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The ability to permeate accross the blood brain barrier (BBB) is essential for drugs acting on the central nervous system (CNS). Thus, systems that allow rapid and inexpensive screening of the BBB-permeability properties of novel lead compounds are of great importance for speeding up the drug discovery process in the CNS-area. We used immortalized porcine brain microvessel endothelial cells (PBMECICl-2) to develop a model for measurement of blood-brain barrier permeation of CNS active drugs. Investigation of different cell culture conditions showed, that a system using C6 astrocyte glioma conditioned medium and addition of a cyclic AMP analog in combination with a type IV phosphodiesterase inhibitor (R020-1724) leads to cell layers with transendothelial electrical resistance values up to 300 Ω.cm2. Permeability studies with U-[14C]sucroseg ave a permeability coefficient Pe of 3.24 + 0.14 × 10−4 cm/min, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro.
"Die wichtigste, schwärendste Portion des Ungeschriebenen und sein entscheidender Einfluss auf die Springprozession des Schreibens liegt nach meinem Eindruck in dem, was dringend dran wäre, gedacht, gesagt und geschrieben zu werden, und was sich dem entzieht. Ist es zu schwer, zu sperrig, zu komplex? Womöglich sind ja die Arme unseres Geistes nicht kräftig genug, das eigentlich Benötigte zu stemmen."
Background: Xanthophyllomyces dendrorhous is a basal agaricomycete with uncertain taxonomic placement, known for its unique ability to produce astaxanthin, a carotenoid with antioxidant properties. It was the aim of this study to elucidate the organization of its CoA-derived pathways and to use the genomic information of X. dendrorhous for a phylogenomic investigation of the Basidiomycota.
Results: The genome assembly of a haploid strain of Xanthophyllomyces dendrorhous revealed a genome of 19.50 Megabases with 6385 protein coding genes. Phylogenetic analyses were conducted including 48 fungal genomes. These revealed Ustilaginomycotina and Agaricomycotina as sister groups. In the latter a well-supported sister-group relationship of two major orders, Polyporales and Russulales, was inferred. Wallemia occupies a basal position within the Agaricomycotina and X. dendrorhous represents the basal lineage of the Tremellomycetes, highlighting that the typical tremelloid parenthesomes have either convergently evolved in Wallemia and the Tremellomycetes, or were lost in the Cystofilobasidiales lineage. A detailed characterization of the CoA-related pathways was done and all genes for fatty acid, sterol and carotenoid synthesis have been assigned.
Conclusions: The current study ascertains that Wallemia with tremelloid parenthesomes is the most basal agaricomycotinous lineage and that Cystofilobasidiales without tremelloid parenthesomes are deeply rooted within Tremellomycetes, suggesting that parenthesomes at septal pores might be the core synapomorphy for the Agaricomycotina. Apart from evolutionary insights the genome sequence of X. dendrorhous will facilitate genetic pathway engineering for optimized astaxanthin or oxidative alcohol production.
Dort, wo der Weg der Geschichte sich gegabelt hat zwischen der Hinnahme des Gewohnten und dem Ausstieg aus ihm, so sanft wie tunlich oder so revolutionär wie nötig, da stoßen wir auf eine Reihe von Neuerern: Kritiker der gesellschaftlichen Verhältnisse oder der überkommenen Denkbahnen, z.T. auch Sprachkritiker, Sprachneuerer. Die "Linkshegelianer" bilden den Grundstock: Strauß, Feuerbach, Bruno Bauer, Stirner, Hess, in ihren Anfängen müssen wir auch Marx und Engels dazu zählen. Sie haben an schon etablierten politischen Lehren weitergearbeitet, aber sie haben, vor allem, neue Lehren und eine Kritik an allem Überkommenen in die Welt gesetzt. Zu einem beträchtlichen Teil haben sie sie nicht selbst erdacht. Bei französischen Revolutionären (oder auch Reformern) von Babeuf und Fourier bis zu Proudhon sind sie in die Lehre gegangen, Marx auch bei Ricardo und den Größen der britischen Nationalökonomie. Auf die Nachzeichnung jener Lehren soll es hier ankommen. Dazu greife ich einen heraus, der interessant ist, weil er von den Anfängen seiner Reflexion an, erst mit der Verarbeitung seines Judentums beschäftigt, sich zu einem Mitkämpfer der führenden kommunistischen Führerpersönlichkeiten entwickelt hat, aber auf anarchistische Weise; danach ist er auch noch bei den frühen Sozialdemokraten gelandet, eben Moses Hess.
Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge is derived from case reports or smaller case series. Recently, increasing PN incidence rates have been reported. We aim to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates.
Methods: Retrospective evaluation (1995 to 2011) of the clinical course of and risk factors for PN in patients from 11 hospitals in four European countries (Germany, Austria, Switzerland and The Netherlands). Calculation of population-based estimates of hospitalization rates of PN in Germany (2005 to 2011) using official German nationwide diagnosis-related groups (DRG) hospital statistics.
Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven with extrapulmonary dissemination. Within the 43 patients, major PN risk factors were immunocompromising (83.7%) and/or pulmonary (58.1%; in 27.9% as only comorbidity) comorbidities. Median duration of PN targeted therapy was 12 weeks. Distinguished patterns of resistance were observed (imipenem susceptibility: N. farcinica 33.3%; N. asteroides 66.7%). Overall mortality rate was 18.9%; in disseminated PN 50%. Over time, annual PN hospitalization rates remained unchanged at around 0.04/100′000 with the highest rate among men aged 75–84 years (0.24/100′000).
Conclusion: PN is rare, but potentially life-threatening, and mainly affects immunocompromised elder males. Overall annual hospitalization rates remained stable between 2005 and 2011.
We show a shift in the prevalence of respiratory viral pathogens in community-acquired pneumonia patients during the COVID-19 pandemic. Our data support the efficiency of non-pharmaceutical interventions on virus circulation except for rhinoviruses. The consequences of an altered circulation on subsequent winter seasons remain unclear and support the importance of systematic virological surveillance.