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Connectomic analysis of apical dendrite innervation in pyramidal neurons of mouse cerebral cortex
(2020)
The central goal of this study was to generate synapse-resolution maps of local and long-range innervation on apical dendrites (AD) in mouse cerebral cortex. We used three-dimensional electron microscopy (3D-EM) to first measure the cell-type specific balance in the excitatory and inhibitory input on ADs. Further, we found two inhibitory axon populations with preference for apical dendrites originating from layer 2 and 3/5. Additionally, we used a combination of large-scale volumetric light and electron microscopy to investigate the innervation preference of long-range cortical projections onto ADs. To generate such large-scale 3D-EM datasets, we also developed a software package to automate aberration adjustment.
The balance of excitation and inhibition defines the computational properties of neurons. We, therefore, generated 6 datasets and annotated 26,548 excitatory and inhibitory synapses to map the relative inhibitory strength on the AD of pyramidal neurons in layers 1 and 2 (L1 and 2) of the cortex. We found consistent and cell-type specific patterns of inhibitory strength along the apical dendrite of L2-5 pyramidal neurons in primary somatosensory (S1), secondary visual (V2), posterior parietal (PPC) and anterior cingulate (ACC) cortices. L2 and L5 pyramidal neurons had inhibitory hot-zones at their main bifurcation and distal apical dendrite tuft, respectively. In contrast, L3 neurons had a baseline (~10%) level of inhibition along their apical dendrite. As controls, we quantified the effect of synapse strength (size), dendrite diameter, AD classification and synapse identification methods on the cell-type specific synapse densities. To classify L5 pyramidal subtypes, we performed hierarchical clustering using morphological properties that were described to differentiate slender- and thick-tufted L5 neurons.
We also investigated the distance to soma as a predictor of fractional inhibition around the main bifurcation of apical dendrites. Interestingly, we found a strong exponential relationship that was absent in density of either synapse type. This suggests a distance dependent control mechanism designed specifically for the balance (in synapse numbers) of excitation and inhibition.
Next, we focused on the inhibitory innervation preference for apical dendrite of pyramidal neuron. We, therefore, annotated 5,448 output synapses of AD-targeting inhibitory axons and found two populations specific for either L2 or L3/5 apical dendrites. Together with previous findings on preferential innervation of sub-cellular structures by inhibitory axons, this suggests two distinct inhibitory circuits for control of AD activity in L2 vs. deep-layer pyramidal neurons. This innervation preference was surprisingly consistent across S1, V2, PPC and ACC cortices.
3D-EM data acquisition is a laborious process that is made easier and more popular everyday by technical progress in the laboratory and industrial settings. To make data acquisition robust using our custom-built 3D-EM microscopes, an automatic aberration software was implemented to adjust the objective lens and the stigmators of the electron microscope. This method was used in multiple month-long experiments across 2 microscopes and 10 datasets. The aberration adjustment used the reduction in image details (high-frequency elements) to estimate the level of deviation from optimal focus and stigmator parameters. However, large objects in EM micrographs such as blood vessel and nuclei cross-sections generated anomalous results. We, therefore, added image processing routines based on edge detection combined with morphological operations to exclude such large objects.
Finally, we performed a correlative three-dimensional (3D) light (LM) and electron (EM) microscopy experiment to map the long-range primary visual (V1) and secondary motor (M2) cortical input to ADs in layer 1 of PPC using the “FluoEM” approach. This method allows for identification of the long-range source of projection axons in EM volumes without the need for EM-dense label conversion or heat-induced markings. The long-range source of an axon in EM is identified based on the fluorescent protein that is expressed in its LM counterpart. In comparison to M2 input, Long-range axons from V1 had a higher tendency to target L3 pyramidal neurons in PPC according to our preliminary analysis. In combination with the difference observed in the synapse composition of L2 and L3 apical dendrites, this suggests the need for separate functional and structural analysis of L2 and 3 pyramidal neurons.
