Pseudomonas aeruginosa defense systems against microbicidal oxidants

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139121/1/mmi13768_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139121/2/mmi13768-sup-0004-suppinfo4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139121/3/mmi13768.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139121/4/mmi13768-sup-0001-suppinfo1.pd

MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury

Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death

Do patients with diabetes with new onset acute myocardial infarction present with different symptoms than non-diabetic patients?

Background: The objective of this study was to investigate the differences in presenting symptoms between patients with and without diabetes being diagnosed with an acute myocardial infarction (AMI). Methods: A total of 5,900 patients with a first-time AMI were included into the analysis. All patients aged between 25 and 84 years were recorded by the population-based Myocardial Infarction Registry in Augsburg, Germany, between 2010 and 2017. The presence (yes/no) of 12 AMI typical symptoms during the acute event was assessed within the scope of a face-to-face interview. Multivariable adjusted logistic regression models were calculated to analyze the associations between presenting symptoms and diabetes mellitus in AMI patients. Results: Patients with diabetes had significantly less frequent typical pain symptoms, including typical chest pain. Also, other symptoms like sweating, vomiting/nausea, dizziness/vertigo and fear of death/feeling of annihilation occurred significantly more likely in non-diabetic patients. The only exception was the symptom of shortness of breath, which was found significantly more often in patients with diabetes. In multivariable-adjusted regression models, however, the observed effects were attenuated. In patients younger than 55 years, the associations between diabetes and various symptoms were mainly missing. Conclusions: Type 2 diabetes mellitus is a risk factor not only for the development of AMI, but is also associated with an adverse outcome after AMI. Atypical clinical presentation additionally complicates the diagnostic process. It is therefore essential for physicians to be aware of the more often atypical symptoms that diabetic AMI patients report

¹⁸O analyses of bulk lipids as novel paleoclimate tool in loess research – a pilot study

The analysis of the stable oxygen isotopes 18O and 16O has revolutionized paleoclimate research since the middle of the last century. Particularly, δ18O of ice cores from Greenland and Antarctica is used as a paleotemperature proxy, and δ18O of deep-sea sediments is used as a proxy for global ice volume. Important terrestrial archives to which δ18O as a paleoclimate proxy is successfully applied are speleothems, lake sediments, or tree rings. By contrast, δ18O applications to loess–paleosol sequences (LPSs) are scarce. Here we present a first continuous δ18O record (n=50) for the LPS Crvenka in Serbia, southeastern Europe, spanning the last glacial–interglacial cycle (since 145 ka). From a methodological point of view, we took advantage of a recently proposed paleoclimate/paleohydrological proxy based on bulk δ18O analyses of plant-derived lipids. The Crvenka δ18Obulk lipid values range between −10.2 ‰ and +23.0 ‰ and are systematically more positive in the interglacial and interstadial (paleo-)soils corresponding to marine oxygen-isotope stage (MIS) 1, 3, and 5, compared to the loess layers (MIS 2, 4, and 6). Our Crvenka δ18Obulk lipid record provides no evidence for the occurrence of interstadials and stadials comparable to the Dansgaard–Oeschger events known from the Greenland δ18Oice core records. Concerning the interpretation of our Crvenka δ18Obulk lipid record, plant-derived lipids such as fatty acids and alcohols are certainly strongly influenced by climatic factors such as temperature (via δ18Oprecipitation) and relative air humidity (via 18O enrichment of leaf water due to evapotranspiration). However, pool effects in the form of non-water-correlated lipids such as sterols or the input of root-derived lipids need to be considered, too. Similarly, the input of soil-microbial lipids and oxygen exchange reactions represent uncertainties challenging quantitative paleoclimate/paleohydrological reconstructions based on δ18Obulk lipid analyses from LPSs.Die Analyse der stabilen Sauerstoffisotope 18O und 16O hat die Paläoklimaforschung seit Mitte des letzten Jahrhunderts revolutioniert. Insbesondere wird δ18O von Eisbohrkernen aus Grönland und der Antarktis als Paläo-Temperaturproxy sowie δ18O von Tiefseesedimenten als Proxy für das globale Eisvolumen verwendet. Wenngleich sich in terrestrischen Archiven, wie Speläothemen, Seesedimenten oder Baumringen, paläoklimatische Rekonstruktionen unter der Anwendung von δ18O als Proxy bewährt haben, wurden solche Analysen bislang in Löß-Paläobodensequenzen (LPS) selten durchgeführt. In dieser Studie präsentieren wir einen ersten kontinuierlichen δ18O Datensatz (n=50) für die LPS Crvenka in Serbien, der den letzten Glazial-Interglazial-Zyklus (∼ 145 ka) abdeckt. Die δ18O-Werte basieren auf der Analyse von pflanzlichen Lipiden, deren Anwendung als paläoklimatischer/hydrologischer Proxy vor Kurzem vorgeschlagen wurde. Die δ18Obulk−lipid-Werte von Crvenka liegen zwischen −10.2 ‰ und +23.0 ‰ und sind in den interglazialen und interstadialen (Paläo-)Böden, die den marinen Sauerstoff-Isotopenstufen (MIS) 1, 3 und 5 entsprechen, systematisch positiver als in den Lößlagen (MIS 2, 4 und 6). Sie liefern keine Hinweise für das Auftreten von Interstadialen und Stadialen, die mit den aus den grönländischen δ18Oice−core bekannten Dansgaard-Oeschger-Ereignissen vergleichbar wären. In Bezug auf die Interpretation der δ18Obulk−lipid-Werte gilt es zu berücksichtigen, dass die Isotopie pflanzlicher Lipide, wie z.B. von Fettsäuren und Alkoholen, stark durch die Klimafaktoren Temperatur (über δ18O-Niederschlag) und relativer Luftfeuchtigkeit (über die 18O-Anreicherung des Blattwassers aufgrund von Evapotranspiration) beeinflusst werden. Weiter zu beachtende Faktoren stellen Einträge von Sterolen sowie von generell wurzel-bürtigen Lipiden dar (Pool-Effekte). In ähnlicher Weise bergen der Einfluss von bodenmikrobiellen Lipiden und Sauerstoffaustauschreaktionen Unsicherheiten, die quantitative paläoklimatische/hydrologische Rekonstruktionen auf der Grundlage von δ18Obulk−lipid-Analysen aus LPS erschweren können

