Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing

AbstractTendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation. S100a4-Cre; EP4flox/flox (EP4cKOS100a4) repairs healed with improved gliding function at day 14, followed by impaired gliding at day 28, relative to wild type. Interestingly, EP4cKOS100a4 resulted in only transient deletion of EP4, suggesting up-regulation of EP4 in an alternative cell population in these mice. Loss of EP4 in Scleraxis-lineage cells did not alter gliding function, suggesting that Scx-lineage cells are not the predominant EP4 expressing population. In contrast, a dramatic increase in α-SMA+, EP4+ double-positive cells were observed in EP4cKOS100a4 suggesting that EP4cKOS100a4 repairs heal with increased infiltration of EP4 expressing α-SMA myofibroblasts, identifying a potential mechanism of late up-regulation of EP4 and impaired gliding function in EP4cKOS100a4 tendon repairs.</jats:p

Inferring and Testing Hypotheses of Cladistic Character Dependence by Using Character Compatibility

The notion that two characters evolve independently is of interest for two reasons. First, theories of biological integration often predict that change in one character requires complementary change in another. Second, character independence is a basic assumption of most phylogenetic inference methods, and dependent characters might confound attempts at phylogenetic inference. Previously proposed tests of correlated character evolution require a model phylogeny and therefore assume that nonphylogenetic correlation has a negligible effect on initial tree construction. This paper develops “tree-free” methods for testing the independence of cladistic characters. These methods can test the character independence model as a hypothesis before phylogeny reconstruction, or can be used simply to test for correlated evolution. We first develop an approach for visualizing suites of correlated characters by using character compatibility. Two characters are compatible if they can be used to construct a tree without homoplasy. The approach is based on the examination of mutual compatibilities between characters. The number of times two characters i and j share compatibility with a third character is calculated, and a pairwise shared compatibility matrix is constructed. From this matrix, an association matrix analogous to a dissimilarity matrix is derived. Eigenvector analyses of this association matrix reveal suites of characters with similar compatibility patterns. A priori character subsets can be tested for significant correlation on these axes. Monte Carlo tests are performed to determine the expected distribution of mutual compatibilities, given various criteria from the original data set. These simulated distributions are then used to test whether the observed amounts of nonphylogenetic correlation in character suites can be attributed to chance alone. We have applied these methods to published morphological data for caecilian amphibians. The analyses corroborate instances of dependent evolution hypothesized by previous workers and also identify novel partitions. Phylogenetic analysis is performed after reducing correlated suites to single characters. The resulting cladogram has greater topological resolution and implies appreciably less change among the remaining characters than does a tree derived from the raw data matrix

Optimal swimming speeds reflect preferred swimming speeds of brook charr (Salvelinus fontinalis Mitchill, 1874)

Several measures have been developed to quantify swimming performance to understand various aspects of ecology and behaviour, as well as to help design functional applications for fishways and aquaculture. One of those measures, the optimal swimming speed, is the speed at which the cost of transport (COT) is minimal, where COT is defined as the cost of moving unit mass over unit distance. The experimental protocol to determine the optimal swimming speed involves forced-swimming in a flume or respirometer. In this study, a 4.5–m-long tilted raceway with gradually increasing upstream water speed is used to determine a novel, behaviourally based swimming parameter: the preferred swimming speed. The optimal swimming speed and the preferred swimming speed of brook charr were determined and a comparison of the two reveals that the optimal swimming speed (25.9 ± 4.5 cm s−1 or 1.02 ± 0.47 bl s−1) reflected the preferred swimming speed (between 20 cm s−1 or 0.78 ± 0.02 bl s−1 and 25 cm s−1 or 0.95 ± 0.03 bl s−1). The preferred swimming speed can be advantageous for the determination of swimming speeds for the use in aquaculture studies

Dynamical model of sequential spatial memory: winnerless competition of patterns

We introduce a new biologically-motivated model of sequential spatial memory which is based on the principle of winnerless competition (WLC). We implement this mechanism in a two-layer neural network structure and present the learning dynamics which leads to the formation of a WLC network. After learning, the system is capable of associative retrieval of pre-recorded sequences of spatial patterns.Comment: 4 pages, submitted to PR

Innovative research methods for studying treatments for rare diseases: methodological review

Objective: To examine methods for generating evidence on health outcomes in patients with rare diseases. Design: Methodological review of existing literature. Setting: PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. Main outcome measures We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. Results: We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Conclusions: Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

The Message Design Logics of Responses to HIV Disclosures

This article uses the theory of message design logics to investigate the relative sophistication of responses to disclosure of HIV status. In Study 1, 548 college students imagined a sibling revealing an HIV-positive diagnosis. Their responses to the HIV disclosures were coded as expressive (n= 174), conventional (n= 298), or rhetorical (n= 66). Type of message produced was associated with gender and HIV aversion. In Study 2, 459 individuals living with HIV rated response messages that were taken verbatim from Study 1. Expressive messages were rated lowest in quality, and rhetorical messages were rated highest. The discussion focuses on the utility of message design logics for understanding responses to HIV disclosures and the implications for message design logics

P/2010 A2 LINEAR II: dynamical dust modelling

P/2010 A2 is an object on an asteroidal orbit that was observed to have an extended tail or debris trail in January 2010. In this work, we fit the outburst of P/2010 A2 with a conical burst model, and verify previous suspicions that this was a one--time collisional event rather than an sustained cometary outburst, implying that P/2010 A2 is not a new Main Belt Comet driven by ice sublimation. We find that the best--fit cone opening angle is about 40 to 50 degrees, in agreement with numerical and laboratory simulations of cratering events. Mapping debris orbits to sky positions suggests that the distinctive arc features in the debris correspond to the same debris cone inferred from the extended dust. From the velocity of the debris, and from the presence of a velocity maximum at around 15 cm/s, we infer that the surface of A2 probably has a very low strength (<1 kPa), comparable to lunar regolith.Comment: 14 pages, 25 figures; accepted by Astronomy and Astrophysic

The quality of political information

The article conceptualizes the quality of political information and shows how the concept can be used for empirical research. I distinguish three aspects of quality (intelligibility, relevance, validity) and use them to judge the constituent foundations of political information, that is component claims (statements of alleged facts) and connection claims (argumentative statements created by causally linking two component claims). The resulting conceptual map thus entails six manifestations of information quality (component claimintelligibility, connection claim intelligibility, component claimrelevance, connection claim relevance, component claim validity, and connection claim validity). I explain how the conceptual map can be used to make sense of the eclectic variety of existing research, and how it can advance new empirical research, as a guide for determining variation in information quality, as a conceptual template for the analysis of different types of political messages and their common quality deficiencies, and as a generator of new research questions and theoretical expectations