Extern
Refine
Year of publication
Document Type
- Article (229)
- Conference Proceeding (122)
- Doctoral Thesis (111)
- Postprint (68)
- Working Paper (39)
- Review (15)
- Monograph/Edited Volume (14)
- Preprint (6)
- Master's Thesis (4)
- Habilitation Thesis (2)
Language
- English (612) (remove)
Keywords
- USA (7)
- United States (7)
- climate change (7)
- Arktis (6)
- moderne jüdische Geschichte (6)
- Arctic (5)
- COVID-19 (5)
- modern Jewish history (5)
- 20. Jahrhundert (4)
- 20th century (4)
Institute
- Extern (612)
- Institut für Biochemie und Biologie (66)
- Institut für Physik und Astronomie (51)
- Institut für Geowissenschaften (43)
- Vereinigung für Jüdische Studien e. V. (40)
- Institut für Chemie (39)
- Center for Economic Policy Analysis (CEPA) (32)
- Strukturbereich Kognitionswissenschaften (32)
- Fachgruppe Volkswirtschaftslehre (27)
- Department Psychologie (23)
Under Brazil's ex-president Bolsonaro, deforestation of the Amazon increased dramatically. An Austrian NGO filed a complaint to the Prosecutor of the International Criminal Court (ICC) against Bolsonaro in October 2021, accusing him of crimes against humanity against the backdrop of his involvement in environmental destruction. This paper deals with the question of whether this initi-ative constitutes a promising means of juridification to mitigate conflicts revolving around mass deforestation in Brazil. It thematizes attempts to juridify environmental destruction in international criminal law and examines the Climate Fund Case at the Brazilian Supreme Court. Finally, emerging problems and arguments in favour of starting preliminary examinations at the ICC against Bolsonaro are illuminated. This paper provides arguments as to why the initiative might be a promising undertaking, even though it is unlikely that Bolsonaro will be arrested.
Privacy regulations and the physical distribution of heterogeneous data are often primary concerns for the development of deep learning models in a medical context. This paper evaluates the feasibility of differentially private federated learning for chest X-ray classification as a defense against data privacy attacks. To the best of our knowledge, we are the first to directly compare the impact of differentially private training on two different neural network architectures, DenseNet121 and ResNet50. Extending the federated learning environments previously analyzed in terms of privacy, we simulated a heterogeneous and imbalanced federated setting by distributing images from the public CheXpert and Mendeley chest X-ray datasets unevenly among 36 clients. Both non-private baseline models achieved an area under the receiver operating characteristic curve (AUC) of 0.940.94 on the binary classification task of detecting the presence of a medical finding. We demonstrate that both model architectures are vulnerable to privacy violation by applying image reconstruction attacks to local model updates from individual clients. The attack was particularly successful during later training stages. To mitigate the risk of a privacy breach, we integrated Rényi differential privacy with a Gaussian noise mechanism into local model training. We evaluate model performance and attack vulnerability for privacy budgets ε∈{1,3,6,10}�∈{1,3,6,10}. The DenseNet121 achieved the best utility-privacy trade-off with an AUC of 0.940.94 for ε=6�=6. Model performance deteriorated slightly for individual clients compared to the non-private baseline. The ResNet50 only reached an AUC of 0.760.76 in the same privacy setting. Its performance was inferior to that of the DenseNet121 for all considered privacy constraints, suggesting that the DenseNet121 architecture is more robust to differentially private training.
In this work, binding interactions between biomolecules were analyzed by a technique that is based on electrically controllable DNA nanolevers. The technique was applied to virus-receptor interactions for the first time. As receptors, primarily peptides on DNA nanostructures and antibodies were utilized. The DNA nanostructures were integrated into the measurement technique and enabled the presentation of the peptides in a controllable geometrical order. The number of peptides could be varied to be compatible to the binding sites of the viral surface proteins.
Influenza A virus served as a model system, on which the general measurability was demonstrated. Variations of the receptor peptide, the surface ligand density, the measurement temperature and the virus subtypes showed the sensitivity and applicability of the technology. Additionally, the immobilization of virus particles enabled the measurement of differences in oligovalent binding of DNA-peptide nanostructures to the viral proteins in their native environment.
When the coronavirus pandemic broke out in 2020, work on binding interactions of a peptide from the hACE2 receptor and the spike protein of the SARS-CoV-2 virus revealed that oligovalent binding can be quantified in the switchSENSE technology. It could also be shown that small changes in the amino acid sequence of the spike protein resulted in complete loss of binding. Interactions of the peptide and inactivated virus material as well as pseudo virus particles could be measured. Additionally, the switchSENSE technology was utilized to rank six antibodies for their binding affinity towards the nucleocapsid protein of SARS-CoV-2 for the development of a rapid antigen test device.
