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Müller, C.

Publications and source records attributed to Müller, C..

35 records · Page 2Linked to original sources
bioRxiv2023

Influences of chemotype and parental genotype on metabolic fingerprints of tansy plants uncovered by predictive metabolomics.

Intraspecific plant chemodiversity shapes plant-environment interactions. Within species, chemotypes can be defined according to variation in dominant specialised metabolites belonging to certain classes. Different ecological functions could be assigned to these distinct chemotypes. However, the roles of other metabolic variations and the parental genotype of the chemotypes remain poorly explored. Here, we first compared the capacity of terpenoid profiles and metabolic fingerprints to distinguish five chemotypes of common tansy (Tanacetum vulgare) and depict satellite metabolic differences. Metabolic fingerprints captured higher satellite variation while preserving the ability to define chemotypes. These satellite differences might influence plant performance and interactions with the environment. Next, to characterise the influence of the maternal genotype on chemodiversity, we performed variation partitioning and generalised linear modelling. Our findings revealed that maternal genotype was a higher source of chemical variation than chemotype. Predictive metabolomics unveiled 184 markers predicting maternal genotype with 89% accuracy. These markers included, among others, phenolics, whose functions in plant-environment interactions are well established. Hence, these findings place parental genotype at the forefront of intraspecific chemodiversity. We thus recommend considering this factor when comparing the ecology of various chemotypes. Besides, the combined inclusion of inherited and satellite metabolic variation in computational models may help connecting chemodiversity and evolutionary principles.

ecology↗
bioRxiv2023

Floral volatiles evoke partially similar responses in both florivores and pollinators and are correlated with non-volatile reward chemicals

BackgroundPlants use floral displays to attract mutualists, but simultaneously need to prevent attacks by antagonists. Chemical displays detectable from a distance include attractive or repellent floral volatile organic compounds (FVOCs). Post-landing, visitors perceive contact chemicals including nutrients, but also deterrent or toxic constituents in pollen and nectar, protecting flowers from overexploitation. The composition of FVOCs and pollen chemistry is well known to vary among and within species. However, we lack knowledge about differences and similarities in the detectability of and behavioural responses towards these compounds for insect flower visitor groups of key importance, i.e., mutualistic pollinators versus antagonistic florivores, as well as the correlation between FVOCs and pollen chemodiversity. ScopeWe reviewed how FVOCs and non-volatile floral chemical displays, i.e., nutrients and toxins of pollen, vary in composition and how they affect the detection and behaviour of insect flower visitors. Moreover, we used a meta-analytic approach to evaluate the detection of and responses towards FVOCs by pollinators vs. florivores within the same plant genera. Furthermore, we tested whether the chemodiversity of FVOCs as well as nutrients and toxins stored in pollen are correlated and hence informative about each other. Key ResultsAccording to the available data, florivores are more likely to detect FVOCs than pollinators. Common FVOCs such as linalool and methyl salicylate were often reported as attractive to pollinators and repellent towards florivores. A higher number of FVOCs was found to be attractive to both mutualists and antagonists compared to shared repellent compounds. Furthermore, a negative correlation between FVOC richness and the number of pollen toxin classes was revealed, besides a trend towards a positive correlation between pollen protein amount and the number of pollen toxins. ConclusionsPlants face critical trade-offs when producing floral chemicals, as these partly mediate the same information, particularly attraction but also repellence or toxicity, to both mutualists and antagonists. Moreover, chemodiversity of different floral parts is partly correlated and thus highly relevant for investigations of flower-insect interactions. Further research is needed on more different wild and cultivated plant species and mutualistic and antagonistic interaction partners to test for generalisation of these patterns.

ecology↗
bioRxiv2023

Microbial fingerprints reveal interaction between museum objects, curators and visitors

Microbiomes populate the border between humans and their environment. Whether the microbiome can be leveraged to gain information on human interaction with museum objects is unclear. To answer this question, museum objects varying in material and size from two museums, the Museum fur Naturkunde and the Pergamonmuseum in Berlin, Germany, which forms part of UNESCO World Heritage since 1999, were defined. In total 126 samples of natural and cultural heritage objects were taken with sterile nylon flocked swabs and subsequently subjected to 16S rRNA amplicon sequencing. By comparing the microbial composition of touched and untouched mollusc and fossil natural heritage objects we derived a robust microbial touch signature characterized by increased abundance of microbes known to be present in human skin. Application of this touch signature to cultural heritage objects from the Pergamonmuseum revealed areas of differential exposure to human contact on the Ishtar gate and Samal gate lions. Moreover, we were able to distinguish museum objects and personal office items touched by two different individuals with high sensitivity. Our results demonstrate that the microbial composition of museum objects gives insight into the degree of exposure to human contact, which is an important parameter for conservation and heritage science, and possibly provenance research.

