@article{KimShustaDoran2019,
  author    = {Kim, Brandon J. and Shusta, Eric V. and Doran, Kelly S.},
  title     = {Past and current perspectives in modeling bacteria and blood-brain barrier interactions},
  series = {Frontiers in Microbiology},
  volume    = {10},
  journal   = {Frontiers in Microbiology},
  number    = {1336},
  doi       = {10.3389/fmicb.2019.01336},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201766},
  year      = {2019},
  abstract  = {The central nervous system (CNS) barriers are highly specialized cellular barriers that promote brain homeostasis while restricting pathogen and toxin entry. The primary cellular constituent regulating pathogen entry in most of these brain barriers is the brain endothelial cell (BEC) that exhibits properties that allow for tight regulation of CNS entry. Bacterial meningoencephalitis is a serious infection of the CNS and occurs when bacteria can cross specialized brain barriers and cause inflammation. Models have been developed to understand the bacterial - BEC interaction that lead to pathogen crossing into the CNS, however, these have been met with challenges due to these highly specialized BEC phenotypes. This perspective provides a brief overview and outlook of the in vivo and in vitro models currently being used to study bacterial brain penetration, and opinion on improved models for the future.},
  language  = {en}
}
@article{StreinzerChakravortyNeumayeretal.2019,
  author    = {Streinzer, Martin and Chakravorty, Jharna and Neumayer, Johann and Megu, Karsing and Narah, Jaya and Schmitt, Thomas and Bharti, Himender and Spaethe, Johannes and Brockmann, Axel},
  title     = {Species composition and elevational distribution of bumble bees (Hymenoptera, Apidae, Bombus Latreille) in the East Himalaya, Arunachal Pradesh, India},
  series = {ZooKeys},
  volume    = {851},
  journal   = {ZooKeys},
  doi       = {10.3897/zookeys.851.32956},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201937},
  pages     = {71-89},
  year      = {2019},
  abstract  = {The East Himalaya is one of the world's most biodiverse ecosystems. However, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high elevation insects that fulfil an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Systematic study of Himalayan bumble bees began a few decades ago and the main focus has centred on the western region, while the eastern part of the mountain range has received little attention and only a few species have been verified. During a three-year survey, more than 700 bumble bee specimens of 21 species were collected in Arunachal Pradesh, the largest of the north-eastern states of India. The material included a range of species that were previously known from a limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat, and conservation. Clear elevation patterns of species diversity were observed, which raise important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya.},
  language  = {en}
}
@article{HarnošCanizalJuraseketal.2019,
  author    = {Harnoš, Jakub and Ca{\~n}izal, Maria Consuelo Alonso and Jur{\´a}sek, Miroslav and Kumar, Jitender and Holler, Cornelia and Schambony, Alexandra and Han{\´a}kov{\´a}, Kateřina and Bernat{\´i}k, Ondřej and Zdr{\´a}hal, Zbyn{\^e}k and G{\"o}m{\"o}ryov{\´a}, Krist{\´i}na and Gybeľ, Tom{\´a}š and Radaszkiewicz, Tomasz Witold and Kravec, Marek and Trant{\´i}rek, Luk{\´a}š and Ryneš, Jan and Dave, Zankruti and Fern{\´a}ndez-Llamazares, Ana Iris and V{\´a}cha, Robert and Tripsianes, Konstantinos and Hoffmann, Carsten and Bryja, V{\´i}tězslav},
  title     = {Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-09651-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227837},
  year      = {2019},
  abstract  = {Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.},
  language  = {en}
}
@article{KrausBrinkSiegel2019,
  author    = {Kraus, Amelie J. and Brink, Benedikt G. and Siegel, T. Nicolai},
  title     = {Efficient and specific oligo-based depletion of rRNA},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-48692-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224829},
  year      = {2019},
