Sekundärstoffe – die Geheimwaffen der Pflanzen

Secondary metabolites Already 400 million years ago when land plants evolved, they probably produced secondary metabolites as means of defence against herbivores, microbes and competing plants. Secondary metabolites usually are bioactive agents, which can interfere with molecular targets in animals and microbes. Therefore, many plants and substances isolated from them can serve as valuable drugs in medicine and pharmacy. Some secondary metabolites also serve as signal compounds to attract pollinating animals and seed‐dispersing animals, but also for UV protection, as antioxidants or mobile nitrogen stores. Biology and evolution but also physiological and genetic bases of secondary metabolism are discussed in this overview.     

Gesundheit und Ernährung: Die Macht der Kultur

Health and nutrition: The power of cultural patterns Despite enormous educational efforts and widely spread common knowledge about the subject, today's nutrition as it is practiced by many consumer groups concerning health in Germany, shows great potential to be optimized. On one side this is due to a cognitive dissonance: The knowledge about a healthy nutrition is opposed to a practice that is often detrimental to health. Among other factors, the main reasons for that phenomenon can be found within psychological aspects of nutrition: Practices that are tried and tested have a stabilizing effect and lead to emotional security. On the other side nutritional systems in principle change slowly and are difficult to control, especially since food itself and communicating about it function as ideological placings, as a representation of status or are matter of distinction in a society driven by modern lifestyles. Oftentimes supposedly reasonable nutritional practices hardly show any commonalities with these realities. Furthermore people who live in Germany but who were socialized with a different cultural background tend to have conceptions of a valuable nutrition that are often contradictorily to scientific findings. That also counts for people who obtain information from internet platforms that are not scientifically oriented. There they pick up superficial knowledge, esoteric beliefs or ideology‐based hints delivered through a science‐based appearance.     

Auf Exkursion in Südmähren

South Moravia in the south of the Czech Republic is a region of high faunistic diversity. This is due to both, the geologically diverse landscape, e. g. in the area of the cross‐border Thayatal National Park, and the fact that there the Hercynian woodland of Western Europe meets the Pannonian steppe of Southeast Europe. During ten one‐week zoological excursions with biology students of the University of Duisburg‐Essen between 2009 and 2018, a whole string of fascinating animal species of this area could be observed or caught and was subsequently discussed. The main focus was on the avifauna, with many different breeding species like corn bunting, black stork, Eurasian hoopoe, European bee‐eater or kingfisher and great reed warbler. A second emphasis was on the herpetofauna. European green lizard and Aesculapian snake are locally abundant and well observable, European tree frog, fire salamander and European fire‐bellied toad can also be found. One of the most remarkable mammals is the European ground squirrel. Among the invertebrates there are also charismatic species like the spiders Philaeus chrysops and Eresus moravicus or the bush cricket Saga pedo. In this article many species are discussed in the context of their habitats, complemented by a list of all vertebrates successfully determined during the excursions.     

Characterization of a dorsal‐eye Gal4 Line in Drosophila

In Drosophila, the Gal4‐UAS system is used to drive ectopic gene expression in a tissue‐specific manner. In this system, transgenic flies expressing tissue specific Gal4 are crossed to a line in which the gene to be expressed is under the control of a Gal4‐responsive UAS sequence. The resulting progeny express the gene of interest in the pattern of the particular Gal4 line. Since a given UAS‐transgene can be driven by any Gal4 line, this system is predominantly limited by available Gal4 lines. Here we report the characterization of a novel line, DE‐Gal4, which in the eye is expressed in the dorsal compartment for the majority of development. Furthermore, we use functional tests to show that the DE‐Gal4 line is a useful tool with which to manipulate gene expression in half of the developing eye. genesis 48:3–7, 2010. © 2009 Wiley‐Liss, Inc.     

