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The suitability of a newly developed cell-based functional assay was tested for the detection of the activity of a range of neurotoxins and neuroactive pharmaceuticals which act by stimulation or inhibition of calcium-dependent neurotransmitter release. In this functional assay, a reporter enzyme is released concomitantly with the neurotransmitter from neurosecretory vesicles. The current study showed that the release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) can be stimulated by a carbachol-mediated activation of the Gq-coupled muscarinic-acetylcholine receptor and by the Ca2+-channel forming spider toxin α-latrotoxin. Carbachol-stimulated luciferase release was completely inhibited by the muscarinic acetylcholine receptor antagonist atropine and α-latrotoxin-mediated release by the Ca2+-chelator EGTA, demonstrating the specificity of luciferase-release stimulation. SIMA-hPOMC1-26-GLuc cells express mainly L- and N-type and to a lesser extent T-type VGCC on the mRNA and protein level. In accordance with the expression profile a depolarization-stimulated luciferase release by a high K+-buffer was effectively and dose-dependently inhibited by L-type VGCC inhibitors and to a lesser extent by N-type and T-type inhibitors. P/Q- and R-type inhibitors did not affect the K+-stimulated luciferase release. In summary, the newly established cell-based assay may represent a versatile tool to analyze the biological efficiency of a range of neurotoxins and neuroactive pharmaceuticals which mediate their activity by the modulation of calcium-dependent neurotransmitter release.
Mental health problems remain among the main generators of costs within and beyond the health care system. Psychotherapy, the tool of choice in their treatment, is qualified by social interaction, and cooperation within the therapist-patient-dyad. Research into the factors influencing therapy success to date is neither exhaustive nor conclusive. Among many others, the quality of the relationship between therapist and patient stands out regardless of the followed psychotherapy school. Emerging research points to a connection between interpersonal synchronization within the sessions and therapy outcome. Consequently, it can be considered significant for the shaping of this relationship. The framework of Embodied Cognition assumes bodily and neuronal correlates of thinking. Therefore, the present paper reviews investigations on interpersonal, non-verbal synchrony in two domains: firstly, studies on interpersonal synchrony in psychotherapy are reviewed (synchronization of movement). Secondly, findings on neurological correlates of interpersonal synchrony (assessed with EEG, fMRI, fNIRS) are summarized in a narrative manner. In addition, the question is asked whether interpersonal synchrony can be achieved voluntarily on an individual level. It is concluded that there might be mechanisms which could give more insights into therapy success, but as of yet remain uninvestigated. Further, the framework of embodied cognition applies more to the current body of evidence than classical cognitivist views. Nevertheless, deeper research into interpersonal physical and neurological processes utilizing the framework of Embodied Cognition emerges as a possible route of investigation on the road to lower drop-out rates, improved and quality-controlled therapeutic interventions, thereby significantly reducing healthcare costs.
Reciprocal space slicing
(2021)
An experimental technique that allows faster assessment of out-of-plane strain dynamics of thin film heterostructures via x-ray diffraction is presented. In contrast to conventional high-speed reciprocal space-mapping setups, our approach reduces the measurement time drastically due to a fixed measurement geometry with a position-sensitive detector. This means that neither the incident (ω) nor the exit (2θ) diffraction angle is scanned during the strain assessment via x-ray diffraction. Shifts of diffraction peaks on the fixed x-ray area detector originate from an out-of-plane strain within the sample. Quantitative strain assessment requires the determination of a factor relating the observed shift to the change in the reciprocal lattice vector. The factor depends only on the widths of the peak along certain directions in reciprocal space, the diffraction angle of the studied reflection, and the resolution of the instrumental setup. We provide a full theoretical explanation and exemplify the concept with picosecond strain dynamics of a thin layer of NbO2.
The co-occurrence of warm spells and droughts can lead to detrimental socio-economic and ecological impacts, largely surpassing the impacts of either warm spells or droughts alone. We quantify changes in the number of compound warm spells and droughts from 1979 to 2018 in the Mediterranean Basin using the ERA5 data set. We analyse two types of compound events: 1) warm season compound events, which are extreme in absolute terms in the warm season from May to October and 2) year-round deseasonalised compound events, which are extreme in relative terms respective to the time of the year. The number of compound events increases significantly and especially warm spells are increasing strongly – with an annual growth rates of 3.9 (3.5) % for warm season (deseasonalised) compound events and 4.6 (4.4) % for warm spells –, whereas for droughts the change is more ambiguous depending on the applied definition. Therefore, the rise in the number of compound events is primarily driven by temperature changes and not the lack of precipitation. The months July and August show the highest increases in warm season compound events, whereas the highest increases of deseasonalised compound events occur in spring and early summer. This increase in deseasonalised compound events can potentially have a significant impact on the functioning of Mediterranean ecosystems as this is the peak phase of ecosystem productivity and a vital phenophase.