  abstract  = {In most organisms, ribosomal RNA (rRNA) contributes to >85\% of total RNA. Thus, to obtain useful information from RNA-sequencing (RNA-seq) analyses at reasonable sequencing depth, typically, mature polyadenylated transcripts are enriched or rRNA molecules are depleted. Targeted depletion of rRNA is particularly useful when studying transcripts lacking a poly(A) tail, such as some non-coding RNAs (ncRNAs), most bacterial RNAs and partially degraded or immature transcripts. While several commercially available kits allow effective rRNA depletion, their efficiency relies on a high degree of sequence homology between oligonucleotide probes and the target RNA. This restricts the use of such kits to a limited number of organisms with conserved rRNA sequences. In this study we describe the use of biotinylated oligos and streptavidin-coated paramagnetic beads for the efficient and specific depletion of trypanosomal rRNA. Our approach reduces the levels of the most abundant rRNA transcripts to less than 5\% with minimal off-target effects. By adjusting the sequence of the oligonucleotide probes, our approach can be used to deplete rRNAs or other abundant transcripts independent of species. Thus, our protocol provides a useful alternative for rRNA removal where enrichment of polyadenylated transcripts is not an option and commercial kits for rRNA are not available.},
  language  = {en}
}
@article{KimAmoresKangetal.2019,
  author    = {Kim, Bo-Mi and Amores, Angel and Kang, Seunghyun and Ahn, Do-Hwan and Kim, Jin-Hyoung and Kim, Il-Chan and Lee, Jun Hyuck and Lee, Sung Gu and Lee, Hyoungseok and Lee, Jungeun and Kim, Han-Woo and Desvignes, Thomas and Batzel, Peter and Sydes, Jason and Titus, Tom and Wilson, Catherine A. and Catchen, Julian M. and Warren, Wesley C. and Schartl, Manfred and Detrich, H. William III and Postlethwait, John H. and Park, Hyun},
  title     = {Antarctic blackfin icefish genome reveals adaptations to extreme environments},
  series = {Nature Ecology \& Evolution},
  volume    = {3},
  journal   = {Nature Ecology \& Evolution},
  doi       = {10.1038/s41559-019-0812-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325811},
  pages     = {469-478},
  year      = {2019},
  abstract  = {Icefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.},
  language  = {en}
}
@article{GotruvanGeffenNagyetal.2019,
  author    = {Gotru, Sanjeev Kiran and van Geffen, Johanna P. and Nagy, Magdolna and Mammadova-Bach, Elmina and Eilenberger, Julia and Volz, Julia and Manukjan, Georgi and Schulze, Harald and Wagner, Leonard and Eber, Stefan and Schambeck, Christian and Deppermann, Carsten and Brouns, Sanne and Nurden, Paquita and Greinacher, Andreas and Sachs, Ulrich and Nieswandt, Bernhard and Hermanns, Heike M. and Heemskerk, Johan W. M. and Braun, Attila},
  title     = {Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-44751-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227455},
  year      = {2019},
  abstract  = {Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d-/- mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2-/- mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2-/- and Unc13d-/- mice, and the impairment could be partially restored by extracellular Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.},
  language  = {en}
}
@article{NerreterLetschertGoetzetal.2019,
  author    = {Nerreter, Thomas and Letschert, Sebastian and G{\"o}tz, Ralph and Doose, S{\"o}ren and Danhof, Sophia and Einsele, Hermann and Sauer, Markus and Hudecek, Michael},
  title     = {Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-10948-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232258},
  year      = {2019},
  abstract  = {Immunotherapy with chimeric antigen receptor-engineered T-cells (CAR-T) is under investigation in multiple myeloma. There are reports of myeloma remission after CD19 CAR-T therapy, although CD19 is hardly detectable on myeloma cells by flow cytometry (FC). We apply single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM), and demonstrate CD19 expression on a fraction of myeloma cells (10.3-80\%) in 10 out of 14 patients (density: 13-5,000 molecules per cell). In contrast, FC detects CD19 in only 2 of these 10 patients, on a smaller fraction of cells. Treatment with CD19 CAR-T in vitro results in elimination of CD19-positive myeloma cells, including those with <100 CD19 molecules per cell. Similar data are obtained by dSTORM analyses of CD20 expression on myeloma cells and CD20 CAR-T. These data establish a sensitivity threshold for CAR-T and illustrate how super-resolution microscopy can guide patient selection in immunotherapy to exploit ultra-low density antigens.},
  language  = {en}
}
@article{SchurrSpindlerKurzetal.2019,
  author    = {Schurr, Yvonne and Spindler, Markus and Kurz, Hendrikje and Bender, Markus},
  title     = {The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-44183-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234966},
  year      = {2019},
