), Acciones Cooperativas y Complementarias Intramurales (ACCI) from CIBERER (ISCIII), and Fundación SENEFRO. MdMwas supported by Roche Farma SA and Foundation Domingo Martínez. VA was financed by Consejería de Educación, Juventud y Deporte of Comunidad de Madrid and by Fondo Social Europeo (Programa Operativo de Empleo Juvenil, and Iniciativa de Empleo Juvenil (YEI), (PEJ15/BIO/AI/0045). DA-V was supported by the intramural research program of the Xunta de Galicia (Programa de Consolidación e Estructuración de Unidades de Investigación Competitivas, grant ED341b 2017/19), by the Instituto de Salud Carlos III (grant number: PI08-1449) and the European Regional Development Fund, FEDER and by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP

Optical properties of organic/inorganic perovskite microcrystals through the characterization of Fabry-Perot resonances

[EN] A precise knowledge of the optical properties, specifically the refractive index, of organic/inorganic perovskites, is essential for pushing forward the performance of the current photovoltaic devices that are being developed from these materials. Here we show a robust method for determining the real and the imaginary part of the refractive index of MAPbBr(3) thin films and micrometer size single crystals with planar geometry. The simultaneous fit of both the optical transmittance and the photoluminescence spectra to theoretical models defines unambiguously the refractive index and the crystal thickness. Because the method relies on the optical resonance phenomenon occurring in these microstructures, it can be used to further develop optical microcavities from perovskites or from other optical materials.This work was supported by the Spanish ministry of Economy, Industry and Competitiveness (MINECO) through the projects TEC2015-74405-JIN, MAT2015-69669-P as well as the regional projects of both Provincia Autonoma di Trento (PAT) of Italy, through the call Grandi Progetti 2012: SIQURO and the Comunidad Valenciana of Spain project PrometeoII/2014/026.Ramiro Manzano, F.; García-Aboal, R.; Fenollosa Esteve, R.; Biasi, S.; Rodriguez, I.; Atienzar Corvillo, PE.; Meseguer Rico, FJ. (2020). Optical properties of organic/inorganic perovskite microcrystals through the characterization of Fabry-Perot resonances. Dalton Transactions. 49(36):12798-12804. https://doi.org/10.1039/d0dt02254c1279812804493

Modulating charge carrier density and mobility in doped graphene by covalent functionalization

