| 1. |
- Crosas-Molist, Eva, et al.
(författare)
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Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome
- 2015
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 35:4, s. 960-972
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-β signaling. TGF-β is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-β signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan's syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level.APPROACH AND RESULTS: Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (α-smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1) and collagen I in comparison with healthy aortas. VSMC explanted from Marfan aortic aneurysms showed increased in vitro expression of these phenotypic markers and also of myocardin, a transcription factor essential for VSMC-specific differentiation. These alterations were generally reduced after pharmacological inhibition of the TGF-β pathway. Marfan VSMC in culture showed more robust actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by increased focal adhesion components and higher nuclear localization of myosin-related transcription factor A. Marfan VSMC and extracellular matrix measured by atomic force microscopy were both stiffer than their respective controls.CONCLUSIONS: In Marfan VSMC, both in tissue and in culture, there are variable TGF-β-dependent phenotypic changes affecting contractile proteins and collagen I, leading to greater cellular and extracellular matrix stiffness. Altogether, these alterations may contribute to the known aortic rigidity that precedes or accompanies Marfan's syndrome aneurysm formation.
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| 2. |
- McNamee, Sara E., et al.
(författare)
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Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters : A comparison of methods of analysis
- 2016
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Ingår i: Harmful Algae. - : Elsevier BV. - 1568-9883 .- 1878-1470. ; 55, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (VDU /DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 x 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. (C) 2016 Elsevier B.V. All rights reserved.
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| 3. |
- Moreno, Noelia, et al.
(författare)
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Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:31844
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Tidskriftsartikel (refereegranskat)abstract
- Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge.
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| 4. |
- Sánchez-García, Laura, et al.
(författare)
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Molecular biomarkers in the subsurface of the Salar Grande (Atacama, Chile) evaporitic deposits
- 2018
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Ingår i: Biogeochemistry. - : Springer. - 0168-2563 .- 1573-515X. ; 140:1, s. 31-52
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Tidskriftsartikel (refereegranskat)abstract
- The Late Miocene–Pliocene aged hyperarid evaporitic system of Salar Grande is a unique, halite-rich sedimentary basin in the Cordillera de la Costa of the Central Andes (Chile) whose bio-sedimentary record is poorly understood. The persistence of hyperacidity over millions of years, the hypersalinity, and the intense UV radiation make it a terrestrial analogue to assess the potential presence of organic matter in the halite deposits found on Mars. We investigated the occurrence and distribution of biomolecules along a 100-m depth drill down to the ~ 9 Ma old detrital deposits topped by La Soledad Formation (ESF). We have identified two well-defined mineralogical and geochemical units by X-ray diffractometry (XRD) and ion chromatography: a nearly pure halite down to 40 m, and a detrital one down to 100 m depth. One-dimensional GC–MS and two-dimensional GC × GC-TOF–MS gas chromatography–mass spectrometry techniques allowed us to detect a variety of lipidic compounds (n-alkanes, n-alkanols, isoprenoids, steroids, and hopanoids), and a relative abundance of functionalized hydrocarbons (n-fatty acids or n-aldehydes), mostly in the upper halite. We also detected biopolymers and microbial markers by fluorescence sandwich-microarray immunoassays. A dominant prokaryotic origin was associated with halophile bacteria and archaea, with minor contributions of lichens, macrophytes, or higher plants. The lipidic record was also imprinted by oxic (high pristane over phytane ratios) and saline (squalane, and mono-methyl n-alkanes) signatures. The vertical abundance and distribution of biomarkers in the Salar Grande was explained by a generalized effect of xeropreservation, combined with salt encapsulation in the upper halite deposits, or with protective organics-mineral interactions in the deeper detrital unit. The results contribute to the interpretation of terrestrial bio-sedimentary records of halite deposits and their association to environmental conditions. The high potential for preservation of biosignatures at Salar Grande suggests that similar evaporitic deposits in Mars should be priority targets for searching for signs of life.
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