Bacteria constantly attempt to hold up ion gradients across their membranes to maintain their resting potential for routine cell function, while coping with sudden environmental changes. Under abrupt hyperosmotic conditions, as faced when invading a host, most bacteria restore their turgor pressure by taking up potassium ions to prevent death by plasmolysis. Here, the potassium transporter AB, or KtrAB for short, is a key player. KtrAB consists of the membrane-embedded KtrB dimer, which includes two pores organized in tandem, and a cytoplasmic, octameric KtrA ring, which regulates these two pores. The KtrB subunits alone were suggested to function as rather non-selective ion channels translocating potassium and sodium ions. The KtrA subunits confer transport velocity, K+ selectivity as well as Na+ and nucleotide dependency to the Ktr system. The nucleotide regulation by binding to KtrA is rather well characterized. In contrast, the regulatory role of Na+ remains elusive. Controversially discussed is how selective the ion translocation by KtrB is and how KtrA affects it. Although there are several functional and structural data available of KtrAB and its homolog TrkAH, the selectivity of the ion translocation was never thoroughly addressed. The functional characterization of whether KtrAB is a selective ion channel and how selectivity is achieved is in the focus of this thesis. Since selectivity is usually defined by the ion channels’ selectivity filter contained in the pore-forming domain, a particular attention was laid on the ion-translocating subunits KtrB.
KtrB belongs to the superfamily of K+ transporters (SKT). Each KtrB monomer consists of four covalently attached M1-P-M2 motifs, each motif is made of two transmembrane (TM or M) helices that are connected by a pore (P) helix. The four motifs, referred to as domains D1 to D4, are arranged in a pseudo-fourfold symmetry and together form the pore for potassium ion translocation. Each pore contains two structural features thought to be involved in ion selectivity and ion gating. These are the non-canonical selectivity filter and the intramembrane loop. The selectivity filter is localized at the extracellular side of the pore and mostly shaped by the backbone carbonyl groups of the loops connecting the P and M2 helices in each domain. In KtrB, each P-loop contains only one highly conserved glycine residue instead of the classical -TVGYG- signature sequence of a K+ channel. This simple constructed selectivity filter led to the hypothesis that KtrAB would only have low ion selectivity. The intramembrane loop is formed by broken helix D3M2 and is located directly under the selectivity filter. It consists mostly of polar residues and acts as a molecular gate restricting ion fluxes. The intramembrane loop has been shown to be regulated by nucleotide binding to KtrA. Additionally, it could directly or indirectly be affected by Na+ binding. Further, the loop might even be involved in ion selectivity because it presents a physical barrier inside the pore.
To address the ion selectivity of the Ktr system, first, the ion binding specificity of KtrB was investigated. Binding affinities of different cations to KtrB were determined using isothermal titration calorimetry (ITC). For this, KtrB from Vibrio alginolyticus was heterologously produced in and purified from Escherichia coli. 12 L of culture roughly yielded 4 to 8 mg of the functional KtrB dimer in detergent solution. ITC measurements were performed in two different buffers, one choline-Cl-based and one LiCl-based buffer. No differences in the affinity between Na+ (KD = 1.8 mM), K+ (KD = 2.9 mM), Rb+ (KD = 1.9 mM) or Cs+ (KD = 1.6 mM) were detected in the choline-Cl-based buffer; only Li+ did not bind. In contrast, ITC measurements in LiCl-based buffer revealed a significant preference for K+ (KD = 91 µM) over Rb+ (KD = 2.4 mM), Cs+ (KD = 1.7 mM) and particularly Na+ (for which no binding was observed). Similarly, the presence of low millimolar NaCl concentrations in the choline-Cl-based buffer led to a decreased KD value of 260 µM. Hence, small cations, which usually are present in the natural environment, seem to modulate the selectivity filter for a better binding of K+ ions providing K+ selectivity. In fact, the low binding affinities of the other ions could indicate that they do not even bind to the selectivity filter but to the cavity. However, ITC competition experiments showed that all four ions compete for the same or overlapping binding sites, with Rb+ and Cs+ even blocking K+ binding at concentrations 10-fold above their binding affinities. Importantly, at physiological NaCl concentrations of 200 mM, the apparent binding affinity for K+ to KtrB was still 3.5 mM. This suggested that Na+ can also bind to KtrB’s selectivity filter but with a comparably low binding affinity providing an unexpectedly high preference for K+ ions.
...
