198 research outputs found

    FLO1 is a variable green beard gene that drives biofilm-like cooperation in budding yeast

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    The budding yeast, Saccharomyces cerevisiae, has emerged as an archetype of eukaryotic cell biology. Here we show that S. cerevisiae is also a model for the evolution of cooperative behavior by revisiting flocculation, a self-adherence phenotype lacking in most laboratory strains. Expression of the gene FLO1 in the laboratory strain S288C restores flocculation, an altered physiological state, reminiscent of bacterial biofilms. Flocculation protects the FLO1 expressing cells from multiple stresses, including antimicrobials and ethanol. Furthermore, FLO1(+) cells avoid exploitation by nonexpressing flo1 cells by self/non-self recognition: FLO1(+) cells preferentially stick to one another, regardless of genetic relatedness across the rest of the genome. Flocculation, therefore, is driven by one of a few known "green beard genes,'' which direct cooperation toward other carriers of the same gene. Moreover, FLO1 is highly variable among strains both in expression and in sequence, suggesting that flocculation in S. cerevisiae is a dynamic, rapidly evolving social trait

    Costing juvenile idiopathic arthritis: examining patient-based costs during the first year after diagnosis

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    Objectives. There are few data on the treatment patterns and associated cost of treating children with inflammatory arthritis including juvenile idiopathic arthritis (JIA), in the short or long term. The aim of this study was to obtain patient-based costs for treating children with JIA in the UK, in the first year from diagnosis and from the secondary health care payer perspective

    Cohesive properties of alkali halides

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    We calculate cohesive properties of LiF, NaF, KF, LiCl, NaCl, and KCl with ab-initio quantum chemical methods. The coupled-cluster approach is used to correct the Hartree-Fock crystal results for correlations and to systematically improve cohesive energies, lattice constants and bulk moduli. After inclusion of correlations, we recover 95-98 % of the total cohesive energies. The lattice constants deviate from experiment by at most 1.1 %, bulk moduli by at most 8 %. We also find good agreement for spectroscopic properties of the corresponding diatomic molecules.Comment: LaTeX, 10 pages, 1 figure, accepted by Phys. Rev.

    Disease activity and disability in children with juvenile idiopathic arthritis one year following presentation to paediatric rheumatology. Results from the Childhood Arthritis Prospective Study

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    Objective. Inflammatory arthritis in childhood is variable in terms of both presentation and outcome. This analysis describes disease activity in children with juvenile idiopathic arthritis (JIA) during the first year following presentation to a paediatric rheumatologist and identifies predictors of moderate to severe disability [defined using a Childhood HAQ (CHAQ) score ⩾0.75] at 1 year

    Lack of EGF receptor contributes to drug sensitivity of human germline cells

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    Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours

    Rapid-acting antidepressants and the regulation of TrkB neurotrophic signalling-Insights from ketamine, nitrous oxide, seizures and anaesthesia

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    Increased glutamatergic neurotransmission and synaptic plasticity in the prefrontal cortex have been associated with the rapid antidepressant effects of ketamine. Activation of BDNF (brain-derived neurotrophic factor) receptor TrkB is considered a key molecular event for antidepressant-induced functional and structural synaptic plasticity. Several mechanisms have been proposed to underlie ketamine's effects on TrkB, but much remains unclear. Notably, preliminary studies suggest that besides ketamine, nitrous oxide (N2O) can rapidly alleviate depressive symptoms. We have shown nitrous oxide to evoke TrkB signalling preferentially after the acute pharmacological effects have dissipated (ie after receptor disengagement), when slow delta frequency electroencephalogram (EEG) activity is up-regulated. Our findings also demonstrate that various anaesthetics and sedatives activate TrkB signalling, further highlighting the complex mechanisms underlying TrkB activation. We hypothesize that rapid-acting antidepressants share the ability to regulate TrkB signalling during homeostatically evoked slow-wave activity and that this mechanism is important for sustained antidepressant effects. Our observations urge the examination of rapid and sustained antidepressant effects beyond conventional receptor pharmacology by focusing on brain physiology and temporally distributed signalling patterns spanning both wake and sleep. Potential implications of this approach for the improvement of current therapies and discovery of novel antidepressants are discussed.Peer reviewe

    A Systematic Review of Argumentation Related to the Engineering-Designed World

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    Background Across academic disciplines, researchers have found that argumentation‐based pedagogies increase learners\u27 achievement and engagement. Engineering educational researchers and teachers of engineering may benefit from knowledge regarding how argumentation related to engineering has been practiced and studied. Purpose/Hypothesis Drawing from terms and concepts used in national standards for K‐12 education and accreditation requirements for undergraduate engineering education, this study was designed to identify how arguments and argumentation related to the engineering‐designed world were operationalized in relevant literature. Methodology Specified search terms and inclusion criteria were used to identify 117 empirical studies related to engineering argumentation and educational research. A qualitative content analysis was used to identify trends across these studies. Findings Overall, engineering‐related argumentation was associated with a variety of positive learner outcomes. Across many studies, arguments were operationalized in practice as statements regarding whether an existing technology should be adopted in a given context, usually with a limited number of supports (e.g., costs and ethics) provided for each claim. Relatively few studies mentioned empirical practices, such as tests. Most studies did not name the race/ethnicity of participants nor report engineering‐specific outcomes. Conclusions Engineering educators in K‐12 and undergraduate settings can create learning environments in which learners use a range of epistemic practices, including empirical practices, to support a range of claims. Researchers can study engineering‐specific outcomes while specifying relevant demographics of their research participants

    Multidimensional Signals and Analytic Flexibility: Estimating Degrees of Freedom in Human-Speech Analyses

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    Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis that can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling but also from decisions regarding the quantification of the measured behavior. In this study, we gave the same speech-production data set to 46 teams of researchers and asked them to answer the same research question, resulting in substantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further found little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise, or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system, and calibrate their (un)certainty in their conclusions
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