First Record of Cenozoic Bird Footprints from East Asia (Tibet,China)

Cenozoic bird tracks are known largely from North America, Europe, and the Middle East. There have been no reports of Cenozoic bird tracks from East Asia. This paper describes a series of two trackways produced by a galliform-like or gruiform-like bird from the Oligocene to Early Miocene of Tibet. The tracks are represented by tracings collected from a coal mine in Shigatse, Tibet, during the late 1970s. The tracks are comparable to Ornithoformipes and Pavoformipes and likely represent a medium-sized to large cursorial or flightless bird. In relation to modern bird tracks, the tracks bear a striking resemblance to those produced by the North American Wild Turkey (Meleagris gallopavo) except that M. gallopavo tracks often possess a small, elevated hallux impression. Due to the fact that these are tracings, however, a hallux may have been present and simply have been overlooked. The Shigatse trackways were, unfortunately, lost when the mine was closed and then backfilled during the 1980s, and there is little to no likelihood of recovery. Casts can be catalogued as holotype specimens but tracings cannot; however, all the original tracings have been donated to a public institution by their discoverer, Yimin Wu.     

Negative Regulation of Notch Signaling by Xylose

The Notch signaling pathway controls a large number of processes during animal development and adult homeostasis. One of the conserved post-translational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a C-X-S-X-(P/A)-C motif by Protein O-glucosyltransferase 1 (POGLUT1; Rumi in Drosophila). Genetic experiments in flies and mice, and in vivo structure-function analysis in flies indicate that O-glucose residues promote Notch signaling. The O-glucose residues on mammalian Notch1 and Notch2 proteins are efficiently extended by the addition of one or two xylose residues through the function of specific mammalian xylosyltransferases. However, the contribution of xylosylation to Notch signaling is not known. Here, we identify the Drosophila enzyme Shams responsible for the addition of xylose to O-glucose on EGF repeats. Surprisingly, loss- and gain-of-function experiments strongly suggest that xylose negatively regulates Notch signaling, opposite to the role played by glucose residues. Mass spectrometric analysis of Drosophila Notch indicates that addition of xylose to O-glucosylated Notch EGF repeats is limited to EGF14–20. A Notch transgene with mutations in the O-glucosylation sites of Notch EGF16–20 recapitulates the shams loss-of-function phenotypes, and suppresses the phenotypes caused by the overexpression of human xylosyltransferases. Antibody staining in animals with decreased Notch xylosylation indicates that xylose residues on EGF16–20 negatively regulate the surface expression of the Notch receptor. Our studies uncover a specific role for xylose in the regulation of the Drosophila Notch signaling, and suggest a previously unrecognized regulatory role for EGF16–20 of Notch.     

Buchbesprechung (Book Review)

Die Bedeutung insektenpathogener Viren als “Biologische Pflanzenschutzmittel” im System des Integrierten Pflanzenschutzes wird erläutert. Es wird dabei insbesondere auf die “Lückenindikationen” in Kulturpflanzenarten mit geringem Anbauumfang hingewiesen. Zu ihnen werden u.a. Gemüse, Zierpflanzen, Sonderkulturen wie Hopfen, Tabak und Wein, aber auch der Obstbau, gerechnet; daneben gehören aber auch Heil‐und Gewürzpflanzen sowie Rohstoffe für Diät‐und Säuglingsnahrungsmittel dazu. Schließlich wird der Forstschutz als ein wichtiges Refugium für die Anwendung biologischer Pflanzenschutzmittel im allgemeinen und damit auch für insektenpathogene Viren angesehen.

Einen hohen Stellenwert besitzen Unter‐Glas‐Kulturen, da hier biologische Bekämpfungsverfahren schon in einem erheblichen Umfang zur Anwendung kommen.

Die nachfolgenden Beispiele sollen stellvertretend für einen erfolgreichen Einsatz insektenpathogener Viren stehen:

• Bekämpfung von Spodoptera exigua in Chrysanthemenbeständen unter Glas in den Niederlanden mit dem autochthonen Virus und von Mamestra brassicae mit dem spezifischen Kernpolyeder‐Virus in Gewächshauskulturen von Rosen und Paprika (Wirkungsgrad 80 bis 100%) sowie an Kohl im Freiland (Wirkungsgrad 68, 9 bis 100%) in Deutschland.

• Das Granulose‐Virus der Wintersaateule (Agrotis segetum) ergab bei Anwendung gegen den Schädling an Astern Mortalitätswerte zwischen 90, 5 und 94, 1%.

In allen Versuchen erwiesen sich die Viren den als Standard mitgeführten chemischen Insektiziden als gleichwertig.

