TY  - JOUR
A1  - Thomas, H. J. D.
A1  - Myers‐Smith, I. H.
A1  - Bjorkman, A. D.
A1  - Elmendorf, S. C.
A1  - Blok, D.
A1  - Cornelissen, J. H. C.
A1  - Forbes, B. C.
A1  - Hollister, R. D.
A1  - Normand, S.
A1  - Prevéy, J. S.
A1  - Rixen, C.
A1  - Schaepman‐Strub, G.
A1  - Wilmking, M.
A1  - Wipf, S.
A1  - Cornwell, W. K.
A1  - Kattge, J.
A1  - Goetz, S. J.
A1  - Guay, K. C.
A1  - Alatalo, J. M.
A1  - Anadon‐Rosell, A.
A1  - Angers‐Blondin, S.
A1  - Berner, L. T.
A1  - Björk, R. G.
A1  - Buchwal, A.
A1  - Buras, A.
A1  - Carbognani, M.
A1  - Christie, K.
A1  - Siegwart Collier, L.
A1  - Cooper, E. J.
A1  - Eskelinen, A.
A1  - Frei, E. R.
A1  - Grau, O.
A1  - Grogan, P.
A1  - Hallinger, M.
A1  - Heijmans, M. M. P. D.
A1  - Hermanutz, L.
A1  - Hudson, J. M. G.
A1  - Hülber, K.
A1  - Iturrate‐Garcia, M.
A1  - Iversen, C. M.
A1  - Jaroszynska, F.
A1  - Johnstone, J. F.
A1  - Kaarlejärvi, E.
A1  - Kulonen, A.
A1  - Lamarque, L. J.
A1  - Lévesque, E.
A1  - Little, C. J.
A1  - Michelsen, A.
A1  - Milbau, A.
A1  - Nabe‐Nielsen, J.
A1  - Nielsen, S. S.
A1  - Ninot, J. M.
A1  - Oberbauer, S. F.
A1  - Olofsson, J.
A1  - Onipchenko, V. G.
A1  - Petraglia, A.
A1  - Rumpf, S. B.
A1  - Semenchuk, P. R.
A1  - Soudzilovskaia, N. A.
A1  - Spasojevic, M. J.
A1  - Speed, J. D. M.
A1  - Tape, K. D.
A1  - te Beest, M.
A1  - Tomaselli, M.
A1  - Trant, A.
A1  - Treier, U. A.
A1  - Venn, S.
A1  - Vowles, T.
A1  - Weijers, S.
A1  - Zamin, T.
A1  - Atkin, O. K.
A1  - Bahn, M.
A1  - Blonder, B.
A1  - Campetella, G.
A1  - Cerabolini, B. E. L.
A1  - Chapin III, F. S.
A1  - Dainese, M.
A1  - de Vries, F. T.
A1  - Díaz, S.
A1  - Green, W.
A1  - Jackson, R. B.
A1  - Manning, P.
A1  - Niinemets, Ü.
A1  - Ozinga, W. A.
A1  - Peñuelas, J.
A1  - Reich, P. B.
A1  - Schamp, B.
A1  - Sheremetev, S.
A1  - van Bodegom, P. M.
T1  - Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome
JF  - Global Ecology and Biogeography
N2  - Aim
Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits.

Location
Tundra biome.

Time period
Data collected between 1964 and 2016.

Major taxa studied
295 tundra vascular plant species.

Methods
We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits.

Results
Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression.

