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Synaptic plasticity is the activity dependent alteration of the composition, form and strength of synapses and believed to be the underlying mechanism of learning and memory formation. While initial changes in synaptic transmission are caused by second messenger signaling pathways and rapid modifications in the cytoskeleton, to achieve stable and persistent changes at individual synapses, the expression of new mRNAs and proteins is required. The central dogma postulated that the cell body is the only source of newly synthesized proteins. For neurons, with their unique morphology, this meant that proteins would need be transported long distances, often hundreds of microns, to reach their destined locations in dendrites and at spines. To overcome this limitation, neurons have developed a strategy to regulate protein synthesis locally by distributing thousands of mRNAs into neuronal processes and use them for local protein synthesis. Ample research has demonstrated the importance of local protein synthesis to many forms of long-term synaptic plasticity. One potential regulator of mRNA localization and local translation in neurons are non-coding RNAs. Intensive work over the past decades has highlighted the importance of non-coding RNAs in many aspects of brain function. The aim of this thesis is to obtain a better understanding of the role of non-coding RNAs in synaptic function and plasticity in the murine hippocampus. For this, we focused our studies on two classes of non-coding RNAs.
In the first part of my thesis, I describe our efforts on characterizing circular RNAs, a novel and peculiar family of non-coding RNAs, in the murine hippocampus by combining high throughput RNA-Sequencing with fluorescence in situ hybridization. Furthermore, we investigated the mechanisms of circular RNA biogenesis in hippocampal neurons by temporarily inhibiting spliceosome activity and analyzing the differentially regulated circular RNAs.
A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog, but how it occurs in cities is often puzzling. If the growth rates of urban particles are similar to those found in cleaner environments (1–10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below −15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid–base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms.
This article reports an investigation of how inhibition contributes to fluid reasoning when it is decomposed into the reasoning ability, item-position, and speed components to control for possible method effects. Working memory was also taken into consideration. A sample of 223 university students completed a fluid reasoning scale, two tasks tapping prepotent response inhibition, and two working memory tasks. Fixed-links modeling was used to separate the effect of reasoning ability from the effects of item-position and speed. The goodness-of-fit results confirmed the necessity to consider the reasoning ability, item-position, and speed components simultaneously. Prepotent response inhibition was only associated with reasoning ability. This association disappeared when working memory served as a mediator. Taken together, these results reflect the inhomogeneity of what is tapped by the fluid reasoning scale on one hand and, on the other, suggest inhibition as an important component of working memory.
Background: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.
Material and Methods: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients’ demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.
Results: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8–2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.
Conclusions: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.
Human-induced changes in the environment have increased the number of stressors impacting aquatic organism. In the light of climate change and plastic pollution, thermal stress and microplastics (MP) have become two of the most intensively studied stressors in aquatic ecosystems. Previous studies, however, mostly evaluated the impacts of thermal and MP stress in isolation, thereby neglecting joint effects.
To examine the combined effects of both, we exposed the freshwater mussel Dreissena polymorpha to irregular polystyrene MP (6.4, 160, 4000, 100,000 p mL−1) at either 14, 23 or 27 °C for 14 days and analyzed mortality, mussel activity and clearance rate, energy reserves, oxidative stress and the immunological state. Further, we exposed the mussels to diatomite (natural particle equivalent, 100,000 p mL−1) at each of the three water temperatures to compare MP and natural particle toxicity.
An increase in water temperature has a pronounced effect on D. polymorpha and significantly affects the activity, energy reserves, oxidative stress and immune function. In contrast, the effects by MP are limited to a change in the antioxidative capacity without any interactive effects between MP and thermal exposure. The comparison of the MP with a diatomite exposure revealed only limited influence of the particle type on the response of D. polymorpha to high concentrations of suspended particles.
The results indicate that MPs have minor effects on a freshwater mussel compared to thermal stress, neither alone nor as interactive effect. Limited MP toxicity could be based on adaptation mechanism of dreissenids to suspended solids. Nonetheless, MP may contribute to environmental impacts of multiple anthropogenic stressors, especially if their levels increase in the future. Therefore, we suggest integrating MP into the broader context of multiple stressor studies to understand and assess their joint impacts on freshwater ecosystems.
The interaction of microplastics with freshwater biota and their interaction with other stressors is still not very well understood. Therefore, we investigated the ingestion, excretion and toxicity of microplastics in the freshwater gastropod Lymnaea stagnalis.