  abstract  = {Coordinated reorganization of cytoskeletal structures is critical for key aspects of platelet physiology. While several studies have addressed the role of microtubules and filamentous actin in platelet production and function, the significance of their crosstalk in these processes has been poorly investigated. The microtubule-actin cross-linking factor 1 (MACF1; synonym: Actin cross-linking factor 7, ACF7) is a member of the spectraplakin family, and one of the few proteins expressed in platelets, which possess actin and microtubule binding domains thereby facilitating actin-microtubule interaction and regulation. We used megakaryocyte- and platelet-specific Macf1 knockout (Macf1fl/fl, Pf4-Cre) mice to study the role of MACF1 in platelet production and function. MACF1 deficient mice displayed comparable platelet counts to control mice. Analysis of the platelet cytoskeletal ultrastructure revealed a normal marginal band and actin network. Platelet spreading on fibrinogen was slightly delayed but platelet activation and clot traction was unaffected. Ex vivo thrombus formation and mouse tail bleeding responses were similar between control and mutant mice. These results suggest that MACF1 is dispensable for thrombopoiesis, platelet activation, thrombus formation and the hemostatic function in mice.},
  language  = {en}
}
@article{SteuerCostaVanderAuweraGlocketal.2019,
  author    = {Steuer Costa, Wagner and Van der Auwera, Petrus and Glock, Caspar and Liewald, Jana F. and Bach, Maximilian and Sch{\"u}ler, Christina and Wabnig, Sebastian and Oranth, Alexandra and Masurat, Florentin and Bringmann, Henrik and Schoofs, Liliane and Stelzer, Ernst H. K. and Fischer, Sabine C. and Gottschalk, Alexander},
  title     = {A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-12098-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223273},
  year      = {2019},
  abstract  = {Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.},
  language  = {en}
}
@article{DammertBraegelmannOlsenetal.2019,
  author    = {Dammert, Marcel A. and Br{\"a}gelmann, Johannes and Olsen, Rachelle R. and B{\"o}hm, Stefanie and Monhasery, Niloufar and Whitney, Christopher P. and Chalishazar, Milind D. and Tumbrink, Hannah L. and Guthrie, Matthew R. and Klein, Sebastian and Ireland, Abbie S. and Ryan, Jeremy and Schmitt, Anna and Marx, Annika and Ozretić, Luka and Castiglione, Roberta and Lorenz, Carina and Jachimowicz, Ron D. and Wolf, Elmar and Thomas, Roman K. and Poirier, John T. and B{\"u}ttner, Reinhard and Sen, Triparna and Byers, Lauren A. and Reinhardt, H. Christian and Letai, Anthony and Oliver, Trudy G. and Sos, Martin L.},
  title     = {MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-11371-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223569},
  year      = {2019},
  abstract  = {MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.},
  language  = {en}
}
@article{KrahBuentgenSchaeferetal.2019,
  author    = {Krah, Franz-Sebastian and B{\"u}ntgen, Ulf and Schaefer, Hanno and M{\"u}ller, J{\"o}rg and Andrew, Carrie and Boddy, Lynne and Diez, Jeffrey and Egli, Simon and Freckleton, Robert and Gange, Alan C. and Halvorsen, Rune and Heegaard, Einar and Heideroth, Antje and Heibl, Christoph and Heilmann-Clausen, Jacob and H{\o}iland, Klaus and Kar, Ritwika and Kauserud, H{\aa}vard and Kirk, Paul M. and Kuyper, Thomas W. and Krisai-Greilhuber, Irmgard and Norden, Jenni and Papastefanou, Phillip and Senn-Irlet, Beatrice and B{\"a}ssler, Claus},
  title     = {European mushroom assemblages are darker in cold climates},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-10767-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224815},
  year      = {2019},
  abstract  = {Thermal melanism theory states that dark-colored ectotherm organisms are at an advantage at low temperature due to increased warming. This theory is generally supported for ectotherm animals, however, the function of colors in the fungal kingdom is largely unknown. Here, we test whether the color lightness of mushroom assemblages is related to climate using a dataset of 3.2 million observations of 3,054 species across Europe. Consistent with the thermal melanism theory, mushroom assemblages are significantly darker in areas with cold climates. We further show differences in color phenotype between fungal lifestyles and a lifestyle differentiated response to seasonality. These results indicate a more complex ecological role of mushroom colors and suggest functions beyond thermal adaption. Because fungi play a crucial role in terrestrial carbon and nutrient cycles, understanding the links between the thermal environment, functional coloration and species' geographical distributions will be critical in predicting ecosystem responses to global warming.},