Main conclusions
Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.
KW  - cluster analysis
KW  - community composition
KW  - ecosystem function
KW  - plant functional groups
KW  - plant functional types
KW  - plant traits
KW  - tundra biome
KW  - vegetation change
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241310
VL  - 28
ER  - 
TY  - JOUR
A1  - Müller, Jörg
A1  - Noss, Reed F.
A1  - Thorn, Simon
A1  - Bässler, Claus
A1  - Leverkus, Alexandro B.
A1  - Lindenmayer, David
T1  - Increasing disturbance demands new policies to conserve intact forest
JF  - Conservation Letters
N2  - Ongoing controversy over logging the ancient Białowieża Forest in Poland symbolizes a global problem for policies and management of the increasing proportion of the earth's intact forest that is subject to postdisturbance logging. We review the extent of, and motivations for, postdisturbance logging in protected and unprotected forests globally. An unprecedented level of logging in protected areas and other places where green-tree harvest would not normally occur is driven by economic interests and a desire for pest control. To avoid failure of global initiatives dedicated to reducing the loss of species, five key policy reforms are necessary: (1) salvage logging must be banned from protected areas; (2) forest planning should address altered disturbance regimes for all intact forests to ensure that significant areas remain undisturbed by logging; (3) new kinds of integrated analyses are needed to assess the potential economic benefits of salvage logging against its ecological, economic, and social costs; (4) global and regional maps of natural disturbance regimes should be created to guide better spatiotemporal planning of protected areas and undisturbed forests outside reserves; and (5) improved education and communication programs are needed to correct widely held misconceptions about natural disturbances.
KW  - anthropogenic disturbance
KW  - forestry
KW  - FSC
KW  - natural disturbance
KW  - protected area management
KW  - sanitary logging
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224256
VL  - 12
ER  - 
TY  - JOUR
A1  - Bahram, Mohammad
A1  - Anslan, Sten
A1  - Hildebrand, Falk
A1  - Bork, Peer
A1  - Tedersoo, Leho
T1  - Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment
JF  - Environmental Microbiology Reports
N2  - High-throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up-to-date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family- to phylum-level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221380
VL  - 11
ER  - 
TY  - JOUR
A1  - König, Kerstin
A1  - Zundel, Petra
A1  - Krimmer, Elena
A1  - König, Christian
A1  - Pollmann, Marie
A1  - Gottlieb, Yuval
A1  - Steidle, Johannes L. M.
T1  - Reproductive isolation due to prezygotic isolation and postzygotic cytoplasmic incompatibility in parasitoid wasps
JF  - Ecology and Evolution
N2  - The reproductive barriers that prevent gene flow between closely related species are a major topic in evolutionary research. Insect clades with parasitoid lifestyle are among the most species-rich insects and new species are constantly described, indicating that speciation occurs frequently in this group. However, there are only very few studies on speciation in parasitoids. We studied reproductive barriers in two lineages of Lariophagus distinguendus (Chalcidoidea: Hymenoptera), a parasitoid wasp of pest beetle larvae that occur in human environments. One of the two lineages occurs in households preferably attacking larvae of the drugstore beetle Stegobium paniceum (“DB-lineage”), the other in grain stores with larvae of the granary weevil Sitophilus granarius as main host (“GW-lineage”). Between two populations of the DB-lineage, we identified slight sexual isolation as intraspecific barrier. Between populations from both lineages, we found almost complete sexual isolation caused by female mate choice, and postzygotic isolation, which is partially caused by cytoplasmic incompatibility induced by so far undescribed endosymbionts which are not Wolbachia or Cardinium. Because separation between the two lineages is almost complete, they should be considered as separate species according to the biological species concept. This demonstrates that cryptic species within parasitoid Hymenoptera also occur in Central Europe in close contact to humans.
KW  - cytoplasmic incompatibility
KW  - endosymbiotic bacteria
KW  - Lariophagus distinguendus
KW  - parasitoid wasps
KW  - sexual isolation
KW  - speciation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222796
VL  - 9
ER  - 
TY  - JOUR
A1  - Hartke, Juliane
A1  - Sprenger, Philipp P.
A1  - Sahm, Jacqueline
A1  - Winterberg, Helena
A1  - Orivel, Jérôme
A1  - Baur, Hannes
A1  - Beuerle, Till
A1  - Schmitt, Thomas
A1  - Feldmeyer, Barbara
A1  - Menzel, Florian
T1  - Cuticular hydrocarbons as potential mediators of cryptic species divergence in a mutualistic ant association
JF  - Ecology and Evolution
N2  - Upon advances in sequencing techniques, more and more morphologically identical organisms are identified as cryptic species. Often, mutualistic interactions are proposed as drivers of diversification. Species of the neotropical parabiotic ant association between Crematogaster levior and Camponotus femoratus are known for highly diverse cuticular hydrocarbon (CHC) profiles, which in insects serve as desiccation barrier but also as communication cues. In the present study, we investigated the association of the ants’ CHC profiles with genotypes and morphological traits, and discovered cryptic species pairs in both genera. To assess putative niche differentiation between the cryptic species, we conducted an environmental association study that included various climate variables, canopy cover, and mutualistic plant species. Although mostly sympatric, the two Camponotus species seem to prefer different climate niches. However in the two Crematogaster species, we could not detect any differences in niche preference. The strong differentiation in the CHC profiles may thus suggest a possible role during speciation itself either by inducing assortative mating or by reinforcing sexual selection after the speciation event. We did not detect any further niche differences in the environmental parameters tested. Thus, it remains open how the cryptic species avoid competitive exclusion, with scope for further investigations.
KW  - environmental association
KW  - integrative taxonomy
KW  - niche differentiation
KW  - population structure
KW  - sexual selection
KW  - speciation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227857
VL  - 9
ER  - 
TY  - JOUR
A1  - Kendall, Liam K.
A1  - Rader, Romina
A1  - Gagic, Vesna
A1  - Cariveau, Daniel P.
A1  - Albrecht, Matthias
A1  - Baldock, Katherine C. R.
A1  - Freitas, Breno M.
A1  - Hall, Mark
A1  - Holzschuh, Andrea
A1  - Molina, Francisco P.
A1  - Morten, Joanne M.
A1  - Pereira, Janaely S.
A1  - Portman, Zachary M.
A1  - Roberts, Stuart P. M.
A1  - Rodriguez, Juanita
A1  - Russo, Laura
A1  - Sutter, Louis
A1  - Vereecken, Nicolas J.
A1  - Bartomeus, Ignasi
T1  - Pollinator size and its consequences: Robust estimates of body size in pollinating insects
JF  - Ecology and Evolution
N2  - Body size is an integral functional trait that underlies pollination-related ecological processes, yet it is often impractical to measure directly. Allometric scaling laws have been used to overcome this problem. However, most existing models rely upon small sample sizes, geographically restricted sampling and have limited applicability for non-bee taxa. Allometric models that consider biogeography, phylogenetic relatedness, and intraspecific variation are urgently required to ensure greater accuracy. We measured body size as dry weight and intertegular distance (ITD) of 391 bee species (4,035 specimens) and 103 hoverfly species (399 specimens) across four biogeographic regions: Australia, Europe, North America, and South America. We updated existing models within a Bayesian mixed-model framework to test the power of ITD to predict interspecific variation in pollinator dry weight in interaction with different co-variates: phylogeny or taxonomy, sexual dimorphism, and biogeographic region. In addition, we used ordinary least squares regression to assess intraspecific dry weight ~ ITD relationships for ten bees and five hoverfly species. Including co-variates led to more robust interspecific body size predictions for both bees and hoverflies relative to models with the ITD alone. In contrast, at the intraspecific level, our results demonstrate that the ITD is an inconsistent predictor of body size for bees and hoverflies. The use of allometric scaling laws to estimate body size is more suitable for interspecific comparative analyses than assessing intraspecific variation. Collectively, these models form the basis of the dynamic R package, “pollimetry,” which provides a comprehensive resource for allometric pollination research worldwide.
KW  - Apoidea
KW  - biogeography
KW  - body size
KW  - dry weight
KW  - pollimetry
KW  - pollination
KW  - predictive models
KW  - R package
KW  - Syrphidae
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325705
VL  - 9
ER  - 
TY  - JOUR
A1  - Baluapuri, Apoorva
A1  - Hofstetter, Julia
A1  - Dudvarski Stankovic, Nevenka
A1  - Endres, Theresa
A1  - Bhandare, Pranjali
A1  - Vos, Seychelle Monique
A1  - Adhikari, Bikash
A1  - Schwarz, Jessica Denise
A1  - Narain, Ashwin
A1  - Vogt, Markus
A1  - Wang, Shuang-Yan
A1  - Düster, Robert
A1  - Jung, Lisa Anna
A1  - Vanselow, Jens Thorsten
A1  - Wiegering, Armin
A1  - Geyer, Matthias
A1  - Maric, Hans Michael
A1  - Gallant, Peter
A1  - Walz, Susanne
A1  - Schlosser, Andreas
A1  - Cramer, Patrick
A1  - Eilers, Martin
A1  - Wolf, Elmar
T1  - MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
JF  - Molecular Cell
N2  - The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.
KW  - MYC
KW  - SPT5
KW  - SUPT5H
KW  - SPT6
KW  - RNA polymerase II