MP ingestion was analyzed as tissues levels in L. stagnalis after 6–96 h of exposure to 5–90 μm spherical polystyrene (PS) microplastics. To understand the excretion, tissue levels were determined after 24 h of exposure followed by a 12 h–7 d depuration period. To assess the toxicity, snails were exposed for 28 d to irregular PS microplastics (<63 μm, 6.4–100,000 particles mL−1), both alone and in combination with copper as additional stressor. To compare the toxicity of natural and synthetic particles, we also included diatomite particles. Microplastics ingestion and excretion significantly depended on the particle size and the exposure/depuration duration. An exposure to irregular PS had no effect on survival, reproduction, energy reserves and oxidative stress. However, we observed slight effects on immune cell phagocytosis. Exposure to microplastics did not exacerbate the reproductive toxicity of copper. In addition, there was no pronounced difference between the effects of microplastics and diatomite. The tolerance towards microplastics may originate from an adaptation of L. stagnalis to particle-rich environments or a general stress resilience. In conclusion, despite high uptake rates, PS fragments do not appear to be a relevant stressor for stress tolerant freshwater gastropods considering current environmental levels of microplastics.
Background and purpose: The aim of the study was to determine the effects of post-traumatically released High Mobility Group Box-1 protein (HMGB1) and extracellular histones on cardiomyocytes (CM). We also evaluated a therapeutic option to capture circulating histones after trauma, using a hemadsorption filter to treat CM dysfunction. Experimental Approach: We evaluated cell viability, calcium handling and mitochondrial respiration of human cardiomyocytes in the presence of HMGB-1 and extracellular histones. In a translational approach, a hemadsorption filter was applied to either directly eliminate extracellular histones or to remove them from blood samples obtained from multiple injured patients. Key results: Incubation of human CM with HMGB-1 or histones is associated with changes in calcium handling, a reduction of cell viability and a substantial reduction of the mitochondrial respiratory capacity. Filtrating plasma from injured patients with a hemadsorption filter reduces histone concentration ex vivo and in vitro, depending on dosage. Conclusion and implications: Danger associated molecular patterns such as HMGB-1 and extracellular histones impair human CM in vitro. A hemadsorption filter could be a therapeutic option to reduce high concentrations of histones.
The Mad Man and the Old God : an essay on Friedrich Nietzsche's apocalypse of human existence
(2020)
The thesis John Calvin (1509-1564) was the religious initiator of modern capitalist mentality is inconsistent with his teaching; just the opposite is true. Calvin represented a very traditional i.e. non- or even ant-capitalist socio-economic position. There one does not find on his doctrine what could have fostered and prepared a so-called spirit of capitalism
EEG microstate periodicity explained by rotating phase patterns of resting-state alpha oscillations
(2020)
Spatio-temporal patterns in electroencephalography (EEG) can be described by microstate analysis, a discrete approximation of the continuous electric field patterns produced by the cerebral cortex. Resting-state EEG microstates are largely determined by alpha frequencies (8-12 Hz) and we recently demonstrated that microstates occur periodically with twice the alpha frequency.
To understand the origin of microstate periodicity, we analyzed the analytic amplitude and the analytic phase of resting-state alpha oscillations independently. In continuous EEG data we found rotating phase patterns organized around a small number of phase singularities which varied in number and location. The spatial rotation of phase patterns occurred with the underlying alpha frequency. Phase rotors coincided with periodic microstate motifs involving the four canonical microstate maps. The analytic amplitude showed no oscillatory behaviour and was almost static across time intervals of 1-2 alpha cycles, resulting in the global pattern of a standing wave.
In n=23 healthy adults, time-lagged mutual information analysis of microstate sequences derived from amplitude and phase signals of awake eyes-closed EEG records showed that only the phase component contributed to the periodicity of microstate sequences. Phase sequences showed mutual information peaks at multiples of 50 ms and the group average had a main peak at 100 ms (10 Hz), whereas amplitude sequences had a slow and monotonous information decay. This result was confirmed by an independent approach combining temporal principal component analysis (tPCA) and autocorrelation analysis.
We reproduced our observations in a generic model of EEG oscillations composed of coupled non-linear oscillators (Stuart-Landau model). Phase-amplitude dynamics similar to experimental EEG occurred when the oscillators underwent a supercritical Hopf bifurcation, a common feature of many computational models of the alpha rhythm.
These findings explain our previous description of periodic microstate recurrence and its relation to the time scale of alpha oscillations. Moreover, our results corroborate the predictions of computational models and connect experimentally observed EEG patterns to properties of critical oscillator networks.