The technique was furthermore employed to show binding of a non-enveloped virus (adenovirus) and a virus-like particle (norovirus-like particle) to antibodies. Apart from binding interactions, the use of DNA origami levers with a length of around 50 nm enabled the switching of virus material. This proved that the technology is also able to size objects with a hydrodynamic diameter larger than 14 nm.
A theoretical work on diffusion and reaction-limited binding interactions revealed that the technique and the chosen parameters enable the determination of binding rate constants in the reaction-limited regime.
Overall, the applicability of the switchSENSE technique to virus-receptor binding interactions could be demonstrated on multiple examples. While there are challenges that remain, the setup enables the determination of affinities between viruses and receptors in their native environment. Especially the possibilities regarding the quantification of oligo- and multivalent binding interactions could be presented.
The central gas in half of all galaxy clusters shows short cooling times. Assuming unimpeded cooling, this should lead to high star formation and mass cooling rates, which are not observed. Instead, it is believed that condensing gas is accreted by the central black hole that powers an active galactic nuclei jet, which heats the cluster. The detailed heating mechanism remains uncertain. A promising mechanism invokes cosmic ray protons that scatter on self-generated magnetic fluctuations, i.e. Alfvén waves. Continuous damping of Alfvén waves provides heat to the intracluster medium. Previous work has found steady state solutions for a large sample of clusters where cooling is balanced by Alfvénic wave heating. To verify modeling assumptions, we set out to study cosmic ray injection in three-dimensional magnetohydrodynamical simulations of jet feedback in an idealized cluster with the moving-mesh code arepo. We analyze the interaction of jet-inflated bubbles with the turbulent magnetized intracluster medium.
Furthermore, jet dynamics and heating are closely linked to the largely unconstrained jet composition. Interactions of electrons with photons of the cosmic microwave background result in observational signatures that depend on the bubble content. Those recent observations provided evidence for underdense bubbles with a relativistic filling while adopting simplifying modeling assumptions for the bubbles. By reproducing the observations with our simulations, we confirm the validity of their modeling assumptions and as such, confirm the important finding of low-(momentum) density jets.
In addition, the velocity and magnetic field structure of the intracluster medium have profound consequences for bubble evolution and heating processes. As velocity and magnetic fields are physically coupled, we demonstrate that numerical simulations can help link and thereby constrain their respective observables. Finally, we implement the currently preferred accretion model, cold accretion, into the moving-mesh code arepo and study feedback by light jets in a radiatively cooling magnetized cluster. While self-regulation is attained independently of accretion model, jet density and feedback efficiencies, we find that in order to reproduce observed cold gas morphology light jets are preferred.
In recent years digital technologies have become a major means for providing health-related services and this trend was strongly reinforced by the current Coronavirus disease 2019 (COVID-19) pandemic. As it is well-known that regular physical activity has positive effects on individual physical and mental health and thus is an important prerequisite for healthy aging, digital technologies are also increasingly used to promote unstructured and structured forms of physical activity. However, in the course of this development, several terms (e.g., Digital Health, Electronic Health, Mobile Health, Telehealth, Telemedicine, and Telerehabilitation) have been introduced to refer to the application of digital technologies to provide health-related services such as physical interventions. Unfortunately, the above-mentioned terms are often used in several different ways, but also relatively interchangeably. Given that ambiguous terminology is a major source of difficulty in scientific communication which can impede the progress of theoretical and empirical research, this article aims to make the reader aware of the subtle differences between the relevant terms which are applied at the intersection of physical activity and Digital Health and to provide state-of-art definitions for them.
Numerical magnitude information is assumed to be spatially represented in the form of a mental number line defined with respect to a body-centred, egocentric frame of reference. In this context, spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind, to the right/left) have been proposed to be relevant for grasping spatial relations between numerical magnitudes on the mental number line. We examined 4- to 5-year-old’s spatial language skills in tasks that allow responses in egocentric and allocentric frames of reference, as well as their relative understanding of numerical magnitude (assessed by a number word comparison task). In addition, we evaluated influences of children’s absolute understanding of numerical magnitude assessed by their number word comprehension (montring different numbers using their fingers) and of their knowledge on numerical sequences (determining predecessors and successors as well as identifying missing dice patterns of a series). Results indicated that when considering responses that corresponded to the egocentric perspective, children’s spatial language was associated significantly with their relative numerical magnitude understanding, even after controlling for covariates, such as children’s SES, mental rotation skills, and also absolute magnitude understanding or knowledge on numerical sequences. This suggests that the use of egocentric reference frames in spatial language may facilitate spatial representation of numbers along a mental number line and thus seem important for preschoolers’ relative understanding of numerical magnitude.
