A novel method to visualise and quantify circadian misalignment

The circadian clock governs virtually all processes in the human body, including sleep-wake behaviour. Circadian misalignment describes the off-set between sleep-wake cycles and clock-regulated physiology. This strain is predominantly caused by external (societal) demands including shift work, early school start times and fast travels across time zones. Sleeping at the 'wrong' internal time can jeopardise health and safety, and we therefore need a good quantification of this phenomenon. Here, we propose a novel method to quantify the mistiming of sleep-wake rhythms and demonstrate its versatility in day workers and shift workers. Based on a single time series, our Composite Phase Deviation method unveils distinct, subject-and schedule-specific geometries ('islands and pancakes') that illustrate how modern work times interfere with sleep. With increasing levels of circadian strain, the resulting shapes change systematically from small, connected forms to large and fragmented patterns. Our method shows good congruence with published measures of circadian misalignment (i.e., Inter-daily Stability and 'Behavioural Entrainment'), but offers added value as to its requirements, e.g., being computable for sleep logs and questionnaires. Composite Phase Deviations will help to understand the mechanisms that link 'living against the clock' with health and disease on an individual basis

Current advances on ABC drug transporters in fish

Most members of the large ATP-binding cassette (ABC) gene family are transporters involved in substrate translocation across biological membranes. In eukaryotes, ABC proteins functioning as drug transporters are located in the plasma membrane and mediate the cellular efflux of a wide range of organic chemicals, with some transporters also transporting certain metals. As the enhanced expression of ABC drug transporters can confer multidrug resistance (MDR) to cancers and multixenobiotic resistance (MXR) to organisms from polluted habitats, these ABC family members are also referred to as MDR or MXR proteins. In mammals, ABC drug transporters show predominant expression in tissues involved in excretion or constituting internal or external body boundaries, where they facilitate the excretion of chemicals and their metabolites, and limit chemical uptake and penetration into "sanctuary" sites of the body. Available knowledge about ABC proteins is still limited in teleost fish, a large vertebrate group of high ecological and economic importance. Using transport activity measurements and immunochemical approaches, early studies demonstrated similarities in the tissue distribution of ABC drug transporters between teleosts and mammals, suggesting conserved roles of the transporters in the biochemical defence against toxicants. Recently, the availability of teleost genome assemblies has stimulated studies of the ABC family in this taxon. This review summarises the current knowledge regarding the genetics, functional properties, physiological function, and ecotoxicological relevance of teleostean ABC transporters. The available literature is reviewed with emphasis on recent studies addressing the tissue distribution, substrate spectrum, regulation, physiological function and phylogenetic origin of teleostean ABC transporters

Evaluation und Klassifikation der Anforderungen an Datenverbindungen mobiler Endgeräte

Mobile Endgeräte erfahren seit einigen Jahren ein sehr starkes Wachstum. Über eine ständige Verbindung mit dem Internet bieten sie eine ideale Plattform für eine Vielzahl an Informations-, Kommunikations- und Unterhaltungsdiensten. Mobile Endgeräte werden mittels verschiedener Mobilfunknetze an das Internet angebunden. Da Funknetze anfälliger für Störungen als Kabelverbindungen sind, müssen diese Störungen kompensiert werden, um einer Applikation eine stabile Verbindung garantieren zu können. Dies ist wichtig bei kritischen Anwendungen, wie in der Medizin oder im Gewerbe, jedoch auch für den alltäglichen Nutzer, um dessen Vertrauen zu stärken und das Endgerät zu einem verlässlichen Begleiter zu machen. In dieser Arbeit wird untersucht, welche Qualitätskriterien bei der Datenverbindung für mobile Anwendungen relevant sind. Aus diesen Qualitätskriterien werden Anforderungen an die Anwendung formuliert anhand dieser Beispielanwendungen untersucht. Anschließend werden einige Probleme und Fehler aufgeführt, welche die Anforderungen beeinflussen. Die Probleme und Fehler werden in Kategorien unterteilt und Fehler und ihre Folgefehler beispielhaft in einer Baumstruktur angeordnet. Danach werden recherchierte Lösungen und welche Fehler sie beheben können vorgestellt. Dabei wird die zuvor aufgestellte Baumstruktur genutzt, um die Fehler auf einer hohen Ebene für so viele Anwendungen wie möglich zu lösen. Im Fazit wird die Frage geklärt, wie man mobile Anwendungen gegen instabile Datenverbindungen absichert, in welchem Kontext dies geschehen muss und welche Probleme derzeit noch nicht zu lösen sind

Eine Technologie für das durchgängige und automatisierte Testen eingebetteter Software

Eingebettete Systeme unterliegen Anforderungen, die den Test der Software erforderlich machen. Zur Automatisierung werden dabei verschiedene Technologien eingesetzt: Für den Test nah am Quelltext sind spezielle Unit-Test Werkzeuge erforderlich, der Test von Steuer- und Regelfunktionen erfordert Model-, Software- und Hardware-in-the-Loop Werkzeuge. In dieser Arbeit wird deren Integrierbarkeit untersucht. Der Fokus liegt auf einer neuen Programmiersprache zur Implementierung von Testfällen

The Simulated Classroom Biology—A simulated classroom environment for capturing the action‐oriented professional knowledge of pre‐service teachers about evolution