microbiology↗
bioRxiv2022

State-dependency of behavioural traits is a function of the life-stage in a holometabolous insect

State variables, such as body condition, are important predictors of behavioural traits. Depending on the state of an individual, the costs and benefits associated with different behavioural decisions can vary. An individuals state could affect its average behavioural response and also the behavioural repeatability. Moreover, even for the same state, different behavioural strategies may be adaptive depending on the individuals life-stage. Here, we manipulated the body condition in larvae and adults of a holometabolous insect species, Athalia rosae, using starvation. We assessed the effects of starvation on the behavioural traits of post-contact immobility (PCI) and activity levels and tested their repeatability. Our results show state-dependency of behaviour, although the effect varied with life-stage. Starved larvae exhibited shorter PCI duration and higher activity levels, whereas starved adults were less active than non-starved individuals. Moreover, although most behavioural repeatability estimates were significant in both life-stages, we did not find any significant effect of starvation on the estimates. Next, we calculated standardised effect sizes to compare starvation effects across life stages. We found that starvation had a larger and opposite effect in the larval stage than during the adult stage for all behavioural traits. Finally, we conducted microcosm and no-choice bioassay experiments to examine the benefits and costs, respectively, of the behaviour elicited by starvation in the larval stage. We observed that starved larvae located food faster than non-starved larvae but were also attacked sooner by a predator, possibly due to their higher activity levels. Together, our results demonstrate that behavioural state-dependence is a function of the life-stage of an individual. Moreover, the behavioural strategy exhibited can be adaptive for a specific life-stage with respect to certain functions, like foraging, but also carry costs, like risk of predation.

animal behavior and cognition↗
bioRxiv2022

The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment

Invasive aspergillosis remains one of the most devastating fungal diseases and is predominantly linked to infections caused by the opportunistic human mold pathogen Aspergillus fumigatus. Major treatment regimens for the disease comprise the administration of antifungals belonging to the azole, polyene and echinocandin drug class. The prodrug 5-fluorocytosine (5FC), which is the only representative of a fourth class, the nucleobase analogs, shows unsatisfactory in vitro activities and is barely used for the treatment of aspergillosis. The main route of 5FC activation in A. fumigatus comprises its deamination into 5-fluorouracil (5FU) by FcyA, which is followed by Uprt-mediated 5FU phosphoribosylation into 5-fluorouridine monophosphate (5FUMP). In this study, we characterized and examined the role of a metabolic bypass that generates this nucleotide via 5-fluorouridine (5FUR) through uridine phosphorylase and uridine kinase activities. Resistance profiling of mutants lacking distinct pyrimidine salvage activities suggested a minor contribution of the alternative route in 5FUMP formation. We further analyzed the contribution of drug efflux in 5FC tolerance and found that A. fumigatus cells exposed to 5FC reduce intracellular fluoropyrimidine levels through their export into the environment. This release, which was particularly high in mutants lacking Uprt, generates a toxic environment for cytosine deaminase lacking mutants as well as mammalian cells. Employing the broad-spectrum fungal efflux pump inhibitor clorgyline, we demonstrate synergistic properties of this compound in combination with 5FC, 5FU as well as 5FUR.

molecular biology↗
bioRxiv2022

Environmental DNA from archived leaves reveals widespread temporal turnover and biotic homogenization in forest arthropod communities

A major limitation of current reports on insect declines is the lack of standardized, long-term, and taxonomically broad time series. Here, we demonstrate the utility of environmental DNA from archived leaf material to characterize plant-associated arthropod communities. We base our work on several multi-decadal leaf time series from tree canopies in four land use types, which were sampled as part of a long-term environmental monitoring program across Germany. Using these highly standardized and well-preserved samples, we analyze temporal changes in communities of several thousand arthropod species belonging to 23 orders using metabarcoding and quantitative PCR. Our data do not support widespread declines of -diversity or genetic variation within sites. Instead, we find a gradual community turnover, which results in temporal and spatial biotic homogenization, across all land use types and all arthropod orders. Our results suggest that insect decline is more complex than mere -diversity loss, but can be driven by {beta}-diversity decay across space and time.

