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Towards A More Comprehensive Understanding of the Physiological Stress Response - Focus on Immune System, Second-Hand Stress, and Altered Physiological Reactivity in Essential Hypertension
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Language change in Japanese-English bilingual returnee children over the course of five years : evidence from accent-rating
No full textFew studies have examined global foreign accent (GFA) in bilingual children, and little is known about how GFA changes over time and what factors determine change. Here, we examine GFA trajectories in Japanese–English bilingual returnees (Japanese children who returned to Japan after having lived in a majority English environment for several years). In two accent-rating tasks, first language (L1) speakers of English or Japanese rated returnee speech excerpts recorded at three time points over a five-year period. The ratings show a decrease in Japanese GFA one year after return to Japan, and an increase in English GFA, but only five years after return. These findings suggest rapid re-exposure effects of the L1 and relatively stable maintenance of the second language (L2). Changes varied by L2 English age of onset (AoO) and exposure to L2 English while abroad, suggesting a crucial role for these individual factors in transitory contexts such as returnee bilingualism.publishe
Einsatz von Schrittzählern zur Trainingssteuerung und Veränderung des Aktivitätsverhaltens bei Typ-2-Diabetikern im Rahmen der Diabetes-Schulung und der nachfolgenden ärztlichen Betreuung : eine multizentrische Interventionsstudie über 12 Monate hinweg
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On randomly periodic strongly dependent time series, with applications to neural respiratory drive data
No full textWe consider time series with a seasonal component that varies randomly in length and shape. The shape parameters of the seasonal process, as well as the noise component, are stationary and exhibit long-range dependence. A functional limit theorem for the estimated parameter process leads to asymptotic inference under suitable conditions on the observational grid. The model is motivated by a study of the effect of body positioning on respiratory muscles during weaning (Walterspacher et al. 2017).publishe
Insights into the impact of small anionic additives on Mg-silicate hydrate nucleation
No full textMagnesium silicate (MS) cement, which uses magnesium silicate hydrate (M-S-H) as its primary binding phase, is a promising low-carbon alternative to Portland cement. However, the slow dissolution of MgO limits the release of Mg ions, which is critical for the formation of M-S-H. To address this issue, solubilizers that complex Mg2+ and promote MgO dissolution have been proposed, provided that they do not significantly hinder M-S-H formation. This study systematically examined the effects of four anionic additives—acetate, citrate, orthophosphate, and carbonate—on M-S-H nucleation and early growth, developing a highly reproducible crystallization scenario. The observed reduction in supersaturation at the nucleation point for specific additive concentrations suggests that Mg-anion complexes may play an active role in M-S-H nucleation, potentially allowing M-S-H to form at lower supersaturation levels, which could be beneficial for MS cement applications. However, as shown here, additives such as citrate, while not inhibiting nucleation, can significantly slow the growth of M-S-H, potentially compromising the strength development of MS cement. Among the additives studied, moderate concentrations of phosphate and carbonate show the most promise, as they have minimal effects on the formation process while potentially reducing the supersaturation for M-S-H nucleation. Although further research is necessary to fully understand the effects of these anions, this study provides valuable insights into their impact on M-S-H nucleation and early growth.publishe
A phosphate-binding pocket in cyclin B3 is essential for XErp1/Emi2 degradation in meiosis I
No full textTo ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation. Yet, the molecular mechanism of XErp1/Emi2 degradation in MI is not well understood. Here, by combining TRIM-Away in oocytes with egg extract and in vitro studies, we demonstrate that a hitherto unknown phosphate-binding pocket in cyclin B3 is essential for efficient XErp1/Emi2 degradation in meiosis I. This pocket enables Cdk1/cyclin B3 to bind pre-phosphorylated XErp1/Emi2 facilitating further phosphorylation events, which ultimately target XErp1/Emi2 for degradation in a Plk1- (Polo-like kinase 1) dependent manner. Key elements of this degradative mechanism are conserved in frog and mouse. Our studies identify a novel, evolutionarily conserved determinant of Cdk/cyclin substrate specificity essential to prevent an untimely oocyte arrest at meiosis I with catastrophic consequences upon fertilization.publishe
Proteomic Profiling of Potential E6AP Substrates via Ubiquitin‐based Photo‐Crosslinking Assisted Affinity Enrichment
No full textThe ubiquitin (Ub) ligase E6AP, encoded by the UBE3A gene, has been causally associated with human diseases including cervical cancer and Angelman syndrome, a neurodevelopmental disorder. Yet, our knowledge about disease‐relevant substrates of E6AP is still limited, presumably because at least some of these interactions are rather transient, a phenomenon observed for many enzyme‐substrate interactions. Here, we introduce a novel approach to trap such potential transient interactions by combining a stable E6AP‐Ub conjugate mimicking the active state of this enzyme with photo‐crosslinking (PCL) followed by affinity enrichment coupled to mass spectrometry (AE‐MS). To enable PCL, we equipped Ub with diazirine moieties at distinct positions. We validated our PCL assisted AE‐MS approach by identification of known (e. g. PSMD4, UCHL5) and potential new (e. g. MSH2) substrates of E6AP. Our findings suggest that PCL assisted AE‐MS is indeed suited to identify substrates of E6AP, thereby providing insights into E6AP‐associated pathologies, and, potentially, of other enzymes of the Ub‐conjugating system.publishe
Diverse Library of 5a-Substituted Carba-Glucosamines
No full textCarba-sugars─carbohydrate mimics in which the ring oxygen is replaced by a methylene group─are carbohydrate analogues of natural or synthetic origin that can have important biological functions. Especially, carba-aminosugars and glycosides containing carba-aminosugars are potent antibiotics. Furthermore, they have been shown to induce the self-cleavage reaction of the glmS riboswitch and thereby inhibit the ability of bacteria to synthesize glucosamine-6-phosphate, which is required to build up the bacterial cell wall. We report the synthesis of a library of 20 carba-glucosamine derivatives with various substituents at the carba-position including amines, alkyl, alkoxy, and aryloxy derivatives, fluorine derivatives, glycosylated derivatives, and a cyclopropane derivative. The compounds were obtained in an efficient way starting from late-stage synthetic intermediates of an earlier-developed synthesis of carba-substituted carba-glucosamines. All carba-glucosamine mimics were tested for their antibacterial properties against Bacillus subtilis, and some of them displayed promising activities in a filter disk assay.publishe
Why a European Citizens' Assembly should replace sortition with liquid democracy
No full textSeveral previous contributions to this debate identify a dilemma in Kalypso Nicolaidis’ thought-provoking proposal for a European Citizens’ Assembly (ECA) (Cristina Lafont and Nadia Urbinati; Richard Bellamy; Svenja Ahlhaus and Eva Schmidt). Nicolaidis aims to promote a “pan-European participatory ecosystem” characterised by a transnational “demoicratic ethos.” She argues that the ECA could foster these goals, enhancing input, throughput and output legitimacy of collective decision-making within the EU. As critics point out, for the ECA to have such an impact on the quality of transnational democracy, it would have to be equipped with some degree of decision-making authority. However, if it did have such authority, it should not rely on selection by lottery. These critical contributions solve the dilemma by downgrading the ECA to a merely consultative body, arguing that we should strengthen traditional forms of electoral democracy instead. We support both Nicolaidis’ ambition to radically reimagine EU institutions beyond elections and the arguments against lottocracy. Our contribution, therefore, suggests a different way forward, one that Jelena Džankić briefly hints at: replacing selection by lottery with liquid democracy.publishe