13 research outputs found

    Semantiske og pragmatiske aspekter ved trykklett visst

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    I denne artikkelen ser vi pü betydningen til trykklett visst og viser hvordan man kan utføre korpusundersøkelser av semantiske og pragmatiske aspekter ved denne typen ikke-sannhetsfunksjonelle ord. Vi foreslür at de mange bruksmütene for ordet kan sammenfattes under ett semantisk oppslag, og med utgangspunkt i relevansteorien (Sperber & Wilson 1995) viser vi hvordan denne semantikken interagerer med generelle prinsipper for pragmatisk beriking og fører til ulike fortolkninger i ulike kontekster. Vi hevder videre at enkelte pragmatisk betingede fortolkninger av visst opptrer sü systematisk at de utgjør det Ariel (2008; 2010) kaller âprominente diskursmønstreâ, og vi argumenterer for at det ü identifisere prominente diskursmønstre er viktig i studier av denne typen ord

    2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes

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    Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

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    Serotonin transporter gene ( SLC6A4

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    Abstract Background The short (s) allele of the 5‐HTTLPR polymorphism in the promoter region of the human serotonin transporter (5‐HTT) gene SLC6A4 has previously been associated with anxiety‐related personality dimensions. However, this relationship has not been confirmed in all studies and may be modified by environmental circumstances and/or psychiatric illness. This study examined whether the temperamental trait sensory processing sensitivity (SPS), characterized by increased responsivity to environmental stimuli, is related to 5‐HTTLPR/rs25531 genotype. Methods 5‐HTTLPR and rs25531 genotypes, level of SPS, self‐reported Revised NEO Personality Inventory (NEO‐PI‐R) and Temperament and Character Inventory (TCI) personality profiles, and symptoms of psychological distress (SCL‐90R Global Severity Index) were determined for 405 healthy volunteers. Results Sensory processing sensitivity was highly correlated with the anxiety‐related dimensions of the NEO‐PI‐R and the TCI models of personality, Neuroticism, and Harm Avoidance, respectively. However, the level of SPS was not associated with the combined 5‐HTTLPR and rs25531 s′/s′ genotype. Neuroticism and Harm Avoidance were also not associated with 5‐HTTLPR/rs25531 s′/s′ genotype. Correcting for symptoms of psychological distress had no effect on the relationships between personality and genotype. Conclusion The level of SPS was not associated with serotonin transporter gene variation. Further, combined 5‐HTTLPR and rs25531 genotype was not associated with other anxiety‐related dimensions

    Multiplex lateral flow assay development for snake venom detection in biological matrices

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    Abstract Bothrops and Lachesis are two of Brazil’s medically most relevant snake genera, causing tens of thousands of bites annually. Fortunately, Brazil has good accessibility to high-quality antivenoms at the genus and inter-genus level, enabling the treatment of many of these envenomings. However, the optimal use of these treatments requires that the snake species responsible for the bite is determined. Currently, physicians use a syndromic approach to diagnose snakebite, which can be difficult for medical personnel with limited training in clinical snakebite management. In this work, we have developed a novel monoclonal antibody-based multiplex lateral flow assay for differentiating Bothrops and Lachesis venoms within 15 min. The test can be read by the naked eye or (semi)-quantitatively by a smartphone supported by a 3D-printed attachment for controlling lighting conditions. The LFA can detect Bothrops and Lachesis venoms in spiked plasma and urine matrices at concentrations spanning six orders of magnitude. The LFA has detection limits of 10–50 ng/mL in spiked plasma and urine, and 50–500 ng/mL in spiked sera, for B. atrox and L. muta venoms. This test could potentially support medical personnel in correctly diagnosing snakebite envenomings at the point-of-care in Brazil, which may help improve patient outcomes and save lives

    Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase

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    Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natural product biosynthesis in plants. The mechanisms underlying POR-mediated CYP metabolism remain poorly understood and to date no ligand binding has been described to regulate the specificity of POR. Here, using a combination of computational modeling and functional assays, we identify ligands that dock on POR and bias its specificity towards CYP redox partners, across mammal and plant kingdom. Single molecule FRET studies reveal ligand binding to alter POR conformational sampling, which results in biased activation of metabolic cascades in whole cell assays. We propose the model of biased metabolism, a mechanism akin to biased signaling of GPCRs, where ligand binding on POR stabilizes different conformational states that are linked to distinct metabolic outcomes. Biased metabolism may allow designing pathway-specific therapeutics or personalized food suppressing undesired, disease-related, metabolic pathways
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