265 research outputs found

    Hochzeiten und Heiraten als 'rite de confirmation': performative Herstellung geschlechtlicher Eindeutigkeiten in Zeiten des Wandels

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    "Die konstatierte Pluralisierung der Lebensweisen und die damit eng verknüpfte Erosion der Arbeitsteilung zwischen den Geschlechtern provozieren die Frage nach deren Auswirkung(en) auf die Kategorie Geschlecht. Am Beispiel sich wandelnder Praxen des Hochzeitens und Heiratens (in Göttingen) soll dieser Frage nachgegangen werden. Denn während die einen von einer De-Thematisierung von Geschlecht und die anderen von nur rhetorischer Modernisierung sprechen, gehen wir davon aus, dass die hier angesprochenen (Darstellungs-)Praktiken dazu dienen, zumindest auf einer symbolischen Ebene ein hierarchisches Geschlechterverhältnis zu inszenieren, das gerade auf der Ebene der empirisch-praktischen Lebensführung von Paaren zu erodieren scheint. Das hier beobachtete Paradox verweist darauf, dass sich die Praktiken der Reproduktion gegenwärtiger Geschlechterverhältnisse verschoben haben könnten." (Autorenreferat)"The established pluralization of lifestyles and closely related erosion of the sexual division of labor are closely linked to the question of their impact(s) on the category of gender. The article explores this question based on the example of changing wedding and marriage practices (in Göttingen). While some people are talking about a de-thematization of gender and others refer to only rhetorical modernization, we assume that the practices mentioned here, at least on a symbolic level, create the hierarchical gender relations that seem to be eroding at the level of couples' empirically observable lifestyle. The observed paradox points to the fact that the practices of the reproduction in current gender relations may well have changed." (author's abstract

    Phase 1 dose escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer-Lack of association between activating AKT mutation and AKT inhibition-derived efficacy

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    This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring th

    Microplastics in European sea salts – An example of exposure through consumer choice and of interstudy methodological discrepancies

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    Microplastics are contaminants of emerging concern, not least due to their global presence in marine surface waters. Unsurprisingly, microplastics have been reported in salts harvested from numerous locations. We extracted microplastics from 13 European sea salts through 30% H2O2 digestion and filtration over 5-µm filters. Filters were visually inspected at magnifications to x100. A subsample of potential microplastics was subjected to Raman spectroscopy. Particle mass was estimated, and human dose exposure calculated. After blank corrections, median concentrations were 466 ± 152 microplastics kg-1 ranging from 74 to 1155 items kg-1. Traditionally harvested salts contained fewer microplastics than most industrially harvested ones (t-test, p < 0.01). Approximately 14 µg of microplastics (< 12 particles) may be absorbed by the human body annually, of which a quarter may derive from a consumer choosing sea salt. We reviewed existing studies, showing that targeting different particle sizes and incomplete filtrations hinder interstudy comparison, indicating the importance of method harmonisation for future studies. Excess salt consumption is detrimental to human health; the hazardousness of ingesting microplastics on the other hand has yet to be shown. A portion of microplastics may enter sea salts through production processes rather than source materials

    A complex pheotype in a girl with a novel heterozygous missense variant (p.Ile56Phe) of the GNAS gene

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    Background: GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele. Patients and methods: We describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples. Results: We found a new heterozygous missense c.166A &gt; T-(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20-25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities. Conclusions: This is the first time that the new variant c.166A &gt; T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain

    The norepinephrine transporter (NET) radioligand (S,S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer’s disease: a post-mortem autoradiographic study.

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    Earlier post-mortem histological and autoradiographic studies have indicated a reduction of cell numbers in the locus coeruleus (LC) and a corresponding decrease in norepinephrine transporter (NET) in brains obtained from Alzheimer's disease (AD) patients as compared to age-matched healthy controls. In order to test the hypothesis that the regional decrease of NET is a disease specific biomarker in AD and as such, it can be used in PET imaging studies for diagnostic considerations, regional differences in the density of NET in various anatomical structures were measured in whole hemisphere human brain slices obtained from AD patients and age-matched control subjects in a series of autoradiographic experiments using the novel selective PET radioligand for NET (S,S)-[F-18]FMeNER-D-2. (S,S)-[F-18]FMeNER-D-2 appears to be a useful imaging biomarker for quantifying the density of NET in various brain structures, including the LC and the thalamus wherein the highest densities are found in physiological conditions. In AD significant decreases of NET densities can be demonstrated with the radioligand in both structures as compared to age-matched controls. The decreases in AD correlate with the progress of the disease as indicated by Braak grades. As the size of the LC is below the spatial resolution of the PET scanners, but the size of the thalamus can be detected with appropriate spatial accuracy in advanced scanners, the present findings confirm our earlier observations with PET that the in vivo imaging of NET with (S,S)-[F-18]FMeNER-D-2 in the thalamus is viable. Nevertheless, further studies are warranted to assess the usefulness of such an imaging approach for the early detection of changes in thalamic NET densities as a disease-specific biomarker and the possible use of (S,S)-[F-18]FMeNER-D-2 as a molecular imaging biomarker in AD. (c) 2010 Elsevier Ltd. All rights reserved

    Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing

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    Bone formation as well as bone healing capacity is known to be impaired in the elderly. Although bone formation is outpaced by bone resorption in aged individuals, we hereby present a novel path that considerably impacts bone formation and architecture: Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. The role of the aging immune system on bone homeostasis and on the bone healing cascade has so far not been considered. Within this study mice at different age and immunological experience were analyzed toward bone properties. Healing was assessed by introducing an osteotomy, immune cells were adoptively transferred to disclose the difference in biological vs. chronological aging. In vitro studies were employed to test the interaction of immune cell products (cytokines) on cells of the musculoskeletal system. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Furthermore, bone formation is also impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. We show the impact of an experienced immune system compared to a naive immune system, demonstrating the substantial differences in the healing capacity and bone homeostasis due to the immune composition. We further showed that in vivo mechanical stimulation changed the immune system phenotype in young mice toward a more naive composition. While this rescue was found to be significant in young individuals, aged mice only showed a trend toward the reconstitution of a more naive immune phenotype. Considering the immune system's experience level in an individual, will likely allow one to differentiate (stratify) and treat (immune-modulate) patients more effectively. This work illustrates the relevance of including immune diagnostics when discussing immunomodulatory therapeutic strategies for the progressively aging population of the industrial countries
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