351 research outputs found

    A cycle of Vam7p release from and PtdIns 3-P–dependent rebinding to the yeast vacuole is required for homotypic vacuole fusion

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    Vacuole fusion requires a coordinated cascade of priming, docking, and fusion. SNARE proteins have been implicated in the fusion itself, although their precise role in the cascade remains unclear. We now report that the vacuolar SNAP-23 homologue Vam7p is a mobile element of the SNARE complex, which moves from an initial association with the cis-SNARE complex via a soluble intermediate to the docking site. Soluble Vam7p is specifically recruited to vacuoles and can rescue a fusion reaction poisoned with antibodies to Vam7p. Both the recombinant Vam7p PX domain and a FYVE domain construct of human Hrs block the recruitment of Vam7p and vacuole fusion, demonstrating that phosphatidylinositol 3-phosphate is a primary receptor of Vam7p on vacuoles. We propose that the Vam7p cycle is linked to the availability of a lipid domain on yeast vacuoles, which is essential for coordinating the fusion reaction prior to and beyond docking

    X-ray absorption spectroscopy study of the electronic and magnetic proximity effects in YBa2Cu3O7/La2/3Ca1/3MnO3{\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7}/{\mathrm{La}}_{2/3}{\mathrm{Ca}}_{1/3}{\mathrm{MnO}}_{3} and {\mathrm{La}}_{2-{}x}{\mathrm{Sr}}_{x}{\mathrm{CuO}}_{4}/{\mathrm{La}}_{2/3}{\mathrm{Ca}}_{1/3}{\mathrm{MnO}}_{3} multilayers

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    With x-ray absorption spectroscopy we investigated the orbital reconstruction and the induced ferromagnetic moment of the interfacial Cu atoms in YBa2Cu3O7/La2/3Ca1/3MnO3 (YBCO/LCMO) and La2−xSrxCuO4/La2/3Ca1/3MnO3 (LSCO/LCMO) multilayers. We demonstrate that these electronic and magnetic proximity effects are coupled and are common to these cuprate/manganite multilayers. Moreover, we show that they are closely linked to a specific interface termination with a direct Cu-O-Mn bond. We furthermore show that the intrinsic hole doping of the cuprate layers and the local strain due to the lattice mismatch between the cuprate and manganite layers are not of primary importance. These findings underline the central role of the covalent bonding at the cuprate/manganite interface in defining the spin-electronic properties

    What our eyes tell us about feelings: Tracking pupillary responses during emotion regulation processes

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    Emotion regulation is essential for adaptive behavior and mental health. Strategies applied to alter emotions are known to differ in their impact on psychological and physiological aspects of the emotional response. However, emotion regulation outcome has primarily been assessed via self‐report, and studies comparing regulation strategies with regard to their peripheral physiological mechanisms are limited in number. In the present study, we therefore aimed to investigate the effects of different emotion regulation strategies on pupil dilation, skin conductance responses, and subjective emotional responses. Thirty healthy females were presented with negative and neutral pictures and asked to maintain or up‐ and downregulate their upcoming emotional responses through reappraisal or distraction. Pupil dilation and skin conductance responses were significantly enhanced when viewing negative relative to neutral pictures. For the pupil, this emotional arousal effect manifested specifically late during the pupillary response. In accordance with subjective ratings, increasing negative emotions through reappraisal led to the most prominent pupil size enlargements, whereas no consistent effect for downregulation was found. In contrast, early peak dilations were enhanced in all emotion regulation conditions independent of strategy. Skin conductance responses were not further modulated by emotion regulation. These results indicate that pupil diameter is modulated by emotional arousal, but is initially related to the extent of mental effort required to regulate automatic emotional responses. Our data thus provide first evidence that the pupillary response might comprise two distinct temporal components reflecting cognitive emotion regulation effort on the one hand and emotion regulation success on the other hand

    Influence of contingency awareness on neural, electrodermal and evaluative responses during fear conditioning