Am Zusammenbruch lokaler Gradationen der Kiefernbuschhornblattwespe Diprion similis in verschiedenen deutschen Bundesländern (Sachsen‐Anhalt, Sachsen) war ein spezifisches Kernpolyeder‐Virus wesentlich mitbeteiligt.     

Liposomes and Liposome-like Vesicles for Drug and DNA Delivery to Mitochondria

Mitochondrial research is presently one of the fastest growing disciplines in biomedicine. Since the early 1990s, it has become increasingly evident that mitochondrial dysfunction contributes to a large variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Most remarkably, mitochondria, the “power house” of the cell, have also become accepted as the “motor of cell death” reflecting their recognized key role during apoptosis. Based on these recent exciting developments in mitochondrial research, increasing pharmacological efforts have been made leading to the emergence of “Mitochondrial Medicine” as a whole new field of biomedical research. The identification of molecular mitochondrial drug targets in combination with the development of methods for selectively delivering biologically active molecules to the site of mitochondria will eventually launch a multitude of new therapies for the treatment of mitochondria-related diseases, which are based either on the selective protection, repair, or eradication of cells. Yet, while tremendous efforts are being undertaken to identify new mitochondrial drugs and drug targets, the development of mitochondria-specific drug carrier systems is lagging behind. To ensure a high efficiency of current and future mitochondrial therapeutics, colloidal vectors, i.e., delivery systems, need to be developed able to selectively transport biologically active molecules to and into mitochondria within living human cells. Here we review ongoing efforts in our laboratory directed toward the development of different phospholipid- and non-phospholipid-based mitochondriotropic drug carrier systems.     

A preliminary assessment of the habitat selection of two Palaearctic migrant passerine species in West Africa

We investigated the habitat selected by two Palaearctic migrants (Pied Flycatcher, Ficedula hypoleuca, Willow Warbler, Phylloscopus trochilus) in a patchy landscape in Ivory Coast and compared it with the habitat selection of Afrotropical species in the same foraging guilds. Transect counts were used to test the hypothesis that migrants use more open and more seasonal habitats and have a broader use of habitats compared with resident species. Habitats compared were, in order of decreasing tree density, gallery forest, an isolated forest and bush/tree savanna. The isolated forest had the most pronounced seasonal changes (deciduous trees) and was the one with the most diverse vegetation structure. The habitat where both migrants were most frequent was the isolated forest, and thus occurred in the habitat with the most pronounced seasonal change. Diversity of habitats selected was highest in migrants but in the Pied Flycatcher this was possibly an artefact due to subdominant individuals being excluded from the preferred habitat by territorial birds. Potential competition for habitat with Afrotropical species was found to be low.     

Multiscale Metabolic Modeling: Dynamic Flux Balance Analysis on a Whole-Plant Scale