Consuming dividends
(2020)
This paper studies why investors buy dividend-paying assets and how they time their consumption accordingly. We combine administrative bank data linking customers’ consumption transactions and income to detailed portfolio data and survey responses on financial behavior. We find that private consumption is excessively sensitive to dividend income. Investors across wealth, income, and age distributions increase spending precisely around days of dividend receipt. Importantly, the consumption response is driven by financially prudent investors who select dividend portfolios, anticipate dividend income, and plan consumption accordingly. Our results contribute to the literature on a dividend clientele and provide evidence of ‘planned’ excess sensitivity.
We survey a representative sample of US households to study how exposure to the COVID-19 stock market crash a↵ects expectations and planned behavior. Wealth shocks are associated with upward adjustments of expectations about retirement age, desired working hours, and household debt, but have only small e↵ects on expected spending. We provide correlational and experimental evidence that beliefs about the duration of the stock market recovery shape households’ expectations about their own wealth and their planned investment decisions and labor market activity. Our findings shed light on the implications of household exposure to stock market crashes for expectation formation.
This working paper suggests to analyse agencification as a double process of institutional and policy centralisation. To that end, it develops a categorisation of agencies that incorporates these two dimensions. More specifically, it is argued that mixed outcomes where the levels of institutional and policy centralisation diverge can be expected to be the rule rather than the exception, in line with the hybrid nature of EU agencies as inbetweeners. Moreover, the fiduciary setting hits important legal constraints given the limits to delegation in the EU context. Against this backdrop a process whereby institutional centralisation develops incrementally and remains limited, yet is accompanied by a process of substantial policy centralisation, appears as the most promising path for EU agencification. A fiduciary setting, where a strong agency enjoys a high degree of independence and operates in a centralised policy space, by contrast, should be the exception. The comparative study of the process of agencification in the energy and banking sector is insightful in the light of these expectations. The incremental nature of institutional change in energy exemplifies the usual path of agencification, which is conducive to a weak agency operating in a relatively centralised policy space. Agencification in banking, by contrast, has led to a rather unusual outcome where the strong agency model combines with a fragmented policy context.
This Policy Letter outlines a pandemic insurance solution through a pandemic-related “Insurance Linked Bond”. It would be originated by governments, with a principal amount to cover significant costs resulting from a pandemic. These bonds, which would be traded on a secondary market, generate a risk-adequate return for private and institutional investors that is financed through the insurance premiums paid by the public domain. In case of a pre-defined pandemic trigger event, the principal of the bond becomes available for the originating governments to cover pandemic-related costs. Through this approach, governments can insure themselves against future pandemic-related risks, while funding comes primarily from private and institutional investors.
leporello #4
(2020)
Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood–brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels >64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3–100) and specificity of 42.9% (17.7–71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0–99.8) and specificity of 42.9% (17.7–71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.
Within the context of eHealth interventions, a shared understanding of what constitutes engagement in and with eHealth technologies is missing. A clearer understanding of engagement could provide a valuable starting point for guidelines relating to the design and development of eHealth technologies. Given the cross-disciplinary use of the term “engagement,” investigating how engagement (and its components) is conceptualized in different domains could lead to determining common components that are deemed important for eHealth technological design. As such, the aim of this paper was 3-fold: (a) to investigate in which domains engagement features, (b) to determine what constitutes engagement in these different domains, and (c) to determine whether there are any common components that seem to be important. A comprehensive systematic scoping review of the existing literature was conducted in order to identify the domains in which engagement is used, to extract the associated definitions of engagement, and to identify the dimensionality or components thereof. A search of five bibliographic databases yielded 1,231 unique records. All titles, abstracts, and full texts were screened based on specific inclusion and exclusion criteria. This led to 69 articles being included for further analyses. The results showed that engagement is used in seven functional domains, categorized as follows: student (n = 18), customer (n = 12), health (n = 11), society (n = 10), work (n = 9), digital (n = 8), and transdisciplinary (n = 1) domains. It seems that some domains are more mature regarding their conceptualization and theorizing on engagement than others. Further, engagement was found to be predominantly conceptualized as a multidimensional construct with three common components (behavior, cognition, and affective) shared between domains. Although engagement is prolifically used in different disciplines, it is evident that little shared consensus as to its conceptualization within and between domains exists. Despite this, engagement is foremost seen as a state of being engaged in/with something, which is part of, but should not be confused with, the process of engagement. Behavior, cognition, and affect are important components of engagement and should be specified for each new context.