KW  - transcription
KW  - elongation rate
KW  - processivity
KW  - directionality
KW  - tumorigenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221438
VL  - 74
ER  - 
TY  - JOUR
A1  - Seitz, Nicola
A1  - vanEngelsdorp, Dennis
A1  - Leonhardt, Sara D.
T1  - Conserving bees in destroyed landscapes: The potentials of reclaimed sand mines
JF  - Global Ecology and Conservation
N2  - Sand mines represent anthropogenically impacted habitats found worldwide, which bear potential for bee conservation. Although floral resources can be limited at these habitats, vegetation free patches of open sandy soils and embankments may offer good nesting possibilities for sand restricted and other bees. We compared bee communities as found in three reclaimed sand mines and at adjacent roadside meadows in Maryland, USA, over two years. Both sand mines and roadsides hosted diverse bee communities with 111 and 88 bee species, respectively. Bee abundances as well as richness and Shannon diversity of bee species were higher in sand mines than at roadsides and negatively correlated with the percentage of vegetational ground cover. Species composition also differed significantly between habitats. Sand mines hosted a higher proportion of ground nesters, more uncommon and more ‘sand loving’ bees similar to natural sandy areas of Maryland. Despite the destruction of the original pre-mining habitat, sand mines thus appear to represent a unique habitat for wild bees, particularly when natural vegetation and open sand spots are encouraged. Considering habitat loss, the lack of natural disturbance regimes, and ongoing declines of wild bees, sand mines could add promising opportunities for bee conservation which has hitherto mainly focused on agricultural and urban habitats.
KW  - bee conservation
KW  - bee decline
KW  - habitat restoration
KW  - land use
KW  - wild bees
KW  - ground nesters
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235877
VL  - 19
ER  - 
TY  - JOUR
A1  - Hofrichter, Michaela A. H.
A1  - Doll, Julia
A1  - Habibi, Haleh
A1  - Enayati, Samaneh
A1  - Mehrjardi, Mohammad Yahya Vahidi
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - Haaf, Thomas
A1  - Vona, Barbara
T1  - Exome-wide copy number variation analysis identifies a COL9A1 in frame deletion that is associated with hearing loss
JF  - European Journal of Medical Genetics
N2  - Pathogenic variants in COL9A1 are primarily associated with autosomal recessive Stickler syndrome. Patients with COL9A1-associated Stickler syndrome (STL) present hearing loss (HL), ophthalmic manifestations and skeletal abnormalities. However, the clinical spectrum of patients with COL9A1 variants can also include multiple epiphyseal dysplasia, as well as non-syndromic HL that was observed in one previously reported proband. Exome sequencing was performed on the genomic DNA of an Iranian patient and his affected brother who both report non-syndromic HL. A 44.6 kb homozygous in-frame deletion spanning exons 6 to 33 of COL9A1 was detected via exome-based copy number variation analysis. The deleted exons were confirmed by PCR in the patient and his affected brother, who both have non-syndromic HL. Segregation analysis via qPCR confirmed the parents as heterozygous deletion carriers. Breakpoint analysis mapped the homozygous deletion spanning introns 5 to 33 (g.70,948,188_70,997,277del, NM_001851.4(COL9A1):c.697–3754_2112+769del, p.(Phe233_Ser704del), with an additional 67 bp of inserted intronic sequence that may have originated due to a fork stalling and template switching/microhomology-mediated break-induced replication (FoSTeS/MMBIR) mechanism. This mechanism has not been previously implicated in HL or STL. This is also the first reported copy number variation in COL9A1 that was identified through an exome data set in an Iranian family with apparent non-syndromic HL. The present study emphasizes the importance of exome-wide copy number variation analysis in molecular diagnosis and provides supporting evidence to associate COL9A1 with autosomal recessive non-syndromic HL.
KW  - COL9A1
KW  - copy number variation
KW  - FoSTeS/MMBIR mechanism
KW  - non-syndromic hearing loss
KW  - Stickler syndrome
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-322008
VL  - 62
ER  - 
TY  - JOUR
A1  - Mooij, Wolf M
A1  - van Wijk, Dianneke
A1  - Beusen, Arthur HW
A1  - Brederveld, Robert J
A1  - Chang, Manqi
A1  - Cobben, Marleen MP
A1  - DeAngelis, Don L
A1  - Downing, Andrea S
A1  - Green, Pamela
A1  - Gsell, Alena S
A1  - Huttunen, Inese
A1  - Janse, Jan H
A1  - Janssen, Annette BG
A1  - Hengeveld, Geerten M
A1  - Kong, Xiangzhen
A1  - Kramer, Lilith
A1  - Kuiper, Jan J
A1  - Langan, Simon J
A1  - Nolet, Bart A
A1  - Nuijten, Rascha JM
A1  - Strokal, Maryna
A1  - Troost, Tineke A
A1  - van Dam, Anne A
A1  - Teurlincx, Sven
T1  - Modeling water quality in the Anthropocene: directions for the next-generation aquatic ecosystem models
JF  - Current Opinion in Environmental Sustainability
N2  - “Everything changes and nothing stands still” (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models — and ecological models in general — as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224173
VL  - 36
ER  - 
TY  - JOUR
A1  - Milanese, Alessio
A1  - Mende, Daniel R
A1  - Paoli, Lucas
A1  - Salazar, Guillem
A1  - Ruscheweyh, Hans-Joachim
A1  - Cuenca, Miguelangel
A1  - Hingamp, Pascal
A1  - Alves, Renato
A1  - Costea, Paul I
A1  - Coelho, Luis Pedro
A1  - Schmidt, Thomas S. B.
A1  - Almeida, Alexandre
A1  - Mitchell, Alex L
A1  - Finn, Robert D.
A1  - Huerta-Cepas, Jaime
A1  - Bork, Peer
A1  - Zeller, Georg
A1  - Sunagawa, Shinichi
T1  - Microbial abundance, activity and population genomic profiling with mOTUs2
JF  - Nature Communications
N2  - 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).
KW  - microbiome
KW  - software
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224089
VL  - 10
ER  - 
TY  - JOUR
A1  - Krah, Franz-Sebastian
A1  - Büntgen, Ulf
A1  - Schaefer, Hanno
A1  - Müller, Jörg
A1  - Andrew, Carrie
A1  - Boddy, Lynne
A1  - Diez, Jeffrey
A1  - Egli, Simon
A1  - Freckleton, Robert
A1  - Gange, Alan C.
A1  - Halvorsen, Rune
A1  - Heegaard, Einar
A1  - Heideroth, Antje
A1  - Heibl, Christoph
A1  - Heilmann-Clausen, Jacob
A1  - Høiland, Klaus
A1  - Kar, Ritwika
A1  - Kauserud, Håvard
A1  - Kirk, Paul M.
A1  - Kuyper, Thomas W.
A1  - Krisai-Greilhuber, Irmgard
A1  - Norden, Jenni
A1  - Papastefanou, Phillip
A1  - Senn-Irlet, Beatrice
A1  - Bässler, Claus
T1  - European mushroom assemblages are darker in cold climates
JF  - Nature Communications
N2  - 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.
KW  - evolutionary ecology
KW  - fungal ecology
KW  - fungal evolution
KW  - macroecology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224815
VL  - 10
ER  - 
TY  - JOUR
A1  - Woodcock, B. A.
A1  - Garratt, M. P. D.
A1  - Powney, G. D.
A1  - Shaw, R. F.
A1  - Osborne, J. L.
A1  - Soroka, J.
A1  - Lindström, S. A. M.
A1  - Stanley, D.
A1  - Ouvrard, P.
A1  - Edwards, M. E.
A1  - Jauker, F.
A1  - McCracken, M. E.
A1  - Zou, Y.
A1  - Potts, S. G.
A1  - Rundlöf, M.
A1  - Noriega, J. A.
A1  - Greenop, A.
A1  - Smith, H. G.
A1  - Bommarco, R.
A1  - van der Werf, W.
A1  - Stout, J. C.
A1  - Steffan-Dewenter, I.
A1  - Morandin, L.
A1  - Bullock, J. M.
A1  - Pywell, R. F.
T1  - Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield
JF  - Nature Communications
N2  - 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.
KW  - agroecology
KW  - agriculture
KW  - ecosystem services
KW  - environmental sciences
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233787
VL  - 10
ER  - 
TY  - JOUR
A1  - Nerreter, Thomas
A1  - Letschert, Sebastian
A1  - Götz, Ralph
A1  - Doose, Sören
A1  - Danhof, Sophia
A1  - Einsele, Hermann
A1  - Sauer, Markus
A1  - Hudecek, Michael
T1  - Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T
JF  - Nature Communications
N2  - 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.
KW  - cancer imaging
KW  - cancer immunotherapy
KW  - imaging
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232258
VL  - 10
ER  - 
TY  - JOUR
A1  - Mercier, Rebecca
A1  - Wolmarans, Annemarie
A1  - Schubert, Jonathan
A1  - Neuweiler, Hannes
A1  - Johnson, Jill L.
A1  - LaPointe, Paul
T1  - The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation
JF  - Nature Communications
N2  - 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.
KW  - biophysics
KW  - cell growth
KW  - chaperones
KW  - enzymes
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224007
VL  - 10
ER  - 
TY  - JOUR
A1  - Lübcke, Paul M.
A1  - Ebbers, Meinolf N. B.
A1  - Volzke, Johann
A1  - Bull, Jana
A1  - Kneitz, Susanne
A1  - Engelmann, Robby
A1  - Lang, Hermann
A1  - Kreikemeyer, Bernd
A1  - Müller-Hilke, Brigitte
T1  - Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss
JF  - Scientific Reports
N2  - 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.
KW  - rheumatic diseases
KW  - rheumatology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237355
VL  - 9
ER  - 
TY  - JOUR
A1  - Lu, Yuan
A1  - Boswell, Wiliam
A1  - Boswell, Mikki
A1  - Klotz, Barbara
A1  - Kneitz, Susanne
A1  - Regneri, Janine
A1  - Savage, Markita
A1  - Mendoza, Cristina
A1  - Postlethwait, John
A1  - Warren, Wesley C.
A1  - Schartl, Manfred
A1  - Walter, Ronald B.
T1  - Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model
JF  - Scientific Reports
