RNA chaperone activity and RNA-binding properties of the E. coli protein StpA

The E. coli protein StpA has RNA annealing and strand displacement activities and it promotes folding of RNAs by loosening their structures. To understand the mode of action of StpA, we analysed the relationship of its RNA chaperone activity to its RNA-binding properties. For acceleration of annealing of two short RNAs, StpA binds both molecules simultaneously, showing that annealing is promoted by crowding. StpA binds weakly to RNA with a preference for unstructured molecules. Binding of StpA to RNA is strongly dependent on the ionic strength, suggesting that the interactions are mainly electrostatic. A mutant variant of the protein, with a glycine to valine change in the nucleic-acid-binding domain, displays weaker RNA binding but higher RNA chaperone activity. This suggests that the RNA chaperone activity of StpA results from weak and transient interactions rather than from tight binding to RNA. We further discuss the role that structural disorder in proteins may play in chaperoning RNA folding, using bioinformatic sequence analysis tools, and provide evidence for the importance of conformational disorder and local structural preformation of chaperone nucleic-acid-binding sites

Rechtspopulismus und organisierte Zivilgesellschaft

Rechtspopulist*innen intervenieren in die Zivilgesellschaft, wobei sie die etablierten Akteure auf der Basis ihrer korporatistischen Einbindung als Teil des Establishments angreifen und bestehende Konflikte nach populistischer Logik umdeuten. Die Reaktionen der zivilgesellschaftlichen Organisationen erfolgen situativ und changieren zwischen wertebezogener Abgrenzung und inhaltlicher Auseinandersetzung. Die Zivilgesellschaft ist herausgefordert, ihre inneren Widersprüche zu bearbeiten, um nicht als Einfallstor für, sondern als Schutzfaktor gegen Rechtspopulismus zu wirken

Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: A post hoc subgroup analysis of a randomized trial

Background: Spontaneous breathing is desirable in most ventilated patients. We therefore studied the influence of isoflurane versus propofol sedation on early spon taneous breathing in ventilated surgical intensive care patients and evaluated poten tial mediation by opioids and arterial carbon dioxide during the first 20 h of study sedation. Methods: We included a single-center subgroup of 66 patients, who participated in a large multi-center trial assessing efficacy and safety of isoflurane sedation, with 33 patients each randomized to isoflurane or propofol sedation. Both sedatives were titrated to a sedation depth of −4 to −1 on the Richmond Agitation Sedation Scale. The primary outcome was the fraction of time during which patients breathed spontaneously. Results: Baseline characteristics of isoflurane and propofol-sedated patients were well balanced. There were no substantive differences in management or treatment aside from sedation, and isoflurane and propofol provided nearly identical sedation depths. The mean fraction of time spent spontaneously breathing was 82% [95% CI: 69, 90] in patients sedated with isoflurane compared to 35% [95% CI: 22, 51] in those assigned to propofol: median difference: 61% [95% CI: 14, 89], p < .001. After ad justments for sufentanil dose and arterial carbon dioxide partial pressure, patients sedated with isoflurane were twice as likely to breathe spontaneously than those se dated with propofol: adjusted risk ratio: 2.2 [95%CI: 1.4, 3.3], p < .001. Conclusions: Isoflurane compared to propofol sedation promotes early spontaneous breathing in deeply sedated ventilated intensive care patients. The benefit appears to be a direct effect isoflurane rather than being mediated by opioids or arterial carbon dioxide

Successful treatment of metastatic uveal melanoma with ipilimumab and nivolumab after severe progression under tebentafusp: a case report

Metastatic uveal melanoma (UM) is a rare form of melanoma differing from cutaneous melanoma by etiology, prognosis, driver mutations, pattern of metastases and poor response rate to immune checkpoint inhibitors (ICI). Recently, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, tebentafusp, has been approved for the treatment of HLA-A*02:01 metastatic or unresectable UM. While the treatment regime is complex with weekly administrations and close monitoring, the response rate is limited. Only a few data exist on combined ICI in UM after previous progression on tebentafusp. In this case report, we present a patient with metastatic UM who first suffered extensive progression under treatment with tebentafusp but in the following had an excellent response to combined ICI. We discuss possible interactions that could explain responsiveness to ICI after pretreatment with tebentafusp in advanced UM

Plattformökonomie und Crowdworking: eine Analyse der Strategien und Positionen zentraler Akteure

In dieser Kurzexpertise werden die Positionen erhoben, systematisiert und analysiert, die maßgebliche Akteure auf nationaler, europäischer und internationaler Ebene zum Phänomen der Plattformökonomie artikulieren. Der Fokus liegt auf dem Bereich Crowdworking beziehungsweise Cloud- und Gigworking als plattformvermittelter Arbeit. Dabei werden sowohl die grundlegenden Einschätzungen über die aktuelle Bedeutung und zukünftige Entwicklung des Phänomens, als auch die konkreten Bewertungen der Akteure dargestellt. Der Schwerpunkt der Expertise liegt auf den von den Akteuren formulierten Regulierungsperspektiven. Die von den Akteuren favorisierten Regulierungsvorschläge und -forderungen werden systematisiert und den drei zentralen Diskursen - dem Transformations-, dem Wachstums- sowie dem Sicherheits- und Beteiligungsdiskurs - zugeordnet

Dynamics of pulmonary hypertension severity in the first 48 h in neonates with prenatally diagnosed congenital diaphragmatic hernia

IntroductionPulmonary hypertension (PH) is one of the major contributing factors to the high morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). The severity and duration of postnatal PH are an established risk factor for patient outcome; however, the early postnatal dynamics of PH have not been investigated. This study aims to describe the early course of PH in CDH infants, and its relation to established prognostic markers and outcome measures.MethodsWe performed a monocentric retrospective review of neonates with prenatally diagnosed CDH, who received three standardized echocardiographic examinations at 2–6 h, 24, and 48 h of life. The degree of PH was graded as one of three categories: mild/no, moderate, or severe PH. The characteristics of the three groups and their course of PH over 48 h were compared using univariate and correlational analyses.ResultsOf 165 eligible CDH cases, initial PH classification was mild/no in 28%, moderate in 35%, and severe PH in 37%. The course of PH varied markedly based on the initial staging. No patient with initial no/mild PH developed severe PH, required extracorporeal membrane oxygenation (ECMO)-therapy, or died. Of cases with initial severe PH, 63% had persistent PH at 48 h, 69% required ECMO, and 54% died. Risk factors for any PH included younger gestational age, intrathoracic liver herniation, prenatal fetoscopic endoluminal tracheal occlusion (FETO)-intervention, lower lung to head ratio (LHR), and total fetal lung volume (TFLV). Patients with moderate and severe PH showed similar characteristics, except liver position at 24- (p = 0.042) and 48 h (p = 0.001), mortality (p = 0.001), and ECMO-rate (p = 0.035).DiscussionTo our knowledge, this is the first study to systematically assess the dynamics of PH in the first postnatal 48 h at three defined time points. CDH infants with initial moderate and severe PH have a high variation in postnatal PH severity over the first 48 h of life. Patients with mild/no PH have less change in PH severity, and an excellent prognosis. Patients with severe PH at any point have a significantly higher risk for ECMO and mortality. Assessing PH within 2–6 h should be a primary goal in the care for CDH neonates

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location

Aims Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. Methods and results A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. Conclusion Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severit