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    In an fMRI study, effects of contingency awareness on conditioned responses were assessed in three groups comprising 118 subjects. A differential fear-conditioning paradigm with visual conditioned stimuli, an electrical unconditioned stimulus and two distractors was applied. The instructed aware group was informed about the contingencies, whereas the distractors prevented contingency detection in the unaware group. The third group (learned aware) was not informed about the contingencies, but learned them despite the distractors. Main effects of contingency awareness on conditioned responses emerged in several brain structures. Post hoc tests revealed differential dorsal anterior cingulate, insula and ventral striatum responses in aware conditioning only, whereas the amygdala was activated independent of contingency awareness. Differential responses of the hippocampus were specifically observed in learned aware subjects, indicating a role in the development of contingency awareness. The orbitofrontal cortex showed varying response patterns: lateral structures showed higher responses in instructed aware than unaware subjects, the opposite was true for medial parts. Conditioned subjective and electrodermal responses emerged only in the two aware groups. These results confirm the independence of conditioned amygdala responses from contingency awareness and indicate specific neural circuits for different aspects of fear acquisition in unaware, learned aware and instructed aware subjects

    START adolescents: study protocol of a randomised controlled trial to investigate the efficacy of a low-threshold group treatment programme in traumatised adolescent refugees

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    Introduction No evaluated therapeutic approaches, that can efficiently be established in routine mental healthcare, are currently available for traumatised adolescent refugees in Germany. This study evaluates the efficacy of the Stress-Traumasymptoms-Arousal-Regulation-Treatment (START) programme to reduce trauma-related symptoms and psychological distress in traumatised adolescent refugees based in Germany. Methods and analysis This randomised, waiting-list-controlled, multicentre trial with a 12-week follow-up will include 174 refugee minors with partial or full post-traumatic stress disorder who are fluent in either Arabic, Dari, English, German or Somali. Eligible refugee minors will be randomised to the START or waiting-list control groups. The manualised 8-week START programme is based on techniques of dialectical behaviour therapy (DBT), fosters adaptive coping with emotional distress and traumatic symptoms and comprises eight therapy modules and a booster session. Study assessments are planned at baseline, post-treatment (ie, after programme participation or waiting time), booster session at week 12 or 12-week waiting time, and at the 12-week follow-up. Primary and coprimary outcomes are changes in psychological distress and traumatic symptoms at post-treatment and will be analysed as response variables in linear mixed regression models. Secondary outcomes are changes in further trauma-related and other psychopathological symptoms, emotion regulation and intermediate effects of the programme at follow-up. We will also assess effects of the programme with ecological momentary assessments and on neuroendocrine stress parameters using hair cortisol. Ethics and dissemination This study has been approved by the lead ethics committee of Rhineland-Palatinate and the ethics committees of participating sites. The study results will be disseminated through peer-reviewed publications and scientific conferences

    Neotectonic fault structures in the Lake Thun area (Switzerland)

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    Strong historic earthquakes (i.e. intensities I0 ≥ V) are well documented by the earthquake catalogue of Switzerland ECOS-09 (e.g. Frutigen, 1729 AD, Mw=5.2, I0=VI). Many of these strong events can be recognized paleoseismically by large subaquatic, earthquake-triggered mass movements that occur frequently in Swiss Lakes. Some of these represent the occasional occurrence of even stronger earthquakes (i.e. Mw ~6.5) in the Alpine region (Strasser et al., 2013), which are expected to produce noticeable surface ruptures. However, convincing evidence for Quaternary displacements with offset surface expressions have scarcely been found (e.g., Wiemer et al., 2009). Applying a multi-disciplinary approach, this study presents potential candidates for such faults in the larger Lake Thun area at the edge of the Alps. The overdeepened basin of Lake Thun is situated at the northern Alpine front, which extends orthogonally to the general strike direction of the Alpine nappe front. The northern shoreline is predominantly shaped by the front of the Subalpine Molasse, which is in strong contrast to the south western shore built by the structurally higher units of the Middle and Lower Penninic nappes. This pattern with obvious differences of both lake sides suggests a major fault along the lake axis and high tectonic activity during nappe emplacement, i.e. from Eocene times throughout the Late Miocene. The area is dominated today by a strike-slip stress regime with a slight normal faulting component (Kastrup et al., 2004). As part of a multi-disciplinary study, attempting to find potential neotectonically active fault structures in the Lake Thun area, a 2D ground penetrating radar (GPR) survey was conducted. The aim of the GPR survey was to link observations from a multichannel reflection seismic survey and a multibeam bathymetric survey carried out in Lake Thun with findings in a nearby gravel quarry revealing suspicious deformation features such as rotated gravel clast as well as significantly offset horizons. The GPR data reveal the occurrence of several morphologic depressions from gypsum cones and clearly dipping reflections. The reflection seismic data set shows prominent reflections, characteristic seismic facies and a few sets of normal and reverse faults in the north western part of the lake basin within the glacio-lacustrine deposits that may point to a transpressional strike-slip regime. A first neotectonic analysis links these prominent lake floor features with geomorphologic patterns from the surrounding landscape, pointing to a potential candidate for a fault that is active in the Quaternary period