ecology↗
bioRxiv2022

Chemical defense acquired via pharmacophagy can lead to herd protection in a sawfly

Predation is an important selection pressure acting on organisms, with organisms evolving diverse anti-predator strategies to combat it. One such widespread strategy is chemical defense in which organisms either synthesize or extrinsically acquire defensive chemicals. Little is known about the intraspecific transfer of such chemicals and if such chemicals acquired from conspecifics can also serve as defense against predation. Here, we used adults of the turnip sawfly, Athalia rosae, which can acquire neo-clerodane diterpenoids ( clerodanoids) via pharmacophagy after exposure to the plant, Ajuga reptans. We show that clerodanoid access mediates protection against predation by mantids for the sawflies, both in a no-choice feeding assay and a microcosm setup. Moreover, even indirect access to clerodanoids, via nibbling on conspecifics that had access to the plant, resulted in protection against predation albeit to a much lower degree than direct access. Furthermore, sawflies that had no direct access to clerodanoids were less consumed by mantids when they were grouped with conspecifics that had direct access. Most, but not all, of such initially undefended sawflies could acquire clerodanoids from conspecifics that had direct access to the plant, although in low quantities. Together our results demonstrate that clerodanoids serve as chemical defense that can be intraspecifically transferred. Moreover, the presence of chemically defended individuals in a group can confer protection onto conspecifics that had no direct access to clerodanoids, suggesting a herd-protection effect.

ecology↗
bioRxiv2021

Live-cell microscopy or fluorescence anisotropy with budded baculoviruses - which way to go with measuring ligand binding to M4 muscarinic receptors?

M4 muscarinic receptor is a G protein-coupled receptor that has been associated with alcohol and cocaine abuse, Alzheimers disease and schizophrenia which makes it an interesting drug target. For many G protein-coupled receptors, the development of high-affinity fluorescence ligands has expanded the options for high throughput screening of drug candidates and serve as useful tools in fundamental receptor research. So far, the lack of suitable fluorescence ligands has limited studying M4 receptor ligand binding. Here, we explored the possibilities of using fluorescence-based methods for studying binding affinity and kinetics to M4 receptor of both labeled and unlabeled ligands. We used two TAMRA-labeled fluorescence ligands, UR-MK342 and UR-CG072, for assay development. Using budded baculovirus particles as M4 receptor preparation and fluorescence anisotropy method, we determined the affinities and binding kinetics of both fluorescence ligands. The fluorescence ligands could also be used as reported probes for determining binding affinities of a set of unlabeled ligands. Based on these results, we took a step further towards a more natural signaling system and developed a method using live CHO-K1-hM4R cells and automated fluorescence microscopy suitable for routine determination of unlabeled ligand affinities. For quantitative image analysis, we developed random forest and deep learning-based pipelines for cell segmentation. The pipelines were integrated into the user-friendly open-source Aparecium software. Both developed methods were suitable for measuring fluorescence ligand saturation binding, association and dissociation kinetics as well as for screening binding affinities of unlabeled ligands. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/473643v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@17dfac6org.highwire.dtl.DTLVardef@1db1760org.highwire.dtl.DTLVardef@dba2a0org.highwire.dtl.DTLVardef@191f149_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗
bioRxiv2021

Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here we find that expression of the tetraspan-transmembrane protein CMTM5 (Chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and CNS myelin. Genetic disruption of the Cmtm5-gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5-deficiency causes an early-onset progressive axonopathy, which we also observe in global and in tamoxifen-induced oligodendroglial Cmtm5-mutants. Presence of the Wlds mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis.

