1,776 research outputs found

    Material kids oder: (V)erwachsene Kinder

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    'Im vorliegenden Text werden die VerĂ€nderung von Sozialisation und Kindheit und ihre VerursachungszusammenhĂ€nge im Zuge der 'postmodernen' sozioökonomischen Entwicklung dargestellt. Hierbei wird die These entwickelt, daß mit sich verschĂ€rfender Tendenz schon in der Phase der Kindheit unter BeschrĂ€nkung kreativer FreirĂ€ume bĂŒrgerliche Verhaltensanforderungen und Denkmuster ansozialisiert werden, was sich beobachtbar in '(v)erwachsenen' Kindern dokumentiert. Die Chance normalbiographischer Reifung zur stabilen, 'erwachsenen' Persönlichkeit wird damit betrĂ€chtlich erschwert. Das kann dann zu einer 'Verkindlichung' der Erwachsenen fĂŒhren, die, da sie die phasenspezifischen Krisen der Kindheit und Jugend nicht in der zu einer selbstbewußten Ich-IdentitĂ€t und Ich-StĂ€rke fĂŒhrenden Weise bewĂ€ltigen konnten, in kindlichen Verhaltensmustern befangen bleiben.' (Autorenreferat

    Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration

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    Background: Tumor spreading is the major threat for cancer patients. The recently published anti-cancer drug salinomycin raised hope for an improved treatment by targeting therapy-refractory cancer stem cells. However, an unambiguous role of salinomycin against cancer cell migration and metastasis formation remains elusive. Findings: We report that salinomycin effectively inhibits cancer cell migration in a variety of cancer types as determined by Boyden chamber assays. Additionally, cells were treated with doxorubicin at a concentration causing a comparable low cytotoxicity, emphasizing the anti-migratory potential of salinomycin. Moreover, single-cell tracking by time-lapse microscopy demonstrated a remarkable effect of salinomycin on breast cancer cell motility. Ultimately, salinomycin treatment significantly reduced the metastatic tumor burden in a syngenic mouse tumor model. Conclusions: Our findings clearly show that salinomycin can strongly inhibit cancer cell migration independent of the induction of cell death. We furthermore demonstrate for the first time that salinomycin treatment reduces metastasis formation in vivo, strengthening its role as promising anti-cancer therapeutic

    Keeping Up with the Joneses: Instagram Use and its Influence on Conspicuous Consumption

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    So far research in the area of social networking sites (SNS) has drawn surprisingly little attention to users’ conspicuous consumption (CC), even though the constant rise of younger people’s debts seems to go hand in hand with the rise of SNS. To fill this research gap, we conducted two studies based on social comparison and normative influence theory. In a preliminary study, we show that Instagram use is positively related to users’ CC. In the main study, using a sample of 283 German Instagram users, we find possible explanations for this association. While norms on Instagram seem not to account for the link between Instagram use and CC, our results suggest a mediating effect of envy. We contribute to the literature by providing insights on SNS use and CC while offering first explanations for its potentially harmful economic outcomes. Acknowledgment This work has been funded by the Federal Ministry of Education and Research of Germany (BMBF) under grant no. 16DII116 (“Deutsches Internet-Institut”)

    The Drosophila LEM-domain protein MAN1 antagonizes BMP signaling at the neuromuscular junction and the wing crossveins

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    AbstractBMP signaling responses are refined by distinct secreted and intracellular antagonists in different cellular and temporal contexts. Here, we show that the nuclear LEM-domain protein MAN1 is a tissue-specific antagonist of BMP signaling in Drosophila. MAN1 contains two potential Mad-binding sites. We generated MAN1ΔC mutants, harbouring a MAN1 protein that lacks part of the C-terminus including the RNA recognition motif, a putative Mad-binding domain. MAN1ΔC mutants show wing crossvein (CV) patterning defects but no detectable alterations in nuclear morphology. MAN1ΔC pupal wings display expanded phospho-Mad (pMad) accumulation and ectopic expression of the BMP-responsive gene crossveinless-2 (cv-2) indicating that MAN1 restricts BMP signaling. Conversely, MAN1 overexpression in wing imaginal discs inhibited crossvein development and BMP signaling responses. MAN1 is expressed at high levels in pupal wing veins and can be activated in intervein regions by ectopic BMP signaling. The specific upregulation of MAN1 in pupal wing veins may thus represent a negative feedback circuit that limits BMP signaling during CV formation. MAN1ΔC flies also show reduced locomotor activity, and electrophysiology recordings in MAN1ΔC larvae uncover a new presynaptic role of MAN1 at the neuromuscular junction (NMJ). Genetic interaction experiments suggest that MAN1 is a BMP signaling antagonist both at the NMJ and during CV formation

    Comparison of Habitual and Maximal Gait Speed and their Impact on Sarcopenia Quantification in German Nursing Home Residents.

