Effect of daptomycin and vancomycin on Staphylococcus epidermidis biofilms: An in vitro assessment using fluorescence in situ hybridization

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells

Student Perceptions of Learner-Centered Teaching

The learner-centered paradigm departs from traditional teaching models by focusing on students more than teachers and learning more than teaching. Thus, classes are more egalitarian; they emphasize critical thinking, active learning, and real-world assignments. Graduate students in learner-centered classrooms were surveyed about perceptions of their experiences in relation to the key dimensions of the learner-centered paradigm and noted that the approach contributed to their feeling respected as learners, developed their critical thinking skills, and encouraged their self-directedness. Based on these findings, post-secondary instructors are encouraged to experiment with learning-centered approaches to further explore this promising model

Doing transnational family im Kontext von Flucht und Krisenmigration: Stand der Forschung

In den vergangenen Jahren ist die Zahl gewaltsam Vertriebener stetig gestiegen, und auch die Anzahl der Menschen, die in weiter entfernte Staaten fliehen, hat laut UNHCR weltweit stark zugenommen. In Deutschland wurden im Zeitraum von 2015 bis 2017 fast 1,4 Mio. Asylerstanträge gestellt, hauptsächlich von Menschen aus Syrien, Afghanistan, Irak sowie Eritrea. Aufgrund der Aktualität des Themas hat sich seit Kurzem eine eigen-ständige Forschung zu Flucht und Geflüchteten in Deutschland entwickelt, wobei sich die deutsche Forschungslandschaft über die Disziplinen hinweg vor allem auf die Themen Aufnahme und Teilhabe von Geflüchteten in Deutschland konzentriert. Bisher gibt es nur sehr wenige Arbeiten, die sich mit Familien von Geflüchteten auseinandersetzen, obwohl unbestritten ist, dass Familien sowohl für die Migrationsentscheidung als auch für die Integration und Teilhabe im Zielland eine wichtige Rolle spielen. In Vorbereitung auf eine eigene empirische Studie, die diese Forschungslücke schließen möchte, wurde das vorliegende Working Paper erstellt. Es fasst die internationale Literatur zu den Fragen nach der Entstehung, Beibehaltung und Veränderung von transnationalen Familien, den transnationalen Alltagspraktiken sowie Unterstützungsleistungen und den Konsequenzen von Transnationalität auf die Beziehungsstabilität und -qualität zwischen Partnern, Kindern und Eltern sowie deren (subjektivem) Wohlbefinden, Einstellungen und Geschlechterrollen zusammen. Das Working Paper versucht darüber hinaus, die Anschlussfähigkeit der vorliegenden Studien zu transnationalen Familien auf den Fluchtkontext herzustellen und Forschungslücken im Themenfeld transnationaler Familien und Fluchtmigration aufzuzeigen

Characterization of a small tRNA-binding protein that interacts with the archaeal proteasome complex

Authors acknowledge financial support from the French Agence Nationale de la Recherche (grant [ANR-18-CE11-0018-01] to B.F. and [ANR-16-CE12-0016-01] to B.C.O). This work used the platforms of the Grenoble Instruct-ERIC Centre (ISBG: UMS3518 CNRS-CEA-UGA-EMBL) with support from FRISBI (ANR-10-INBS-05-02) and GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003) within the Grenoble Partnership for Structural Biology. The IBS Electron Microscope facility is supported by the Auvergne Rhône-Alpes Region, the Fonds Feder, the Fondation pour la Recherche Médicale and GIS-IBiSA.The proteasome system allows the elimination of functional or structurally impaired proteins. This includes the degradation of nascent peptides. In Archaea, how the proteasome complex interacts with the translational machinery remains to be described. Here, we characterised a small orphan protein, Q9UZY3 (Uniprot ID) conserved in Thermococcales. The protein was identified in native pull-down experiments using the proteasome regulatory complex (PAN) as bait. X-ray crystallography and SAXS experiments revealed that the protein is monomeric and adopts a β-barrel core structure with an Oligonucleotide/oligosaccharide-Binding (OB) fold, typically found in translation elongation factors. Mobility shift experiment showed that Q9UZY3 displays tRNA binding properties. Pull-downs, co-immunoprecipitation and ITC studies revealed that Q9UZY3 interacts in vitro with PAN. Native pull-downs and proteomic analysis using different versions of Q9UZY3 showed that the protein interacts with the assembled PAN-20S proteasome machinery in Pyrococcus abyssi cellular extracts. The protein was therefore named Pbp11, for Proteasome Binding Protein of 11 kDa. Interestingly, the interaction network of Pbp11 also includes ribosomal proteins, tRNA processing enzymes and exosome subunits dependent on Pbp11's N-terminal domain that was found to be essential for tRNA binding. Together these data suggest that Pbp11 participates in an interface between the proteasome and the translational machinery.Publisher PDFPeer reviewe

Evolution of white matter damage in amyotrophic lateral sclerosis

Objective To characterize disease evolution in amyotrophic lateral sclerosis using an event‐based model designed to extract temporal information from cross‐sectional data. Conventional methods for understanding mechanisms of rapidly progressive neurodegenerative disorders are limited by the subjectivity inherent in the selection of a limited range of measurements, and the need to acquire longitudinal data. Methods The event‐based model characterizes a disease as a series of events, each comprising a significant change in subject state. The model was applied to data from 154 patients and 128 healthy controls selected from five independent diffusion MRI datasets acquired in four different imaging laboratories between 1999 and 2016. The biomarkers modeled were mean fractional anisotropy values of white matter tracts implicated in amyotrophic lateral sclerosis. The cerebral portion of the corticospinal tract was divided into three segments. Results Application of the model to the pooled datasets revealed that the corticospinal tracts were involved before other white matter tracts. Distal corticospinal tract segments were involved earlier than more proximal (i.e., cephalad) segments. In addition, the model revealed early ordering of fractional anisotropy change in the corpus callosum and subsequently in long association fibers. Interpretation These findings represent data‐driven evidence for early involvement of the corticospinal tracts and body of the corpus callosum in keeping with conventional approaches to image analysis, while providing new evidence to inform directional degeneration of the corticospinal tracts. This data‐driven model provides new insight into the dynamics of neuronal damage in amyotrophic lateral sclerosis

Extreme oceanographic forcing and coastal response due to the 2015-2016 El Nino

The El Niño-Southern Oscillation is the dominant mode of interannual climate variability across the Pacific Ocean basin, with influence on the global climate. The two end members of the cycle, El Niño and La Niña, force anomalous oceanographic conditions and coastal response along the Pacific margin, exposing many heavily populated regions to increased coastal flooding and erosion hazards. However, a quantitative record of coastal impacts is spatially limited and temporally restricted to only the most recent events. Here we report on the oceanographic forcing and coastal response of the 2015–2016 El Niño, one of the strongest of the last 145 years. We show that winter wave energy equalled or exceeded measured historical maxima across the US West Coast, corresponding to anomalously large beach erosion across the region. Shorelines in many areas retreated beyond previously measured landward extremes, particularly along the sediment-starved California coast