570 Biowissenschaften; Biologie
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The grapevine berry surface is covered by a cuticle consisting of cutin and various lipophilic wax compounds. The latter build the main barrier for transpirational water loss and protect the fruit against environmental factors e.g. pests, mechanical impacts or radiation. The integrety of the fruit surface is one important key factor for post-harvest quality and storage of fruits. Nonetheless, the developmental pattern of cuticular wax was so far only investigated for a very limited number of fruits. Therefore, we performed comparative investigations on the compositional and morphological nature of epicuticular wax crystals and underlying wax during fruit development in Vitis vinifera. The main compound oleanolic acid belongs to the pentacyclic triterpenoids, which occur very early in the development in high amounts inside the cuticle. The amount increases until veraison and decreases further during ripening. In general, very-long chain aliphatic (VLCA) compounds are present in much smaller amounts and alcohols and aldehydes follow the same trend during development. In contrast, the amount of fatty acids constantly increases from fruit set to ripening while wax esters only occur in significant amount at veraison and increase further. Wax crystals at the fruit surface are solely composed of VLCAs and the morphology changes during development according to the compositional changes of the VLCA wax compounds. The remarkable compositional differences between epicuticular wax crystals and the underlying wax are important to understand in terms of studying grape-pest interactions or the influence of environmental factors, since only wax crystals directly face the environment.
Hepatitis B virus (HBV) replicates its 3 kb DNA genome through capsid-internal reverse transcription, initiated by assembly of 120 core protein (HBc) dimers around a complex of viral pregenomic (pg) RNA and polymerase. Following synthesis of relaxed circular (RC) DNA capsids can be enveloped and secreted as stable virions. Upon infection of a new cell, however, the capsid disintegrates to release the RC-DNA into the nucleus for conversion into covalently closed circular (ccc) DNA. HBc´s interactions with nucleic acids are mediated by an arginine-rich C terminal domain (CTD) with intrinsically strong non-specific RNA binding activity. Adaptation to the changing demands for nucleic acid binding during the viral life cycle is thought to involve dynamic phosphorylation / dephosphorylation events. However, neither the relevant enzymes nor their target sites in HBc are firmly established. Here we developed a bacterial coexpression system enabling access to definably phosphorylated HBc. Combining Phos-tag gel electrophoresis, mass spectrometry and mutagenesis we identified seven of the eight hydroxy amino acids in the CTD as target sites for serine-arginine rich protein kinase 1 (SRPK1); fewer sites were phosphorylated by PKA and PKC. Phosphorylation of all seven sites reduced nonspecific RNA encapsidation as drastically as deletion of the entire CTD and altered CTD surface accessibility, without major structure changes in the capsid shell. The bulk of capsids from human hepatoma cells was similarly highly, yet non-identically, phosphorylated as by SRPK1. While not proving SRPK1 as the infection-relevant HBc kinase the data suggest a mechanism whereby high-level HBc phosphorylation principally suppresses RNA binding whereas one or few strategic dephosphorylation events enable selective packaging of the pgRNA/polymerase complex. The tools developed in this study should greatly facilitate the further deciphering of the role of HBc phosphorylation in HBV infection and its evaluation as a potential new therapeutic target.
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure. Despite the important role these cells play in pathogenesis, understanding the environmental stimuli that drive the morphological transition, and the molecular mechanisms underlying their unique biology, has been hampered by the lack of a reproducible in vitro induction system. Here we demonstrate reproducible in vitro Titan cell induction in response to environmental stimuli consistent with the host lung. In vitro Titan cells exhibit all the properties of in vivo generated Titan cells, the current gold standard, including altered capsule, cell wall, size, high mother cell ploidy, and aneuploid progeny. We identify the bacterial peptidoglycan subunit Muramyl Dipeptide as a serum compound associated with shift in cell size and ploidy, and demonstrate the capacity of bronchial lavage fluid and bacterial co-culture to induce Titanisation. Additionally, we demonstrate the capacity of our assay to identify established (cAMP/PKA) and previously undescribed (USV101) regulators of Titanisation in vitro. Finally, we investigate the Titanisation capacity of clinical isolates and their impact on disease outcome. Together, these findings provide new insight into the environmental stimuli and molecular mechanisms underlying the yeast-to-Titan transition and establish an essential in vitro model for the future characterization of this important morphotype.