In intervention research, single-case experimental designs are an important way to gain insights into the causes of individual changes that yield high internal validity. They are commonly applied to examine the effectiveness of classroom-based interventions to reduce problem behavior in schools. At the same time, there is no consensus on good design characteristics of single-case experimental designs when dealing with behavioral problems in schools. Moreover, specific challenges arise concerning appropriate approaches to analyzing behavioral data. Our study addresses the interplay between the test power of piecewise regression analysis and important design specifications of single-case research designs. Here, we focus on the influence of the following specifications of single-case research designs: number of measurement times, the initial frequency of the behavior, intervention effect, and data trend. We conducted a Monte-Carlo study. First, simulated datasets were created with specific design conditions based on reviews of published single-case intervention studies. Following, data were analyzed using piecewise Poisson-regression models, and the influence of specific design specifications on the test power was investigated. Our results indicate that piecewise regressions have a high potential of adequately identifying the effects of interventions for single-case studies. At the same time, test power is strongly related to the specific design specifications of the single-case study: Few measurement times, especially in phase A, and low initial frequencies of the behavior make it impossible to detect even large intervention effects. Research designs with a high number of measurement times show robust power. The insights gained are highly relevant for researchers in the field, as decisions during the early stage of conceptualizing and planning single-case experimental design studies may impact the chance to identify an existing intervention effect during the research process correctly.
The aim of this review was to describe and summarize the scientific literature on programming parameters related to jump or plyometric training in male and female soccer players of different ages and fitness levels. A literature search was conducted in the electronic databases PubMed, Web of Science and Scopus using keywords related to the main topic of this study (e.g., “ballistic” and “plyometric”). According to the PICOS framework, the population for the review was restricted to soccer players, involved in jump or plyometric training. Among 7556 identified studies, 90 were eligible for inclusion. Only 12 studies were found for females. Most studies (n = 52) were conducted with youth male players. Moreover, only 35 studies determined the effectiveness of a given jump training programming factor. Based on the limited available research, it seems that a dose of 7 weeks (1–2 sessions per week), with ~80 jumps (specific of combined types) per session, using near-maximal or maximal intensity, with adequate recovery between repetitions (<15 s), sets (≥30 s) and sessions (≥24–48 h), using progressive overload and taper strategies, using appropriate surfaces (e.g., grass), and applied in a well-rested state, when combined with other training methods, would increase the outcome of effective and safe plyometric-jump training interventions aimed at improving soccer players physical fitness. In conclusion, jump training is an effective and easy-to-administer training approach for youth, adult, male and female soccer players. However, optimal programming for plyometric-jump training in soccer is yet to be determined in future research.
Quantifying neurological disorders from voice is a rapidly growing field of research and holds promise for unobtrusive and large-scale disorder monitoring. The data recording setup and data analysis pipelines are both crucial aspects to effectively obtain relevant information from participants. Therefore, we performed a systematic review to provide a high-level overview of practices across various neurological disorders and highlight emerging trends. PRISMA-based literature searches were conducted through PubMed, Web of Science, and IEEE Xplore to identify publications in which original (i.e., newly recorded) datasets were collected. Disorders of interest were psychiatric as well as neurodegenerative disorders, such as bipolar disorder, depression, and stress, as well as amyotrophic lateral sclerosis amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease, and speech impairments (aphasia, dysarthria, and dysphonia). Of the 43 retrieved studies, Parkinson's disease is represented most prominently with 19 discovered datasets. Free speech and read speech tasks are most commonly used across disorders. Besides popular feature extraction toolkits, many studies utilise custom-built feature sets. Correlations of acoustic features with psychiatric and neurodegenerative disorders are presented. In terms of analysis, statistical analysis for significance of individual features is commonly used, as well as predictive modeling approaches, especially with support vector machines and a small number of artificial neural networks. An emerging trend and recommendation for future studies is to collect data in everyday life to facilitate longitudinal data collection and to capture the behavior of participants more naturally. Another emerging trend is to record additional modalities to voice, which can potentially increase analytical performance.