N2  - Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug developmental process. Phenotype screening using intact research animals is attractive because it can help identify small molecule candidate compounds that have a high probability of proceeding to clinical use. Most FDA approved, first-in-class small molecules were identified from phenotypic screening. However, phenotypic screening using rodent models is labor intensive, low-throughput, and very expensive. As a novel alternative for small molecule screening, we have been developing gene expression disease profiles, termed the Transcriptional Disease Signature (TDS), as readout of small molecule screens for therapeutic molecules. In this concept, compounds that can reverse, or otherwise affect known disease-associated gene expression patterns in whole animals may be rapidly identified for more detailed downstream direct testing of their efficacy and mode of action. To establish proof of concept for this screening strategy, we employed a transgenic strain of a small aquarium fish, medaka (Oryzias latipes), that overexpresses the malignant melanoma driver gene xmrk, a mutant egfr gene, that is driven by a pigment cell-specific mitf promoter. In this model, melanoma develops with 100% penetrance. Using the transgenic medaka malignant melanoma model, we established a screening system that employs the NanoString nCounter platform to quantify gene expression within custom sets of TDS gene targets that we had previously shown to exhibit differential transcription among xmrk-transgenic and wild-type medaka. Compound-modulated gene expression was identified using an internet-accessible custom-built data processing pipeline. The effect of a given drug on the entire TDS profile was estimated by comparing compound-modulated genes in the TDS using an activation Z-score and Kolmogorov-Smirnov statistics. TDS gene probes were designed that target common signaling pathways that include proliferation, development, toxicity, immune function, metabolism and detoxification. These pathways may be utilized to evaluate candidate compounds for potential favorable, or unfavorable, effects on melanoma-associated gene expression. Here we present the logistics of using medaka to screen compounds, as well as, the development of a user-friendly NanoString data analysis pipeline to support feasibility of this novel TDS drug-screening strategy.
KW  - bioinformatics
KW  - phenotypic screening
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237322
VL  - 9
ER  - 
TY  - JOUR
A1  - Kraus, Amelie J.
A1  - Brink, Benedikt G.
A1  - Siegel, T. Nicolai
T1  - Efficient and specific oligo-based depletion of rRNA
JF  - Scientific Reports
N2  - 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.
KW  - parasite biology
KW  - RNA sequencing
KW  - transcriptomics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224829
VL  - 9
ER  - 
TY  - JOUR
A1  - Kim, Bo-Mi
A1  - Amores, Angel
A1  - Kang, Seunghyun
A1  - Ahn, Do-Hwan
A1  - Kim, Jin-Hyoung
A1  - Kim, Il-Chan
A1  - Lee, Jun Hyuck
A1  - Lee, Sung Gu
A1  - Lee, Hyoungseok
A1  - Lee, Jungeun
A1  - Kim, Han-Woo
A1  - Desvignes, Thomas
A1  - Batzel, Peter
A1  - Sydes, Jason
A1  - Titus, Tom
A1  - Wilson, Catherine A.
A1  - Catchen, Julian M.
A1  - Warren, Wesley C.
A1  - Schartl, Manfred
A1  - Detrich, H. William III
A1  - Postlethwait, John H.
A1  - Park, Hyun
T1  - Antarctic blackfin icefish genome reveals adaptations to extreme environments
JF  - Nature Ecology & Evolution
N2  - 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.
KW  - animal physiology
KW  - evolutionary genetics
KW  - genomics
KW  - ichthyology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325811
VL  - 3
ER  - 
TY  - JOUR
A1  - Dörk, Thilo
A1  - Peterlongo, Peter
A1  - Mannermaa, Arto
A1  - Bolla, Manjeet K.
A1  - Wang, Qin
A1  - Dennis, Joe
A1  - Ahearn, Thomas
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Augustinsson, Annelie
A1  - Beane Freeman, Laura E.
A1  - Beckmann, Matthias W.
A1  - Beeghly-Fadiel, Alicia
A1  - Behrens, Sabine
A1  - Bermisheva, Marina
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Burwinkel, Barbara
A1  - Canzian, Federico
A1  - Chan, Tsun L.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Choi, Ji-Yeob
A1  - Christiansen, Hans
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - dos-Santos-Silva, Isabel
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ekici, Arif B.
A1  - Eriksson, Mikael
A1  - Evans, D. Gareth
A1  - Fasching, Peter A.
A1  - Figueroa, Jonine
A1  - Flyger, Henrik
A1  - Fritschi, Lin
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Gao, Chi
A1  - Gapstur, Susan M.
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - Guenél, Pascal
A1  - Haeberle, Lothar
A1  - Haimann, Christopher A.
A1  - Håkansson, Niclas
A1  - Hall, Per
A1  - Hamann, Ute
A1  - Hartman, Mikael
A1  - Hauke, Jan
A1  - Hein, Alexander
A1  - Hillemanns, Peter
A1  - Hogervorst, Frans B. L.
A1  - Hooning, Maartje J.
A1  - Hopper, John L.
A1  - Howell, Tony
A1  - Huo, Dezheng
A1  - Ito, Hidemi
A1  - Iwasaki, Motoki
A1  - Jakubowska, Anna
A1  - Janni, Wolfgang
A1  - John, Esther M.
A1  - Jung, Audrey
A1  - Kaaks, Rudolf
A1  - Kang, Daehee
A1  - Kapoor, Pooja Middha
A1  - Khusnutdinova, Elza
A1  - Kim, Sung-Won
A1  - Kitahara, Cari M.
A1  - Koutros, Stella
A1  - Kraft, Peter
A1  - Kristensen, Vessela N.
A1  - Kwong, Ava
A1  - Lambrechts, Diether
A1  - Le Marchand, Loic
A1  - Li, Jingmei
A1  - Lindström, Sara
A1  - Linet, Martha
A1  - Lo, Wing-Yee
A1  - Long, Jirong
A1  - Lophatananon, Artitaya
A1  - Lubiński, Jan
A1  - Manoochehri, Mehdi
A1  - Manoukian, Siranoush
A1  - Margolin, Sara
A1  - Martinez, Elena
A1  - Matsuo, Keitaro
A1  - Mavroudis, Dimitris
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Milne, Roger L.
A1  - Mohd Taib, Nur Aishah
A1  - Muir, Kenneth
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Neven, Patrick
A1  - Newman, William G.
A1  - Offit, Kenneth
A1  - Olopade, Olufunmilayo I.
A1  - Olshan, Andrew F.
A1  - Olson, Janet E.
A1  - Olsson, Håkan
A1  - Park, Sue K.
A1  - Park-Simon, Tjoung-Won
A1  - Peto, Julian
A1  - Plaseska-Karanfilska, Dijana
A1  - Pohl-Rescigno, Esther
A1  - Presneau, Nadege
A1  - Rack, Brigitte
A1  - Radice, Paolo
A1  - Rashid, Muhammad U.
A1  - Rennert, Gad
A1  - Rennert, Hedy S.
A1  - Romero, Atocha
A1  - Ruebner, Matthias
A1  - Saloustros, Emmanouil
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Schneider, Michael O.
A1  - Schoemaker, Minouk J.
A1  - Scott, Christopher
A1  - Shen, Chen-Yang
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Slager, Susan
A1  - Smichkoska, Snezhana
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Stone, Jennifer
A1  - Surowy, Harald
A1  - Swerdlow, Anthony J.
A1  - Tamimi, Rulla M.
A1  - Tapper, William J.
A1  - Teo, Soo H.
A1  - Terry, Mary Beth
A1  - Toland, Amanda E.
A1  - Tollenaar, Rob A. E. M.
A1  - Torres, Diana
A1  - Torres-Mejía, Gabriela
A1  - Troester, Melissa A.
A1  - Truong, Thérèse
A1  - Tsugane, Shoichiro
A1  - Untch, Michael
A1  - Vachon, Celine M.
A1  - van den Ouweland, Ans M. W.
A1  - van Veen, Elke M.
A1  - Vijai, Joseph
A1  - Wendt, Camilla
A1  - Wolk, Alicja
A1  - Yu, Jyh-Cherng
A1  - Zheng, Wei
A1  - Ziogas, Argyrios
A1  - Ziv, Elad
A1  - Dunnig, Alison
A1  - Pharaoh, Paul D. P.
A1  - Schindler, Detlev
A1  - Devilee, Peter
A1  - Easton, Douglas F.
T1  - Two truncating variants in FANCC and breast cancer risk
JF  - Scientific Reports
N2  - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW  - oncology
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL  - 9
ER  - 
TY  - JOUR
A1  - Dammert, Marcel A.
A1  - Brägelmann, Johannes
A1  - Olsen, Rachelle R.
A1  - Böhm, Stefanie
A1  - Monhasery, Niloufar
A1  - Whitney, Christopher P.
A1  - Chalishazar, Milind D.
A1  - Tumbrink, Hannah L.
A1  - Guthrie, Matthew R.
A1  - Klein, Sebastian
A1  - Ireland, Abbie S.
A1  - Ryan, Jeremy
A1  - Schmitt, Anna
A1  - Marx, Annika
A1  - Ozretić, Luka
A1  - Castiglione, Roberta
A1  - Lorenz, Carina
A1  - Jachimowicz, Ron D.
A1  - Wolf, Elmar
A1  - Thomas, Roman K.
A1  - Poirier, John T.
A1  - Büttner, Reinhard
A1  - Sen, Triparna
A1  - Byers, Lauren A.
A1  - Reinhardt, H. Christian
A1  - Letai, Anthony
A1  - Oliver, Trudy G.
A1  - Sos, Martin L.
T1  - MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer
JF  - Nature Communications
N2  - 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.
KW  - genetic engineering
KW  - oncogenes
KW  - small-cell lung cancer
KW  - targeted therapies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223569
VL  - 10
ER  - 
TY  - JOUR
A1  - Steuer Costa, Wagner
A1  - Van der Auwera, Petrus
A1  - Glock, Caspar
A1  - Liewald, Jana F.
A1  - Bach, Maximilian
A1  - Schüler, Christina
A1  - Wabnig, Sebastian
A1  - Oranth, Alexandra
A1  - Masurat, Florentin
A1  - Bringmann, Henrik
A1  - Schoofs, Liliane
A1  - Stelzer, Ernst H. K.
A1  - Fischer, Sabine C.
A1  - Gottschalk, Alexander
T1  - A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics
JF  - Nature Communications
N2  - 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.
KW  - cellular neuroscience
KW  - neural circuits
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223273
VL  - 10
ER  - 
TY  - JOUR
A1  - Annunziata, Ida
A1  - van de Vlekkert, Diantha
A1  - Wolf, Elmar
A1  - Finkelstein, David
A1  - Neale, Geoffrey
A1  - Machado, Eda
A1  - Mosca, Rosario
A1  - Campos, Yvan
A1  - Tillman, Heather
A1  - Roussel, Martine F.
A1  - Weesner, Jason Andrew
A1  - Fremuth, Leigh Ellen
A1  - Qiu, Xiaohui
A1  - Han, Min-Joon
A1  - Grosveld, Gerard C.
A1  - d'Azzo, Alessandra
T1  - MYC competes with MiT/TFE in regulating lysosomal biogenesis and autophagy through an epigenetic rheostat
JF  - Nature Communications
N2  - 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.
KW  - autophagy
KW  - cancer
KW  - cancer metabolism
KW  - cell biology
KW  - mechanisms of disease
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221189
VL  - 10
ER  - 
TY  - JOUR
A1  - Coelho, Luis Pedro
A1  - Alves, Renato
A1  - Monteiro, Paulo
A1  - Huerta-Cepas, Jaime
A1  - Freitas, Ana Teresa
A1  - Bork, Peer
T1  - NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language
JF  - Microbiome
N2  - Background
Shotgun metagenomes contain a sample of all the genomic material in an environment, allowing for the characterization of a microbial community. In order to understand these communities, bioinformatics methods are crucial. A common first step in processing metagenomes is to compute abundance estimates of different taxonomic or functional groups from the raw sequencing data.