Long-term immunologic induction of donor-specific tolerance to skin allografts by bone marrow transplant in rabbits

The induction of donor-specific tolerance to skin allografts was investigated in rabbits using bone marrow transplantation techniques reported to be effective in mice. Various routes of bone marrow transplantation (i.e., intravenous, portal venous, or intraosseous) were also examined. In regimen A, the animals were treated with portal venous injection of bone marrow cells from the donor on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen B, the animals were treated with portal venous and intraosseous injections of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen C, the animals were given intraosseous injection of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. It was found that regimens B and C were more effective than regimen A in prolonging allograft survival. The results demonstrate that induction of allograft tolerance can be achieved by bone marrow transplantation in a rabbit model. This protocol deserves further study in other large animal models.     

Variability in intraosseous pressure induced by saline flush of an intraosseous cannula by multiple practitioners

Intraosseous cannulation is an accepted means to achieve vascular access when peripheral venous access is not available. It is common practice to flush the intraosseous cannula with saline prior to establishing infusions. The objective of this study was to evaluate changes in intraosseous pressure during the flush procedure and to assess the variability of pressure changes induced by different practitioners. Two intraosseous cannulas were placed in an isolated cadaveric femur collected from a swine. Intraosseous pressure and the rate of change in pressure were recorded continuously during a series of saline flushes into a distal femoral intraosseous cannula by 21 members of the veterinary research staff at the authors' institution. Median peak intraosseous pressures exceeded 600 mmHg, and an inverse relationship was noted between peak intraosseous pressure and the duration of flush. Bone marrow fat emboli were grossly evident in flush effluents and their presence was confirmed by microscopic examination. Until the practitioners were informed of the pressure changes induced by the intraosseous cannula flush, few had appreciated the magnitude of the pressures that they had generated, suggesting that an instrumented intraosseous flush preparation like the one used in this study may prove useful as a training tool for flush procedures.     

Chronopharmakologie

Chronopharmacology All living systems are highly organized in time, both in health and disease. Disturbances in the physiological daily [circadian] and seasonal rhythmic patterns of this system, e.g. in phramacokinetics, cardiovascular functions, sleep regulation to mention but a few can be regarded as warning signs of an increased risk and they can be of predictive value. There is now convincing evidence that most of these rhythms – from single cells to the highly complex human organism – are driven by biological clocks. The aim of this paper is to give a small overview on the circadian organisation of humans and to demonstrate its impact on drug treatment in cardiovascular diseases, pharmacokinetics and sleep disturbances. The data presented clearly show that the circadian organisation of the human physiology and pathophysiology and the time‐of‐day of drug dosing has to be included in the design of clinical trials in order to better treat the patients and to avoid false conclusion on the effectiveness and side effects of drugs.     

Inhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia

The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19⁺ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.     

Real‐time detection of cellular death receptor‐4 activation by fluorescence resonance energy transfer

Targeted therapy involving the activation of death receptors DR4 and/or DR5 by its ligand, TRAIL, can selectively induce apoptosis in certain tumor cells. In order to profile the dynamic activation or trimerization of TRAIL–DR4 in live cells in real‐time, the development of an apoptosis reporter cell line is essential. Fluorescence resonance energy transfer (FRET) technology via a FRET pair, cyan fluorescence protein (CFP) and yellow fluorescence protein (YFP), was used in this study. DR4‐CFP and DR4‐YFP were stably expressed in human lung cancer PC9 cells. Flow cytometer sorting and limited dilution coupled with fluorescence microscopy were used to select a monoclonal reporter cell line with high and compatible expression levels of DR4‐CFP and DR4‐YFP. FRET experiments were conducted and FRET efficiencies were monitored according to the Siegel's YFP photobleaching FRET protocol. Upon TRAIL induction a significant increase in FRET efficiencies from 5% to 9% demonstrated the ability of the DR4‐CFP/YFP reporter cell line in monitoring the dynamic activation of TRAIL pathways. 3D reconstructed confocal images of DR4‐CFP/YFP reporter cells exhibited a colocalized expression of DR4‐CFP and DR4‐YFP mainly on cell membranes. FRET results obtained during this study complements the use of epi‐fluorescence microscopy for FRET analysis. The real‐time FRET analysis allows the dynamic profiling of the activation of TRAIL pathways by using the time‐lapse fluorescence microscopy. Therefore, DR4‐CFP/YFP PC9 reporter cells along with FRET technology can be used as a tool for anti‐cancer drug screening to identify compounds that are capable of activating TRAIL pathways. Biotechnol. Bioeng. 2013; 110: 1396–1404. © 2012 Wiley Periodicals, Inc.     

