34 research outputs found

    Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid. Our results show that both N-glycomes exhibit highly similar glycosylation patterns, consisting mainly of diantennary and triantennary complex type N-glycans with high levels (>95 %) of galactosylation and sialylation (mostly NeuGc) and a medium degree of core fucosylation (30 %). Moreover, MS/MS structural analysis, assisted by linkage-specific derivatization of sialic acids, revealed the presence of O-acetylated sialic acids as well as disialylated antennae ("branching sialylation") characterized by the presence of α2-6-linked NeuGc on the GlcNAc of the NeuGcα2-3-Galβ1-3-GlcNAc terminal motif. A significant decrease of (core) fucosylation together with an increase of both α2-3-linked NeuGc and "branching sialylation" were observed in N-glycomes of mice challenged with zymosan, but not in control mice injected with PBS. Importantly, substantial changes in glycosylation were already observed 12 h after induction of peritonitis, thereby demonstrating an unexpected velocity of the biological mechanisms involved.Dutch Arthritis Association (Reumafonds) LLP-24 Innovative Medicines Initiative Joint Undertaking (IMI JU)/ 115142-2 Netherlands Genomic Initiative/93511033 info:eu-repo/grantAgreement/EC/FP7/278535info:eu-repo/grantAgreement/EC/FP7/27853

    Association between weight or Body Mass Index and hand osteoarthritis: a systematic review

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    Objective: To investigate the association between weight or Body Mass Index (BMI) and the development of hand osteoarthritis (OA). Methods: Systematic review of observational studies. Medical databases were searched up to April 2008. Articles which presented data on the association between weight and hand OA were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring syst

    Diagnóstico de la producción de plantas forestales en los viveros de la Municipalidad de Guatemala; evaluación del enraizamiento de matilisguate (Tabebuia rosea bertol) y servicios realizados en el Vivero Municipal Acatán, Zona 16, Ciudad De Guatemala, Guatemala, C.A.

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    El presente trabajo de investigación se orientó hacia la producción de plantas forestales de los viveros de la Municipalidad de Guatemala, referente a distintos criterios de selección del material al momento de plantarse en campo, así como principales modos de propagación que se utilizan en los viveros para abastecer a los distintos proyectos de jardinización y arborización urbana. Mediante el diagnóstico se puedo conoce la situación actual de los sistemas de producción de plantas forestales en los viveros, se determinaron las principales características de las especies forestales que se utilizan para arborización urbana, jardinización, criterios de selección y modos de propagación, encontrándose como principal medio de propagación la semilla y no otras alternativas que agilicen la obtención masal de plántulas de mayor tamaño en el menor tiempo posible. La investigación se dirigió a establecer el un método alternativo para la propagación vegetativa de una especie ampliamente utilizada para arborización urbana: Tabebuia rosea bertol. Se evaluó la respuesta al enraizamiento en vástago, en función de tres concentraciones del ácido Indol3Butírico y tres diámetros de estaca, en plantas en fase de vivero con material juvenil para propagar. La investigación tuvo una duración de 4 meses. El estudio se realizó en el Huerto y Vivero Urbano Municipal Acatán zona 16, ciudad de Guatemala. El resultado de la investigación, demostró que existe respuesta a la propagación vegetativa por la especie bajo estudio, la respuesta fue mayor para el caso de propagación por vástago de 2.5cm. de diámetro y 2500ppm del regulador. Los resultados se midieron en presencia de callo, de raíces, y de brotes; además, peso seco de raíces, altura de la planta. Este resultado es de importancia ya que permite obtener plantas de matilisguate de mayor tamaño en menos tiempo y esto se vería reflejado en el arbolado urbano

    Markedly Different Pathogenicity of Four Immunoglobulin G Isotype-Switch Variants of an Antierythrocyte Autoantibody Is Based on Their Capacity to Interact in Vivo with the Low-Affinity Fcγ Receptor III

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    Using three different Fcγ receptor (FcγR)-deficient mouse strains, we examined the induction of autoimmune hemolytic anemia by each of the four immunoglobulin (Ig)G isotype-switch variants of a 4C8 IgM antierythrocyte autoantibody and its relation to the contributions of the two FcγR, FcγRI, and FcγRIII, operative in the phagocytosis of opsonized particles. We found that the four IgG isotypes of this antibody displayed striking differences in pathogenicity, which were related to their respective capacity to interact in vivo with the two phagocytic FcγRs, defined as follows: IgG2a > IgG2b > IgG3/IgG1 for FcγRI, and IgG2a > IgG1 > IgG2b > IgG3 for FcγRIII. Accordingly, the IgG2a autoantibody exhibited the highest pathogenicity, ∼20–100-fold more potent than its IgG1 and IgG2b variants, respectively, while the IgG3 variant, which displays little interaction with these FcγRs, was not pathogenic at all. An unexpected critical role of the low-affinity FcγRIII was revealed by the use of two different IgG2a anti–red blood cell autoantibodies, which displayed a striking preferential utilization of FcγRIII, compared with the high-affinity FcγRI. This demonstration of the respective roles in vivo of four different IgG isotypes, and of two phagocytic FcγRs, in autoimmune hemolytic anemia highlights the major importance of the regulation of IgG isotype responses in autoantibody-mediated pathology and humoral immunity

    Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

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    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P <10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P <5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.Peer reviewe

    An emerging player in knee osteoarthritis: the infrapatellar fat pad

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    Pathophysiology and treatment of rheumatic disease
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