neuroscience↗
bioRxiv2021

Immune stimulation alters chemical profiles of Tribolium castaneum

Group-living individuals experience immerse risk of disease transmission and parasite infection. Especially in social, but also in some non-social insects, disease control with immunomodulation takes place not only via individual immune defenses, but also via infochemicals such as contact cues and (defensive) volatiles to mount a group level immunity. However, little is known about whether an activation of the immune system leads to changes in chemical phenotypes, which may mediate these responses. We here asked whether individual immune experience resulting from wounding or injection of heat-killed Bacillus thuringiensis leads to changes in the chemical profiles of female and male adult red flour beetles (Tribolium castaneum), which are non-social but gregarious. We analyzed insect extracts using GC-FID to study the chemical composition of (1) cuticular hydrocarbons (CHCs) as candidates for the transfer of immunity-related information between individuals via contact, and (2) stink gland secretions, with target analysis of benzoquinones as main active compounds regulating external immunity. Despite a pronounced sexual dimorphism in CHC profiles, wounding stimulation led to similar profile changes in males and females with increases in the proportion of methyl-branched alkanes compared to naive beetles. While changes in the overall secretion profiles were less pronounced, absolute amounts of benzoquinones were transiently elevated in wounded compared to naive females. We suggest that the changes in different infochemicals may mediate immune status signaling in the context of both internal and external immune responses in groups of this non-social insect, thus showing parallels to social immunity.

evolutionary biology↗
bioRxiv2021

Sex and origin-specific inbreeding effects on flower attractiveness to specialised pollinators

We investigate whether inbreeding has particularly fatal consequences for dioecious plants by diminishing their floral attractiveness and the associated pollinator visitation rates disproportionally in females. We also test whether the magnitude of such effects depends on the evolutionary histories of plant populations. We recorded spatial, olfactory, colour and rewarding flower attractiveness traits as well as pollinator visitation rates in experimentally inbred and outbred, male and female Silene latifolia plants from European and North American populations differing in their evolutionary histories. We found that inbreeding specifically impairs spatial and olfactory attractiveness. Our results support that sex-specific selection and gene expression partially magnified these inbreeding costs for females, and that divergent evolutionary histories altered the genetic architecture underlying inbreeding effects across population origins. Moreover, they highlight that inbreeding effects on olfactory attractiveness have a huge potential to disrupt interactions among plants and specialist moth pollinators, which are mediated by elaborate chemical communication.

ecology↗
bioRxiv2020

Novelty at second glance: A critical appraisal of the novel-object paradigm based onmeta-analysis.

The study of consistent individual differences in behaviour has become an important focus in research on animal behaviour. Behavioural phenotypes are typically measured through standardized testing paradigms and one frequently used paradigm is the novel object test. In novel object tests, animals are exposed to new (unknown) objects and their reaction is quantified. When repeating trials to assess the temporal consistency of individual differences, researchers face the dilemma of whether to use the same or different novel objects, since the same stimulus can result in habituation, while exposure to different objects can result in context-dependent responses. We performed a quantitative assessment of 254 effect sizes from 113 studies on novel-object trials to evaluate the properties of this testing paradigm, in particular the effect of object novelty and time interval between novel-object trials on estimates of individual consistency. We found an increase of sample sizes and an increase of estimates of repeatabilities with time. The vast majority of short-term studies ( one month) used either the same or different novel objects about equally often. The average estimate for individual consistency was r = 0.47 (short-term r = 0.52, long-term r = 0.44). Novelty, time interval between trials and their interaction together explained only 3% of the total heterogeneity. Overall, novelobject trials reliably estimate individual differences in behaviour, but results were very heterogeneous even within the same study species, suggesting susceptibility to unknown details in testing conditions. Most studies that measure novel-object responses in association with food label the trait as neophobia, while novel-object trials in a neutral context are labelled variously as boldness/shyness, exploratory behaviour or neophobia/neophilia. Neophobia/neophilia is also the term most specific to novel object presentations. To avoid ambiguity, we suggest object neophobia/neophilia as the most specific label for novel-object responses.

animal behavior and cognition↗
bioRxiv2020

C/EBPβ regulates hypertrophic versus hyperplastic fat tissue growth

Chronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged - hypertrophic - adipocytes that are a source of inflammatory mediators, which is seen as causal for developing metabolic disorders. Yet, in certain healthy obese individuals fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. In a previous study we demonstrated that C/EBP{beta}-LIP deficient, yet C/EBP{beta}-LAP proficient mice show an expanded health and lifespan. Here we show that in mice on a high-fat diet LIP-deficiency results in adipocyte hyperplasia as well as efficient fat storage in subcutaneous depots associated with metabolic and inflammatory improvements. Our data identify C/EBP{beta} as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.

physiology↗
bioRxiv2019

Morphologically and physiologically diverse fruits of two Lepidium species differ in allocation of glucosinolates into immature and mature seed and pericarp