Single‐molecule force spectroscopy applied to heparin‐induced thrombocytopenia

Heparin‐induced thrombocytopenia (HIT), occurring up to approximately 1% to 5% of patients receiving the antithrombotic drug heparins, has a complex pathogenesis involving multiple partners ranging from small molecules to cells/platelets. Recently, insights into the mechanism of HIT have been achieved by using single‐molecule force spectroscopy (SMFS), a methodology that allows direct measurements of interactions among HIT partners. Here, the potential of SMFS in unraveling the mechanism of the initial steps in the pathogenesis of HIT at single‐molecule resolution is highlighted. The new findings ranging from the molecular binding strengths and kinetics to the determination of the boundary between risk and non‐risk heparin drugs or platelet‐surface and platelet‐platelet interactions will be reviewed. These novel results together have contributed to elucidate the mechanisms underlying HIT and demonstrate how SMFS can be applied to develop safer drugs with a reduced risk profile.     

Die Eh da‐Initiative

The “Eh da”‐Initiative: more space for Biological Diversity in Cultural Landscapes The “Eh da”‐initiative is based on the principle that definite land in cultural landscapes is “available anyway” (what ?eh da“ means in German) and has the potential for ecological upgrading without relevant limitations of land use. “Eh da” could be the acronym “Ecological habitat development areas.” This land is located in open landscapes: along waysides, on uncropped plots in farmland, it could be communal lawn and other land categories. The initiative uses geodata in order to detect and quantify “Eh da”‐sites. According to an analysis based on geodata in selected landscapes “Eh da”‐land constitutes 2–6 per cent of the total area of Germany. “Eh da“‐sites are mostly narrow, longitudinal and spread like a net all over the landscape. Mainly insects and other invertebrate animals can be supported by upgrading of “Eh da”‐land. Since these sites often form corridors, they may be part of communal biodiversity protection initiatives under the perspective of ecological networks, or they may be used for distinct projects. Communication is a key element of any local initiative in which not only the ecological upgrading options, but also potential trade‐offs (like increase of agricultural pests and weeds, neophyta and pyrrolizidine containing or allergenic plants) should be discussed.     

Der Census of Marine Life zieht Bilanz. Globale “Volkszählung” unter Wasser

Global Underwater Census – a large‐scale project is taking stock The Census of Marine Life, an international large‐scale project to assess the diversity of life in the ocean, will end this fall after a decade of discovery with a grand finale in London. Many so‐called field projects were established to study life from tropical beaches, seamounts, hydrothermal vents, to polar seas and abyssal plains in order to get a better estimate of marine species diversity and gain insight into processes that influence the diversity of life in the oceans. Some of the field projects are presented, including the project CeDAMar under the leadership of the Senckenberg Institute. The study area of CeDAMar is abyssal plains, which comprise about half of the Earth's surface yet are very little known. Mankind's growing demand on minerals and other resources has awoken the industry's interest in a part of the ocean that so far has been relatively pristine. CeDAMar scientists have helped with their expertise to establish guidelines for the protection of the seafloor in international waters, thus demonstrating how concrete the influence of deep‐sea exploration on human society can become.     

