@article{RojasJimenezRieckWurzbacheretal.2019, author = {Rojas-Jimenez, Keilor and Rieck, Angelika and Wurzbacher, Christian and J{\"u}rgens, Klaus and Labrenz, Matthias and Grossart, Hans-Peter}, title = {A Salinity Threshold Separating Fungal Communities in the Baltic Sea}, series = {Frontiers in Microbiology}, volume = {10}, journal = {Frontiers in Microbiology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-302X}, doi = {10.3389/fmicb.2019.00680}, pages = {9}, year = {2019}, abstract = {Salinity is a significant factor for structuring microbial communities, but little is known for aquatic fungi, particularly in the pelagic zone of brackish ecosystems. In this study, we explored the diversity and composition of fungal communities following a progressive salinity decline (from 34 to 3 PSU) along three transects of ca. 2000 km in the Baltic Sea, the world's largest estuary. Based on 18S rRNA gene sequence analysis, we detected clear changes in fungal community composition along the salinity gradient and found significant differences in composition of fungal communities established above and below a critical value of 8 PSU. At salinities below this threshold, fungal communities resembled those from freshwater environments, with a greater abundance of Chytridiomycota, particularly of the orders Rhizophydiales, Lobulomycetales, and Gromochytriales. At salinities above 8 PSU, communities were more similar to those from marine environments and, depending on the season, were dominated by a strain of the LKM11 group (Cryptomycota) or by members of Ascomycota and Basidiomycota. Our results highlight salinity as an important environmental driver also for pelagic fungi, and thus should be taken into account to better understand fungal diversity and ecological function in the aquatic realm.}, language = {en} } @article{GonzalezFortesTassiTrucchietal.2019, author = {Gonzalez-Fortes, Gloria M. and Tassi, F. and Trucchi, E. and Henneberger, K. and Paijmans, Johanna L. A. and Diez-del-Molino, D. and Schroeder, H. and Susca, R. R. and Barroso-Ruiz, C. and Bermudez, F. J. and Barroso-Medina, C. and Bettencourt, A. M. S. and Sampaio, H. A. and Salas, A. and de Lombera-Hermida, A. and Fabregas Valcarce, Ram{\´o}n and Vaquero, M. and Alonso, S. and Lozano, Marina and Rodriguez-Alvarez, Xose Pedro and Fernandez-Rodriguez, C. and Manica, Andrea and Hofreiter, Michael and Barbujani, Guido}, title = {A western route of prehistoric human migration from Africa into the Iberian Peninsula}, series = {Proceedings of the Royal Society of London : B, Biological sciences}, volume = {286}, journal = {Proceedings of the Royal Society of London : B, Biological sciences}, number = {1895}, publisher = {Royal Society}, address = {London}, issn = {0962-8452}, doi = {10.1098/rspb.2018.2288}, pages = {10}, year = {2019}, abstract = {Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar.}, language = {en} } @article{AlkerSchwerdtleSchomburgetal.2019, author = {Alker, Wiebke and Schwerdtle, Tanja and Schomburg, Lutz and Haase, Hajo}, title = {A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum}, series = {International journal of molecular sciences}, volume = {20}, journal = {International journal of molecular sciences}, number = {16}, publisher = {MDPI}, address = {Basel}, issn = {1661-6596}, doi = {10.3390/ijms20164006}, pages = {13}, year = {2019}, abstract = {Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual's zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body's zinc status, and its suitability as a future biomarker for an individual's zinc status.}, language = {en} } @article{ZeitlerYeAndreyevaetal.2019, author = {Zeitler, Stefanie and Ye, Lian and Andreyeva, Aksana and Schumacher, Fabian and Monti, Juliana and N{\"u}rnberg, Bernd and Nowak, Gabriel and Kleuser, Burkhard and Reichel, Martin and Fejtova, Anna and Kornhuber, Johannes and Rhein, Cosima and Friedland, Kristina}, title = {Acid sphingomyelinase - a regulator of canonical transient receptor potential channel 6 (TRPC6) activity}, series = {Journal of neurochemistry}, volume = {150}, journal = {Journal of neurochemistry}, number = {6}, publisher = {Wiley}, address = {Hoboken}, issn = {0022-3042}, doi = {10.1111/jnc.14823}, pages = {678 -- 690}, year = {2019}, abstract = {Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM-induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non-selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John's wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin-induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6-mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration-related way. This effect was confirmed in whole-cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin-1-positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine-tuning their physical properties.