[EN] Covalent B-functionalization of B-doped graphene has been performed for the first time. The electronic properties and Hall effect of functionalized N- and B-doped graphene can be tuned by tailoring the electron-donating/-withdrawing properties of the organic addend.The authors appreciate support from the Ministerio de Economia y Competitividad (MINECO) of Spain (projects CTQ2015-69153-CO2-1, CTQ2016-79189-R and MAT2015-69669-P) and the Junta de Comunidades de Castilla-La Mancha (project SBPLY/17/180501/000254). L. M. A. thanks MINECO (CTQ2016-79189-R) for a doctoral FPI grant.Arellano, LM.; Yue, S.; Atienzar Corvillo, PE.; Gómez-Escalonilla, MJ.; Ortega Higueruelo, FJ.; Fierro, JLG.; García Gómez, H.... (2019). Modulating charge carrier density and mobility in doped graphene by covalent functionalization. Chemical Communications. 55(67):9999-10002. https://doi.org/10.1039/c9cc04571fS9999100025567Wang, X., Sun, G., Routh, P., Kim, D.-H., Huang, W., & Chen, P. (2014). Heteroatom-doped graphene materials: syntheses, properties and applications. Chem. Soc. Rev., 43(20), 7067-7098. doi:10.1039/c4cs00141aLavorato, C., Primo, A., Molinari, R., & Garcia, H. (2013). N-Doped Graphene Derived from Biomass as a Visible-Light Photocatalyst for Hydrogen Generation from Water/Methanol Mixtures. Chemistry - A European Journal, 20(1), 187-194. doi:10.1002/chem.201303689Latorre-Sánchez, M., Primo, A., & García, H. (2013). P-Doped Graphene Obtained by Pyrolysis of Modified Alginate as a Photocatalyst for Hydrogen Generation from Water-Methanol Mixtures. Angewandte Chemie International Edition, 52(45), 11813-11816. doi:10.1002/anie.201304505Duan, J., Chen, S., Jaroniec, M., & Qiao, S. Z. (2015). Heteroatom-Doped Graphene-Based Materials for Energy-Relevant Electrocatalytic Processes. ACS Catalysis, 5(9), 5207-5234. doi:10.1021/acscatal.5b00991Putri, L. K., Ong, W.-J., Chang, W. S., & Chai, S.-P. (2015). Heteroatom doped graphene in photocatalysis: A review. Applied Surface Science, 358, 2-14. doi:10.1016/j.apsusc.2015.08.177Niu, L., Li, Z., Hong, W., Sun, J., Wang, Z., Ma, L., … Yang, S. (2013). Pyrolytic synthesis of boron-doped graphene and its application as electrode material for supercapacitors. Electrochimica Acta, 108, 666-673. doi:10.1016/j.electacta.2013.07.025Sahoo, M., Sreena, K. P., Vinayan, B. P., & Ramaprabhu, S. (2015). Green synthesis of boron doped graphene and its application as high performance anode material in Li ion battery. Materials Research Bulletin, 61, 383-390. doi:10.1016/j.materresbull.2014.10.049Khai, T. V., Na, H. G., Kwak, D. S., Kwon, Y. J., Ham, H., Shim, K. B., & Kim, H. W. (2012). Comparison study of structural and optical properties of boron-doped and undoped graphene oxide films. Chemical Engineering Journal, 211-212, 369-377. doi:10.1016/j.cej.2012.09.081Osumi, S., Saito, S., Dou, C., Matsuo, K., Kume, K., Yoshikawa, H., … Yamaguchi, S. (2016). Boron-doped nanographene: Lewis acidity, redox properties, and battery electrode performance. Chemical Science, 7(1), 219-227. doi:10.1039/c5sc02246kXu, Q., Jiang, X., Zhu, W., Chen, C., Hu, G., & Li, Q. (2016). Synthesis, preliminary biological evaluation and 3D-QSAR study of novel 1,5-disubstituted-2(1H)-pyridone derivatives as potential anti-lung cancer agents. Arabian Journal of Chemistry, 9(5), 721-735. doi:10.1016/j.arabjc.2015.08.001Pimenta, M. A., Dresselhaus, G., Dresselhaus, M. S., Cançado, L. G., Jorio, A., & Saito, R. (2007). Studying disorder in graphite-based systems by Raman spectroscopy. Phys. Chem. Chem. Phys., 9(11), 1276-1290. doi:10.1039/b613962kVoggu, R., Rout, C. S., Franklin, A. D., Fisher, T. S., & Rao, C. N. R. (2008). Extraordinary Sensitivity of the Electronic Structure and Properties of Single-Walled Carbon Nanotubes to Molecular Charge-Transfer. The Journal of Physical Chemistry C, 112(34), 13053-13056. doi:10.1021/jp805136eBiswal, M., Zhang, X., Schilter, D., Lee, T. K., Hwang, D. Y., Saxena, M., … Ruoff, R. S. (2017). Sodide and Organic Halides Effect Covalent Functionalization of Single-Layer and Bilayer Graphene. Journal of the American Chemical Society, 139(11), 4202-4210. doi:10.1021/jacs.7b00932Vizuete, M., Gómez-Escalonilla, M. J., Fierro, J. L. G., Ohkubo, K., Fukuzumi, S., Yudasaka, M., … Langa, F. (2014). Photoinduced electron transfer in a carbon nanohorn–C60 conjugate. Chemical Science, 5(5), 2072. doi:10.1039/c3sc53342eAllongue, P., Delamar, M., Desbat, B., Fagebaume, O., Hitmi, R., Pinson, J., & Savéant, J.-M. (1997). Covalent Modification of Carbon Surfaces by Aryl Radicals Generated from the Electrochemical Reduction of Diazonium Salts. Journal of the American Chemical Society, 119(1), 201-207. doi:10.1021/ja963354sBarrejón, M., Gómez-Escalonilla, M. J., Fierro, J. L. G., Prieto, P., Carrillo, J. R., Rodríguez, A. M., … Langa, F. (2016). Modulation of the exfoliated graphene work function through cycloaddition of nitrile imines. Physical Chemistry Chemical Physics, 18(42), 29582-29590. doi:10.1039/c6cp05285aBarrejón, M., Primo, A., Gómez-Escalonilla, M. J., Fierro, J. L. G., García, H., & Langa, F. (2015). Covalent functionalization of N-doped graphene by N-alkylation. Chemical Communications, 51(95), 16916-16919. doi:10.1039/c5cc06285cSu, C.-Y., Xu, Y., Zhang, W., Zhao, J., Tang, X., Tsai, C.-H., & Li, L.-J. (2009). Electrical and Spectroscopic Characterizations of Ultra-Large Reduced Graphene Oxide Monolayers. Chemistry of Materials, 21(23), 5674-5680. doi:10.1021/cm902182

Immunological features of patients affected by Barraquer-Simons syndrome

Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. Results: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti- FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population). Conclusions: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.This work was supported by Instituto de Salud Carlos III (Ministerio de Ciencia, Innovación y Universidades, Gobierno de España) and Fondos FEDER (PI15–00255 to M.L-T. and PI08–1449 to D.A-V.), Complemento II-CM network (B2017/BMD3673 to M.L-T), the intramural research program of the Xunta de Galicia (Programa de Consolidación e Estructuración de Unidades de Investigación Competitivas, grant ED341b 2017/19 to D.A-V.), the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP) (to D.A-V., to F.C. and to P.N.