Das Präkambrium. Die Wiege des Lebens

The Precambrian is the cradle of life. With a time span of about 4 Billion years it represents the largest part of earth history. Life changed the planet during the Precambrian by a lot of interactions with plate tectonics and raised into better qualities. A special milestone was the release of free oxygen by the stromatolithes at about 2.5 Billion years. An extreme bottleneck for the evolution of life was the Snowball Earth representing the freezing of the entire earth surface and the covering by an ice sheet. Plate tectonic processes were responsible for the melting of the ice sheet. In the aftermath of that glaciation the rapid radiation of the first complex higher life forms begun. These were represented by the so‐called Ediacara Biota, which occurred in the time span of about 630 and 543 Million years before today. The Ediacara Biota are unique in the evolution of life and existed in a close interaction with a leather‐like biomat at the sea‐floor which provided stability, hide and food. Among the Ediacara Biota the first primitive arthropods, the molluscs and the anthozoans occurred. In addition, in the fossil record are reported a lot of mystic life forms without a good or any classification. The Ediacara Biota represent the critical evolutionary step to pave the way for the explosion‐like radiation of life during the Cambrian that started at 542 Million years before present.     

Das Rätsel der Metastasierung

The riddle of the metastatic process Despite all progress in the understanding of the molecular basis of malignant tumours, the chances for being cured has not changed dramatically for the better in the last decades for many clinically important cancers as those of lung, pancreas, colon and ovary. The lack of success can be attributed to the early formation of distant metastases, which can generally not be cured. Without a deeper understanding of the metastatic process, it will be difficult to achieve therapeutic success. An additional problem is posed by the fact, that larger primary tumours as well as metastases develop an interstitial fluid pressure, which hinder the influx of drugs into them. This problem creates an additional obstacle for successful cancer therapy.     

Soft‐Bodied Fossils Are Not Simply Rotten Carcasses – Toward a Holistic Understanding of Exceptional Fossil Preservation

Exceptionally preserved fossils are the product of complex interplays of biological and geological processes including burial, autolysis and microbial decay, authigenic mineralization, diagenesis, metamorphism, and finally weathering and exhumation. Determining which tissues are preserved and how biases affect their preservation pathways is important for interpreting fossils in phylogenetic, ecological, and evolutionary frameworks. Although laboratory decay experiments reveal important aspects of fossilization, applying the results directly to the interpretation of exceptionally preserved fossils may overlook the impact of other key processes that remove or preserve morphological information. Investigations of fossils preserving non‐biomineralized tissues suggest that certain structures that are decay resistant (e.g., the notochord) are rarely preserved (even where carbonaceous components survive), and decay‐prone structures (e.g., nervous systems) can fossilize, albeit rarely. As we review here, decay resistance is an imperfect indicator of fossilization potential, and a suite of biological and geological processes account for the features preserved in exceptional fossils.     

Vogelstimmen

Avian vocalizations Avian vocalizations are part of biodiversity. They are involved in species formation. In many cases, bird songs are known to develop by imitation learning from a species‐specific model and are transmitted between generations of singers. By this way, also dialects can be formed. Bird sounds can be transformed into visual patterns called sonograms. Recognizing songs, calls and instrumental sounds of birds in the wild is a difficult task for many people. With the help of sonograms and other media this task can be overcome more easily. Knowing and discovering bird sounds is a pleasure and a cognitive hobby for an increasing number of people.     

Wie wachsen Tropenbäume? Jahrringe als Ausdruck von Klimabedingungen und Lebensform

Growth of tropical trees is largely depending on the seasonality of the local climate. In many trees growing in areas with a distinct dry season, cambial activity ceases resulting in the formation of annual rings. In very humid mountain rainforests, trees stop to grow already after short rainless periods. By a combination of increment measurements and wood anatomical analyses, the climatic control of wood formation can be assessed. Intra‐annual wood density variations and content of various stable isotopes enable the climatological interpretation of the “wood signals”.     

Experimente mit Hefe (2)

The so‐called iodine test is ideal for demonstrating the role of the enzyme “amylase” in simple experiments based on a colour reaction when a yeast dough rises, when carbohydrates are digested or when dishes are washed in the dishwasher. The experiments presented can be used to clarify the question of which everyday substances are capable of degrading starch or whether a food contains starch or not. The central question of the experiments is, how yeast makes the bread dough rise despite of its “starch intolerance”.