Given the breadth of the field, computational solutions need to be flexible and extensible, enabling the combination of different tools into a larger pipeline.

Results
We present NGLess and NG-meta-profiler. NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility. It provides built-in support for many common operations on sequencing data and is extensible with external tools with configuration files.

Using this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible.

Conclusions
NG-meta-profiler is a high-performance solution for metagenomics processing built on NGLess. It can be used as-is to execute standard analyses or serve as the starting point for customization in a perfectly reproducible fashion.

NGLess and NG-meta-profiler are open source software (under the liberal MIT license) and can be downloaded from https://ngless.embl.de or installed through bioconda.
KW  - metagenomics
KW  - next-generation sequencing
KW  - domain-specific language
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223161
VL  - 7
IS  - 84
ER  - 
TY  - JOUR
A1  - Breitenbach, Tim
A1  - Lorenz, Kristina
A1  - Dandekar, Thomas
T1  - How to steer and control ERK and the ERK signaling cascade exemplified by looking at cardiac insufficiency
JF  - International Journal of Molecular Sciences
N2  - Mathematical optimization framework allows the identification of certain nodes within a signaling network. In this work, we analyzed the complex extracellular-signal-regulated kinase 1 and 2 (ERK1/2) cascade in cardiomyocytes using the framework to find efficient adjustment screws for this cascade that is important for cardiomyocyte survival and maladaptive heart muscle growth. We modeled optimal pharmacological intervention points that are beneficial for the heart, but avoid the occurrence of a maladaptive ERK1/2 modification, the autophosphorylation of ERK at threonine 188 (ERK\(^{Thr188}\) phosphorylation), which causes cardiac hypertrophy. For this purpose, a network of a cardiomyocyte that was fitted to experimental data was equipped with external stimuli that model the pharmacological intervention points. Specifically, two situations were considered. In the first one, the cardiomyocyte was driven to a desired expression level with different treatment strategies. These strategies were quantified with respect to beneficial effects and maleficent side effects and then which one is the best treatment strategy was evaluated. In the second situation, it was shown how to model constitutively activated pathways and how to identify drug targets to obtain a desired activity level that is associated with a healthy state and in contrast to the maleficent expression pattern caused by the constitutively activated pathway. An implementation of the algorithms used for the calculations is also presented in this paper, which simplifies the application of the presented framework for drug targeting, optimal drug combinations and the systematic and automatic search for pharmacological intervention points. The codes were designed such that they can be combined with any mathematical model given by ordinary differential equations.
KW  - optimal pharmacological modulation
KW  - efficient intervention points
KW  - ERK signaling
KW  - optimal treatment strategies
KW  - optimal drug targeting
KW  - optimal drug combination
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285164
SN  - 1422-0067
VL  - 20
IS  - 9
ER  - 
TY  - JOUR
A1  - Bartel, Karin
A1  - Pein, Helmut
A1  - Popper, Bastian
A1  - Schmitt, Sabine
A1  - Janaki-Raman, Sudha
A1  - Schulze, Almut
A1  - Lengauer, Florian
A1  - Koeberle, Andreas
A1  - Werz, Oliver
A1  - Zischka, Hans
A1  - Müller, Rolf
A1  - Vollmar, Angelika M.
A1  - Schwarzenberg, Karin von
T1  - Connecting lysosomes and mitochondria – a novel role for lipid metabolism in cancer cell death
JF  - Cell Communication and Signaling
N2  - Background
The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.

Methods
LC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements.

Results
Our data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells.

Conclusion
This study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors.
KW  - lysosome
KW  - V-ATPase
KW  - mitochondria
KW  - fission
KW  - apoptosis
KW  - lipid metabolism
KW  - cardiolipin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221524
VL  - 17
ER  - 
TY  - JOUR
A1  - Thölken, Clemens
A1  - Thamm, Markus
A1  - Erbacher, Christoph
A1  - Lechner, Marcus
T1  - Sequence and structural properties of circular RNAs in the brain of nurse and forager honeybees (Apis mellifera)
JF  - BMC Genomics
N2  - Background 
The honeybee (Apis mellifera) represents a model organism for social insects displaying behavioral plasticity. This is reflected by an age-dependent task allocation. The most protruding tasks are performed by young nurse bees and older forager bees that take care of the brood inside the hive and collect food from outside the hive, respectively. The molecular mechanism leading to the transition from nurse bees to foragers is currently under intense research. Circular RNAs, however, were not considered in this context so far. As of today, this group of non-coding RNAs was only known to exist in two other insects, Drosophila melanogaster and Bombyx mori. Here we complement the state of circular RNA research with the first characterization in a social insect.

Results
We identified numerous circular RNAs in the brain of A. mellifera nurse bees and forager bees using RNA-Seq with exonuclease enrichment. Presence and circularity were verified for the most abundant representatives. Back-splicing in honeybee occurs further towards the end of transcripts and in transcripts with a high number of exons. The occurrence of circularized exons is correlated with length and CpG-content of their flanking introns. The latter coincides with increased DNA-methylation in the respective loci. For two prominent circular RNAs the abundance in worker bee brains was quantified in TaqMan assays. In line with previous findings of circular RNAs in Drosophila, circAmrsmep2 accumulates with increasing age of the insect. In contrast, the levels of circAmrad appear age-independent and correlate with the bee's task. Its parental gene is related to amnesia-resistant memory.