Compound weather events may lead to extreme impacts that can affect many aspects of society including agriculture. Identifying the underlying mechanisms that cause extreme impacts, such as crop failure, is of crucial importance to improve their understanding and forecasting. In this study, we investigate whether key meteorological drivers of extreme impacts can be identified using the least absolute shrinkage and selection operator (LASSO) in a model environment, a method that allows for automated variable selection and is able to handle collinearity between variables. As an example of an extreme impact, we investigate crop failure using annual wheat yield as simulated by the Agricultural Production Systems sIMulator (APSIM) crop model driven by 1600 years of daily weather data from a global climate model (EC-Earth) under present-day conditions for the Northern Hemisphere. We then apply LASSO logistic regression to determine which weather conditions during the growing season lead to crop failure. We obtain good model performance in central Europe and the eastern half of the United States, while crop failure years in regions in Asia and the western half of the United States are less accurately predicted. Model performance correlates strongly with annual mean and variability of crop yields; that is, model performance is highest in regions with relatively large annual crop yield mean and variability. Overall, for nearly all grid points, the inclusion of temperature, precipitation and vapour pressure deficit is key to predict crop failure. In addition, meteorological predictors during all seasons are required for a good prediction. These results illustrate the omnipresence of compounding effects of both meteorological drivers and different periods of the growing season for creating crop failure events. Especially vapour pressure deficit and climate extreme indicators such as diurnal temperature range and the number of frost days are selected by the statistical model as relevant predictors for crop failure at most grid points, underlining their overarching relevance. We conclude that the LASSO regression model is a useful tool to automatically detect compound drivers of extreme impacts and could be applied to other weather impacts such as wildfires or floods. As the detected relationships are of purely correlative nature, more detailed analyses are required to establish the causal structure between drivers and impacts.
Leveraging large-deviation statistics to decipher the stochastic properties of measured trajectories
(2021)
Extensive time-series encoding the position of particles such as viruses, vesicles, or individualproteins are routinely garnered insingle-particle tracking experiments or supercomputing studies.They contain vital clues on how viruses spread or drugs may be delivered in biological cells.Similar time-series are being recorded of stock values in financial markets and of climate data.Such time-series are most typically evaluated in terms of time-averaged mean-squareddisplacements (TAMSDs), which remain random variables for finite measurement times. Theirstatistical properties are different for differentphysical stochastic processes, thus allowing us toextract valuable information on the stochastic process itself. To exploit the full potential of thestatistical information encoded in measured time-series we here propose an easy-to-implementand computationally inexpensive new methodology, based on deviations of the TAMSD from itsensemble average counterpart. Specifically, we use the upper bound of these deviations forBrownian motion (BM) to check the applicability of this approach to simulated and real data sets.By comparing the probability of deviations fordifferent data sets, we demonstrate how thetheoretical bound for BM reveals additional information about observed stochastic processes. Weapply the large-deviation method to data sets of tracer beads tracked in aqueous solution, tracerbeads measured in mucin hydrogels, and of geographic surface temperature anomalies. Ouranalysis shows how the large-deviation properties can be efficiently used as a simple yet effectiveroutine test to reject the BM hypothesis and unveil relevant information on statistical propertiessuch as ergodicity breaking and short-time correlations.
Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates
(2021)
Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form.
Mehr Schein als Sein
(2021)
In this paper I am concerned with the idiomatic constructions fr. avoir l'air (de) and sp. tener el aire (de). I describe these form-function pairs from a constructionist perspective and analyze them as cases of evidential strategies in French and Spanish.
The present study aims to identify the optimal body-size/shape and maturity characteristics associated with superior fitness test performances having controlled for body-size, sex, and chronological-age differences. The sample consisted of 597 Tunisian children (396 boys and 201 girls) aged 8 to 15 years. Three sprint speeds recorded at 10, 20 and 30 m; two vertical and two horizontal jump tests; a change-of-direction and a handgrip-strength tests, were assessed during physical-education classes. Allometric modelling was used to identify the benefit of being an early or late maturer. Findings showed that being tall and light is the ideal shape to be successful at most physical fitness tests, but the height-to-weight “shape” ratio seems to be test-dependent. Having controlled for body-size/shape, sex, and chronological age, the model identified maturity-offset as an additional predictor. Boys who go earlier/younger through peak-height-velocity (PHV) outperform those who go at a later/older age. However, most of the girls’ physical-fitness tests peaked at the age at PHV and decline thereafter. Girls whose age at PHV was near the middle of the age range would appear to have an advantage compared to early or late maturers. These findings have important implications for talent scouts and coaches wishing to recruit children into their sports/athletic clubs.
This study aimed to compare the training load of a professional under-19 soccer team (U-19) to that of an elite adult team (EAT), from the same club, during the in-season period. Thirty-nine healthy soccer players were involved (EAT [n = 20]; U-19 [n = 19]) in the study which spanned four weeks. Training load (TL) was monitored as external TL, using a global positioning system (GPS), and internal TL, using a rating of perceived exertion (RPE). TL data were recorded after each training session. During soccer matches, players’ RPEs were recorded. The internal TL was quantified daily by means of the session rating of perceived exertion (session-RPE) using Borg’s 0–10 scale. For GPS data, the selected running speed intensities (over 0.5 s time intervals) were 12–15.9 km/h; 16–19.9 km/h; 20–24.9 km/h; >25 km/h (sprint). Distances covered between 16 and 19.9 km/h, > 20 km/h and >25 km/h were significantly higher in U-19 compared to EAT over the course of the study (p = 0.023, d = 0.243, small; p = 0.016, d = 0.298, small; and p = 0.001, d = 0.564, small, respectively). EAT players performed significantly fewer sprints per week compared to U-19 players (p = 0.002, d = 0.526, small). RPE was significantly higher in U-19 compared to EAT (p = 0.001, d = 0.188, trivial). The external and internal measures of TL were significantly higher in the U-19 group compared to the EAT soccer players. In conclusion, the results obtained show that the training load is greater in U19 compared to EAT.