Abstract Escherichia coli ( E. coli ) exhibits considerable physiological and metabolic versatility and includes a variety of non-pathogenic, commensal variants, which belong to the normal gut flora ...of humans and warm-blooded animals. Additionally, several pathogenic variants have been identified which cause various types of intestinal or extraintestinal infections in humans and animals. In contrast to intestinal pathogenic E. coli (IPEC), which are obligate pathogens, extraintestinal pathogenic E. coli (ExPEC) are facultative pathogens which belong to the normal gut flora of a certain fraction of the healthy population where they live as commensals. Comparative genomics and epidemiological studies have been applied to study genomic diversity, markers, and phenotypic traits that may support discrimination of different E. coli pathotypes. Whereas IPEC are often epidemiologically and phylogenetically distinct from ExPEC and non-pathogenic, commensal strains, many ExPEC and non-pathogenic E. coli share large genomic fractions. Furthermore, extraintestinal infections of elderly or immunocompromised patients can be caused by E. coli variants which differ in their geno- and phenotypes from archetypal ExPEC. Thus, strain typing based on the detection of a limited number of ExPEC virulence/fitness-related genes may be ambiguous. A limited number of ExPEC-dominated clonal complexes can be identified in the E. coli population by multi locus sequence typing. Nevertheless, ExPEC and non-pathogenic E. coli cannot be clearly discriminated by molecular epidemiological approaches. Increased knowledge of the phylogeny, virulence and fitness traits, and host factors contributing to host susceptibility of the different groups of ExPEC variants is required for a better understanding of the biological basis of ExPEC infections.
We study the spatiotemporal patterns that emerge when an active nematic film is topologically constraint. These topological constraints allow to control the non-equilibrium dynamics of the active ...system. We consider ellipsoidal shapes for which the resulting defects are 1/2 disclinations and analyze the relation between their location and dynamics and local geometric properties of the ellipsoid. We highlight two dynamic modes: a tunable periodic state that oscillates between two defect configurations on a spherical shape and a tunable rotating state for oblate spheroids. We further demonstrate the relation between defects and high Gaussian curvature and umbilical points and point out limits for a coarse-grained description of defects as self-propelled particles.
Isolation of two-coordinate compounds of heavier Group 15 elements in low oxidation state is challenging due to the preferential formation of dimers or oligomers. Herein, we report the first examples ...of donor-stabilized two-coordinate Sb(I) and Bi(I) ions. The reduction of antimony and bismuth trihalides with KC8 in the presence of cyclic alkyl(amino) carbene (cAAC) afforded Sb(I) and Bi(I) cations in the form of triflate salts (cAAC)2SbOTf (1) and (cAAC)2BiOTf (2). Compounds 1 and 2 belong to a new class of acyclic cations of Group 15 with eight valence electrons and are heavier valence isoelectronic analogues of carbones. Both compounds are isolated and well-characterized by NMR spectroscopy, cyclic voltammetry, single-crystal X-ray diffraction, and computational studies.
Terahertz (THz) radiation produced by the filamentation of two-color pulses over long distances in argon is numerically investigated using a comprehensive model in full space-time-resolved geometry. ...We show that the dominant physical mechanism for THz generation in the filamentation regime at clamping intensity is based on quasi-dc plasma currents. The calculated THz spectra for different pump pulse energies and pulse durations are in agreement with previously reported experimental observations. For the same pulse parameters, near-infrared pump pulses at 2 μm are shown to generate a more than 1 order of magnitude greater THz yield than pumps centered at 800 nm.
Steroid receptor drugs have been available for more than half a century, but details of the ligand binding mechanism have remained elusive. We solved X-ray structures of the glucocorticoid and ...mineralocorticoid receptors to identify a conserved plasticity at the helix 6–7 region that extends the ligand binding pocket toward the receptor surface. Since none of the endogenous ligands exploit this region, we hypothesized that it constitutes an integral part of the binding event. Extensive all-atom unbiased ligand exit and entrance simulations corroborate a ligand binding pathway that gives the observed structural plasticity a key functional role. Kinetic measurements reveal that the receptor residence time correlates with structural rearrangements observed in both structures and simulations. Ultimately, our findings reveal why nature has conserved the capacity to open up this region, and highlight how differences in the details of the ligand entry process result in differential evolutionary constraints across the steroid receptors.
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•X-Ray structures of MR and GR reveal a conserved plasticity near helices 6 and 7•Ligand binding simulations provide a functional role to the observed plasticity•Residence time measurements correlate with the proposed binding mechanism•Differences in receptor blueprints promote differential evolutionary constraints
Edman et al. combined X-ray crystallography, computational simulations, and residence time measurements to uncover the ligand entry and exit processes of steroid hormone receptors. Subsequent bioinformatics analyses confirmed that differences in the details of the ligand entry mechanism lead to differential selection pressure across the receptor family.
