Global transcriptome analysis of murine embryonic stem cell-derived cardiomyocytes

Microarray analysis reveals that the specific pattern of gene expression in cardiomyocytes derived from embryonic stem cells reflects the biological, physiological and functional processes occurring in mature cardiomyocytes

Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland

BACKGROUND: The contribution of community and hospital sources to the transmission of extended-spectrum β-lactamase producing Enterobacterales (ESBL-PE) remains elusive. AIM: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel. METHODS: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification. RESULTS: Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 10$^{2}$ vs. 1.6 × 10$^{2}$ CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21). CONCLUSION: ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent

In Prostate Cancer Cells Cytokines are early Responders to Gravitational Changes occurring in Parabolic Flights

The high mortality in men with metastatic prostate cancer (PC) establishes the need for diagnostic optimization by new biomarkers. Mindful of the effect of real microgravity on metabolic pathways of carcinogenesis, we attended a parabolic flight (PF) mission to perform an experiment with the PC cell line PC-3, and submitted the resulting RNA to next generation sequencing (NGS) and quantitative real-time PCR (qPCR). After the first parabola, alterations of the F-actin cytoskeleton-like stress fibers and pseudopodia are visible. Moreover, numerous significant transcriptional changes are evident. We were able to identify a network of relevant PC cytokines and chemokines showing differential expression due to gravitational changes, particularly during the early flight phases. Together with differentially expressed regulatory lncRNAs and micro RNAs, we present a portfolio of 298 potential biomarkers. Via qPCR we identified IL6 and PIK3CB to be sensitive to vibration effects and hypergravity, respectively. Per NGS we detected five upregulated cytokines (CCL2, CXCL1, IL6, CXCL2, CCL20), one zink finger protein (TNFAIP3) and one glycoprotein (ICAM1) related to c-REL signaling and thus relevant for carcinogenesis as well as inflammatory aspects. We found regulated miR-221 and the co-localized lncRNA MIR222HG induced by PF maneuvers. miR-221 is related to the PC-3 growth rate and MIR222HG is a known risk factor for glioma susceptibility. These findings in real microgravity may further improve our understanding of PC and contribute to the development of new diagnostic tools

Extended-spectrum β-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland

BackgroundThe involvement of non-human-to-human transmission of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread.AimWe aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city.MethodsChicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing.ResultsAmong 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107).ConclusionOur findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations. One subtype, PFA-1c, was enriched for 1q gain and had a relatively poor outcome, while patients with PFA-2c ependymomas showed an overall survival at 5 years of > 90%. Unlike other ependymomas, PFA-2c tumors express high levels of OTX2, a potential biomarker for this ependymoma subtype with a good prognosis. We also discovered recurrent mutations among PFA ependymomas. H3 K27M mutations were present in 4.2%, occurring only in PFA-1 tumors, and missense mutations in an uncharacterized gene, CXorf67, were found in 9.4% of PFA ependymomas, but not in other groups. We detected high levels of wildtype or mutant CXorf67 expression in all PFA subtypes except PFA-1f, which is enriched for H3 K27M mutations. PFA ependymomas are characterized by lack of H3 K27 trimethylation (H3 K27-me3), and we tested the hypothesis that CXorf67 binds to PRC2 and can modulate levels of H3 K27-me3. Immunoprecipitation/mass spectrometry detected EZH2, SUZ12, and EED, core components of the PRC2 complex, bound to CXorf67 in the Daoy cell line, which shows high levels of CXorf67 and no expression of H3 K27-me3. Enforced reduction of CXorf67 in Daoy cells restored H3 K27-me3 levels, while enforced expression of CXorf67 in HEK293T and neural stem cells reduced H3 K27-me3 levels. Our data suggest that heterogeneity among PFA ependymomas could have clinicopathologic utility and that CXorf67 may have a functional role in these tumors

"Umwuchtungen" : die wechselvolle Geschichte der ZfL-Bibliothek

Für Jorge Luis Borges ist die Bibliothek Ort unermesslichen Wissens und Metapher für die Unendlichkeit. Umberto Eco beschreibt sie in "Der Name der Rose" als einen Raum voller Kräfte, als Schatzhaus voller Geheimnisse. Mögen sich die Bibliotheken über die Jahrhunderte auch einen Teil dieses Zaubers bewahrt haben, sind sie heute mehr denn je moderne Informationseinrichtungen in einer digitalen Gesellschaft. Vor allem in großen wissenschaftlichen Bibliotheken ist dieser Wandel spürbar; als Dienstleistungsunternehmen ist ihre Atmosphäre von Betriebsamkeit und Anonymität geprägt. Kleinere Institutsbibliotheken hingegen haben sich stärker einen Teil des Magischen bewahren können. In gewisser Weise verfügen sie über eine besondere Atmosphäre, einen "spirit", geformt von dem Ort selbst und den dort anwesenden Menschen. Auch in der Bibliothek des Leibniz-Zentrums für Literatur- und Kulturforschung (ZfL) liegt ein ganz besonderer Bücherduft in der Luft, in dem die Zeit konserviert scheint. Die Geschichte dieser Bibliothek ist geprägt von etlichen Brüchen und Umbrüchen und spiegelt damit, gleichsam als Gedächtnis ihrer wechselnden Trägereinrichtungen, nicht zuletzt auch deutsch-deutsche Geschichte wider

Maßnahmen zur Hitzestress-Reduzierung anhand Verdunstungsabkühlung

Großflächig versiegelte und hoch verdichtete Stadtstrukturen mit einer geringen Begrünung lassen aufgrund des Klimawandels und zunehmend heiße Tage sogenannte Hitze-Inseln in der Stadt entstehen (Urban-Heat-Island Effekt). Wasser, das verdunstet, kühlt das Mikroklima. Daher sind Maßnahmen günstig, die Regenwasser nicht abführen, sondern längere Zeit speichern, damit es in Hitzeperioden verdunsten kann. Feuchte Böden, Feuchtvegetation, bewässerte Fassaden und gut mit Wasser versorgte Bäume haben die höchsten Verdunstungswerte und kühlen damit am besten. Intelligente Techniken und Verfahren für eine dezentrale Regenwasserbewirtschaftung können im Zusammenspiel mit anderen Maßnahmen einen Beitrag für ein gesundes Stadtklima und die Hitzevorsoge leisten. Sie tragen auch zu einem naturnahen Wasserhaushalt bei und dienen der Überflutungsvorsorge, sind bislang allerdings keine gängige Praxis. Measures for heat stress reduction by evaporative cooling: Due to climate change and increasingly hot days, so-called urban heat islands are being created in the city due to large-scale sealed and highly dense urban structures with poor vegetation cover (urban-heat-island effect). Water which evaporates cools the microclimate. Measures that do not drain rainwater away but store it for a longer period of time so that it can evaporate during heat periods are therefore favourable. Humid soils, wet vegetation, irrigated facades and trees that are well supplied with water have the highest evaporation values and therefore cool best. Intelligent technologies and processes for decentralised rainwater management can, in combination with other measures, contribute to a healthy urban climate and heat prediction. They also contribute to a near-natural water balance and serve to prevent flooding, but are not yet common practic