A homeostatic function of CXCR2 signalling in articular cartilage

Funding This work was funded by Arthritis Research UK (grants 17859, 17971, 19654), INNOCHEM EU FP6 (grant LSHB-CT-2005-51867), MRC (MR/K013076/1) and the William Harvey Research FoundationPeer reviewedPublisher PD

Antibody-mediated inhibition of syndecan-4 dimerisation reduces interleukin (IL)-1 receptor trafficking and signalling.

OBJECTIVE: Syndecan-4 (sdc4) is a cell-anchored proteoglycan that consists of a transmembrane core protein and glucosaminoglycan (GAG) side chains. Binding of soluble factors to the GAG chains of sdc4 may result in the dimerisation of sdc4 and the initiation of downstream signalling cascades. However, the question of how sdc4 dimerisation and signalling affects the response of cells to inflammatory stimuli is unknown. METHODS: Sdc4 immunostaining was performed on rheumatoid arthritis (RA) tissue sections. Interleukin (IL)-1 induced extracellular signal-regulated kinases (ERK) phosphorylation and matrix metalloproteinase-3 production was investigated. Il-1 binding to sdc4 was investigated using immunoprecipitation. IL-1 receptor (IL1R1) staining on wild-type, sdc4 and IL1R1 knockout fibroblasts was performed in fluorescence-activated cell sorting analyses. A blocking sdc4 antibody was used to investigate sdc4 dimerisation, IL1R1 expression and the histological paw destruction in the human tumour necrosis factor-alpha transgenic mouse. RESULTS: We show that in fibroblasts, the loss of sdc4 or the antibody-mediated inhibition of sdc4 dimerisation reduces the cell surface expression of the IL-1R and regulates the sensitivity of fibroblasts to IL-1. We demonstrate that IL-1 directly binds to sdc4 and in an IL-1R-independent manner leads to its dimerisation. IL-1-induced dimerisation of sdc4 regulates caveolin vesicle-mediated trafficking of the IL1R1, which in turn determines the responsiveness to IL-1. Administration of antibodies (Ab) against the dimerisation domain of sdc4, thus, strongly reduces the expression IL1R1 on arthritic fibroblasts both in vitro and an animal model of human RA. CONCLUSION: Collectively, our data suggest that Ab that specifically inhibit sdc4 dimerisation may support anti-IL-1 strategies in diseases such as inflammatory arthritis

Optimal General Matchings

Given a graph $G=(V,E)$ and for each vertex $v \in V$ a subset $B(v)$ of the set $\{0,1,\ldots, d_G(v)\}$, where $d_G(v)$ denotes the degree of vertex $v$ in the graph $G$, a $B$-factor of $G$ is any set $F \subseteq E$ such that $d_F(v) \in B(v)$ for each vertex $v$, where $d_F(v)$ denotes the number of edges of $F$ incident to $v$. The general factor problem asks the existence of a $B$-factor in a given graph. A set $B(v)$ is said to have a {\em gap of length} $p$ if there exists a natural number $k \in B(v)$ such that $k+1, \ldots, k+p \notin B(v)$ and $k+p+1 \in B(v)$. Without any restrictions the general factor problem is NP-complete. However, if no set $B(v)$ contains a gap of length greater than $1$, then the problem can be solved in polynomial time and Cornuejols \cite{Cor} presented an algorithm for finding a $B$-factor, if it exists. In this paper we consider a weighted version of the general factor problem, in which each edge has a nonnegative weight and we are interested in finding a $B$-factor of maximum (or minimum) weight. In particular, this version comprises the minimum/maximum cardinality variant of the general factor problem, where we want to find a $B$-factor having a minimum/maximum number of edges. We present an algorithm for the maximum/minimum weight $B$-factor for the case when no set $B(v)$ contains a gap of length greater than $1$. This also yields the first polynomial time algorithm for the maximum/minimum cardinality $B$-factor for this case

Differences in assigning probabilities to coastal inundation hazard estimators: event versus response approaches

This is the accepted version of the following article: Sanuy, M, Jiménez, JA, Ortego, MI, Toimil, A. Differences in assigning probabilities to coastal inundation hazard estimators: Event versus response approaches. J Flood Risk Management. 2020; 13 (Suppl. 1):e12557. https://doi.org/10.1111/jfr3.12557, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1111/jfr3.12557.Coastal flood risk assessment requires a reliable estimation of the frequency of inundation hazards, that is, characterising the hazard magnitude and assigning a probability of occurrence. In this work we analyse the uncertainty introduced in the assessment associated to the method to assign the probability of occurrence to coastal flood hazards. To this end we have compared the use of two general methods, the response and the event approaches. Different procedures are used to characterise coastal inundation hazards depending on the analysis scale and data availability. Thus, a range of possibilities has been analysed, from simple estimators such as run-up to modelled flood-prone areas. The analysis has been performed for all wave and water level conditions around the Spanish coast. The results show that the differences between the methods are location-dependent, and thus, determined by the exposure to wave and water level conditions. When using the event approach, the run-up or total water level (with good correlation between waves and surge) distributions reasonably approximate those of the response approach with low associated uncertainty. When the assessment aims to output overtopping discharges or inundation maps, observed differences suggest that the event approach would produce misleading conclusions in inundation-related coastal management and decision-making.Peer ReviewedPostprint (author's final draft