No history without media and no media without history. This book explores the question, how media studies shape the relations between media and history in their historiography. On the basis of two ...case studies, Dolf Sternberger's Panorama of the 19th Century and Friedrich Kittler's Discourse Networks 1800/1900, differing methods and procedures by which media history can be written are exemplified. Ohne Medien keine Geschichte und kein Medium ohne Geschichte. Das Buch geht der Frage nach, wie die komplexen Verhältnisse zwischen Medien und Geschichte in medienwissenschaftlichen Historiographien ausgestaltet werden. Mediale Historiographien reflektieren, dass Medien nicht nur historische Gegenstände, sondern auch gegenwärtige Bedingungen von Geschichtsschreibung sind. Christian Köhler untersucht, wie zwei Autoren in ihren Werken Mediengeschichte schreiben. Dolf Sternbergers Panorama oder Ansichten vom 19. Jahrhundert (1938) und Friedrich Kittlers Aufschreibesysteme 1800/1900 (1985) setzen Verfahren medialer Historiographie um, die Medien und Geschichte auf unterschiedliche Art und Weise in Beziehung zueinander setzen. Die Untersuchung dieser Beziehungen und ihrer Implikationen zeigt, wie wichtig es ist, die Methodenreflexion der Mediengeschichtsschreibung voranzutreiben.
Synthetic glucocorticoids (GC) are essential for the treatment of a broad range of inflammatory diseases. However, their use is limited by target related adverse effects on, e.g., glucose homeostasis ...and bone metabolism. Starting from a nonsteroidal GR ligand (4) that is a full agonist in reporter gene assays, we exploited key functional triggers within the receptor, generating a range of structurally diverse partial agonists. Of these, only a narrow subset exhibited full anti-inflammatory efficacy and a significantly reduced impact on adverse effect markers in human cell assays compared to prednisolone. This led to the discovery of AZD9567 (15) with excellent in vivo efficacy when dosed orally in a rat model of joint inflammation. Compound 15 is currently being evaluated in clinical trials comparing the efficacy and side effect markers with those of prednisolone.
We demonstrate the application of cyclic electrodeposition of PtCu alloy to fabricate porous platinum electrodes for implantable glucose fuel cells. Depending on the number of deposition cycles, ...electrodes with controllable specific surface area can be fabricated, their roughness factors ranging from 20 (slightly roughened) to 3100 (highly porous). Adjusting the specific surface area of the electrode from low to high determines whether it functions as cathode or anode, respectively. Compared to state of the art, this process is beneficial due to shorter fabrication times, lower temperatures, and the requirement of only one process for the fabrication of both electrodes. Correspondingly fabricated glucose fuel cells showed a power density of 5.1 μW cm–2 under close to physiological conditions, which is an improvement by 16% compared to earlier designs. During continuous operation over 90 days the fuel cell showed a mean continuous decay of about 0.8% per day, which is related to catalyst poisoning at the anode. Future work will thus have to focus on the improvement of long-term stability instead of power density.
Covid-19 is associated with a high risk of venous thromboembolism. In addition, cases of arterial thromboembolism were also reported. We investigated the effect of antiplatelet therapy on the disease ...course.
We evaluated a cohort of inpatients with Covid-19 (n = 152). We recorded the patient’s demographic data, their comorbidities, medication use including the use of antiplatelets and anticoagulants, laboratory findings and data about mechanical ventilation. We then separated the patient’s outcomes into either being „bad” (dead or referral to higher level of care) or „good” (discharged). Then we evaluated the factors that contributed to the patient needing ventilatory support and to showing typical radiological findings.
In our cohort, 21 patients received ventilatory support whereas 131 did not require the use of ventilators. 127 patients had good outcomes and 25 had bad outcomes. By using multivariate analysis, we found that the need for ventilatory support was the strongest predictor of a bad outcome. All patients who were on ventilators displayed typical radiological findings. The factors predicting the need for ventilatory support were LDH and CRP levels, the presence of cardiac conduction abnormalities as well as chronic lung conditions. Cardiac conduction abnormalities, LDH and CRP levels, and the use of antiplatelets, were factors that predicted typical radiological findings.
There was a higher incidence of typical radiological findings in patients on antiplatelet medication. However, it did not translate into changes in the ventilation requirement or in the outcome. The need for mechanical ventilation was the strongest predictor of a bad outcome.
•Covid-19 can be accompanied by arterial and/or venous thromboembolism.•Platelets play a role in arterial thrombosis and inflammation.•The use of antiplatelet therapy had no beneficial effect in Covid-19 patients.•The need for ventilatory support was the main predictor of disease outcome.
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