    Correlation between the Josephson coupling energy and the condensation energy in bilayer cuprate superconductors

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    We review some previous studies concerning the intra-bilayer Josephson plasmons and present new ellipsometric data of the c-axis infrared response of almost optimally doped Bi_{2}Sr_{2}CaCu_{2}O_{8}. The c-axis conductivity of this compound exhibits the same kind of anomalies as that of underdoped YBa_{2}Cu_{3}O_{7-delta}. We analyze these anomalies in detail and show that they can be explained within a model involving the intra-bilayer Josephson effect and variations of the electric field inside the unit cell. The Josephson coupling energies of different bilayer compounds obtained from the optical data are compared with the condensation energies and it is shown that there is a reasonable agreement between the values of the two quantities. We argue that the Josephson coupling energy, as determined by the frequency of the intra-bilayer Josephson plasmon, represents a reasonable estimate of the change of the effective c-axis kinetic energy upon entering the superconducting state. It is further explained that this is not the case for the estimate based on the use of the simplest ``tight-binding'' sum rule. We discuss possible interpretations of the remarkable agreement between the Josephson coupling energies and the condensation energies. The most plausible interpretation is that the interlayer tunneling of the Cooper pairs provides the dominant contribution to the condensation energy of the bilayer compounds; in other words that the condensation energy of these compounds can be accounted for by the interlayer tunneling theory. We suggest an extension of this theory, which may also explain the high values of T_{c} in the single layer compounds Tl_{2}Ba_{2}CuO_{6} and HgBa_{2}CuO_{4}, and we make several experimentally verifiable predictions.Comment: 16 pages (including Tables) and 7 figures; accepted for publication in Physical Review

    Magnetic Proximity Effect in YBa₂Cu₃O₇/La<sub>2/3</sub>Ca<sub>1/3</sub>MnO₃ and YBa₂Cu₃O₇/LaMnO₃₊ Superlattices

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    Using neutron reflectometry and resonant x-ray techniques we studied the magnetic proximity effect (MPE) in superlattices composed of superconducting YBa₂Cu₃O₇ and ferromagnetic-metallic La0.67Ca0.33MnO₃ or ferromagnetic-insulating LaMnO₃₊. We find that the MPE strongly depends on the electronic state of the manganite layers, being pronounced for the ferromagnetic-metallic La0.67Ca0.33MnO₃ and almost absent for ferromagnetic-insulating LaMnO₃₊. We also detail the change of the magnetic depth profile due to the MPE and provide evidence for its intrinsic nature

    Enhancing precision in human neuroscience

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    Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience

    Adaptation to flood risk: Results of international paired flood event studies

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    As flood impacts are increasing in large parts of the world, understanding the primary drivers of changes in risk is essential for effective adaptation. To gain more knowledge on the basis of empirical case studies, we analyze eight paired floods, that is, consecutive flood events that occurred in the same region, with the second flood causing significantly lower damage. These success stories of risk reduction were selected across different socioeconomic and hydro-climatic contexts. The potential of societies to adapt is uncovered by describing triggered societal changes, as well as formal measures and spontaneous processes that reduced flood risk. This novel approach has the potential to build the basis for an international data collection and analysis effort to better understand and attribute changes in risk due to hydrological extremes in the framework of the IAHSs Panta Rhei initiative. Across all case studies, we find that lower damage caused by the second event was mainly due to significant reductions in vulnerability, for example, via raised risk awareness, preparedness, and improvements of organizational emergency management. Thus, vulnerability reduction plays an essential role for successful adaptation. Our work shows that there is a high potential to adapt, but there remains the challenge to stimulate measures that reduce vulnerability and risk in periods in which extreme events do not occur
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