Plant metabolism is characterized by a unique complexity on the cellular, tissue, and organ levels. On a whole-plant scale, changing source and sink relations accompanying plant development add another level of complexity to metabolism. With the aim of achieving a spatiotemporal resolution of source-sink interactions in crop plant metabolism, a multiscale metabolic modeling (MMM) approach was applied that integrates static organ-specific models with a whole-plant dynamic model. Allowing for a dynamic flux balance analysis on a whole-plant scale, the MMM approach was used to decipher the metabolic behavior of source and sink organs during the generative phase of the barley (Hordeum vulgare) plant. It reveals a sink-to-source shift of the barley stem caused by the senescence-related decrease in leaf source capacity, which is not sufficient to meet the nutrient requirements of sink organs such as the growing seed. The MMM platform represents a novel approach for the in silico analysis of metabolism on a whole-plant level, allowing for a systemic, spatiotemporally resolved understanding of metabolic processes involved in carbon partitioning, thus providing a novel tool for studying yield stability and crop improvement.Plants are of vital significance as a source of food (Grusak and DellaPenna, 1999; Rogalski and Carrer, 2011), feed (Lu et al., 2011), energy (Tilman et al., 2006; Parmar et al., 2011), and feedstocks for the chemical industry (Metzger and Bornscheuer, 2006; Kinghorn et al., 2011). Given the close connection between plant metabolism and the usability of plant products, there is a growing interest in understanding and predicting the behavior and regulation of plant metabolic processes. In order to increase crop quality and yield, there is a need for methods guiding the rational redesign of the plant metabolic network (Schwender, 2009).Mathematical modeling of plant metabolism offers new approaches to understand, predict, and modify complex plant metabolic processes. In plant research, the issue of metabolic modeling is constantly gaining attention, and different modeling approaches applied to plant metabolism exist, ranging from highly detailed quantitative to less complex qualitative approaches (for review, see Giersch, 2000; Morgan and Rhodes, 2002; Poolman et al., 2004; Rios-Estepa and Lange, 2007).A widely used modeling approach is flux balance analysis (FBA), which allows the prediction of metabolic capabilities and steady-state fluxes under different environmental and genetic backgrounds using (non)linear optimization (Orth et al., 2010). Assuming steady-state conditions, FBA has the advantage of not requiring the knowledge of kinetic parameters and, therefore, can be applied to model detailed, large-scale systems. In recent years, the FBA approach has been applied to several different plant species, such as maize (Zea mays; Dal’Molin et al., 2010; Saha et al., 2011), barley (Hordeum vulgare; Grafahrend-Belau et al., 2009b; Melkus et al., 2011; Rolletschek et al., 2011), rice (Oryza sativa; Lakshmanan et al., 2013), Arabidopsis (Arabidopsis thaliana; Poolman et al., 2009; de Oliveira Dal’Molin et al., 2010; Radrich et al., 2010; Williams et al., 2010; Mintz-Oron et al., 2012; Cheung et al., 2013), and rapeseed (Brassica napus; Hay and Schwender, 2011a, 2011b; Pilalis et al., 2011), as well as algae (Boyle and Morgan, 2009; Cogne et al., 2011; Dal’Molin et al., 2011) and photoautotrophic bacteria (Knoop et al., 2010; Montagud et al., 2010; Boyle and Morgan, 2011). These models have been used to study different aspects of metabolism, including the prediction of optimal metabolic yields and energy efficiencies (Dal’Molin et al., 2010; Boyle and Morgan, 2011), changes in flux under different environmental and genetic backgrounds (Grafahrend-Belau et al., 2009b; Dal’Molin et al., 2010; Melkus et al., 2011), and nonintuitive metabolic pathways that merit subsequent experimental investigations (Poolman et al., 2009; Knoop et al., 2010; Rolletschek et al., 2011). Although FBA of plant metabolic models was shown to be capable of reproducing experimentally determined flux distributions (Williams et al., 2010; Hay and Schwender, 2011b) and generating new insights into metabolic behavior, capacities, and efficiencies (Sweetlove and Ratcliffe, 2011), challenges remain to advance the utility and predictive power of the models.Given that many plant metabolic functions are based on interactions between different subcellular compartments, cell types, tissues, and organs, the reconstruction of organ-specific models and the integration of these models into interacting multiorgan and/or whole-plant models is a prerequisite to get insight into complex plant metabolic processes organized on a whole-plant scale (e.g. source-sink interactions). Almost all FBA models of plant metabolism are restricted to one cell type (Boyle and Morgan, 2009; Knoop et al., 2010; Montagud et al., 2010; Cogne et al., 2011; Dal’Molin et al., 2011), one tissue or one organ (Grafahrend-Belau et al., 2009b; Hay and Schwender, 2011a, 2011b; Pilalis et al., 2011; Mintz-Oron et al., 2012), and only one model exists taking into account the interaction between two cell types by specifying the interaction between mesophyll and bundle sheath cells in C4 photosynthesis (Dal’Molin et al., 2010). So far, no model representing metabolism at the whole-plant scale exists.Considering whole-plant metabolism raises the problem of taking into account temporal and environmental changes in metabolism during plant development and growth. Although classical static FBA is unable to predict the dynamics of metabolic processes, as the network analysis is based on steady-state solutions, time-dependent processes can be taken into account by extending the classical static FBA to a dynamic flux balance analysis (dFBA), as proposed by Mahadevan et al. (2002). The static (SOA) and dynamic optimization approaches introduced in this work provide a framework for analyzing the transience of metabolism by integrating kinetic expressions to dynamically constrain exchange fluxes. Due to the requirement of knowing or estimating a large number of kinetic parameters, so far dFBA has only been applied to a plant metabolic model once, to study the photosynthetic metabolism in the chloroplasts of C3 plants by a simplified model of five biochemical reactions (Luo et al., 2009). Integrating a dynamic model into a static FBA model is an alternative approach to perform dFBA.In this study, a multiscale metabolic modeling (MMM) approach was applied with the aim of achieving a spatiotemporal resolution of cereal crop plant metabolism. To provide a framework for the in silico analysis of the metabolic dynamics of barley on a whole-plant scale, the MMM approach integrates a static multiorgan FBA model and a dynamic whole-plant multiscale functional plant model (FPM) to perform dFBA. The performance of the novel whole-plant MMM approach was tested by studying source-sink interactions during the seed developmental phase of barley plants.