Fibroblasts activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses

Background. Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. Objectives. To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. Methods. We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. Results. Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. Conclusions. Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS.This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2013-43475R, SAF2017-88908-R and SAF2017-86810-R); from Instituto de Salud Carlos III and CIBERER, cofunded with European Regional Development Funds (ERDF) (PT13/0001/0007, PI14/00931, PI15/00716, PI15/00956, PT17/0009/0006 and PI17/01747); and from the European Union (HEALTH-F2-2011-261392 and H2020-INFRADEV-1-2015-1/ELIXIR-EXCELERATEref. 676559). Additional funding from Comunidad de Madrid (AvanCell-CM S2017/BMD-3692); Catalan Government (AGAUR 2014_SGR_603); ‘Fundacio' La Marató de TV3, 01331-30’; CERCA Programme/Generalitat de Catalunya; and ‘Fundación Científica de la Asociación Española Contra el Cáncer’, Spain

Effects of rapeseed variety and oil extraction method on the content and ileal digestibility of crude protein and amino acids in rapeseed cake and softly processed rapeseed meal fed to broiler chickens

We examined the effects of rapeseed variety and oil extraction method on crude protein (CP) and amino acid (AA) content in rapeseed co-products, and determined their coefficient of apparent (AID) and standardised ileal digestibility (SID) in broiler chickens. Sixteen rapeseed samples were de-oiled; four were cold-pressed producing rapeseed cake (RSC) and twelve were mild processed and hexane-extracted producing soft rapeseed meal (SRSM). One batch of the variety Compass, grown on the same farm, was processed using both methods obtaining Compass RSC and Compass SRSM. DK Cabernet rapeseed variety, grown on three different farms, was used to produce two SRSM batches and one RSC batch. All rapeseed co-products were ground through a 4 mm screen and mixed into semi-synthetic diets at a level of 500 g/kg. Day-old Ross 308 male broilers were fed a commercial diet for 14 days. A total of 96 pairs of birds were then allotted to 1 of 16 dietary treatments (n = 6) and fed a test diet for 8 days. Birds were then culled allowing removal of ileal digesta from Meckel’s diverticulum to the ileal-caecal junction. Digestibility of CP and AA was determined using titanium dioxide as an inert marker. The SRSM samples had an increased content of CP (419–560 g/kg DM) compared to RSC samples (293–340 g/kg DM). Both AID and SID of lysine, and SID of arginine, histidine and threonine were greater in Compass RSC compared to its SRSM counterpart (P 0.05). The SID of lysine was on average 0.03 units greater (P < 0.001) in RSC than in SRSM. The SRSM produced from variety PR46W21 showed similar or greater AID and SID of individual AA than the RSC from four other rapeseed varieties. It is concluded that selection of rapeseed varieties, and extraction method have a potential to deliver high-protein dietary ingredients with a good digestibility value

Total Elbow Arthroplasty

Total elbow arthroplasty has continued to evolve over time. Elbow implants may be linked or unlinked. Unlinked implants are attractive for patients with relatively well preserved bone stock and ligaments, but many favor linked implants, since they prevent instability and allow replacement for a wider spectrum of indications. Inflammatory arthropathies such as rheumatoid arthritis represent the classic indication for elbow arthroplasty. Indications have been expanded to include posttraumatic osteoarthritis, acute distal humerus fractures, distal humerus nonunions and reconstruction after tumor resection. Elbow arthroplasty is very successful in terms of pain relief, motion and function. However, its complication rate remains higher than arthroplasty of other joints. The overall success rate is best for patients with inflammatory arthritis and elderly patients with acute distal humerus fractures, worse for patients with posttraumatic osteoarthritis. The most common complications of elbow arthroplasty include infection, loosening, wear, triceps weakness and ulnar neuropathy. When revision surgery becomes necessary, bone augmentation techniques provide a reasonable outcome

The extent and variability of storm-induced temperature changes in lakes measured with long-term and high-frequency data