Perspektivwechsel: Migrationsberichterstattung in ausgewählten afrikanischen Ländern und Deutschland aus Migrant*innensicht

Spätestens seit dem Jahr 2015 sind Migration und Zuwanderung fester Gegenstand politischer Debatten in Deutschland. Verschiedene kommunikationswissenschaftliche Studien widmen sich daher der medialen Berichterstattung zu diesen Themen und untersuchen, wie diese auf die Wahrnehmung von Migranten innerhalb der deutschen Bevölkerung wirkt (z.B. Arlt & Wolling, 2017). In Abgrenzung dazu widmet sich die hier vorliegende Studie der Frage, wie Migranten selbst die Migrationsberichterstattung rezipieren, wie sie diese wahrnehmen und wie diese persönliche Migrations- und Integrationshandlungen prägt. Dazu wurden zwei Fokusgruppendiskussionen mit Migranten aus Subsahara-Afrika geführt. Diskutiert wurden sowohl die Rezeption und Bewertung der Migrationsberichterstattung im Herkunftsland als auch in Deutschland. Die Ergebnisse zeigen, dass das Thema Migration kaum Gegenstand der in den Herkunftsländern rezipierten Berichterstattung war, weshalb persönliche Migrationsentscheidungen vor allem durch interpersonale Kommunikation beeinflusst wurden. Die Migrationsberichterstattung in Deutschland nahmen die afrikanischen Teilnehmer als zu einseitig und zu reduziert auf die Subthemen Armut und Krieg wahr.Since 2015, migration and immigration have been relevant topics of political debate in Germany. Therefore, various communication studies researched the media reporting on these issues and examined how it affects the perception of migrants within the German population (e.g. Arlt & Wolling, 2017). In distinction to this, the present study addresses the question of how migrants themselves receive migration reporting, how they perceive it, and how it shapes their personal migration and integration actions. We conducted two focus group discussions with migrants from Sub-Saharan Africa. The participants discussed both the reception and evaluation of migration reporting in their country of origin and in Germany. The results show that the topic of migration was hardly reported in the countries of origin, which is why personal migration decisions were more influenced by interpersonal communication. In Germany, the African participants perceive media reports about migration issues as too one-sided and as reduced to the sub-themes of poverty and war