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    OBJECTIVES Sarcopenia is characterized by loss of muscle strength and muscle mass. The EWGSOP2 specifications include physical functioning determination for quantification of the sarcopenia severity. However, there is a lack in the use of habitual and maximal gait speed and their influence on sarcopenia quantification. We hypothesize differences in sarcopenia quantification using habitual and maximal gait speed. METHODS Sixty-six residents from five nursing homes were examined. Habitual and maximal gait speed were measured by 4-meter-walking-Test. McNemar-Test and χ2-test were used to identify quantification differences. Effect sizes of both gait speeds were calculated with Spearman's rank-correlation-coefficient. RESULTS Significant difference was identified for twenty-two residents in physical functioning classification by McNemar-Test (p<.001). χ2-Test identified a significant frequency distribution for sarcopenia categories between both gait speeds (χ2 (df2)=11.215, p=.004; Cramer's V=.412). Significant correlations (p<.05) were only shown for maximal gait speed in variables falls in the last three months (|rs|=.326), Barthel-Index (|rs|=.415), and SARC-F (|rs|=.335). CONCLUSIONS The use of habitual and maximal gait speed has a significant impact on sarcopenia quantification in nursing home residents. An adapted standardization in the EWGSOP2 specifications should follow

    Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

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    Supramolecular templating techniques have been widely used to direct the formation of porous materials with the goal of introducing permanent mesoporosity. While surfactant-directed self-assembly has been exploited for inorganic materials such as titania, silica, organosilica, and zeolites, it has rarely been applied to metal-organic frameworks (MOFs) and coordination polymers. Here we introduce a new family of gemini surfactant-directed zinc imidazolates, referred to as mesostructured imidazolate frameworks (MIFs), and present a detailed study on the influence of different gemini-type surfactants on the formation mechanism and structures of the resulting zinc imidazolates. The proposed formation mechanism for MIF-type materials involves co-assembly and crystallization processes that yield lamellar mesostructured imidazolate frameworks. Understanding and controlling such processes also has implications for the syntheses of microporous zinc imidazolate framework (ZIF) materials, whose formation can be suppressed in surfactant-rich solutions, whereas formation of MIF materials is favored in the presence of surfactants and triggered by the addition of halogenides. Solid-state 2D 13C1H HETCOR NMR measurements on prototypic CTAB-directed MIF-1 establish that the head group moieties of the surfactant molecules interact strongly with the zinc-imidazolate-bromide sheets. Additionally, the NMR analyses suggest that MIF-1 has a significant fraction of surfactant molecules that are interdigitated between the zinc-imidazolate-bromide sheets with an antiparallel stacking arrangement, consistent with the high thermal and chemical stability of the MIF hybrid materials

    Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

    Get PDF
    Supramolecular templating techniques have been widely used to direct the formation of porous materials with the goal of introducing permanent mesoporosity. While surfactant-directed self-assembly has been exploited for inorganic materials such as titania, silica, organosilica, and zeolites, it has rarely been applied to metal-organic frameworks (MOFs) and coordination polymers. Here we introduce a new family of gemini surfactant-directed zinc imidazolates, referred to as mesostructured imidazolate frameworks (MIFs), and present a detailed study on the influence of different gemini-type surfactants on the formation mechanism and structures of the resulting zinc imidazolates. The proposed formation mechanism for MIF-type materials involves co-assembly and crystallization processes that yield lamellar mesostructured imidazolate frameworks. Understanding and controlling such processes also has implications for the syntheses of microporous zinc imidazolate framework (ZIF) materials, whose formation can be suppressed in surfactant-rich solutions, whereas formation of MIF materials is favored in the presence of surfactants and triggered by the addition of halogenides. Solid-state 2D 13C1H HETCOR NMR measurements on prototypic CTAB-directed MIF-1 establish that the head group moieties of the surfactant molecules interact strongly with the zinc-imidazolate-bromide sheets. Additionally, the NMR analyses suggest that MIF-1 has a significant fraction of surfactant molecules that are interdigitated between the zinc-imidazolate-bromide sheets with an antiparallel stacking arrangement, consistent with the high thermal and chemical stability of the MIF hybrid materials

    New cysteine protease inhibitors : electrophilic (het)arenes and unexpected prodrug identification for the trypanosoma protease rhodesain

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    Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly active prodrug inhibitor, the liberated carboxylic acid represents a highly potent inhibitor of rhodesain (Ki = 4.0 nM). The simulations indicate that, after the cleavage of the ester, the carboxylic acid leaves the active site and re-binds to the enzyme in an orientation that allows the formation of a very stable π-complex between the catalytic dyad (Cys-25/His-162) of rhodesain and the electrophilic aromatic moiety. The reversible inhibition mode results because the SNAr reaction, which is found in an alkaline solvent containing a low molecular weight thiol, is hindered within the enzyme due to the presence of the positively charged imidazolium ring of His-162. Comparisons between measured and calculated NMR shifts support this interpretation
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