Facing the environmental crisis, new technologies are needed to sustain our society. In this context, this thesis aims to describe the properties and applications of carbon-based sustainable materials. In particular, it reports the synthesis and characterization of a wide set of porous carbonaceous materials with high nitrogen content obtained from nucleobases. These materials are used as cathodes for Li-ion capacitors, and a major focus is put on the cathode preparation, highlighting the oxidation resistance of nucleobase-derived materials. Furthermore, their catalytic properties for acid/base and redox reactions are described, pointing to the role of nitrogen speciation on their surfaces. Finally, these materials are used as supports for highly dispersed nickel loading, activating the materials for carbon dioxide electroreduction.
Sulfur is an important element that is incorporated into many biomolecules in humans. The incorporation and transfer of sulfur into biomolecules is, however, facilitated by a series of different sulfurtransferases. Among these sulfurtransferases is the human mercaptopyruvate sulfurtransferase (MPST) also designated as tRNA thiouridine modification protein (TUM1). The role of the human TUM1 protein has been suggested in a wide range of physiological processes in the cell among which are but not limited to involvement in Molybdenum cofactor (Moco) biosynthesis, cytosolic tRNA thiolation and generation of H2S as signaling molecule both in mitochondria and the cytosol. Previous interaction studies showed that TUM1 interacts with the L-cysteine desulfurase NFS1 and the Molybdenum cofactor biosynthesis protein 3 (MOCS3). Here, we show the roles of TUM1 in human cells using CRISPR/Cas9 genetically modified Human Embryonic Kidney cells. Here, we show that TUM1 is involved in the sulfur transfer for Molybdenum cofactor synthesis and tRNA thiomodification by spectrophotometric measurement of the activity of sulfite oxidase and liquid chromatography quantification of the level of sulfur-modified tRNA. Further, we show that TUM1 has a role in hydrogen sulfide production and cellular bioenergetics.
In late summer, migratory bats of the temperate zone face the challenge of accomplishing two energy-demanding tasks almost at the same time: migration and mating. Both require information and involve search efforts, such as localizing prey or finding potential mates. In non-migrating bat species, playback studies showed that listening to vocalizations of other bats, both con-and heterospecifics, may help a recipient bat to find foraging patches and mating sites. However, we are still unaware of the degree to which migrating bats depend on con-or heterospecific vocalizations for identifying potential feeding or mating opportunities during nightly transit flights. Here, we investigated the vocal responses of Nathusius’ pipistrelle bats, Pipistrellus nathusii, to simulated feeding and courtship aggregations at a coastal migration corridor. We presented migrating bats either feeding buzzes or courtship calls of their own or a heterospecific migratory species, the common noctule, Nyctalus noctula. We expected that during migratory transit flights, simulated feeding opportunities would be particularly attractive to bats, as well as simulated mating opportunities which may indicate suitable roosts for a stopover. However, we found that when compared to the natural silence of both pre-and post-playback phases, bats called indifferently during the playback of conspecific feeding sounds, whereas P. nathusii echolocation call activity increased during simulated feeding of N. noctula. In contrast, the call activity of P. nathusii decreased during the playback of conspecific courtship calls, while no response could be detected when heterospecific call types were broadcasted. Our results suggest that while on migratory transits, P. nathusii circumnavigate conspecific mating aggregations, possibly to save time or to reduce the risks associated with social interactions where aggression due to territoriality might be expected. This avoidance behavior could be a result of optimization strategies by P. nathusii when performing long-distance migratory flights, and it could also explain the lack of a response to simulated conspecific feeding. However, the observed increase of activity in response to simulated feeding of N. noctula, suggests that P. nathusii individuals may be eavesdropping on other aerial hawking insectivorous species during migration, especially if these occupy a slightly different foraging niche.
Genetic divergence and the frequency of hybridization are central for defining species delimitations, especially among cryptic species where morphological differences are merely absent. Rotifers are known for their high cryptic diversity and therefore are ideal model organisms to investigate such patterns. Here, we used the recently resolved Brachionus calyciflorus species complex to investigate whether previously observed between species differences in thermotolerance and gene expression are also reflected in their genomic footprint. We identified a Heat Shock Protein gene (HSP 40 kDa) which exhibits cross species pronounced sequence variation. This gene exhibits species-specific fixed sites, alleles, and sites putatively under positive selection. These sites are located in protein binding regions involved in chaperoning and may therefore reflect adaptive diversification. By comparing three genetic markers (ITS, COI, HSP 40 kDa), we revealed hybridization events between the cryptic species. The low frequency of introgressive haplotypes/alleles suggest a tight, but not fully impermeable boundary between the cryptic species.