The intensity and frequency of storms are projected to increase in many regions of the world because of climate change. Storms can alter environmental conditions in many ecosystems. In lakes and reservoirs, storms can reduce epilimnetic temperatures from wind-induced mixing with colder hypolimnetic waters, direct precipitation to the lake's surface, and watershed runoff. We analyzed 18 long-term and high-frequency lake datasets from 11 countries to assess the magnitude of wind- vs. rainstorm-induced changes in epilimnetic temperature. We found small day-to-day epilimnetic temperature decreases in response to strong wind and heavy rain during stratified conditions. Day-to-day epilimnetic temperature decreased, on average, by 0.28 degrees C during the strongest windstorms (storm mean daily wind speed among lakes: 6.7 +/- 2.7 m s(-1), 1 SD) and by 0.15 degrees C after the heaviest rainstorms (storm mean daily rainfall: 21.3 +/- 9.0 mm). The largest decreases in epilimnetic temperature were observed >= 2 d after sustained strong wind or heavy rain (top 5(th) percentile of wind and rain events for each lake) in shallow and medium-depth lakes. The smallest decreases occurred in deep lakes. Epilimnetic temperature change from windstorms, but not rainstorms, was negatively correlated with maximum lake depth. However, even the largest storm-induced mean epilimnetic temperature decreases were typicallyPeer reviewe

Storm impacts on phytoplankton community dynamics in lakes

In many regions across the globe, extreme weather events such as storms have increased in frequency, intensity, and duration due to climate change. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. High winds and precipitation associated with storms can affect lakes via short-term runoff events from watersheds and physical mixing of the water column. In addition, lakes connected to rivers and streams will also experience flushing due to high flow rates. Although we have a well-developed understanding of how wind and precipitation events can alter lake physical processes and some aspects of biogeochemical cycling, our mechanistic understanding of the emergent responses of phytoplankton communities is poor. Here we provide a comprehensive synthesis that identifies how storms interact with lake and watershed attributes and their antecedent conditions to generate changes in lake physical and chemical environments. Such changes can restructure phytoplankton communities and their dynamics, as well as result in altered ecological function (e.g., carbon, nutrient and energy cycling) in the short- and long-term. We summarize the current understanding of storm-induced phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions across a gradient of lake types and environmental conditions.Peer reviewe