A new endstation for extreme-ultraviolet spectroscopy of free clusters and nanodroplets

We present a new endstation for the AMOLine of the ASTRID2 synchrotron at Aarhus University, which combines a cluster and nanodroplet beam source with a velocity map imaging and time-of-flight spectrometer for coincidence imaging spectroscopy. Extreme-ultraviolet spectroscopy of free nanoparticles is a powerful tool for studying the photophysics and photochemistry of resonantly excited or ionized nanometer-sized condensed-phase systems. Here we demonstrate this capability by performing photoelectron-photoion coincidence (PEPICO) experiments with pure and doped superfluid helium nanodroplets. Different doping options and beam sources provide a versatile platform to generate various van der Waals clusters as well as He nanodroplets. We present a detailed characterization of the new setup and present examples of its use for measuring high-resolution yield spectra of charged particles, time-of-flight ion mass spectra, anion-cation coincidence spectra, multi-coincidence electron spectra and angular distributions. A particular focus of the research with this new endstation is on intermolecular charge and energy-transfer processes in heterogeneous nanosystems induced by valence-shell excitation and ionization.Comment: 28 pages, 17 figures, submitted to Review of Scientific Instrument

ACL reconstruction with physiological graft tension by intraoperative adjustment of the anteroposterior translation to the uninjured contralateral knee

Purpose: Fixation of anterior cruciate ligament (ACL) substitutes with non-physiological anteroposterior translation (APT) worsens outcome. The aim was to present a technique for physiological APT adjustment of the transplant in ACL reconstruction and its outcome at midterm. Methods: In a consecutive series of 28 patients (age 32±11years, 24 male), chronic ACL deficiency was treated by bone-patella-tendon-bone reconstruction. Transplant APT was adjusted to that of the contralateral uninjured ACL, measured 3, 6, and 12months postoperatively using the Rolimeter®. At a median follow-up of 5.3years (3-8years), 82% of the patients were re-evaluated with APT measurement and using IKDC-, Tegner-, Lysholm-Scores, conventional radiographs and MRI. Results: No differences in APT (mean±SD) between uninjured and reconstructed knees were observed after adjustment (6±1 versus 6±1mm, n.s.). Three months postoperatively, a statistically significant increase in APT (7±1mm) and a further increase at midterm (9±2mm) were observed. Patients scored "normal” or "nearly normal”, respectively, in 79% (IKDC) and 4 (3-9) points (Tegner; median, range) or 89±9 points (Lysholm; mean±SD). Radiological evaluation showed no, minimal or moderate joint degeneration in 5, 20 and 75% of patients, respectively. MRI confirmed intact ACL transplants in all patients. Conclusion: ACL reconstruction using the presented technique was considered successful, as patients did not suffer from subjective instability, radiographic analysis did not provide evidence for graft rupture at midterm. However, APT increase and occurrence of degenerative changes in reconstructed knees at the midterm might not be prevented even by restoration of a physiological APT in ACL reconstruction. The Rolimeter can be used for quick and easy intraoperative indirect control of the applied tension to the ACL transplant by measuring the APT to obtain physiological tensioning resulting in a satisfying outcome at midterm. Level of evidence: IV

Are psychotic-like experiences associated with aberrant prosocial decision-making behavior?

IntroductionDeficits in social functioning and decision-making are well-documented in schizophrenia, but their relationship with positive symptoms and social conflicts is poorly understood. We created a new paradigm based on the Dictator Game (DG) to explore differences in social decision-making between individuals experiencing high levels of psychotic-like experiences (PLEs), particularly hallucinations and delusions, and controls with less PLEs.MethodsA large community sample (N = 1,161) completed a DG in an online study whereby extreme groups were built based on the positive subscale of the CAPE.ResultsOverall, participants experiencing PLEs did not act less prosocial than controls but showed a somewhat aberrant decision-making behavior, particularly a pattern of behaving more prosocial in fair situations and generally favoring punishment over compensation relative to controls. Mediation analyses suggest that measures of empathy and Machiavellism have predictive power for prosocial behavior beyond group status.DiscussionThe present study raises the possibility that individuals with high levels of PLEs may be less able to adapt their behavior to the situation at hand than controls. These irregularities might be due to deficits in social cognition which may elicit conflict, thus compromising social functioning and possibly contributing to the formation of positive symptoms