This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0–10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1%, JIA 11.1%, obesity 20%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6%; obesity 13.1%; JIA 5%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany.
Research within the framework of Basic Psychological Need Theory (BPNT) finds strong associations between basic need frustration and depressive symptoms. This study examined the role of rumination as an underlying mechanism in the association between basic psychological need frustration and depressive symptoms. A cross-sectional sample of N = 221 adults (55.2% female, mean age = 27.95, range = 18–62, SD = 10.51) completed measures assessing their level of basic psychological need frustration, rumination, and depressive symptoms. Correlational analyses and multiple mediation models were conducted. Brooding partially mediated the relation between need frustration and depressive symptoms. BPNT and Response Styles Theory are compatible and can further advance knowledge about depression vulnerabilities.
In numerical processing, the functional role of Spatial-Numerical Associations (SNAs, such as the association of smaller numbers with left space and larger numbers with right space, the Mental Number Line hypothesis) is debated. Most studies demonstrate SNAs with lateralized responses, and there is little evidence that SNAs appear when no response is required. We recorded passive holding grip forces in no-go trials during number processing. In Experiment 1, participants performed a surface numerical decision task (“Is it a number or a letter?”). In Experiment 2, we used a deeper semantic task (“Is this number larger or smaller than five?”). Despite instruction to keep their grip force constant, participants' spontaneous grip force changed in both experiments: Smaller numbers led to larger force increase in the left than in the right hand in the numerical decision task (500–700 ms after stimulus onset). In the semantic task, smaller numbers again led to larger force increase in the left hand, and larger numbers increased the right-hand holding force. This effect appeared earlier (180 ms) and lasted longer (until 580 ms after stimulus onset). This is the first demonstration of SNAs with passive holding force. Our result suggests that (1) explicit motor response is not a prerequisite for SNAs to appear, and (2) the timing and strength of SNAs are task-dependent. (216 words).
We investigate whether political ideology has an observable effect on decarbonization ambition, renewable power aims, and preferences for power system balancing technologies in four European countries. Based on the Energy Logics framework, we identify ideologically different transition strategies (state-centered, market-centered, grassroots-centered) contained in government policies and opposition party programs valid in 2019. We compare these policies and programs with citizen poll data. We find that ideology has a small effect: governments and political parties across the spectrum have similar, and relatively ambitious, decarbonization and renewables targets. This mirrors citizens' strong support for ambitious action regardless of their ideological self-description. However, whereas political positions on phasing out fossil fuel power are clear across the policy space, positions on phasing in new flexibility options to balance intermittent renewables are vague or non-existent. As parties and citizens agree on strong climate and renewable power aims, the policy ambition is likely to remain high, even if governments change.
Background
Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet.
Methods
The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release.
Results
While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity.
Conclusion(s)
Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research.
Flood risk management in Germany follows an integrative approach in which both private households and businesses can make an important contribution to reducing flood damage by implementing property-level adaptation measures. While the flood adaptation behavior of private households has already been widely researched, comparatively less attention has been paid to the adaptation strategies of businesses. However, their ability to cope with flood risk plays an important role in the social and economic development of a flood-prone region. Therefore, using quantitative survey data, this study aims to identify different strategies and adaptation drivers of 557 businesses damaged by a riverine flood in 2013 and 104 businesses damaged by pluvial or flash floods between 2014 and 2017. Our results indicate that a low perceived self-efficacy may be an important factor that can reduce the motivation of businesses to adapt to flood risk. Furthermore, property-owners tended to act more proactively than tenants. In addition, high experience with previous flood events and low perceived response costs could strengthen proactive adaptation behavior. These findings should be considered in business-tailored risk communication.
Selenium (Se) is an essential trace element that is ubiquitously present in the environment in small concentrations. Essential functions of Se in the human body are manifested through the wide range of proteins, containing selenocysteine as their active center. Such proteins are called selenoproteins which are found in multiple physiological processes like antioxidative defense and the regulation of thyroid hormone functions. Therefore, Se deficiency is known to cause a broad spectrum of physiological impairments, especially in endemic regions with low Se content. Nevertheless, being an essential trace element, Se could exhibit toxic effects, if its intake exceeds tolerable levels. Accordingly, this range between deficiency and overexposure represents optimal Se supply. However, this range was found to be narrower than for any other essential trace element. Together with significantly varying Se concentrations in soil and the presence of specific bioaccumulation factors, this represents a noticeable difficulty in the assessment of Se
epidemiological status. While Se is acting in the body through multiple selenoproteins, its intake occurs mainly in form of small organic or inorganic molecular mass species. Thus, Se exposure not only depends on daily intake but also on the respective chemical form, in which it is present.