Storm impacts on phytoplankton community dynamics in lakes

In many regions across the globe, extreme weather events, such as storms, have increased in frequency, intensity and duration. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. For lake ecosystems, high winds and rainfall associated with storms are linked by short term runoff events from catchments and physical mixing of the water column. Although we have a well-developed understanding of how such wind and precipitation events alter lake physical processes, our mechanistic understanding of how these short-term disturbances 48 translate from physical forcing to changes in phytoplankton communities is poor. Here, we provide a conceptual model that identifies how key storm features (i.e., the frequency, intensity, and duration of wind and precipitation) interact with attributes of lakes and their watersheds to generate changes in a lake’s physical and chemical environment and subsequently phytoplankton community structure and dynamics. We summarize the current understanding of storm-phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions by generating testable hypotheses across a global gradient of lake types and environmental conditions.Fil: Stockwell, Jason D.. University of Vermont; Estados UnidosFil: Adrian, Rita. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Andersen, Mikkel. Dundalk Institute of Technology; IrlandaFil: Anneville, Orlane. Institut National de la Recherche Agronomique; FranciaFil: Bhattacharya, Ruchi. University of Missouri; Estados UnidosFil: Burns, Wilton G.. University of Vermont; Estados UnidosFil: Carey, Cayelan C.. Virginia Tech University; Estados UnidosFil: Carvalho, Laurence. Freshwater Restoration & Sustainability Group; Reino UnidoFil: Chang, ChunWei. National Taiwan University; República de ChinaFil: De Senerpont Domis, Lisette N.. Netherlands Institute of Ecology; Países BajosFil: Doubek, Jonathan P.. University of Vermont; Estados UnidosFil: Dur, Gaël. Shizuoka University; JapónFil: Frassl, Marieke A.. Griffith University; AustraliaFil: Gessner, Mark O.. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Hejzlar, Josef. Biology Centre of the Czech Academy of Sciences; República ChecaFil: Ibelings, Bas W.. University of Geneva; SuizaFil: Janatian, Nasim. Estonian University of Life Sciences; EstoniaFil: Kpodonu, Alfred T. N. K.. City University of New York; Estados UnidosFil: Lajeunesse, Marc J.. University of South Florida; Estados UnidosFil: Lewandowska, Aleksandra M.. Tvarminne Zoological Station; FinlandiaFil: Llames, Maria Eugenia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Matsuzaki, Shin-ichiro S.. National Institute for Environmental Studies; JapónFil: Nodine, Emily R.. Rollins College; Estados UnidosFil: Nõges, Peeter. Estonian University of Life Sciences; EstoniaFil: Park, Ho-Dong. Shinshu University; JapónFil: Patil, Vijay P.. US Geological Survey; Estados UnidosFil: Pomati, Francesco. Swiss Federal Institute of Water Science and Technology; SuizaFil: Rimmer, Alon. Kinneret Limnological Laboratory; IsraelFil: Rinke, Karsten. Helmholtz-Centre for Environmental Research; AlemaniaFil: Rudstam, Lars G.. Cornell University; Estados UnidosFil: Rusak, James A.. Ontario Ministry of the Environment and Climate Change; CanadáFil: Salmaso, Nico. Research and Innovation Centre - Fondazione Mach; ItaliaFil: Schmitt, François. Laboratoire d’Océanologie et de Géosciences; FranciaFil: Seltmann, Christian T.. Dundalk Institute of Technology; IrlandaFil: Souissi, Sami. Universite Lille; FranciaFil: Straile, Dietmar. University of Konstanz; AlemaniaFil: Thackeray, Stephen J.. Lancaster Environment Centre; Reino UnidoFil: Thiery, Wim. Vrije Unviversiteit Brussel; Bélgica. Institute for Atmospheric and Climate Science; SuizaFil: Urrutia Cordero, Pablo. Uppsala University; SueciaFil: Venail, Patrick. Universidad de Ginebra; SuizaFil: Verburg, Piet. 8National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Williamson, Tanner J.. Miami University; Estados UnidosFil: Wilson, Harriet L.. Dundalk Institute of Technology; IrlandaFil: Zohary, Tamar. Israel Oceanographic & Limnological Research; IsraelGLEON 20: All Hands' MeetingRottnest IslandAustraliaUniversity of Western AustraliaUniversity of AdelaideGlobal Lake Ecological Observatory Networ

Development of three-dimensional tissue engineered bone-oral mucosal composite models

Tissue engineering of bone and oral mucosa have been extensively studied independently. The aim of this study was to develop and investigate a novel combination of bone and oral mucosa in a single 3D in vitro composite tissue mimicking the natural structure of alveolar bone with an overlying oral mucosa. Rat osteosarcoma (ROS) cells were seeded into a hydroxyapatite/tri-calcium phosphate scaffold and bone constructs were cultured in a spinner bioreactor for 3 months. An engineered oral mucosa was fabricated by air/liquid interface culture of immortalized OKF6/TERET-2 oral keratinocytes on collagen gel-embedded fibroblasts. EOM was incorporated into the engineered bone using a tissue adhesive and further cultured prior to qualitative and quantitative assessments. Presto Blue assay revealed that ROS cells remained vital throughout the experiment. The histological and scanning electron microscope examinations showed that the cells proliferated and densely populated the scaffold construct. Micro computed tomography (micro-CT) scanning revealed an increase in closed porosity and a decrease in open and total porosity at the end of the culture period. Histological examination of bone-oral mucosa model showed a relatively differentiated parakeratinized epithelium, evenly distributed fibroblasts in the connective tissue layer and widely spread ROS cells within the bone scaffold. The feasibility of fabricating a novel bone-oral mucosa model using cell lines is demonstrated. Generating human ‘normal’ cell-based models with further characterization is required to optimize the model for in vitro and in vivo applications

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research