109 research outputs found

    Patterns of total suspended solids concentration and the influence of antecedent conditions on hydrograph response to precipitation events on Beaver Creek, Ontario

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    This study explored relationships between suspended solids concentration and discharge, the influence of antecedent conditions on event hydrograhs and the state of dynamic equilibrium in a second-order stream (Beaver Creek), draining an agricultural basin in southern Ontario, near the City of Waterloo. Beaver creek was monitored for nineteen weeks from July to November of 2005. Thirteen precipitation events of various magnitude and duration were examined within the study period. Discharge and total suspended soils were sampled throughout the events. Cross sectional profiles of six transects were measured prior to and after each event. Base flow, antecedent conditions and event response were quantified. A strong (R2=0.79) positive relationship was found between antecedent conditions and basin response to precipitation events, whereby, wetter conditions in the basin prior to a storm resulted in greater changes in discharge compared to changes in discharge seen with dryer antecedent conditions. Suspended solids/discharge patterns during storm flow were best described using a hysteretic clockwise loop indicating a change in supply source throughout a given event. Rapid changes in suspended soils concentrations were related to decreased detachment by rainfall splash rather than source exhaustion or dilution. Average suspended solids flux showed only a 34% difference between input and output from the study area. Also, cross sectional bed profiles showed that over the duration of this study the creek was in a state of low morphological activity. For design of monitoring programs as well as planning development within a basin, knowledge of storm sediment patterns, the influence of antecedent conditions on basin response to a precipitation event and resulting sediment flux in agricultural creeks is significant. These patterns should be taken as benchmarks for continued assessment of the impacts of human activities around water ways

    A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

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    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

    Rights in mind: Thinking differently about dementia and disability

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    The aim of this paper is to argue for the utility of a relational model of disability, as a way of conceptualizing dementia. We explore whether dementia should be considered as a disability, and whether people with dementia might consider themselves as disabled people. We review examples of, and issues raised by, the political activism of people with dementia. We consider how language constructs dementia negatively. We discuss how the environment influences the experience of dementia. In conclusion, we show that a relational model of dementia lays the basis for a human rights approach to the condition, based on collaborative partnerships between people with dementia and people from other disability communities

    Oxidative stress homeostasis in grapevine (Vitis vinifera L.)

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    Plants can maintain growth and reproductive success by sensing changes in the environment and reacting through mechanisms at molecular, cellular, physiological, and developmental levels. Each stress condition prompts a unique response although some overlap between the reactions to abiotic stress (drought, heat, cold, salt or high light) and to biotic stress (pathogens) does occur. A common feature in the response to all stresses is the onset of oxidative stress, through the production of reactive oxygen species (ROS). As hydrogen peroxide and superoxide are involved in stress signaling, a tight control in ROS homeostasis requires a delicate balance of systems involved in their generation and degradation. If the plant lacks the capacity to generate scavenging potential, this can ultimately lead to death. In grapevine, antioxidant homeostasis can be considered at whole plant levels and during the development cycle. The most striking example lies in berries and their derivatives, such as wine, with nutraceutical properties associated with their antioxidant capacity. Antioxidant homeostasis is tightly regulated in leaves, assuring a positive balance between photosynthesis and respiration, explaining the tolerance of many grapevine varieties to extreme environments. In this review we will focus on antioxidant metabolites, antioxidant enzymes, transcriptional regulation and cross-talk with hormones prompted by abiotic stress conditions. We will also discuss three situations that require specific homeostasis balance: biotic stress, the oxidative burst in berries at veraison and in vitro systems. The genetic plasticity of the antioxidant homeostasis response put in evidence by the different levels of tolerance to stress presented by grapevine varieties will be addressed. The gathered information is relevant to foster varietal adaptation to impending climate changes, to assist breeders in choosing the more adapted varieties and suitable viticulture practice

    EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients

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    Background Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. Methods The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. Discussion C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022

    The Functions of Mediator in Candida albicans Support a Role in Shaping Species-Specific Gene Expression

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    The Mediator complex is an essential co-regulator of RNA polymerase II that is conserved throughout eukaryotes. Here we present the first study of Mediator in the pathogenic fungus Candida albicans. We focused on the Middle domain subunit Med31, the Head domain subunit Med20, and Srb9/Med13 from the Kinase domain. The C. albicans Mediator shares some roles with model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, such as functions in the response to certain stresses and the role of Med31 in the expression of genes regulated by the activator Ace2. The C. albicans Mediator also has additional roles in the transcription of genes associated with virulence, for example genes related to morphogenesis and gene families enriched in pathogens, such as the ALS adhesins. Consistently, Med31, Med20, and Srb9/Med13 contribute to key virulence attributes of C. albicans, filamentation, and biofilm formation; and ALS1 is a biologically relevant target of Med31 for development of biofilms. Furthermore, Med31 affects virulence of C. albicans in the worm infection model. We present evidence that the roles of Med31 and Srb9/Med13 in the expression of the genes encoding cell wall adhesins are different between S. cerevisiae and C. albicans: they are repressors of the FLO genes in S. cerevisiae and are activators of the ALS genes in C. albicans. This suggests that Mediator subunits regulate adhesion in a distinct manner between these two distantly related fungal species

    Einbeziehen statt ausschließen. [Symposion 16. Sonderpädagogik in Europa - Tendenzen, Entwicklungen, Perspektiven im Vergleich]

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    Die Kommission Sonderpädagogik in der Deutschen Gesellschaft für Erziehungswissenschaft hatte dieses vergleichende Symposion zur Vielfalt sonderpädagogischer Konzepte in Europa vorbereitet. Die Referenten aus sechs europäischen Nachbarländern waren bemüht, Übereinstimmungen und Unterschiede hinsichtlich der Erziehung und Bildung von Behinderten aus historischer und aktueller Sicht aufzuzeigen. Im vorliegenden Beitrag gibt der Autor einen internationalen Situationsbericht, in dem er auch auf Probleme in Entwicklungsländern eingeht. Aussagen zur Situation in Großbritannien werden nur knapp berührt. (DIPF/Ba.

    It's Our Convention: Use It or Lose It?

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    <p>Unless action is taken now, at national and local levels, to ensure that the world’s one billion people with disabilities derive real and lasting benefits, the United Nations Convention on the Rights of Persons with Disabilities is in danger of being consigned to the graveyard of missed opportunities. Although many governments have signed and ratified the Convention, evidence of actual implementation is an immediate priority, especially in the midst of a global recession.</p><p>The scene is now set for governments to bring their policies into line with the principles and Articles of the Convention and to provide regular reports to the Disabled Persons’ Committee of the United Nations High Commission on Human Rights. Use of the internet can ensure that accountability is made public and includes the full participation of people with disabilities.</p

    Influences génétiques et mésologiques sur les aptitudes lingustiques.

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    Cette recherche vise à déterminer l'influence des facteurs génétiques et des facteurs de milieu sur l'expression des capacités psycho- linguistiques. L'auteur utilise l'I. T. P. A., un test basé sur le modèle d'Osgood, et qui est composé de neuf subtests correspondant à autant de fonctions linguistiques. Les deux méthodes utilisées (méthode gémellaire et comparaison d'enfants non-jumaux de classes sociales différentes) aboutissent aux mimes constats : les influences relatives de l'hérédité et du milieu sont très différentes selon l'aspect linguistique considéré.Mittler Peter. Influences génétiques et mésologiques sur les aptitudes lingustiques.. In: Enfance, tome 25, n°5, 1972. Recherches sur l'acquisition du langage chez l'enfant. pp. 519-530
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