Zielsetzung: Ziel dieser Studie war die Überprüfung der Machbarkeit einer softwaregestützten radiologischen Evaluation der Cageposition und Quantifizierung einer möglichen Cagemigration und -sinterung anhand computertomographisch gewonnener DICOM-Daten im Rahmen des Heilungsprozesses interkorporell fusionierter Patienten. Zusätzlich dazu wurde eine mögliche Korrelation zum Fusionsverhalten des Cages sowie zum klinischen Outcome der Patienten analysiert.
Material und Methoden: In den postoperativen CT Datensätzen von 67 Patienten nach monosegmentaler, dorsal instrumentierter TLIF wurde mithilfe der Software VGStudio Max die Cageposition bestimmt. Eine im postoperativen Verlauf eingetretene Lageänderung ≥ 1 mm bzw. ≥ 3° wurde hierbei als minimale Migration / Sinterung, eine Lageänderung ≥ 3 mm bzw. ≥ 10° als deutliche Migration / Sinterung des Cages gewertet. Um zu prüfen, ob das Migrations- und Sinterungsverhalten einen Einfluss auf die Osteogenese hat, erfolgte auf Basis der von Bridwell et al publizierten Fusionskriterien in den 12 Monate postoperativen CT-Aufnahmen eine Evaluation des Fusionstatus‘. Zur klinischen Beurteilung wurden der Oswestry Disability Index, die Visuelle Analogskala, der Schmerzmittelbedarf und der modifizierte Pationnaire Questionnaire der Patienten ausgewertet.
Ergebnisse: Die Messung der Cageposition mittels VGStudio Max ist eine präzise und reliable Methode zur Quantifizierung einer Cagemigration und -sinterung. Insgesamt war bei 85,1% der Patienten eine Migration (61,2% minimal, 23,9% deutlich) und bei 58,2% der Patienten eine Sinterung (32,8% minimal, 25,4% deutlich) des Cages nachweisbar. Radiologische Zeichen einer Pseudarthrose fanden sich bei 5 Patienten (7,5%). Die übrigen 92,5% der Patienten wiesen eine Grad I bzw. II Fusion auf.
Cagemigration und -sinterung hatten keinen signifikanten Einfluss auf das Fusionsverhalten und das klinische Outcome. Eine Korrelation zwischen Fusionsergebnis und klinischem Outcome bestand ebenfalls nicht.
Schlussfolgerung: Die Inzidenz der Cagemigration ist - unter Berücksichtigung auch geringfügiger Lageänderungen der Cages - deutlich höher als vorbeschrieben. Auf Basis des Migrations- bzw. Sinterungsverhaltens von Cages können jedoch keine Rückschlüsse auf das Fusionsergebnis gezogen werden. Als Kriterium in der Fusionsbeurteilung eignet sich der Nachweis einer Cagemigration bzw. -sinterung daher nicht in dem Ausmaß wie bisher vermutet.
Inflation ist ein Konstrukt. Sie wird von unterschiedlichen Akteur*innen unterschiedlich wahrgenommen. Zum Teil passiert dies, weil Warenkörbe differieren, zum Teil weil Erwartungen unterschiedlich gebildet werden. Dieser Beitrag diskutiert die Heterogenität der Infl ation und ihrer Wahrnehmung und was dies für die Zielgröße der Zentralbankpolitik bedeutet.
Inflation ist ein Konstrukt. Sie wird von unterschiedlichen Akteuren unterschiedlich wahrgenommen. Zum Teil passiert dies, weil Warenkörbe differieren, zum Teil weil Erwartungen unterschiedlich gebildet werden. Dieser Beitrag diskutiert die Heterogenität der Inflation und ihrer Wahrnehmung und was dies für die Zielgröße der Zentralbankpolitik bedeutet.
The ability to vocalize is ubiquitous in vertebrates, but neural networks underlying vocal control remain poorly understood. Here, we performed simultaneous neuronal recordings in the frontal cortex and dorsal striatum (caudate nucleus, CN) during the production of echolocation pulses and communication calls in bats. This approach allowed us to assess the general aspects underlying vocal production in mammals and the unique evolutionary adaptations of bat echolocation. Our data indicate that before vocalization, a distinctive change in high-gamma and beta oscillations (50–80 Hz and 12–30 Hz, respectively) takes place in the bat frontal cortex and dorsal striatum. Such precise fine-tuning of neural oscillations could allow animals to selectively activate motor programs required for the production of either echolocation or communication vocalizations. Moreover, the functional coupling between frontal and striatal areas, occurring in the theta oscillatory band (4–8 Hz), differs markedly at the millisecond level, depending on whether the animals are in a navigational mode (that is, emitting echolocation pulses) or in a social communication mode (emitting communication calls). Overall, this study indicates that fronto-striatal oscillations could provide a neural correlate for vocal control in bats.