}, language = {en} } @article{BeckmannBeckerKadowetal.2019, author = {Beckmann, Nadine and Becker, Katrin Anne and Kadow, Stephanie and Schumacher, Fabian and Kramer, Melanie and Kuehn, Claudine and Schulz-Schaeffer, Walter J. and Edwards, Michael J. and Kleuser, Burkhard and Gulbins, Erich and Carpinteiro, Alexander}, title = {Acid Sphingomyelinase Deficiency Ameliorates Farber Disease}, series = {International journal of molecular sciences}, volume = {20}, journal = {International journal of molecular sciences}, number = {24}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms20246253}, pages = {18}, year = {2019}, abstract = {Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can't achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.}, language = {en} } @article{AndresDelgadoErnstGalardiCastillaetal.2019, author = {Andr{\´e}s-Delgado, Laura and Ernst, Alexander and Galardi-Castilla, Mar{\´i}a and Bazaga, David and Peralta, Marina and M{\"u}nch, Juliane and Gonzalez-Rosa, Juan M. and Marques, In{\^e}s and Tessadori, Federico and de la Pompa, Jos{\´e} Luis and Vermot, Julien and Mercader, Nadia}, title = {Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells}, series = {Development : Company of Biologists}, volume = {146}, journal = {Development : Company of Biologists}, number = {13}, publisher = {The Company of Biologists Ltd}, address = {Cambridge}, issn = {0950-1991}, doi = {10.1242/dev.174961}, pages = {15}, year = {2019}, abstract = {The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis, the epicardium arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium (DP) close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using a zebrafish model and a combination of genetic tools, pharmacological agents and quantitative in vivo imaging, we reveal that a coordinated collective movement of DP cells drives PE formation. We found that Bmp signaling and the actomyosin cytoskeleton promote constriction of the DP, which enables PE cells to extrude apically. We provide evidence that cell extrusion, which has been described in the elimination of unfit cells from epithelia and the emergence of hematopoietic stem cells, is also a mechanism for PE cells to exit an organized mesothelium and fulfil their developmental fate to form a new tissue layer, the epicardium.}, language = {en} } @article{RadchukReedTeplitskyetal.2019, author = {Radchuk, Viktoriia and Reed, Thomas and Teplitsky, Celine and van de Pol, Martijn and Charmantier, Anne and Hassall, Christopher and Adamik, Peter and Adriaensen, Frank and Ahola, Markus P. and Arcese, Peter and Miguel Aviles, Jesus and Balbontin, Javier and Berg, Karl S. and Borras, Antoni and Burthe, Sarah and Clobert, Jean and Dehnhard, Nina and de Lope, Florentino and Dhondt, Andre A. and Dingemanse, Niels J. and Doi, Hideyuki and Eeva, Tapio and Fickel, J{\"o}rns and Filella, Iolanda and Fossoy, Frode and Goodenough, Anne E. and Hall, Stephen J. G. and Hansson, Bengt and Harris, Michael and Hasselquist, Dennis and Hickler, Thomas and Jasmin Radha, Jasmin and Kharouba, Heather and Gabriel Martinez, Juan and Mihoub, Jean-Baptiste and Mills, James A. and Molina-Morales, Mercedes and Moksnes, Arne and Ozgul, Arpat and Parejo, Deseada and Pilard, Philippe and Poisbleau, Maud and Rousset, Francois and R{\"o}del, Mark-Oliver and Scott, David and Carlos Senar, Juan and Stefanescu, Constanti and Stokke, Bard G. and Kusano, Tamotsu and Tarka, Maja and Tarwater, Corey E. and Thonicke, Kirsten and Thorley, Jack and Wilting, Andreas and Tryjanowski, Piotr and Merila, Juha and Sheldon, Ben C. and Moller, Anders Pape and Matthysen, Erik and Janzen, Fredric and Dobson, F. Stephen and Visser, Marcel E. and Beissinger, Steven R. and Courtiol, Alexandre and Kramer-Schadt, Stephanie}, title = {Adaptive responses of animals to climate change are most likely insufficient}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-019-10924-4}, pages = {14}, year = {2019}, abstract = {Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.}, language = {en} } @article{SchroeterNeugartSchreineretal.2019, author = {Schr{\"o}ter, David and Neugart, Susanne and Schreiner, Monika and Grune, Tilman and Rohn, Sascha and Ott, Christiane}, title = {Amaranth's 2-Caffeoylisocitric Acid—An Anti-Inflammatory Caffeic Acid Derivative That Impairs NF-κB Signaling in LPS-Challenged RAW 264.7 Macrophages}, series = {Nutrients}, volume = {11}, journal = {Nutrients}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu11030571}, pages = {14}, year = {2019}, abstract = {For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth's anti-inflammatory properties and highlights C-IA's potential as a health-beneficial compound for future research.