The essential functions of selenium have been known for a long time and its primary forms in different food sources have been described. Nevertheless, analytical capabilities for a comprehensive investigation of Se species and their derivatives have been introduced only in the last decades. A new Se compound was identified in 2010 in the blood and tissues of bluefin tuna. It was called selenoneine (SeN) since it is an isologue of naturally occurring antioxidant ergothioneine (ET), where Se replaces sulfur. In the following years, SeN was identified in a number of edible fish species and attracted attention as a new dietary Se source and potentially strong antioxidant. Studies in populations whose diet largely relies on fish revealed that SeN
represents the main non-protein bound Se pool in their blood. First studies, conducted with enriched fish extracts, already demonstrated the high antioxidative potential of SeN and its possible function in the detoxification of methylmercury in fish. Cell culture studies demonstrated, that SeN can utilize the same transporter as ergothioneine, and SeN metabolite was found in human urine.
Until recently, studies on SeN properties were severely limited due to the lack of ways to obtain the pure compound. As a predisposition to this work was firstly a successful approach to SeN synthesis in the University of Graz, utilizing genetically modified yeasts. In the current study, by use of HepG2 liver carcinoma cells, it was demonstrated, that SeN does not cause toxic effectsup to 100 μM concentration in hepatocytes. Uptake experiments showed that SeN is not bioavailable to the used liver cells.
In the next part a blood-brain barrier (BBB) model, based on capillary endothelial cells from the porcine brain, was used to describe the possible transfer of SeN into the central nervous system (CNS). The assessment of toxicity markers in these endothelial cells and monitoring of barrier conditions during transfer experiments demonstrated the absence of toxic effects from SeN on the BBB endothelium up to 100 μM concentration. Transfer data for SeN showed slow but substantial transfer. A statistically significant increase was observed after 48 hours following SeN incubation from the blood-facing side of the barrier. However, an increase in Se content was clearly visible already after 6 hours of incubation with 1 μM of SeN. While the transfer rate of SeN after application of 0.1 μM dose was very close to that for 1 μM, incubation with 10 μM of SeN resulted in a significantly decreased transfer rate. Double-sided application of SeN caused no side-specific transfer of SeN, thus suggesting a passive diffusion mechanism of SeN across the BBB. This data is in accordance with animal studies, where ET accumulation was observed in the rat brain, even though rat BBB does not have the primary ET transporter – OCTN1. Investigation of capillary endothelial cell monolayers after incubation with SeN and reference selenium compounds showed no significant increase of intracellular selenium concentration. Speciesspecific Se measurements in medium samples from apical and basolateral compartments, as good as in cell lysates, showed no SeN metabolization. Therefore, it can be concluded that SeN may reach the brain without significant transformation.
As the third part of this work, the assessment of SeN antioxidant properties was performed in Caco-2 human colorectal adenocarcinoma cells. Previous studies demonstrated that the intestinal epithelium is able to actively transport SeN from the intestinal lumen to the blood side and accumulate SeN. Further investigation within current work showed a much higher antioxidant potential of SeN compared to ET. The radical scavenging activity after incubation with SeN was close to the one observed for selenite and selenomethionine. However, the SeN effect on the viability of intestinal cells under oxidative conditions was close to the one caused by ET. To answer the question if SeN is able to be used as a dietary Se source and induce the activity of selenoproteins, the activity of glutathione peroxidase (GPx) and the secretion of selenoprotein P (SelenoP) were measured in Caco-2 cells, additionally. As expected, reference selenium compounds selenite and selenomethionine caused efficient induction of GPx activity. In contrast to those SeN had no effect on GPx activity. To examine the possibility of SeN being embedded into the selenoproteome, SelenoP was measured in a culture medium. Even though Caco-2 cells effectively take up SeN in quantities much higher than selenite or selenomethionine, no secretion of SelenoP was observed after SeN incubation.
Summarizing, we can conclude that SeN can hardly serve as a Se source for selenoprotein synthesis. However, SeN exhibit strong antioxidative properties, which appear when sulfur in ET is exchanged by Se. Therefore, SeN is of particular interest for research not as part of Se metabolism, but important endemic dietary antioxidant.