Complement genetic variants and FH desialylation in S. pneumoniae-Haemolytic Uraemic Syndrome

15 p.-8 fig.-3 tab.Haemolytic Uraemic Syndrome associated with Streptococcus pneumoniae infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to E. coli infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients. Five patients presented rare complement variants of unknown significance, but the frequency of the risk haplotypes in the CFH-CFHR3-CFHR1 region was similar to the observed in aHUS. Moreover, we observed desialylation of Factor H (FH) and the FH-Related proteins in plasma samples from 2 Spanish and 4 Hungarian SP-HUS patients. To analyze the functional relevance of this finding, we compared the ability of native and “in vitro” desialylated FH in: (a) binding to C3b-coated microtiter plates; (b) proteolysis of fluid-phase and surface-bound C3b by Factor I; (c) dissociation of surface bound-C3bBb convertase; (d) haemolytic assays on sheep erythrocytes. We found that desialylated FH had reduced capacity to control complement activation on sheep erythrocytes, suggesting a role for FH sialic acids on binding to cellular surfaces. We conclude that aHUS-risk variants in the CFH-CFHR3-CFHR1 region could also contribute to disease-predisposition to SP-HUS, and that transient desialylation of complement FH by the pneumococcal neuraminidase may have a role in disease pathogenesis.This study was funded by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund from the European Union (grants PI16/00723 and PI19/00970 to PS-C). IG and EA are supported by the Spanish Autonomous Region of Madrid (Complement II-CM network; S2017/BMD-3673). IG was also supported by the Spanish Fundación Senefro (http://www.senefro.org/). The study was also supported by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic programme of the Semmelweis University, by the National Office for Innovation and Research (KH130355 to ZP), and by the MSCA-ITN (Horizon 2020) CORVOS (Grant 860044 to ZP). DC was supported by the Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences (PPD2018-016/2018).Peer reviewe

Revista de Vertebrados de la Estación Biológica de Doñana

Página 298 con error de impresiónEstudio cariológico en dos especies de Serránidos del Mediterráneo (Peces: PerciformesRelaciones morfométricas de Atherina boyeri Risso (Pisces: Atherinidae) de la laguna de Zoñar (Córdoba, España)Contribución al conocimiento de la biometríay osteología de Barbus barbus bocagei, Steindachner, 1866 (Pisces: CyprinidaeLa actividad de la salamandra, Salamandra salamandra (L.), en Galicia.Estudios sobre el sapo corredor (Bufo calamita) en el Sur de España.1. BiometríaEstudios sobre el sapo corredor (Bufo calamita) en el Sur de España. II. AlimentaciónBiología de la reproducción de Rana iberica Boulenger 1879 en zonas simpátridas con Rana temporaria Linneo, 1758Nuevos datos sobre la distribución geográfica de Lacerta monticola cantabrica Mertens, 1929. (Sauria, lacertidae).Datos sobre Lacerta monticola Boulenger, 1905 (Saurio: lacertidae)en el oeste del Sistema Central.Nueva especie de Anolis (lacertilia, Iguanidae) para CubaEtograma cuantificado del cortejo en Falco naumannOntogénesis del comportamiento predador en Falco naumanniContaminación xenobiótica del Parque Nacional de Doñana. 1. Residuos de insecticidas organoclorados, bifenilos policlorados y mercurio en anseriformes y gruiformesReproducción del críalo (Clamator glandarius) en Sierra Morena CentraNidificación de Picus viridis en taludes de arcilla en Ramblas de Guadix (Granada)Comportamiento del calamón Porphyrio porphyrio (Linnaeus, 1758) en Doñana, Marismas del GuadalquiviBiología y ecología de la malvasía (Oxyura leucocephala) en Andalucía.On the differential diet of Carnivora in islands:a method for analysing it and a particular case.Notas sobre la distribución pasada y actual del meloncillo Herpestes ichneumon (L.) en la Península IbéricaEstructuración de las interacciones en una camada de lobos (Canís lupus)Nuevos datos sobre la distribución del Cottus gobio L. (pisces, cottidae) en EspañaSobre la alimentación de Callopistes maculatus (Reptilia,teiidaeObservación de Lacerta lepida depredando un nido de Alectoris rufaNueva cita del galápago leproso Mauremys leprosa (Scheigger, 1812) en los pirineosPrimera cita de Psammodromus hispanicus (Fitzinger) para GaliciaSobre la presencia de Gallotia (=Lacerta) atlantica (Peters y Doria, 1882) en Gran CanariaNota sobre las Lacerta monticola Boulenger, 1905 de las zonas del norte de GaliciaPrimeras notas herpetológicas de la provincia de Soria.Datos sobre selección de hábitat y ecología alimenticia del porrón pardo (Aythya nyroca)Probable nueva área de cría del pechiazul (Luscinia svecica cyanecula) en el sistema central. PerisPredación de Falco peregrinus y Falco subbuteo sobre quirópterosResultados de la producción de Oxyura leucocephala en el año 1981 en las lagunas de Zóñar y el rincónAnálisis de la dieta de Tyto alba en un medio árido antropógeno de los alrededores de Almería¿Son Eudocimus ruber y E. albus distintas especies?EL Estornino pinto (Sturnus vulgaris) en Canarias: nueva especie nidifiante en el archipiélagoDatos sobre la alimentación otoñal del cárabo (Strix aluco) en la sierra de CádizObservación primaveral de rapaces y otras aves en el páramo del estado de Mérida (Venezuela).Murciélago hematófago (Desmodus rotundus) parasitando a un chigüire (Hidrochoerus hydrochaeris)Observaciones sobre la reproducción del zacatuche o teporinho Romerolagus diazi (Mammalia: lagomorpha)Estudio electroforético de hemoglobinas y esterasas sanguíneas en Rhinolophus ferrumequinum (Chiroptera: rhinolophidae) y de hemoglobinas en Tadaria taeniotis (chiroptera: molossidae)Peer reviewe