}, language = {en} } @article{LiuFengGuetal.2019, author = {Liu, Junzhong and Feng, Lili and Gu, Xueting and Deng, Xian and Qiu, Qi and Li, Qun and Zhang, Yingying and Wang, Muyang and Deng, Yiwen and Wang, Ertao and He, Yuke and B{\"a}urle, Isabel and Li, Jianming and Cao, Xiaofeng and He, Zuhua}, title = {An H3K27me3 demethylase-HSFA2 regulatory loop orchestrates transgenerational thermomemory in Arabidopsis}, series = {Cell research}, volume = {29}, journal = {Cell research}, number = {5}, publisher = {Nature Publ. Group}, address = {London}, issn = {1001-0602}, doi = {10.1038/s41422-019-0145-8}, pages = {379 -- 390}, year = {2019}, abstract = {Global warming has profound effects on plant growth and fitness. Plants have evolved sophisticated epigenetic machinery to respond quickly to heat, and exhibit transgenerational memory of the heat-induced release of post-transcriptional gene silencing (PTGS). However, how thermomemory is transmitted to progeny and the physiological relevance are elusive. Here we show that heat-induced HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2) directly activates the H3K27me3 demethylase RELATIVE OF EARLY FLOWERING 6 (REF6), which in turn derepresses HSFA2. REF6 and HSFA2 establish a heritable feedback loop, and activate an E3 ubiquitin ligase, SUPPRESSOR OF GENE SILENCING 3 (SGS3)-INTERACTING PROTEIN 1 (SGIP1). SGIP1-mediated SGS3 degradation leads to inhibited biosynthesis of trans-acting siRNA (tasiRNA). The REF6-HSFA2 loop and reduced tasiRNA converge to release HEAT-INDUCED TAS1 TARGET 5 (HTT5), which drives early flowering but attenuates immunity. Thus, heat induces transmitted phenotypes via a coordinated epigenetic network involving histone demethylases, transcription factors, and tasiRNAs, ensuring reproductive success and transgenerational stress adaptation.}, language = {en} } @article{BrauneGuetschowBlaut2019, author = {Braune, Annett and G{\"u}tschow, Michael and Blaut, Michael}, title = {An NADH-Dependent Reductase from Eubacterium ramulus Catalyzes the Stereospecific Heteroring Cleavage of Flavanones and Flavanonols}, series = {Applied and environmental microbiology}, volume = {85}, journal = {Applied and environmental microbiology}, number = {19}, publisher = {American Society for Microbiology}, address = {Washington}, issn = {0099-2240}, doi = {10.1128/AEM.01233-19}, pages = {15}, year = {2019}, abstract = {The human intestinal anaerobe Eubacterium ramulus is known for its ability to degrade various dietary flavonoids. In the present study, we demonstrate the cleavage of the heterocyclic C-ring of flavanones and flavanonols by an oxygen-sensitive NADH-dependent reductase, previously described as enoate reductase, from E. ramulus. This flavanone- and flavanonol-cleaving reductase (Fcr) was purified following its heterologous expression in Escherichia coli and further characterized. Fcr cleaved the flavanones naringenin, eriodictyol, liquiritigenin, and homoeriodictyol. Moreover, the flavanonols taxifolin and dihydrokaempferol served as substrates. The catalyzed reactions were stereospecific for the (2R)-enantiomers of the flavanone substrates and for the (25,35)-configured flavanonols. The enantioenrichment of the nonconverted stereoisomers allowed for the determination of hitherto unknown flavanone racemization rates. Fcr formed the corresponding dihydrochalcones and hydroxydihydrochalcones in the course of an unusual reductive cleavage of cyclic ether bonds. Fcr did not convert members of other flavonoid subclasses, including flavones, flavonols, and chalcones, the latter indicating that the reaction does not involve a chalcone intermediate. This view is strongly supported by the observed enantiospecificity of Fcr. Cinnamic acids, which are typical substrates of bacterial enoate reductases, were also not reduced by Fcr. Based on the presence of binding motifs for dinucleotide cofactors and a 4Fe-4S cluster in the amino acid sequence of Fcr, a cofactor-mediated hydride transfer from NADH onto C-2 of the respective substrate is proposed. IMPORTANCE Gut bacteria play a crucial role in the metabolism of dietary flavonoids, thereby contributing to their activation or inactivation after ingestion by the human host. Thus, bacterial activities in the intestine may influence the beneficial health effects of these polyphenolic plant compounds. While an increasing number of flavonoid-converting gut bacterial species have been identified, knowledge of the responsible enzymes is still limited. Here, we characterized Fcr as a key enzyme involved in the conversion of flavonoids of several subclasses by Eubacterium ramulus, a prevalent human gut bacterium. Sequence similarity of this enzyme to hypothetical proteins from other flavonoid-degrading intestinal bacteria in databases suggests a more widespread occurrence of this enzyme. Functional characterization of gene products of human intestinal microbiota enables the assignment of metagenomic sequences to specific bacteria and, more importantly, to certain activities, which is a prerequisite for targeted modulation of gut microbial functionality.}, language = {en} }