Neuroendocrine cells communicate via neuropeptides to regulate behaviour and physiology. This study examines how STIM (Stromal Interacting Molecule), an ER-Ca2+ sensor required for Store-operated Ca2+ entry, regulates neuropeptides required for Drosophila development under nutrient restriction (NR). We find two STIM-regulated peptides, Corazonin and short Neuropeptide F, to be required for NR larvae to complete development. Further, a set of secretory DLP (Dorso lateral peptidergic) neurons which co -express both peptides was identified. Partial loss of dSTIM caused peptide accumulation in the DLPs, and reduced systemic Corazonin signalling. Upon NR, larval development correlated with increased peptide levels in the DLPs, which failed to occur when dSTIM was reduced. Comparison of systemic and cellular phenotypes associated with reduced dSTIM, with other cellular perturbations, along with genetic rescue experiments, suggested that dSTIM primarily compromises neuroendocrine function by interfering with neuropeptide release. Under chronic stimulation, dSTIM also appears to regulate neuropeptide synthesis.
In order to understand the degradation potential of plastics in the marine environment, microorganisms that preferentially colonize and interact with plastic surfaces, as opposed to generalists potentially colonising everything, need to be identified. Accordingly, it was hypothesized that i.) plastic “specific” microorganisms are closely attached to the polymeric surface and ii.) that specificity of plastics biofilms are rather related to members of the rare biosphere. To answer these hypotheses, a three phased experiment to stepwise uncover closely attached microbes was conducted. In Phase 1, nine chemically distinct plastic films and glass were incubated in situ for 21 months in a seawater flow through system. In Phase 2, a high-pressure water jet treatment technique was used to remove the upper biofilm layers to further, in Phase 3, enrich a plastic “specific” community. To proof whether microbes colonizing different plastics are distinct from each other and from other inert hard substrates, the bacterial communities of these different substrates were analysed using 16S rRNA gene tag sequencing. Our findings indicate that tightly attached microorganisms account to the rare biosphere and suggest the presence of plastic “specific” microorganisms/assemblages which could benefit from the given plastic properties or at least grow under limited carbon resources.
Extracellular vesicles (EVs) released by cells have a role in intercellular communication to regulate a wide range of biological processes. Two types of EVs can be recognized. Exosomes, which are released from multi-vesicular bodies upon fusion with the plasma membrane, and ectosomes, which directly bud from the plasma membrane. How cells regulate the quantity of EV release is largely unknown. One of the initiating events in vesicle biogenesis is the regulated transport of phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. This process is catalyzed by P4-ATPases. The role of these phospholipid transporters in intracellular vesicle transport has been established in lower eukaryotes and is slowly emerging in mammalian cells. In Caenorhabditis elegans (C. elegans), deficiency of the P4-ATPase member TAT-5 resulted in enhanced EV shedding, indicating a role in the regulation of EV release. In this study, we investigated whether the mammalian ortholog of TAT-5, ATP9A, has a similar function in mammalian cells. We show that knockdown of ATP9A expression in human hepatoma cells resulted in a significant increase in EV release that was independent of caspase-3 activation. Pharmacological blocking of exosome release in ATP9A knockdown cells did significantly reduce the total number of EVs. Our data support a role for ATP9A in the regulation of exosome release from human cells.
Deadwood is an important structural component in forest ecosystems and plays a significant role in global carbon and nutrient cycling. Relatively little is known about the formation and decomposition of CWD by microbial communities in situ and about the factors controlling the associated processes. In this study, we intensively analyzed the molecular fungal community composition and species richness in relation to extracellular enzyme activity and differences in decomposing sapwood and heartwood of 13 temperate tree species (four coniferous and nine deciduous species, log diameter 30–40 cm and 4 m long) in an artificial experiment involving placing the logs on the forest soil for six years. We observed strong differences in the molecular fungal community composition and richness among the 13 tree species, and specifically between deciduous and coniferous wood, but unexpectedly no difference was found between sapwood and heartwood. Fungal species richness correlated positively with wood extractives and negatively with fungal biomass. A distinct fungal community secreting lignocellulolytic key enzymes seemed to dominate the decomposition of the logs in this specific phase. In particular, the relative sequence abundance of basidiomycetous species of the Meruliaceae (e.g. Bjerkandera adusta) correlated with ligninolytic manganese peroxidase activity. Moreover, this study reveals abundant white-rot causing Basidiomycota and soft-rot causing Ascomycota during this phase of wood decomposition.