  language  = {en}
}
@article{MilaneseMendePaolietal.2019,
  author    = {Milanese, Alessio and Mende, Daniel R and Paoli, Lucas and Salazar, Guillem and Ruscheweyh, Hans-Joachim and Cuenca, Miguelangel and Hingamp, Pascal and Alves, Renato and Costea, Paul I and Coelho, Luis Pedro and Schmidt, Thomas S. B. and Almeida, Alexandre and Mitchell, Alex L and Finn, Robert D. and Huerta-Cepas, Jaime and Bork, Peer and Zeller, Georg and Sunagawa, Shinichi},
  title     = {Microbial abundance, activity and population genomic profiling with mOTUs2},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-08844-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224089},
  year      = {2019},
  abstract  = {Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30\% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites).},
  language  = {en}
}
@article{LeeLiRuanetal.2019,
  author    = {Lee, Hong-Jen and Li, Chien-Feng and Ruan, Diane and He, Jiabei and Montal, Emily D. and Lorenz, Sonja and Girnun, Geoffrey D. and Chan, Chia-Hsin},
  title     = {Non-proteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-10374-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236445},
  year      = {2019},
  abstract  = {Enormous efforts have been made to target metabolic dependencies of cancer cells for developing new therapies. However, the therapeutic efficacy of glycolysis inhibitors is limited due to their inability to elicit cell death. Hexokinase 2 (HK2), via its mitochondrial localization, functions as a central nexus integrating glycolysis activation and apoptosis resilience. Here we identify that K63-linked ubiquitination by HectH9 regulates the mitochondrial localization and function of HK2. Through stable isotope tracer approach and functional metabolic analyses, we show that HectH9 deficiency impedes tumor glucose metabolism and growth by HK2 inhibition. The HectH9/HK2 pathway regulates cancer stem cell (CSC) expansion and CSC-associated chemoresistance. Histological analyses show that HectH9 expression is upregulated and correlated with disease progression in prostate cancer. This work uncovers that HectH9 is a novel regulator of HK2 and cancer metabolism. Targeting HectH9 represents an effective strategy to achieve long-term tumor remission by concomitantly disrupting glycolysis and inducing apoptosis.},
  language  = {en}
}
@article{MercierWolmaransSchubertetal.2019,
  author    = {Mercier, Rebecca and Wolmarans, Annemarie and Schubert, Jonathan and Neuweiler, Hannes and Johnson, Jill L. and LaPointe, Paul},
  title     = {The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-09299-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224007},
  year      = {2019},
  abstract  = {Hsp90 is a dimeric molecular chaperone that is essential for the folding and activation of hundreds of client proteins. Co-chaperone proteins regulate the ATP-driven Hsp90 client activation cycle. Aha-type co-chaperones are the most potent stimulators of the Hsp90 ATPase activity but the relationship between ATPase regulation and in vivo activity is poorly understood. We report here that the most strongly conserved region of Aha-type co-chaperones, the N terminal NxNNWHW motif, modulates the apparent affinity of Hsp90 for nucleotide substrates. The ability of yeast Aha-type co-chaperones to act in vivo is ablated when the N terminal NxNNWHW motif is removed. This work suggests that nucleotide exchange during the Hsp90 functional cycle may be more important than rate of catalysis.},
  language  = {en}
}
@article{LuebckeEbbersVolzkeetal.2019,
  author    = {L{\"u}bcke, Paul M. and Ebbers, Meinolf N. B. and Volzke, Johann and Bull, Jana and Kneitz, Susanne and Engelmann, Robby and Lang, Hermann and Kreikemeyer, Bernd and M{\"u}ller-Hilke, Brigitte},
  title     = {Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-44512-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237355},
  year      = {2019},