Conclusions
We provide the first characterization of circRNAs in a social insect. Many of the RNAs identified here show homologies to circular RNAs found in Drosophila and Bombyx, indicating that circular RNAs are a common feature among insects. We find that exon circularization is correlated to DNA-methylation at the flanking introns. The levels of circAmrad suggest a task-dependent abundance that is decoupled from age. Moreover, a GO term analysis shows an enrichment of task-related functions. We conclude that circular RNAs could be relevant for task allocation in honeybee and should be investigated further in this context.
KW  - circRNA
KW  - circular transcriptome sequencing
KW  - honeybee
KW  - brain
KW  - neuronal
KW  - Methylation
KW  - CpG
KW  - alternative splicing
KW  - behavioral plasticity
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241302
VL  - 20
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Grebinyk, Sergii
A1  - Prylutskyy, Yuriy
A1  - Ritter, Uwe
A1  - Matyshevska, Olga
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - Complexation with C\(_{60}\) fullerene increases doxorubicin efficiency against leukemic cells in vitro
JF  - Nanoscale Research Letters
N2  - Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C\(_{60}\) fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C\(_{60}\) fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C\(_{60}\)-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C\(_{60}\) fullerene considerable nanocarrier function.The results of this study indicated that C\(_{60}\) fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.
KW  - C-60 fullerene
KW  - doxorubicin
KW  - noncovalent complex
KW  - leukemic cells
KW  - cytotoxicity
KW  - accumulation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228257
VL  - 14
IS  - 61
ER  - 
TY  - JOUR
A1  - Ruiz, E. Josue
A1  - Diefenbacher, Markus E.
A1  - Nelson, Jessica K.
A1  - Sancho, Rocio
A1  - Pucci, Fabio
A1  - Chakraborty, Atanu
A1  - Moreno, Paula
A1  - Annibaldi, Alessandro
A1  - Liccardi, Gianmaria
A1  - Encheva, Vesela
A1  - Mitter, Richard
A1  - Rosenfeldt, Mathias
A1  - Snijders, Ambrosius P.
A1  - Meier, Pascal
A1  - Calzado, Marco A.
A1  - Behrens, Axel
T1  - LUBAC determines chemotherapy resistance in squamous cell lung cancer
JF  - Journal of Experimental Medicine
N2  - Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
KW  - Solid tumors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227146
VL  - 216
IS  - 2
ER  - 
TY  - JOUR
A1  - Villalobos, Alvaro S.
A1  - Wiese, Jutta
A1  - Imhoff, Johannes F.
A1  - Dorador, Cristina
A1  - Keller, Alexander
A1  - Hentschel, Ute
T1  - Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake
JF  - Microorganisms
N2  - Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.
KW  - cold adaptation
KW  - Subtercola vilae
KW  - genome analysis
KW  - systematic affiliation
KW  - Llullaillaco Volcano
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197394
SN  - 2076-2607
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Chepurna, Oksana
A1  - Grebinyk, Sergii
A1  - Prylutskyy, Yuriy
A1  - Ritter, Uwe
A1  - Ohulchanskyy, Tymish Y.
A1  - Matyshevska, Olga
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - Synergy of chemo- and photodynamic therapies with C\(_{60}\) Fullerene-Doxorubicin nanocomplex
JF  - Nanomaterials
N2  - A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C\(_{60}\) fullerene (C\(_{60}\)) were applied in 1:1 and 2:1 molar ratio, exploiting C\(_{60}\) both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C\(_{60}\)'s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C\(_{60}\)'s photoinduced pro-oxidant activity. When cells were treated with 2:1 C\(_{60}\)-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C\(_{60}\)-Dox enabled a nanomolar concentration of Dox and C\(_{60}\) to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC\(_{50}\) 16, 9 and 7 × 10\(^3\)-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C\(_{60}\)'s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C\(_{60}\)-mediated Dox delivery and C\(_{60}\) photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C\(_{60}\)-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
KW  - photodynamic chemotherapy
KW  - synergistic effect
KW  - C\(_{60}\) fullerene
KW  - Doxorubicin
KW  - nanocomplex
KW  - leukemic cells
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193140
SN  - 2079-4991
VL  - 9
IS  - 11
ER  - 
TY  - JOUR
A1  - Molinas-González, Carlos R.
A1  - Castro, Jorge
A1  - González-Megías, Adela
A1  - Leverkus, Alexandro B.
T1  - Effects of post-fire deadwood management on soil macroarthropod communities
JF  - Forests
N2  - Dead wood comprises a vast amount of biological legacies that set the scene for ecological regeneration after wildfires, yet its removal is the most frequent management strategy worldwide. Soil-dwelling organisms are conspicuous, and they provide essential ecosystem functions, but their possible affection by different post-fire management strategies has so far been neglected. We analyzed the abundance, richness, and composition of belowground macroarthropod communities under two contrasting dead-wood management regimes after a large wildfire in the Sierra Nevada Natural and National Park (Southeast Spain). Two plots at different elevation were established, each containing three replicates of two experimental treatments: partial cut, where trees were cut and their branches lopped off and left over the ground, and salvage logging, where all the trees were cut, logs were piled, branches were mechanically masticated, and slash was spread on the ground. Ten years after the application of the treatments, soil cores were extracted from two types of microhabitat created by these treatments: bare-soil (in both treatments) and under-logs (in the partial cut treatment only). Soil macroarthropod assemblages were dominated by Hemiptera and Hymenoptera (mostly ants) and were more abundant and richer in the lowest plot. The differences between dead-wood treatments were most evident at the scale of management interventions: abundance and richness were lowest after salvage logging, even under similar microhabitats (bare-soil). However, there were no significant differences between microhabitat types on abundance and richness within the partial cut treatment. Higher abundance and richness in the partial cut treatment likely resulted from higher resource availability and higher plant diversity after natural regeneration. Our results suggest that belowground macroarthropod communities are sensitive to the manipulation of dead-wood legacies and that management through salvage logging could reduce soil macroarthropod recuperation compared to other treatments with less intense management even a decade after application.
KW  - forest fire
KW  - burnt-wood
KW  - species richness
KW  - soil fauna
KW  - post-fire management
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193079
SN  - 1999-4907
VL  - 10
IS  - 11
ER  - 
TY  - JOUR
A1  - Vey, Johannes
A1  - Kapsner, Lorenz A.
A1  - Fuchs, Maximilian
A1  - Unberath, Philipp
A1  - Veronesi, Giulia
A1  - Kunz, Meik
T1  - A toolbox for functional analysis and the systematic identification of diagnostic and prognostic gene expression signatures combining meta-analysis and machine learning
JF  - Cancers
N2  - The identification of biomarker signatures is important for cancer diagnosis and prognosis. However, the detection of clinical reliable signatures is influenced by limited data availability, which may restrict statistical power. Moreover, methods for integration of large sample cohorts and signature identification are limited. We present a step-by-step computational protocol for functional gene expression analysis and the identification of diagnostic and prognostic signatures by combining meta-analysis with machine learning and survival analysis. The novelty of the toolbox lies in its all-in-one functionality, generic design, and modularity. It is exemplified for lung cancer, including a comprehensive evaluation using different validation strategies. However, the protocol is not restricted to specific disease types and can therefore be used by a broad community. The accompanying R package vignette runs in ~1 h and describes the workflow in detail for use by researchers with limited bioinformatics training.
KW  - bioinformatics tool
KW  - R package
KW  - machine learning
KW  - meta-analysis
KW  - biomarker signature
KW  - gene expression analysis
KW  - survival analysis
KW  - functional analysis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193240
SN  - 2072-6694
VL  - 11
IS  - 10
ER  - 
TY  - JOUR
A1  - Schmidt, Thomas S. B.
A1  - Hayward, Matthew R.
A1  - Coelho, Luiis P.
A1  - Li, Simone S.
A1  - Costea, Paul I.
A1  - Voigt, Anita Y.
A1  - Wirbel, Jakob
A1  - Maistrenko, Oleksandr M.
A1  - Alves, Renato J. C.
A1  - Bergsten, Emma
A1  - de Beaufort, Carine
A1  - Sobhani, Iradj
A1  - Heintz-Buschart, Anna
A1  - Sunagawa, Shinichi
A1  - Zeller, Georg
A1  - Wilmes, Paul
A1  - Bork, Peer
T1  - Extensive transmission of microbes along the gastrointestinal tract
JF  - eLife
N2  - The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
KW  - Colonization
KW  - Annotation
KW  - Dynamics
KW  - Accurate
KW  - Strains
KW  - Barrier
KW  - Health
KW  - Acids
KW  - Research Article
KW  - Computational and Systems Biology
KW  - Microbiology and Infectious Disease
KW  - microbiome
KW  - gastrointestinal tract
KW  - colorectal cancer
KW  - rheumatoid arthritis
KW  - metagenomics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228954
VL  - 8
ER  - 
TY  - JOUR
A1  - Sauer, Markus
A1  - Juranek, Stefan A.
A1  - Marks, James
A1  - De Magis, Alessio
A1  - Kazemier, Hinke G
A1  - Hilbig, Daniel
A1  - Benhalevy, Daniel
A1  - Wang, Xiantao
A1  - Hafner, Markus
A1  - Paeschke, Katrin
T1  - DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
JF  - Nature Communications
N2  - Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.
KW  - RNA metabolism
KW  - Translation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227486
VL  - 10
IS  - 2421
ER  - 
TY  - JOUR
A1  - Mayer, Alexander E.
A1  - Löffler, Mona C.
A1  - Loza Valdés, Angel E.
A1  - Schmitz, Werner
A1  - El-Merahbi, Rabih
A1  - Trujillo-Viera, Jonathan
A1  - Erk, Manuela
A1  - Zhang, Thianzhou
A1  - Braun, Ursula
A1  - Heikenwalder, Mathias
A1  - Leitges, Michael
A1  - Schulze, Almut
A1  - Sumara, Grzegorz
T1  - The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling
JF  - Science Signaling