The morphology and physiology of diaspores play crucial roles in determining the fate of seeds in unpredictable habitats. In some genera of the Brassicaceae different types of diaspores can be found. Lepidium appelianum produces non-dormant seeds within indehiscent fruits while in L. campestre dormant seeds are released from dehiscent fruits. These different diaspore types offer an excellent model system to analyse the allocation of relevant defence compounds into different tissues, which may maximise diaspore fitness. Total glucosinolate concentration and composition were analysed in immature and mature seeds and pericarps of L. appelianum and L. campestre using high-performance liquid chromatography. Moreover, transgenic RNAi L. campestre lines were used for comparison that produce indehiscent fruits due to silencing of LcINDEHISCENCE, the INDEHISCENCE ortholog of L. campestre. Total glucosinolate concentrations were lower in green compared to mature seeds in all studied Lepidium species and transgenic lines. In contrast, indehiscent fruits of L. appelianum maintained their total glucosinolate concentration in mature pericarps compared to green ones, while in dehiscent L. campestre and in indehiscent RNAi-LcIND L. campestre a significant decrease in total glucosinolate concentrations from green to mature pericarps could be detected. Regarding the distribution of glucosinolate classes, high concentrations of 4-methoxyindol-3-ylmethyl glucosinolate were found in mature seeds of L. appelianum, while no indole glucosinolates were detected in mature diaspores of L. campestre. The diaspores of the latter species may rather depend on aliphatic and aromatic glucosinolates for long-term protection. The allocation patterns of glucosinolates correlate with the morpho-physiologically distinct fruits of L. appelianum and L. campestre and may be explained by the distinct dispersal strategies and the dormancy status of both species.

plant biology↗
bioRxiv2019

ResQ, a release factor-dependent ribosome rescue factor in the Gram-positive bacterium Bacillus subtilis

Rescue of the ribosomes from dead-end translation complexes, such as those on truncated (non-stop) mRNA, is essential for the cell. Whereas bacteria use trans-translation for ribosome rescue, some Gram-negative species possess alternative and release factor (RF)-dependent rescue factors, which enable an RF to catalyze stop codon-independent polypeptide release. We now discover that the Gram-positive Bacillus subtilis has an evolutionarily distinct ribosome rescue factor named ResQ. Genetic analysis shows that B. subtilis requires the function of either trans-translation or ResQ for growth, even in the absence of proteotoxic stresses. Biochemical and cryo-EM characterization demonstrates that ResQ binds to non-stop stalled ribosomes, recruits homologous RF2, but not RF1, and induces its transition into an open active conformation. Although ResQ is distinct from E. coli ArfA, they use convergent strategies in terms of mode of action and expression regulation, indicating that many bacteria may have evolved as yet unidentified ribosome rescue systems.

molecular biology↗
bioRxiv2019

Arabidopsis glutathione reductase 2 is indispensable in plastids, while mitochondrial glutathione is safeguarded by additional reduction and transport systems

O_LIA highly negative glutathione redox potential (EGSH) is maintained in the cytosol, plastids and mitochondria of plant cells to support fundamental processes, including antioxidant defence, redox regulation and iron-sulfur cluster biogenesis. Out of two glutathione reductase (GR) proteins in Arabidopsis, GR2 is predicted to be dual-targeted to plastids and mitochondria, but its differential roles in these organelles remain unclear.\nC_LIO_LIWe dissected the role of GR2 in organelle glutathione redox homeostasis and plant development using a combination of genetic complementation and stacked mutants, biochemical activity studies, immunogold labelling and in vivo biosensing.\nC_LIO_LIOur data demonstrate that GR2 is dual-targeted to plastids and mitochondria, but embryo lethality of gr2 null mutants is caused specifically in plastids. Whereas lack of mitochondrial GR2 leads to a partially oxidised glutathione pool in the matrix, the ABC transporter ATM3 and the mitochondrial thioredoxin system provide functional backup and maintain plant viability.\nC_LIO_LIWe identify GR2 as essential in the plastid stroma, where it counters GSSG accumulation and developmental arrest. By contrast a functional triad of GR2, ATM3 and the thioredoxin system in the mitochondria provides resilience to excessive glutathione oxidation.\nC_LI

plant biology↗
bioRxiv2018

Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice

Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBP {beta} -LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the C/EBP {beta}-mRNA. Here we describe that reduced C/EBP {beta} -LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBP {beta}{Delta}uORF mice display an extended lifespan. Since LIP levels increase upon aging in wt mice, our data reveal an important role for C/EBP{beta} in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBP {beta} -LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

cell biology↗