Border effects among Catalan dialects

In this study, we investigate which factors influence the linguistic distance of Catalan dialectal pronunciations from standard Catalan. We use pronunciations from three regions where the northwestern variety of the Catalan language is spoken (Catalonia, Aragon and Andorra). In contrast to Aragon, Catalan has an official status in both Catalonia and Andorra, which likely influences standardization. Because we are interested in the potentially large range of differences that standardization might promote, we examine 357 words in Catalan varieties and in particular their pronunciation distances with respect to the standard. In order to be sensitive to differences among the words, we fitted a generalized additive mixed-effects regression model to this data. This allows us to examine simultaneously the general (i.e. aggregate) patterns in pronunciation distance and to detect those words that diverge substantially from the general pattern. The results revealed higher pronunciation distances from standard Catalan in Aragon than in the other regions. Furthermore, speakers in Catalonia and Andorra, but not in Aragon, showed a clear standardization pattern, with younger speakers having dialectal pronunciations closer to the standard than older speakers. This clearly indicates the presence of a border effect within a single country with respect to word pronunciation distances. Since a great deal of scholarship focuses on single segment changes, we compare our analysis to the analysis of three segment changes that have been discussed in the literature on Catalan. This comparison revealed that the pattern observed at the word pronunciation level was supported by two of the three cases examined. As not all individual cases conform to the general pattern,

Amniotic Epithelial Cells from the Human Placenta Potently Suppress a Mouse Model of Multiple Sclerosis

Human amniotic epithelial cells (hAEC) have stem cell-like features and immunomodulatory properties. Here we show that hAEC significantly suppressed splenocyte proliferation in vitro and potently attenuated a mouse model of multiple sclerosis (MS). Central nervous system (CNS) CD3+ T cell and F4/80+ monocyte/macrophage infiltration and demyelination were significantly reduced with hAEC treatment. Besides the known secretion of prostaglandin E2 (PGE2), we report the novel finding that hAEC utilize transforming growth factor-β (TGF-β) for immunosuppression. Neutralization of TGF-β or PGE2 in splenocyte proliferation assays significantly reduced hAEC-induced suppression. Splenocytes from hAEC-treated mice showed a Th2 cytokine shift with significantly elevated IL-5 production. While transferred CFSE-labeled hAEC could be detected in the lung, none were identified in the CNS or in lymphoid organs. This is the first report documenting the therapeutic effect of hAEC in a MS-like model and suggest that hAEC may have potential for use as therapy for MS

IL-6-Dependent PGE2 Secretion by Mesenchymal Stem Cells Inhibits Local Inflammation in Experimental Arthritis

BACKGROUND: Based on their capacity to suppress immune responses, multipotent mesenchymal stromal cells (MSC) are intensively studied for various clinical applications. Although it has been shown in vitro that the immunomodulatory effect of MSCs mainly occurs through the secretion of soluble mediators, the mechanism is still not completely understood. The aim of the present study was to better understand the mechanisms underlying the suppressive effect of MSCs in vivo, using cells isolated from mice deficient in the production of inducible nitric oxide synthase (iNOS) or interleukin (IL)-6 in the murine model of collagen-induced arthritis. PRINCIPAL FINDINGS: In the present study, we show that primary murine MSCs from various strains of mice or isolated from mice deficient for iNOS or IL-6 exhibit different immunosuppressive potential. The immunomodulatory function of MSCs was mainly attributed to IL-6-dependent secretion of prostaglandin E2 (PGE2) with a minor role for NO. To address the role of these molecules in vivo, we used the collagen-induced arthritis as an experimental model of immune-mediated disorder. MSCs effectively inhibited collagen-induced inflammation during a narrow therapeutic window. In contrast to wild type MSCs, IL-6-deficient MSCs and to a lesser extent iNOS-deficient MSCs were not able to reduce the clinical signs of arthritis. Finally, we show that, independently of NO or IL-6 secretion or Treg cell induction, MSCs modulate the host response by inducing a switch to a Th2 immune response. SIGNIFICANCE: Our data indicate that mscs mediate their immunosuppressive effect via two modes of action: locally, they reduce inflammation through the secretion of anti-proliferative mediators, such as NO and mainly PGE2, and systemically they switch the host response from a Th1/Th17 towards a Th2 immune profile

Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

The corneal pocket assay

The cornea in most species is physiologically avascular, and thus this assay allows the measurement of newly formed vessels. The continuous monitoring of neovascular growth in the same animal allows the evaluation of drugs acting as suppressors or stimulators of angiogenesis. Under anesthesia a micropocket is produced in the cornea thickness and the angiogenesis stimulus (tumor tissue, cell suspension, growth factor) is placed into the pocket in order to induce vascular outgrowth from the limbal capillaries. Neovascular development and progression can be modified by the presence of locally released or applied inhibitory factors or by systemic treatments. In this chapter the experimental details of the avascular cornea assay, the technical challenges, and advantages and disadvantages in different species are discussed. Protocols for local drug treatment and tissue sampling for histology and pharmacokinetic profile are reported

Pb Isotopic Composition of Panamanian Colonial Majolica by LA-ICP-MS

Panama ́ Viejo, founded in 1519 by the Spanish explorer Pedrarias Da ́vila, was the first permanent European settlement on the Pacific Ocean, and became a city, by royal decree, in 1521. Shortly after its creation, the city became an important base for trade with Spain. In 1671, the English pirate Henry Morgan waged an attack on Panama ́ Viejo, which resulted in a fire that destroyed the entire city. A new settlement built a few miles west, called Casco Antiguo or San Felipe, is now the historic district of modern Panama City. The Pb isotopic compositions of the glazes on the surface of sixteenth to seventeenth century majolica pottery sherds from Panama Viejo and Casco Antiguo (both in Panama), and Lima (Peru) were determined via non-destructive laser ablation multi-collector ICP-MS (LA-MC-ICP-MS). The contrast in Pb isotopic compositions in the glazes on ceramics recovered in different locations demonstrate that early majolica pottery production during this period used Pb obtained from the Andes. However, the Pb used in later majolica production in Panama is of Spanish origin. After Panama ́ Viejo was burned to the ground, Panamanian majolica production ended

Protocol for a pragmatic randomised controlled trial to evaluate effects of a brief intervention for emergency department attendees who present with moderate or high levels of non-specific psychological distress: a pilot study

BACKGROUND: Screening and brief intervention in the emergency department (ED) has almost exclusively focused on individuals with alcohol-use problems. The early detection of mental health problems before problems become severe will enable early intervention and support which may improve health and prevent further deterioration. The main aim of this pilot study is to provide evidence of the acceptance of a telephone intervention aimed at ED attendees with moderate or high psychological distress. This will be determined by recruitment rates, retention rates and participant satisfaction with the intervention. Secondary outcomes include whether socio-demographic variables have an impact on retention rates, and whether the intervention had any impact on psychological distress. METHODS/DESIGN: This study will be a single-site pragmatic randomised controlled pilot study. Consenting ED attendees will be screened with the Kessler Psychological Distress Scales (K10). There will be three arms to the study: a moderate/high psychological distress group with or without intervention, and a low psychological distress group. Those with severe psychological distress will be excluded. All included participants will be followed-up at 1, 3, 6 and 12 months post-recruitment. Retention rates will be determined by successful completion of surveys at the follow-up time-points. Psychological distress will be measured by the K10 at all follow-up time-points. DISCUSSION: This study will provide information regarding the potential for screening and recruitment at an opportunistic hospital presentation. It will provide data for a future larger study with regard to participants accepting to be included in this study. Participant acceptability will be measured in terms of recruitment rates and retention rates measured by successful follow-ups over the following 12 months post-recruitment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12614000031662. Registered 10/01/2014