N2  - Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and cholesterol content in the livers of PKD3-deficient mice fed a high-fat diet. Conversely, hepatic-specific overexpression of a constitutively active PKD3 mutant suppressed insulin-induced signaling and caused insulin resistance. Our results indicate that PKD3 provides feedback on hepatic lipid production and suppresses insulin signaling. Therefore, manipulation of PKD3 activity could be used to decrease hepatic lipid content or improve hepatic insulin sensitivity.
KW  - Protein kinase D3 (PKD3)
KW  - cholesterol
KW  - diacylglycerol (DAG)
KW  - liver
KW  - metabolism
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250025
ET  - accepted manuscript
ER  - 
TY  - JOUR
A1  - Roth, Nicolas
A1  - Doerfler, Inken
A1  - Bässler, Claus
A1  - Blaschke, Markus
A1  - Bussler, Heinz
A1  - Gossner, Martin M.
A1  - Heideroth, Antje
A1  - Thorn, Simon
A1  - Weisser, Wolfgang W.
A1  - Müller, Jörg
T1  - Decadal effects of landscape-wide enrichment of dead wood on saproxylic organisms in beech forests of different historic management intensity
JF  - Diversity and Distributions
N2  - Aim: European temperate forests have lost dead wood and the associated biodiversity owing to intensive management over centuries. Nowadays, some of these forests are being restored by enrichment with dead wood, but mostly only at stand scales. Here, we investigated effects of a seminal dead-wood enrichment strategy on saproxylic organisms at the landscape scale. 
Location: Temperate European beech forest in southern Germany. 
Methods: In a before-after control-impact design, we compared assemblages and gamma diversities of saproxylic organisms in strictly protected old-growth forest areas (reserves) and historically moderately and intensively managed forest areas before and a decade after starting a landscape-wide strategy of dead-wood enrichment. 
Results: Before enrichment with dead wood, the gamma diversity of saproxylic organisms in historically intensively managed forest stands was significantly lower than in reserves and historically moderately managed forest stands; this difference disappeared after 10 years of dead-wood enrichment. The species composition of beetles in forest stands of the three historical management intensities differed before the enrichment strategy, but a decade thereafter, the species compositions of previously intensively logged and forest reserve plots were similar. However, the differences in fungal species composition between historical management categories before and after 10 years of enrichment persisted. 
Main conclusions: Our results demonstrate that intentional enrichment of dead wood at the landscape scale is a powerful tool for rapidly restoring saproxylic beetle communities and for restoring wood-inhabiting fungal communities, which need longer than a decade for complete restoration. We propose that a strategy of area-wide active restoration combined with some permanent strict refuges is a promising means of promoting the biodiversity of age-long intensively managed Central European beech forests.
KW  - dead-wood enrichment
KW  - integrative management strategy
KW  - land sharing
KW  - lowland beech forests
KW  - saproxylic organisms
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227061
VL  - 25
IS  - 3
ER  - 
TY  - JOUR
A1  - Kühnisch, Jirko
A1  - Herbst, Christopher
A1  - Al‐Wakeel‐Marquard, Nadya
A1  - Dartsch, Josephine
A1  - Holtgrewe, Manuel
A1  - Baban, Anwar
A1  - Mearini, Giulia
A1  - Hardt, Juliane
A1  - Kolokotronis, Konstantinos
A1  - Gerull, Brenda
A1  - Carrier, Lucie
A1  - Beule, Dieter
A1  - Schubert, Stephan
A1  - Messroghli, Daniel
A1  - Degener, Franziska
A1  - Berger, Felix
A1  - Klaassen, Sabine
T1  - Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3
JF  - Clinical Genetics
N2  - The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum of primary CMP in a large cohort of patients ≤18 years referred to a tertiary center. Eighty unrelated index patients with pediatric primary CMP underwent genetic testing with a panel‐based next‐generation sequencing approach of 89 genes. At least one pathogenic or probably pathogenic variant was identified in 30/80 (38%) index patients. In all CMP subgroups, patients carried most frequently variants of interest in sarcomere genes suggesting them as a major contributor in pediatric primary CMP. In MYH7, MYBPC3, and TNNI3, we identified 18 pathogenic/probably pathogenic variants (MYH7 n = 7, MYBPC3 n = 6, TNNI3 n = 5, including one homozygous (TNNI3 c.24+2T>A) truncating variant. Protein and transcript level analysis on heart biopsies from individuals with homozygous mutation of TNNI3 revealed that the TNNI3 protein is absent and associated with upregulation of the fetal isoform TNNI1. The present study further supports the clinical importance of sarcomeric mutation—not only in adult—but also in pediatric primary CMP. TNNI3 is the third most important disease gene in this cohort and complete loss of TNNI3 leads to severe pediatric CMP.
KW  - cardiomyopathy
KW  - genetics
KW  - pediatrics
KW  - sarcomere
KW  - TNNI3
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213958
VL  - 96
IS  - 6
SP  - 549
EP  - 559
ER  - 
TY  - JOUR
A1  - Eisenreich, Wolfgang
A1  - Rudel, Thomas
A1  - Heesemann, Jürgen
A1  - Goebel, Werner
T1  - How viral and intracellular bacterial pathogens reprogram the metabolism of host cells to allow their intracellular replication
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication and proliferation during infection. In human infections, the cell types which both groups of pathogens are using as hosts are indeed quite similar and include phagocytic immune cells, especially monocytes/macrophages (MOs/MPs) and dendritic cells (DCs), as well as nonprofessional phagocytes, like epithelial cells, fibroblasts and endothelial cells. These terminally differentiated cells are normally in a metabolically quiescent state when they are encountered by these pathogens during infection. This metabolic state of the host cells does not meet the extensive need for nutrients required for efficient intracellular replication of viruses and especially IBPs which, in contrast to the viral pathogens, have to perform their own specific intracellular metabolism to survive and efficiently replicate in their host cell niches. For this goal, viruses and IBPs have to reprogram the host cell metabolism in a pathogen-specific manner to increase the supply of nutrients, energy, and metabolites which have to be provided to the pathogen to allow its replication. In viral infections, this appears to be often achieved by the interaction of specific viral factors with central metabolic regulators, including oncogenes and tumor suppressors, or by the introduction of virus-specific oncogenes. Less is so far known on the mechanisms leading to metabolic reprogramming of the host cell by IBPs. However, the still scant data suggest that similar mechanisms may also determine the reprogramming of the host cell metabolism in IBP infections. In this review, we summarize and compare the present knowledge on this important, yet still poorly understood aspect of pathogenesis of human viral and especially IBP infections.
KW  - metabolic adaptation
KW  - viruses
KW  - intracellular bacterial pathogens
KW  - metabolism of infected and uninfected host cells
KW  - reprogamming of host cell metabolism
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197188
SN  - 2235-2988
VL  - 9
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Buchelnikov, Anatoliy
A1  - Tverdokhleb, Nina
A1  - Grebinyk, Sergii
A1  - Evstigneev, Maxim
A1  - Matyshevska, Olga
A1  - Cherepanov, Vsevolod
A1  - Prylutskyy, Yuriy
A1  - Yashchuk, Valeriy
A1  - Naumovets, Anton
A1  - Ritter, Uwe
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells
JF  - Pharmaceutics
N2  - A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV–Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C\(_{60}\) binding in an aqueous solution. Complexation with C\(_{60}\) was found to promote Ber intracellular uptake. By increasing C\(_{60}\) concentration, the C\(_{60}\)-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C\(_{60}\)-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C\(_{60}\) improved its in vitro efficiency against cancer cells.
KW  - C60 fullerene
KW  - Berberine
KW  - noncovalent nanocomplex
KW  - UV–Vis
KW  - DLS and AFM measurements
KW  - drug release
KW  - leukemic cells
KW  - uptake
KW  - cytotoxicity
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193216
SN  - 1999-4923
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Paponov, Ivan A.
A1  - Dindas , Julian
A1  - Król , Elżbieta
A1  - Friz, Tatyana
A1  - Budnyk, Vadym
A1  - Teale, William
A1  - Paponov, Martina
A1  - Hedrich , Rainer
A1  - Palme, Klaus
T1  - Auxin-Induced plasma membrane depolarization is regulated by Auxin transport and not by AUXIN BINDING PROTEIN1
JF  - Frontiers in Plant Science
N2  - Auxin is a molecule, which controls many aspects of plant development through both transcriptional and non-transcriptional signaling responses. AUXIN BINDING PROTEIN1 (ABP1) is a putative receptor for rapid non-transcriptional auxin-induced changes in plasma membrane depolarization and endocytosis rates. However, the mechanism of ABP1-mediated signaling is poorly understood. Here we show that membrane depolarization and endocytosis inhibition are ABP1-independent responses and that auxin-induced plasma membrane depolarization is instead dependent on the auxin influx carrier AUX1. AUX1 was itself not involved in the regulation of endocytosis. Auxin-dependent depolarization of the plasma membrane was also modulated by the auxin efflux carrier PIN2. These data establish a new connection between auxin transport and non-transcriptional auxin signaling.
KW  - auxin
KW  - ABP1
KW  - plasma membrane depolarization
KW  - AUX1
KW  - endocytosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195914
SN  - 1664-462X
VL  - 9
ER  - 
TY  - JOUR
A1  - Gebert, Friederike
A1  - Steffan-Dewenter, Ingolf
A1  - Moretto, Philippe
A1  - Peters, Marcell K.
T1  - Climate rather than dung resources predict dung beetle abundance and diversity along elevational and land use gradients on Mt. Kilimanjaro
JF  - Journal of Biogeography
N2  - Aim: While elevational gradients in species richness constitute some of the best depicted patterns in ecology, there is a large uncertainty concerning the role of food resource availability for the establishment of diversity gradients in insects. Here, we
analysed the importance of climate, area, land use and food resources for determining diversity gradients of dung beetles along extensive elevation and land use gradients on Mt. Kilimanjaro, Tanzania.