  abstract  = {Recent studies indicate a causal relationship between the periodontal pathogen P. gingivalis and rheumatoid arthritis involving the production of autoantibodies against citrullinated peptides. We therefore postulated that therapeutic eradication P. gingivalis may ameliorate rheumatoid arthritis development and here turned to a mouse model in order to challenge our hypothesis. F1 (DBA/1 x B10.Q) mice were orally inoculated with P. gingivalis before collagen-induced arthritis was provoked. Chlorhexidine or metronidazole were orally administered either before or during the induction phase of arthritis and their effects on arthritis progression and alveolar bone loss were compared to intraperitoneally injected methotrexate. Arthritis incidence and severity were macroscopically scored and alveolar bone loss was evaluated via microcomputed tomography. Serum antibody titres against P. gingivalis were quantified by ELISA and microbial dysbiosis following oral inoculation was monitored in stool samples via microbiome analyses. Both, oral chlorhexidine and metronidazole reduced the incidence and ameliorated the severity of collagen-induced arthritis comparable to methotrexate. Likewise, all three therapies attenuated alveolar bone loss. Relative abundance of Porphyromonadaceae was increased after oral inoculation with P. gingivalis and decreased after treatment. This is the first study to describe beneficial effects of non-surgical periodontal treatment on collagen-induced arthritis in mice and suggests that mouthwash with chlorhexidine or metronidazole may also be beneficial for patients with rheumatoid arthritis and a coexisting periodontitis. Methotrexate ameliorated periodontitis in mice, further raising the possibility that methotrexate may also positively impact on the tooth supporting tissues of patients with rheumatoid arthritis.},
  language  = {en}
}
@article{WoodcockGarrattPowneyetal.2019,
  author    = {Woodcock, B. A. and Garratt, M. P. D. and Powney, G. D. and Shaw, R. F. and Osborne, J. L. and Soroka, J. and Lindstr{\"o}m, S. A. M. and Stanley, D. and Ouvrard, P. and Edwards, M. E. and Jauker, F. and McCracken, M. E. and Zou, Y. and Potts, S. G. and Rundl{\"o}f, M. and Noriega, J. A. and Greenop, A. and Smith, H. G. and Bommarco, R. and van der Werf, W. and Stout, J. C. and Steffan-Dewenter, I. and Morandin, L. and Bullock, J. M. and Pywell, R. F.},
  title     = {Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-09393-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233787},
  year      = {2019},
  abstract  = {How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.},
  language  = {en}
}
@article{AnnunziatavandeVlekkertWolfetal.2019,
  author    = {Annunziata, Ida and van de Vlekkert, Diantha and Wolf, Elmar and Finkelstein, David and Neale, Geoffrey and Machado, Eda and Mosca, Rosario and Campos, Yvan and Tillman, Heather and Roussel, Martine F. and Weesner, Jason Andrew and Fremuth, Leigh Ellen and Qiu, Xiaohui and Han, Min-Joon and Grosveld, Gerard C. and d'Azzo, Alessandra},
  title     = {MYC competes with MiT/TFE in regulating lysosomal biogenesis and autophagy through an epigenetic rheostat},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-11568-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221189},
  year      = {2019},
  abstract  = {Coordinated regulation of the lysosomal and autophagic systems ensures basal catabolism and normal cell physiology, and failure of either system causes disease. Here we describe an epigenetic rheostat orchestrated by c-MYC and histone deacetylases that inhibits lysosomal and autophagic biogenesis by concomitantly repressing the expression of the transcription factors MiT/TFE and FOXH1, and that of lysosomal and autophagy genes. Inhibition of histone deacetylases abates c-MYC binding to the promoters of lysosomal and autophagy genes, granting promoter occupancy to the MiT/TFE members, TFEB and TFE3, and/or the autophagy regulator FOXH1. In pluripotent stem cells and cancer, suppression of lysosomal and autophagic function is directly downstream of c-MYC overexpression and may represent a hallmark of malignant transformation. We propose that, by determining the fate of these catabolic systems, this hierarchical switch regulates the adaptive response of cells to pathological and physiological cues that could be exploited therapeutically.},
  language  = {en}
}
@article{HersterBittnerCodreaetal.2019,
  author    = {Herster, Franziska and Bittner, Zsofia and Codrea, Marius Cosmin and Archer, Nathan K. and Heister, Martin and L{\"o}ffler, Markus W. and Heumos, Simon and Wegner, Joanna and Businger, Ramona and Schindler, Michael and Stegner, David and Sch{\"a}kel, Knut and Grabbe, Stephan and Ghoreschi, Kamran and Miller, Lloyd S. and Weber, Alexander N. R.},
  title     = {Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2019.01867},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320175},
  year      = {2019},
  abstract  = {Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.},
  language  = {en}
}