The nests of advanced eusocial ant species can be considered ecological islands with a diversity of ecological niches inhabited by not only the ants and their brood, but also a multitude of other organisms adapted to particular niches. In the current paper, we describe the myrmecophilous behavior and the exocrine glands that enable the staphylinid beetle Dinarda dentata to live closely with its host ants Formica sanguinea. We confirm previous anecdotal descriptions of the beetle’s ability to snatch regurgitated food from ants that arrive with a full crop in the peripheral nest chambers, and describe how the beetle is able to appease its host ants and dull initial aggression in the ants.
Cardio- and cerebrovascular diseases (CVDs), such as myocardial infarction and ischemic stroke, are the leading cause of death worldwide, caused by overshooting platelet activation and subsequent thrombus formation. However, at sites of vascular injury this tightly-regulated, multi¬step process is critical to limit blood loss and to prevent bleeding. Anti-platelet agents, such as aspirin or clopidogrel, have been proven to be beneficial in prevention of CVDs, but are associated with an elevated bleeding risk and therefore are often contraindicative.
In recent years, the (hem)ITAM-bearing receptors GPVI and CLEC-2 have been identified as critical regulators of platelet activation and thrombus formation, rendering them promising targets for novel anti-platelet drugs. Yet, they are also involved in a plethora of (patho)physiological processes. Consequently, interference with the (hem)ITAM signaling cascade may lead to severe side-effects. In this context, GPV has previously been identified as a mediator of thrombotic and hemostatic function, while its mode of action remains elusive. Therefore, this thesis focused on the function of GPV in thrombotic and hemostatic processes.
Extensive characterization of GPV-deficient mice as well as generation and analysis of anti-GPV antibodies and mice with a mutation rendering GPV uncleavable by thrombin (Gp5Kin/Kin) revealed an unexpected role of GPV as a central modulator of platelet activation and thrombus formation. Gp5-/- as well as Gp5Kin/Kin mice restored the thrombotic and hemostatic defect in the absence of both (hem)ITAM receptors. The in-house generated monoclonal anti-GPV antibodies 89F12 and 5G2 were found to reproduce the knockout phenotype and extended the thrombus-modulatory role of GPV beyond (hem)ITAM receptors, pointing to a critical role of thrombin-cleaved soluble GPV (sGPV). Surprisingly, recombinant sGPV had a strong antithrombotic effect in in vivo throm¬bosis models as well as in in vitro flow adhesion assays using human or murine blood, without affecting hemostasis. These data establish GPV as a key player in platelet physiology. Although data gained from studies using genetically modified mice cannot always directly be transferred to humans, the findings presented in this thesis may serve as basis for the generation of novel treatment options for bleeding complications (anti-GPV antibodies) and thrombotic diseases (sGPV) with a good safety profile. The newly generated humanized GPV mouse provides a valuable tool to study human GPV in vivo.
A second part of this thesis focused on the analysis of protein kinase C (PKC) ι/λ. PKC family of serine/threonine kinases is involved in several physiological processes regulating platelet activation. However, little is known about atypical PKC isoforms and particularly PKCι/λ has never been studied before in platelets. Therefore, platelet- and megakaryocyte-specific PKCι/λ knockout mice were used to assess its role in platelet function in vitro and in vivo. Surprisingly, PKCι/λ was found to be dispensable for platelet function in thrombosis and hemostasis.
Exploratory behavior of re-orienting foragers differs from other flight patterns of honeybees
(2018)
Honeybees, Apis mellifera, perform re-orientation flights to learn about the new surroundings of the hive when their hive is transported to a new location. Since the pattern of re-orientation flights has not yet been studied, we asked whether this form of exploratory behavior differs from the well described exploratory orientation flights performed by young honeybees before they start foraging. We also investigated whether the exploratory components of re-orientation flights differ from foraging flights and if so how. We recorded re-orientation flights using harmonic radar technology and compared the patterns and flight parameters of these flights with the first exploratory orientation flights of young honeybees and foraging flights of experienced foragers. Just as exploratory orientation flights of young honeybees, re-orientation flights can be classified into short- and long-range flights, and most short-range re-orientation flights were performed under unfavorable weather conditions. This indicates that bees adapt the flight pattern of their re-orientation and orientation flights to changing weather conditions in a similar way. Unlike exploratory orientation flights, more than one sector of the landscape was explored during a long-range re-orientation flight, and significantly longer flight durations and flight distances were observed. Thus, re-orienting bees explored a larger terrain than bees performing their first exploratory orientation flight. By displacing some bees after their first re-orientation flight, we could demonstrate that a single re-orientation flight seems to be sufficient to learn the new location of the hive. The flight patterns of re-orientation flights differed clearly from those of foraging flights. Thus, re-orientation flights represent a special exploratory behavior that is triggered by a change in the location of the hive.