Background: The professional knowledge of pre-service teachers is highly important for effective and successful teaching. In recent years, many research groups have been engaged in developing simulated classroom environments to capture especially the pedagogical knowledge (PK) of pre-service teachers, neglecting the content-related facets of professional knowledge such as pedagogical content knowledge (PCK). Objectives: In the present study, we describe the development of a simulated class- room environment — the Simulated Classroom Biology (SCR Bio) — and provide evidence regarding its validity to assess pre-service biology teachers' action-oriented PCK in the area of evolution. Methods: This study examined the evidence supporting the validity of using the SCR Bio to investigate action-oriented PCK of pre-service biology teachers. The (1) evidence based on test content (expert ratings) and the (2) evidence based on relation to other variables (known-groups comparison) was obtained. We tested the SCR Bio with N = 76 German pre-service biology teachers. Results and Conclusions: Our results show the successfully operationalized PCK in the SCR Bio through explicit allocation of specific misconceptions to each virtual student's answer and the valid measurement of pre-service biology teachers' action-oriented PCK. This results in a validated simulated classroom environment for pre-service but also in-service teachers. In the future, the SCR Bio will be developed from an assessment instrument to a training tool to simulate explicit teaching situations. This allows to complement the predominantly theoretical components of university-based teacher education with practice-based simulated classroom environments

Abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos

BACKGROUND: In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish embryos against adverse compounds dissolved in the water. RESULTS: Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in embryo tissue and sensitivity of embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in embryo tissue and sensitivity of embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a polycyclic aromatic hydrocarbon) and galaxolide and tonalide (two polycyclic musks). CONCLUSIONS: We show that zebrafish Abcb4 is a cellular toxicant transporter and provides protection of embryos against toxic chemicals dissolved in the water. Zebrafish Abcb4 thus is functionally similar to mammalian ABCB1, but differs from mammalian ABCB4, which is not involved in cellular resistance to chemicals but specifically transports phospholipids in the liver. Our data have important implications: Abcb4 could affect bioavailability - and thus toxicologic and pharmacologic potency - of chemicals to zebrafish embryos and inhibition of Abcb4 therefore causes chemosensitization, that is, enhanced sensitivity of embryos to toxicants. These aspects should be considered in (eco)toxicologic and pharmacologic chemical screens with the zebrafish embryo, a major vertebrate model

Chronotypes in the US - Influence of age and sex

An individual's chronotype reflects how the circadian system embeds itself into the 24-h day with rhythms in physiology, cognition and behavior occurring accordingly earlier or later. In view of an increasing number of people working at unusual times and linked health and safety risks, the wide range in human chronotypes may provide opportunities to allow people to work (and sleep) at times that are in synch with their circadian physiology. We aimed at estimating the distribution of chronotypes in the US population by age and sex. Twelve years (2003-2014) of pooled diary data from the American Time Use Survey were used to calculate chronotype based on mid-point of sleep on weekends (MSFWe, n = 53,689). We observed a near-normal distribution overall and within each age group. The distribution's mean value is systematically different with age, shifting later during adolescence, showing a peak in 'lateness' at similar to 19 years, and shifting earlier thereafter. Men are typically later chronotypes than women before 40, but earlier types after 40. The greatest differences are observed between 15 and 25 for both sexes, equaling more than 50% of the total chronotype difference across all age groups. The variability in chronotype decreases with age, but is generally higher in males than females. This is the first study to estimate the distribution and prevalence of individual chronotypes in the US population based on a large-scale, nationally representative sample. Our finding that adolescents are on average the latest chronotypes supports delaying school start times to benefit their sleep and circadian alignment. The generally wide range in chronotypes may provide opportunities for tailored work schedules by matching external and internal time, potentially decreasing long- and short-term health and safety risks

Organic vs. Conventional Grassland Management: Do 15N and 13C Isotopic Signatures of Hay and Soil Samples Differ?

Distinguishing organic and conventional products is a major issue of food security and authenticity. Previous studies successfully used stable isotopes to separate organic and conventional products, but up to now, this approach was not tested for organic grassland hay and soil. Moreover, isotopic abundances could be a powerful tool to elucidate differences in ecosystem functioning and driving mechanisms of element cycling in organic and conventional management systems. Here, we studied the δ15N and δ13C isotopic composition of soil and hay samples of 21 organic and 34 conventional grasslands in two German regions. We also used Δδ15N (δ15N plant - δ15N soil) to characterize nitrogen dynamics. In order to detect temporal trends, isotopic abundances in organic grasslands were related to the time since certification. Furthermore, discriminant analysis was used to test whether the respective management type can be deduced from observed isotopic abundances. Isotopic analyses revealed no significant differences in δ13C in hay and δ15N in both soil and hay between management types, but showed that δ13C abundances were significantly lower in soil of organic compared to conventional grasslands. Δδ15N values implied that management types did not substantially differ in nitrogen cycling. Only δ13C in soil and hay showed significant negative relationships with the time since certification. Thus, our result suggest that organic grasslands suffered less from drought stress compared to conventional grasslands most likely due to a benefit of higher plant species richness, as previously shown by manipulative biodiversity experiments. Finally, it was possible to correctly classify about two third of the samples according to their management using isotopic abundances in soil and hay. However, as more than half of the organic samples were incorrectly classified, we infer that more research is needed to improve this approach before it can be efficiently used in practice