The EU in Times of COVID-19: Together into a Future Based on (More) Solidarity?

The outbreak of the COVID-19-pandemic in spring 2020 put solidarity within the European Union to the test and called for far-reaching responses by all member states to mitigate the pandemic’s effects. But how does this crisis affect public support for transnational solidarity in the European Union? Are EU citizens willing to collectively overcome a financial crisis caused by the COVID-19-pandemic? And what is the public opinion on the establishment of a fictional EU-wide fund to mitigate future crises? Those questions have been addressed by a multi-country survey run by the ‘Solikris’-project. A resulting analysis in the project’s Policy Brief #5 shows that particularly the macroeconomic differences between countries correlate with attitudes towards solidarity policies and that transnational solidarity is higher in situations of acute crisis.Der Ausbruch der COVID-19-Pandemie im Frühjahr 2020 stellte die Solidarität innerhalb der Europäischen Union auf die Probe und erforderte weitreichende Reaktionen aller Mitgliedsstaaten, um die Auswirkungen der Pandemie zu mildern. Doch wie wirkt sich diese Krise auf die öffentliche Unterstützung für transnationale Solidarität in der Europäischen Union aus? Sind die EU-Bürger*innen bereit, eine durch die COVID-19-Pandemie verursachte Finanzkrise kollektiv zu bewältigen? Und wie ist die öffentliche Meinung zur Einrichtung eines fiktiven EU-weiten Fonds zur Abfederung zukünftiger Krisen? Diese Fragen wurden in einer länderübergreifenden Umfrage des ‘Solikris’-Projekts untersucht. Eine daraus resultierende Analyse im Policy Brief #5 des Projekts zeigt, dass insbesondere die makroökonomischen Unterschiede zwischen den Ländern mit den Einstellungen zur Solidaritätspolitik korrelieren und dass die transnationale Solidarität in akuten Krisensituationen höher is

Die EU in Zeiten von COVID-19: Gemeinsam in eine solidarische(re) Zukunft?

Die Covid-19-Pandemie stellt die europäische Gemeinschaft vor neue Herausforderungen. Sind EU-Bürger:innen gewillt eine durch COVID-19 entstandene Finanzkrise gemeinsam zu bewältigen und wie gestaltet sich das öffentliche Meinungsbild zur Einrichtung eines fiktiven EU-weiten Fonds für die Bekämpfung von zukünftigen Krisen? Die Ergebnisse einer Mehrländer-Befragung zeigen, dass die makroökonomischen Unterschiede der Länder die dominierende Konfliktdimension darstellen

Temperature compensation of NdFeB permanent magnets

Permanent magnet blocks of NdFeB have a relatively high maximum energy product. Because of its relatively low Curie temperature, however, NdFeB has a large temperature coefficient for its residual induction. The temperature coefficients of the relative magnetic fields ({Delta}B/B)/{Delta}T in the air gap of NdFeB dipole magnets were reduced from {minus}1.1 {times} 10{sup {minus}3}/c to less than 2 {times} 10{sup {minus}5}/{degree}C under operating temperatures of {+-} 6 C. This was achieved passively by using 1.25-mm-thick strips of 30%-Ni-Fe alloy as flux shunts for the NdFeB blocks. The magnets with soft-steel poles and flux-return yokes were assembled and measured in a temperature-controlled environment

Investigation of open-loop beam motion at low frequencies at the APS

Sources of transverse beam motion in the APS storage ring have been investigated for ground-motion- and water-system-induced vibrations of the magnet and vacuum systems, and for power supply ripple. The displacement of magnets in a bandwidth of 4-30 Hz have been reduced significantly by inserting viscoelastic damping pads between the girder supports and pedestals, and by welding the magnet cooling headers to the ceiling of the storage ring tunnel. Current ripple on magnet power supplies was identified as a source of horizontal beam motion. Beam motion was measured without the closed-orbit feedback system activated. At {beta}{sub x} = 15.4 m and {beta}{sub y} = 10.4 m the rms beam motion in the 0.02-30 Hz band was 22.7 {mu}m and 6.3 {mu}m in the horizontal and verticle planes, respectively. A few narrow-band structures of the horizontal beam motion spectrum in the 1-4 Hz band have to be investigated further to identify the sources

Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer

Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin. Tested on over 7,000 DNA methylation data sets from several cancer types, it reaches an AUC of 0.92. Although higher levels of DNA methylation are often associated with transcriptional silencing, counter-intuitive positive statistical dependencies between DNA methylation and expression levels have been recently reported for two cancer types. Here, we re-analyze combined expression and DNA methylation data sets, comprising over 5,000 samples, and demonstrate that the conjunction of hypermethylation of bivalent chromatin and up-regulation of the corresponding genes is a general phenomenon in cancer. This up-regulation affects many developmental genes and transcription factors, including dozens of homeobox genes and other genes implicated in cancer. Thus, we reason that the disturbance of bivalent chromatin may be intimately linked to tumorigenesis

The initial step of DNA hairpin folding: a kinetic analysis using fluorescence correlation spectroscopy

Conformational fluctuations of single-stranded DNA (ssDNA) oligonucleotides were studied in aqueous solution by monitoring contact-induced fluorescence quenching of the oxazine fluorophore MR121 by intrinsic guanosine residues (dG). We applied fluorescence correlation spectroscopy as well as steady-state and time-resolved fluorescence spectroscopy to analyze kinetics of DNA hairpin folding. We first characterized the reporter system by investigating bimolecular quenching interactions between MR121 and guanosine monophosphate in aqueous solution estimating rate constants, efficiency and stability for formation of quenched complexes. We then studied the kinetics of complex formation between MR121 and dG residues site-specifically incorporated in DNA hairpins. To uncover the initial steps of DNA hairpin folding we investigated complex formation in ssDNA carrying one or two complementary base pairs (dC–dG pairs) that could hybridize to form a short stem. Our data show that incorporation of a single dC–dG pair leads to non-exponential decays for opening and closing kinetics and reduces rate constants by one to two orders of magnitude. We found positive activation enthalpies independent of the number of dC–dG pairs. These results imply that the rate limiting step of DNA hairpin folding is not determined by loop dynamics, or by mismatches in the stem, but rather by interactions between stem and loop nucleotides

Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.Additional co-authors: Andreas J. Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H. Sahyoun, Sita J. Saunders, Stefan E. Seemann, Andrea Tanzer, Bertram Vogel, Michael T. Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F. Stadler, Stephan Becker, and Manja Marz

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient β-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events

Characterization of the 6-methyl isoxanthopterin (6-MI) base analog dimer, a spectroscopic probe for monitoring guanine base conformations at specific sites in nucleic acids

We here characterize local conformations of site-specifically placed pairs of guanine (G) residues in RNA and DNA, using 6-methyl isoxanthopterin (6-MI) as a conformational probe. 6-MI is a base analog of G and spectroscopic signals obtained from pairs of adjacent 6-MI residues reflect base–base interactions that are sensitive to the sequence context, local DNA conformation and solvent environment of the probe bases. CD signals show strong exciton coupling between stacked 6-MI bases in double-stranded (ds) DNA; this coupling is reduced in single-stranded (ss) DNA sequences. Solvent interactions reduce the fluorescence of the dimer probe more efficiently in ssDNA than dsDNA, while self-quenching between 6-MI bases is enhanced in dsDNA. 6-MI dimer probes closely resemble adjacent GG residues, in that these probes have minimal effects on the stability of dsDNA and on interactions with solvent additive betaine. They also serve as effective template bases, although further polymerase-dependent extension of DNA primers past 6-MI template bases is significantly inhibited. These probes are also used to monitor DNA ‘breathing’ at model replication forks. The 6-MI dimer probe can serve in many contexts as a useful tool to investigate GG conformations at specific sites within the nucleic acid frameworks of functioning macromolecular machines in solution

Revealing a brain network endophenotype in families with idiopathic generalised epilepsy

Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy