Chronic spontaneous urticaria: a survey of 852 cases of childhood-onset systemic Lupus Erythematosus

Data regarding the prevalence of chronic spontaneous urticaria (CSU) in childhood-onset systemic lupus erythematosus (cSLE) patients and possible associated factors are limited to a few case reports. The objectives of this study were to assess CSU in a large cSLE population, in order to evaluate the demographic data, clinical manifestations, disease activity/damage, laboratory abnormalities and treatment. A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services and included 852 cSLE patients. CSU was diagnosed according to the guidelines of the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum and the World Allergy Organization. Patients with CSU (evaluated at urticaria diagnosis) and patients without CSU (evaluated at the last visit) were assessed for lupus clinical/laboratory features and treatment. CSU was observed in 10/852 cSLE patients (1.17%). The median of cSLE duration at urticaria diagnosis was 0 (-3 to 5) years. Comparison of cSLE patients with and without CSU revealed a greater frequency of constitutional symptoms (40 vs. 8%, p = 0.006), reticuloendothelial system involvement (30 vs. 3%, p = 0.003), mucocutaneous (90 vs. 28%, p < 0.0001) and musculoskeletal manifestations (50 vs. 6%, p < 0.0001) and methylprednisolone pulse therapy use (60 vs. 9%, p < 0.0001) in the former group. The frequency of immunosuppressive treatment was lower in patients with CSU (p = 0.018). The median SLE Disease Activity Index 2000 (12 vs. 2, p < 0.0001) and erythrocyte sedimentation rate (40 vs. 19 mm/1st hour, p = 0.024), was higher in patients with CSU. To our knowledge, this is the first study with evidence that CSU may be linked to cSLE. We also demonstrated that this particular skin manifestation occurs predominantly at disease onset and is associated with lupus moderate/high disease activity without major organ involvement1673186192CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ301805/2013-0; 2009/51897-5; 302724/2011-

The unusual persistence of an ozone hole over a southern mid-latitude station during the Antarctic spring 2009: a multi-instrument study

International audienceRecord-low ozone column densities (with a minimum of 212 DU) persisted over three weeks at the Río Gallegos NDACC (Network for the Detection of Atmospheric Composition Change) station (51.5° S, 69.3° W) in November 2009. Total ozone remained two standard deviations below the climatological mean for five consecutive days during this period. The statistical analysis of 30 years of satellite data from the Multi Sensor Reanalysis (MSR) database for Río Gallegos revealed that such a long-lasting low-ozone episode is a rare occurrence. The event is examined using height-resolved ozone lidar measurements at Río Gallegos, and observations from satellite and ground-based instruments. The computed relative difference between the measured total ozone and the climatological monthly mean shows reductions varying between 10 and 30% with an average decrease of 25%. The mean absolute difference of total ozone column with respect to climatological monthly mean ozone column is around 75 DU. Extreme values of the UV index (UVI) were measured at the ground for this period, with the daily maximum UVI of around 13 on 15 and 28 November. The high-resolution MIMOSA-CHIM (Modélisation Isentrope du transport Méso-échelle de l'Ozone Stratosphérique par Advection) model was used to interpret the ozone depletion event. An ozone decrease of about 2 ppmv was observed in mid-November at the 550 K isentropic level (~22 km). The position of Río Gallegos relative to the polar vortex was classified using equivalent latitude maps. During the second week of November, the vortex was over the station at all isentropic levels, but after 20 November and until the end of the month, only the 10 lower levels in the stratosphere were affected by vortex overpasses with ozone poor air masses. A rapid recovery of the ozone column density was observed later, due to an ozone rich filament moving over Río Gallegos between 18 and 24 km in the first two weeks of December 2009

Some aspects of the venom proteome of the Colubridae snake Philodryas olfersii revealed from a Duvernoy’s (venom) gland transcriptome

AbstractWe investigated the putative toxins of Philodryas olfersii (Colubridae), a representative of a family of snakes neglected in venom studies despite their growing medical importance. Transcriptomic data of the venom gland complemented by proteomic analysis of the gland secretion revealed the presence of major toxin classes from the Viperidae family, including serine proteases, metalloproteases, C-type lectins, Crisps, and a C-type natriuretic peptide (CNP). Interestingly, the phylogenetic analysis of the CNP precursor showed it as a linker between two related precursors found in Viperidae and Elapidae snakes. We suggest that these precursors constitute a monophyletic group derived from the vertebrate CNPs

Extracellular vesicles from oral squamous carcinoma cells display pro- and anti-angiogenic properties

BackgroundA new intercellular communication mode established by neoplastic cells and tumor microenvironment components is based on extracellular vesicles (EVs). However, the biological effects of the EVs released by tumor cells on angiogenesis are not completely understood. Here, we aimed to understand the biological effects of EVs isolated from two cell lines of oral squamous cell carcinoma (OSCC) (SCC15 and HSC3) on endothelial cell tubulogenesis. MethodsOSCC-derived EVs were isolated with a polymer-based precipitation method, quantified using nanoparticle tracking analysis and verified for EV markers by dot blot. Functional assays were performed to assess the angiogenic potential of the OSCC-derived EVs. ResultsThe results showed that EVs derived from both cell lines displayed typical spherical-shaped morphology and expressed the EV markers CD63 and Annexin II. Although the average particle concentration and size were quite similar, SCC15-derived EVs promoted a pronounced tubular formation associated with significant migration and apoptosis rates of the endothelial cells, whereas EVs derived from HSC3 cells inhibited significantly endothelial cell tubulogenesis and proliferation. ConclusionThe findings of this study reveal that EVs derived from different OSCC cell lines by a polymer-based precipitation method promote pro- or anti-angiogenic effects.Peer reviewe

Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase

AbstractThe functionality of the disintegrin-like/cysteine-rich domains of snake venom metalloproteinases (SVMPs) has been shown to reside in the cysteine-rich region, which can interact with VWA-containing proteins. Recently, the hyper-variable region (HVR) of the cysteine-rich domain was suggested to constitute a potential protein–protein adhesive interface. Here we show that recombinant proteins of HF3, a hemorrhagic P-III SVMP, containing the cysteine-rich domain (disintegrin-like/cysteine-rich and cysteine-rich proteins) but not the disintegrin-like protein were able to significantly increase leukocyte rolling in the microcirculation. Peptides from the HVR also promoted leukocyte rolling and this activity was inhibited by anti-alphaM/beta2 antibodies. These results show, for the first time, that the cysteine-rich domain and its HVR play a role in triggering pro-inflammatory effects mediated by integrins

Functional characterization and target discovery of glycoside hydrolases from the digestome of the lower termite Coptotermes gestroi

<p>Abstract</p> <p>Background</p> <p>Lignocellulosic materials have been moved towards the forefront of the biofuel industry as a sustainable resource. However, saccharification and the production of bioproducts derived from plant cell wall biomass are complex and lengthy processes. The understanding of termite gut biology and feeding strategies may improve the current state of biomass conversion technology and bioproduct production.</p> <p>Results</p> <p>The study herein shows comprehensive functional characterization of crude body extracts from <it>Coptotermes gestroi </it>along with global proteomic analysis of the termite's digestome, targeting the identification of glycoside hydrolases and accessory proteins responsible for plant biomass conversion. The crude protein extract from <it>C. gestroi </it>was enzymatically efficient over a broad pH range on a series of natural polysaccharides, formed by glucose-, xylose-, mannan- and/or arabinose-containing polymers, linked by various types of glycosidic bonds, as well as ramification types. Our proteomic approach successfully identified a large number of relevant polypeptides in the <it>C. gestroi </it>digestome. A total of 55 different proteins were identified and classified into 29 CAZy families. Based on the total number of peptides identified, the majority of components found in the <it>C. gestroi </it>digestome were cellulose-degrading enzymes. Xylanolytic enzymes, mannan- hydrolytic enzymes, pectinases and starch-degrading and debranching enzymes were also identified. Our strategy enabled validation of liquid chromatography with tandem mass spectrometry recognized proteins, by enzymatic functional assays and by following the degradation products of specific 8-amino-1,3,6-pyrenetrisulfonic acid labeled oligosaccharides through capillary zone electrophoresis.</p> <p>Conclusions</p> <p>Here we describe the first global study on the enzymatic repertoire involved in plant polysaccharide degradation by the lower termite <it>C. gestroi</it>. The biochemical characterization of whole body termite extracts evidenced their ability to cleave all types of glycosidic bonds present in plant polysaccharides. The comprehensive proteomic analysis, revealed a complete collection of hydrolytic enzymes including cellulases (GH1, GH3, GH5, GH7, GH9 and CBM 6), hemicellulases (GH2, GH10, GH11, GH16, GH43 and CBM 27) and pectinases (GH28 and GH29).</p

Biópsia digital em equinos com lamite induzida por sobrecarga de carboidratos

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Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-beta 1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.Peer reviewe

Expanding the knowledge on lignocellulolytic and redox enzymes of worker and soldier castes from the lower termite coptotermes gestroi

Termites are considered one of the most efficient decomposers of lignocelluloses on Earth due to their ability to produce, along with its microbial symbionts, a repertoire of carbohydrate-active enzymes (CAZymes). Recently, a set of Pro-oxidant, Antioxidant, and Detoxification enzymes (PAD) were also correlated with the metabolism of carbohydrates and lignin in termites. The lower termite Coptotermes gestroi is considered the main urban pest in Brazil, causing damage to wood constructions. Recently, analysis of the enzymatic repertoire of C. gestroi unveiled the presence of different CAZymes. Because the gene profile of CAZy/PAD enzymes endogenously synthesized by C. gestroi and also by their symbiotic protists remains unclear, the aim of this study was to explore the eukaryotic repertoire of these enzymes in worker and soldier castes of C. gestroi. Our findings showed that worker and soldier castes present similar repertoires of CAZy/PAD enzymes, and also confirmed that endo-glucanases (GH9) and beta-glucosidases (GH1) were the most important glycoside hydrolase families related to lignocellulose degradation in both castes. Classical cellulases such as exo-glucanases (GH7) and endo-glucanases (GH5 and GH45), as well as classical xylanases (GH10 and GH11), were found in both castes only taxonomically related to protists, highlighting the importance of symbiosis in C. gestroi. Moreover, our analysis revealed the presence of Auxiliary Activity enzyme families (AAs), which could be related to lignin modifications in termite digestomes. In conclusion, this report expanded the knowledge on genes and proteins related to CAZy/PAD enzymes from worker and soldier castes of lower termites, revealing new potential enzyme candidates for second-generation biofuel processes7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140796/2013-4; 310186/2014-5; 442333/2014-511/20977-3; 15/06971-3; 12/19040-0; 14/10351-8; 06/59086-8; 14/20576- 7; 13/03061-0; 10/11469-1; 08/58037-9; 14/50371-8; 08/50114-