Location: Mt. Kilimanjaro, Tanzania.

Taxon: Scarabaeidae (Coleoptera).

Methods: Dung beetles were recorded with baited pitfall traps at 66 study plots along a 3.6 km elevational gradient. In order to quantify food resources for the dung beetle community in form of mammal defecation rates, we assessed mammalian diversity and biomass with camera traps. Using a multi‐model inference framework and path analysis, we tested the direct and indirect links between climate, area, land use and mammal defecation rates on the species richness and abundance of dung beetles.

Results: We found that the species richness of dung beetles declined exponentially with increasing elevation. Human land use diminished the species richness of functional groups exhibiting complex behaviour but did not have a significant influence on total species richness. Path analysis suggested that climate, in particular temperature and to a lesser degree precipitation, were the most important predictors of dung beetle species richness while mammal defecation rate was not supported as a predictor variable.

Main conclusions: Along broad climatic gradients, dung beetle diversity is mainly limited by climatic factors rather than by food resources. Our study points to a predominant role of temperature‐driven processes for the maintenance and origination of species diversity of ectothermic organisms, which will consequently be subject to ongoing climatic changes.
KW  - altitudinal gradients
KW  - diversity gradients
KW  - enercy-richness hypothesis
KW  - food resources
KW  - insect abundance
KW  - land use
KW  - Scarabaeidae
KW  - temperature‐richness hypothesis
KW  - temperature‐mediated resource exploitation hypothesis
KW  - species‐area hypothesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204701
VL  - 47
IS  - 2
SP  - 371
EP  - 381
ER  - 
TY  - JOUR
A1  - Hovestadt, Thomas
A1  - Thomas, Jeremy A.
A1  - Mitesser, Oliver
A1  - Schönrogge, Karsten
T1  - Multiple host use and the dynamics of host-switching in host-parasite systems
JF  - Insect Conservation and Diversity
N2  - The link between multi‐host use and host switching in host–parasite interactions is a continuing area of debate. Lycaenid butterflies in the genus Maculinea, for example, exploit societies of different Myrmica ant species across their ranges, but there is only rare evidence that they simultaneously utilise multiple hosts at a local site, even where alternative hosts are present.
We present a simple population‐genetic model accounting for the proportion of two alternative hosts and the fitness of parasite genotypes on each host. In agreement with standard models, we conclude that simultaneous host use is possible whenever fitness of heterozygotes on alternative hosts is not too low.
We specifically focus on host‐shifting dynamics when the frequency of hosts changes. We find that (i) host shifting may proceed so rapidly that multiple host use is unlikely to be observed, (ii) back and forth transition in host use can exhibit a hysteresis loop, (iii) the parasites' host use may not be proportional to local host frequencies and be restricted to the rarer host under some conditions, and (iv) that a substantial decline in parasite abundance may typically precede a shift in host use.
We conclude that focusing not just on possible equilibrium conditions but also considering the dynamics of host shifting in non‐equilibrium situations may provide added insights into host–parasite systems.
KW  - Host-parasite interaction
KW  - Maculinea butterfly
KW  - Myrmica ant non-equilibrium dynamics
KW  - population genetics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204747
VL  - 12
IS  - 6
ER  - 
TY  - JOUR
A1  - Boetzl, Fabian A.
A1  - Konle, Antonia
A1  - Krauss, Jochen
T1  - Aphid cards – useful model for assessing predation rates or bias prone nonsense?
JF  - Journal of Applied Entomology
N2  - Predation on pest organisms is an essential ecosystem function supporting yields in modern agriculture. However, assessing predation rates is intricate, and they can rarely be linked directly to predator densities or functions. We tested whether sentinel prey aphid cards are useful tools to assess predation rates in the field. Therefore, we looked at aphid cards of different sizes on the ground level as well as within the vegetation. Additionally, by trapping ground‐dwelling predators, we examined whether obtained predation rates could be linked to predator densities and traits. Predation rates recorded with aphid cards were independent of aphid card size. However, predation rates on the ground level were three times higher than within the vegetation. We found both predatory carabid activity densities as well as community weighted mean body size to be good predictors for predation rates. Predation rates obtained from aphid cards are stable over card type and related to predator assemblages. Aphid cards, therefore, are a useful, efficient method for rapidly assessing the ecosystem function predation. Their use might especially be recommended for assessments on the ground level and when time and resource limitations rule out more elaborate sentinel prey methods using exclosures with living prey animals.
KW  - carabid beetles
KW  - ecosystem service
KW  - ground-dwelling predators
KW  - methods
KW  - natural pest control
KW  - sentinel prey
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204798
VL  - 144
IS  - 1-2
ER  - 
TY  - JOUR
A1  - Figueiredo, Ludmilla
A1  - Krauss, Jochen
A1  - Steffan-Dewenter, Ingolf
A1  - Cabral, Juliano Sarmento
T1  - Understanding extinction debts: spatio-temporal scales, mechanisms and a roadmap for future research
JF  - Ecography
N2  - Extinction debt refers to delayed species extinctions expected as a consequence of ecosystem perturbation. Quantifying such extinctions and investigating long‐term consequences of perturbations has proven challenging, because perturbations are not isolated and occur across various spatial and temporal scales, from local habitat losses to global warming. Additionally, the relative importance of eco‐evolutionary processes varies across scales, because levels of ecological organization, i.e. individuals, (meta)populations and (meta)communities, respond hierarchically to perturbations. To summarize our current knowledge of the scales and mechanisms influencing extinction debts, we reviewed recent empirical, theoretical and methodological studies addressing either the spatio–temporal scales of extinction debts or the eco‐evolutionary mechanisms delaying extinctions. Extinction debts were detected across a range of ecosystems and taxonomic groups, with estimates ranging from 9 to 90% of current species richness. The duration over which debts have been sustained varies from 5 to 570 yr, and projections of the total period required to settle a debt can extend to 1000 yr. Reported causes of delayed extinctions are 1) life‐history traits that prolong individual survival, and 2) population and metapopulation dynamics that maintain populations under deteriorated conditions. Other potential factors that may extend survival time such as microevolutionary dynamics, or delayed extinctions of interaction partners, have rarely been analyzed. Therefore, we propose a roadmap for future research with three key avenues: 1) the microevolutionary dynamics of extinction processes, 2) the disjunctive loss of interacting species and 3) the impact of multiple regimes of perturbation on the payment of debts. For their ability to integrate processes occurring at different levels of ecological organization, we highlight mechanistic simulation models as tools to address these knowledge gaps and to deepen our understanding of extinction dynamics.
KW  - Anthropocene
KW  - biotic interaction
KW  - extinction dynamics
KW  - mechanistic modelling
KW  - time lag
KW  - transient dynamics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204859
VL  - 42
IS  - 12
ER  - 
TY  - JOUR
A1  - Pauls, Dennis
A1  - Hamarat, Yasmin
A1  - Trufasu, Luisa
A1  - Schendzielorz, Tim M.
A1  - Gramlich, Gertrud
A1  - Kahnt, Jörg
A1  - Vanselow, Jens
A1  - Schlosser, Andreas
A1  - Wegener, Christian
T1  - Drosophila carboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
JF  - European Journal of Neuroscience
N2  - Neuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well‐characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE ), a key enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD ) in global neuropeptide processing and selected peptide‐regulated behaviours in Drosophila . We found that a deficiency in dCPD results in C‐terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD ‐encoding gene silver in the larva causes lethality, and leads to deficits in starvation‐induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing and peptide‐regulated behaviour in Drosophila . dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
KW  - direct muss spectrometric profiling
KW  - friut fly behaviour
KW  - M14 carboxypeptidasses
KW  - peptidomoics
KW  - protein processing
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204863
VL  - 50
IS  - 9
ER  - 
TY  - JOUR
A1  - Requier, Fabrice
A1  - Paillet, Yoan
A1  - Laroche, Fabienne
A1  - Rutschmann, Benjamin
A1  - Zhang, Jie
A1  - Lombardi, Fabio
A1  - Svoboda, Miroslav
A1  - Steffan-Dewenter, Ingolf
T1  - Contribution of European forests to safeguard wild honeybee
populations
JF  - Conservation Letters
N2  - Abstract
Recent studies reveal the use of tree cavities by wild honeybee colonies in European forests. This highlights the conservation potential of forests for a highly threatened component of the native entomofauna in Europe, but currently no estimate of potential wild honeybee population sizes exists. Here, we analyzed the tree cavity densities of 106 forest areas across Europe and inferred an expected population size of wild honeybees. Both forest and management types affected the density of tree cavities.
Accordingly, we estimated that more than 80,000 wild honeybee colonies could be sustained in European forests. As expected, potential conservation hotspots were identified in unmanaged forests, and, surprisingly, also in other large forest areas across Europe. Our results contribute to the EU policy strategy to halt pollinator declines and reveal the potential of forest areas for the conservation of so far neglected wild honeybee populations in Europe.
KW  - Apis mellifera
KW  - Conservation
KW  - forest management
KW  - honeybees
KW  - native populations
KW  - protected forests
KW  - tree cavities
KW  - unmanaged broadleaved forests
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204407
VL  - 13
IS  - 2
ER  - 
TY  - JOUR
A1  - Diers, J.
A1  - Wagner, J.
A1  - Baum, P.
A1  - Lichthardt, S.
A1  - Kastner, C.
A1  - Matthes, N.
A1  - Löb, S.
A1  - Matthes, H.
A1  - Germer, C.-T.
A1  - Wiegering, A.
T1  - Nationwide in-hospital mortality following colonic cancer
resection according to hospital volume in Germany
JF  - BJS Open
N2  - Background:
Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany.

Methods: 
Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identifed from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume.

Results: 
Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5⋅8 per cent, ranging from 6⋅9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4⋅8 per cent (1239 of 25 825) in very high-volume centres (P < 0⋅001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0⋅75 (95 per cent c.i. 0⋅66 to 0⋅84) in very high-volume hospitals performing a mean of 85⋅0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12⋅7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion.

Conclusion: 
In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204385
VL  - 3
IS  - 5
ER  - 
TY  - JOUR
A1  - Duque, Laura
A1  - Poelman, Erik H.
A1  - Steffan-Dewenter, Ingolf
T1  - Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature
JF  - Scientific Reports
N2  - Abiotic stress by elevated tropospheric ozone and temperature can alter plants’ metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common.
KW  - Ecology
KW  - Environmental impact
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202805
VL  - 9
ER  - 
TY  - JOUR
A1  - Maierhofer, Anna
A1  - Flunkert, Julia
A1  - Oshima, Junko
A1  - Martin, George M.
A1  - Poot, Martin
A1  - Nanda, Indrajit
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Haaf, Thomas
T1  - Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes
JF  - Aging Cell
N2  - Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes.
KW  - (classical and atypical) Werner syndrome
KW  - bisulfite pyrosequencing
KW  - methylation array
KW  - premature aging
KW  - segmental progeria
KW  - transcription deficiency
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202733
VL  - 18
ER  -