Acquired partial lipodystrophy and C3 glomerulopathy: Dysregulation of the complement system as a common mechanism

The activation of the alternative pathway of the complement is involved in the development of several renal diseases, such as atypical haemolytic uraemic syndrome and C3 glomerulopathy. In C3 glomerulopathy, a high percentage of patients have circulating levels of the autoantibody called C3NeF, which causes systemic dysregulation of the complement system. In some cases, the presence of this antibody has been related with abnormalities of adipose tissue, causing acquired partial lipodystrophy (Barraquer–Simons syndrome). Acquired partial lipodystrophy is an extremely rare disorder affecting the distribution of subcutaneous adipose tissue and that mainly onsets during childhood. These patients, in addition to possibly presenting with all the metabolic disorders associated with the adipose tissue defect, present with C3 hypocomplementemia and C3NeF and 25% have developed C3 glomerulopathy. Although it has been known for some time how the dysregulation of the complement system affects the kidneys, it remains unknown how it exactly affects adipose tissue; nevertheless, the relationship is quite clear. In this paper, we describe the connection between the complement system with the biology of the adipose tissue and its pathogenesis reflected from acquired partial lipodystrophy. Resumen: La activación de la vía alternativa del complemento interviene en el desarrollo de varias enfermedades renales, como el síndrome hemolítico urémico atípico o la glomerulopatía C3. En esta última enfermedad un elevado porcentaje de los pacientes presentan niveles circulantes de un autoanticuerpo denominado C3NeF, causante de la desregulación del complemento a nivel sistémico. En ciertos casos, la presencia de este anticuerpo se asocia con alteraciones en el tejido adiposo, causando lipodistrofia parcial adquirida (síndrome de Barraquer-Simons), una enfermedad ultra-rara que afecta a la distribución del tejido adiposo subcutáneo y que comienza principalmente durante la infancia. Estos pacientes, además de poder presentar los problemas metabólicos asociados al defecto en el tejido adiposo, presentan hipocomplementemia C3 junto con la presencia de C3NeF y, en un 25% de los casos desarrollan una glomerulopatía C3. Aunque se sabe desde hace tiempo cómo la desregulación del sistema del complemento afecta al riñón, se desconoce de forma precisa cómo lo hace en el tejido adiposo; no obstante, su relación está bastante clara. En este artículo se va a describir la relación del sistema del complemento con la biología del tejido adiposo y su patogenia reflejada a partir de la lipodistrofia parcial adquirida. Keywords: Complement, Acquired partial lipodystrophy, C3 glomerulopathy, C3NeF, Palabras clave: Complemento, Lipodistrofia parcial adquirida, Glomerulopatía C3, C3Ne