No evidence for parasitism-linked changes in immune function or oxidative physiology over the annual cycle of an avian species

Temporally changing environmental conditions occur in most parts of the world and can exert strong pressure on the immune defense of organisms. Seasonality may result in changes in physiological traits over the year, and such changes may be essential for the optimization of defense against infections. Evidence from field and laboratory studies suggest the existence of links between environmental conditions, such as infection risk, and the ability of animals to mount an immune response or to overcome infections; however, the importance of parasites in mediating seasonal change in immune defense is still debated. In this study, we test the hypothesis that seasonal change in immune function and connected physiological traits is related to parasite infection. We sampled captive house sparrows (Passer domesticus) once every 2 mo over 14 mo and compared the annual variation in 12 measures of condition, immune function, antioxidant status, and oxidative damage among birds naturally infested with coccidians or medicated against these parasites. We found significant variation in 10 of 12 traits over the year. However, we found little support for parasite-mediated change in immune function and oxidative status in captive house sparrows. Of the 12 measures, only one was slightly affected by parasite treatment. In support of the absence of any effect of coccidians on the annual profile of the condition and physiological traits, we found no consistent relationships between the intensity of infestation and these response variables over the year. Our results show that chronic coccidian infections have limited effect on the seasonal changing of physiological traits and that the patterns of these measures are probably more affected by acute infection and/or virulent parasite strains

Electronic and traditional savings accounts in colombia: A spatial agglomeration model

The purpose of this article is to apply a multivariate spatial statistics technique: cluster analysis or spatial agglomeration, in order to classify departments into groups based on behavior in the number of active, inactive electronic savings accounts and savings traditional active accounts, with database available as of September 2017 in the bank of Colombia. The selection of this type of accounts was due to the fact that the financial product with the highest penetration in the Colombian population in September 2017, continued to be the savings account; 73.5% of the population had this financial product. However, this percentage is far from the target of 84% proposed in the National Development Plan. The findings show that the departments where electronic accounts are most used are Cauca, Bogotá, Meta, Casanare, Arauca, Vichada, Huila, Amazonas, Guainía, Vaupés, Caldas, Chocó, Sucre, La Guajira, César, Norte de Santander, however, the levels of penetration of this type of product are very low yet in the Colombian territory

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Detecting spatio-temporal mortality clusters of European countries by sex and ag

[EN] Background: Mortality decreased in European Union (EU) countries during the last century. Despite these similar trends, there are still considerable differences in the levels of mortality between Eastern and Western European countries. Sub-group analysis of mortality in Europe for different age and sex groups is common, however to our knowledge a spatio-temporal methodology as in this study has not been applied to detect significant spatial dependence and interaction with time. Thus, the objective of this paper is to quantify the dynamics of mortality in Europe and detect significant clusters of mortality between European countries, applying spatio-temporal methodology. In addition, the joint evolution between the mortality of European countries and their neighbours over time was studied. Methods: The spatio-temporal methodology used in this study takes into account two factors: time and the geographical location of countries and, consequently, the neighbourhood relationships between them. This methodology was applied to 26 European countries for the period 1990-2012. Results: Principally, for people older than 64 years two significant clusters were obtained: one of high mortality formed by Eastern European countries and the other of low mortality composed of Western countries. In contrast, for ages below or equal to 64 years only the significant cluster of high mortality formed by Eastern European countries was observed. In addition, the joint evolution between the 26 European countries and their neighbours during the period 1990-2012 was confirmed. For this reason, it can be said that mortality in EU not only depends on differences in the health systems, which are a subject to national discretion, but also on supra-national developments. Conclusions: This paper proposes statistical tools which provide a clear framework for the successful implementation of development public policies to help the UE meet the challenge of rethinking its social model (Social Security and health care) and make it sustainable in the medium term.The authors are grateful for the financial support provided by the Ministry of Economy and Competitiveness, project MTM2013-45381-P. Adina Iftimi gratefully acknowledges financial support from the MECyD (Ministerio de Educacion, Cultura y Deporte, Spain) Grant FPU12/04531. Francisco Montes is grateful for the financial support provided by the Spanish Ministry of Economy and Competitiveness, project MTM2016-78917-R. The research by Patricia Carracedo and Ana Debon has been supported by a grant from the Mapfre Foundation.Carracedo-Garnateo, P.; Debón Aucejo, AM.; Iftimi, A.; Montes-Suay, F. (2018). Detecting spatio-temporal mortality clusters of European countries by sex and ag. 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Measurements of polarized photo-pion production on longitudinally polarized HD and Implications for Convergence of the GDH Integral

We report new measurements of inclusive pion production from frozen-spin HD for polarized photon beams covering the Delta(1232) resonance. These provide data simultaneously on both H and D with nearly complete angular distributions of the spin-difference cross sections entering the Gerasimov-Drell-Hearn (GDH) sum rule. Recent results from Mainz and Bonn exceed the GDH prediction for the proton by 22 microbarns, suggesting as yet unmeasured high-energy components. Our pi0 data reveal a different angular dependence than assumed in Mainz analyses and integrate to a value that is 18 microbarns lower, suggesting a more rapid convergence. Our results for deuterium are somewhat lower than published data, considerably more precise and generally lower than available calculations.Comment: 4 pages, 4 figures. Submitted for publication in Physical Review Letter