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.
The aim of this observational study was to follow-up patients with bedtime basal insulin (NPH insulin) added to metformin. In 285 patients with type 2 diabetes, a therapy with bedtime basal insulin added to metformin was started due to failure to achieve a glycaemic goal. Up until July 2019, 272 patients (95.4%) were followed-up (59.5 y, 92.6 kg, diabetes duration 6.6 y, HbA1c 8.4%/68.6 mmol/mol). HbA1c decreased by −1.2% and bodyweight by −1.7 kg after a duration of 31.7 ± 29.1 (range 2–133) months. Severe hypoglycaemia did not occur. In 144/272 patients (52.9%), the therapeutic goal for HbA1c was achieved over 32.7 months. In 69/272 patients (25.4%), the HbA1c target was achieved over 25.0 months (afterwards, therapy with basal insulin was discontinued because HbA1c was under target). In 36/272 patients (13.2%), the HbA1c goal was achieved until the submission of this manuscript (mean duration of treatment 57.4 ± 28.2 (range 13–121) months). Over 90% of patients with type 2 diabetes and failure of metformin reached their HbA1c goal with additional basal insulin at bedtime over several years in association with a reduction of bodyweight and without any event of severe hypoglycaemia.
Young neurons in the adult brain are key to some types of learning and memory. They integrate in the dentate gyrus (DG) of the hippocampus contributing to such cognitive processes following timely developmental events. While experimentally impairing GABAergic transmission through the blockade or elimination of the ionic cotransporter NKCC1 leads to alterations in the proper maturation of young neurons, it is still unknown if the in vivo administration of common use diuretic drugs that block the cotransporter, alters the development of young hippocampal neurons and affects DG-related functions. In this study, we delivered chronically and intracerebroventricularly the NKCC1 blocker bumetanide to young-adult rats. We analyzed doublecortin density and development parameters (apical dendrite length and angle and dendritic arbor length) in doublecortin positive neurons from different subregions in the DG and evaluated the performance of animals in contextual fear learning and memory. Our results show that in bumetanide-treated subjects, doublecortin density is diminished in the infra and suprapyramidal blades of the DG; the length of primary dendrites is shortened in the infrapyramidal blade and; the growth angle of primary dendrites in the infrapyramidal blade is different from control animals. Behaviorally, treated animals showed the typical learning curve in a contextual fear task, and freezing-time displayed during contextual fear memory was not different from controls. Thus, in vivo icv delivery of bumetanide negatively alters DCX density associated to young neurons and its proper development but not to the extent of affecting a DG dependent task as aversive context learning and memory.
Ende November hat Bundesjustizministerin Christine Lamprecht (SPD) vorgeschlagen, das Grundgesetz zu ändern und darin ausdrücklich Kinderrechte zu verankern. Der Vorschlag befindet sich derzeit in der Ressortabstimmung. Auf dem Verfassungsblog hat sich Friederike Wapler kritisch mit diesem Entwurf auseinandergesetzt und am Ende empfohlen, statt einer schlechten Grundgesetzänderung lieber gar keine zu verabschieden. Ich hingegen halte eine solche Grundgesetzänderung für ebenso sinnvoll wie möglich.
Maintaining biodiversity and ecosystem function is critical on national and global scales. However, while only a fraction of the global biodiversity is known, its current decline is unprecedented, making biodiversity hotspots a conservation priority. The Sierra Gorda Biodiversity Reserve (SGBR) in Central Mexico is known for its rich biodiversity. It is an example of the juxtaposition between species discovery and extinction: aquatic species richness is mostly unknown as no efforts have investigated aquatic communities so far, but are already anthropogenically stressed. We hypothesized that invasive species are already well established in various protected areas and investigated this by assessing the threat of invasive species that are already established within the SGBR on the native biodiversity. By combining field sampling with peer-reviewed literature and local reports, we identify the presence of various non-native species in SGBR. Among these non-native species identified were opportunistic predatory fish and potentially-pathogen transmitting molluscs, but also, a habitat engineer capable of modifying ecosystem functions. Moreover, we highlight that these species were introduced despite legislation and without any knowledge among authorities. As a result, we underline the necessity to describe native species, control invasive and prevent the introduction of further non-native species. If accelerated action is not taken, we risk losing a considerable amount of described and unknown freshwater biota. Keywords: Anthropocene, Biodiversity loss, Freshwater, Invasive species, Mexico, Nature reserve.
Der Zweifel muss schweigen, soll ein richterliches Urteil überzeugen. Gewissheit zu verbreiten, ist das nicht allzu heimliche Ziel der juristischen Ausbildung. Der Charme der Gutachtentechnik, alles Mögliche zu erwägen und zu prüfen, wird in der Referendarausbildung durch die Relationstechnik ersetzt und in der richterlichen Urteilspraxis vollends desavouiert. Gewissheitsdenken und Erledigungsökonomie gehen in Führung. Vieles bleibt "dahingestellt", wenn die Entscheidung einmal feststeht. Und die Gutachten von Rechtsexperten hängen dem Interesse der Auftraggeber häufig einen mehr als fadenscheinigen Mantel um. Ungewissheit, das scheint gewiss, ist Sache der juristischen Zunft nicht. ...
In the present paper, we tested the ability of individuals to judge correctly whether athletes are lying or telling the truth. For this purpose, we first generated 28 videos as stimulus material: in half of the videos, soccer players were telling the truth, while in the other half, the same soccer players were lying. Next, we tested the validity of these video clips by asking N = 65 individuals in a laboratory experiment (Study 1a) and N = 52 individuals in an online experiment (Study 1b) to rate the level of veracity of each video clip. Results suggest that participants can distinguish between true and false statements, but only for some clips and not for others, indicating that some players were better at deceiving than others. In Study 2, participants again had to make veracity estimations, but we manipulated the level of information given, as participants (N = 145) were randomly assigned to one of three conditions (regular video clips, mute video clips, and only the audio stream of each statement). The results revealed that participants from the mute condition were less accurate in their veracity ratings. The theoretical and practical implications of these findings are discussed.
Mechanistic understanding of dynamic membrane proteins such as transporters, receptors, and channels requires accurate depictions of conformational ensembles, and the manner in which they interchange as a function of environmental factors including substrates, lipids, and inhibitors. Spectroscopic techniques such as electron spin resonance (ESR) pulsed electron–electron double resonance (PELDOR), also known as double electron–electron resonance (DEER), provide a complement to atomistic structures obtained from x-ray crystallography or cryo-EM, since spectroscopic data reflect an ensemble and can be measured in more native solvents, unperturbed by a crystal lattice. However, attempts to interpret DEER data are frequently stymied by discrepancies with the structural data, which may arise due to differences in conditions, the dynamics of the protein, or the flexibility of the attached paramagnetic spin labels. Recently, molecular simulation techniques such as EBMetaD have been developed that create a conformational ensemble matching an experimental distance distribution while applying the minimal possible bias. Moreover, it has been proposed that the work required during an EBMetaD simulation to match an experimentally determined distribution could be used as a metric with which to assign conformational states to a given measurement. Here, we demonstrate the application of this concept for a sodium-coupled transport protein, BetP. Because the probe, protein, and lipid bilayer are all represented in atomic detail, the different contributions to the work, such as the extent of protein backbone movements, can be separated. This work therefore illustrates how ranking simulations based on EBMetaD can help to bridge the gap between structural and biophysical data and thereby enhance our understanding of membrane protein conformational mechanisms.
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.
Krisen als Normalität
(2020)
Es gibt in Krisenzeiten wenig Verlässliches. Doch auf eines kann man immer zählen: Irgendwann, und meistens früher als später, fällt der Begriff der Ausnahme oder einer seiner zahlreichen Verwandten. Hierzu gehört vor allem die große Schwester der Ausnahme: der Ausnahmezustand. Da unterscheidet sich die Corona-Krise nicht von der Eurozonenkrise, die Eurozonenkrise nicht von der globalen Finanzkrise und diese nicht von der durch die Terroranschläge vom 11. September ausgelöste Sicherheitskrise. Auch wenn wir über den Corona-Virus selbst nicht viel wissen, scheint vieler Orten Gewissheit darüber zu herrschen, dass wir derzeit im Ausnahmezustand leben. ...