TY - JOUR A1 - Rutkowski, Andrzej J. A1 - Erhard, Florian A1 - L'Hernault, Anne A1 - Bonfert, Thomas A1 - Schilhabel, Markus A1 - Crump, Colin A1 - Rosenstiel, Philip A1 - Efstathiou, Stacey A1 - Zimmer, Ralf A1 - Friedel, Caroline C. A1 - Dölken, Lars T1 - Widespread disruption of host transcription termination in HSV-1 infection JF - Nature Communications N2 - Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination. KW - herpes simplex virus KW - RNA polymerase II KW - gene expression KW - alpha-globin KW - motif discovery KW - regulatory protein ICP27 KW - poly(A) site usage KW - pre-messenger RNA KW - splicing inhibition KW - type 1 ICP27 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148643 VL - 6 IS - 7126 ER - TY - JOUR A1 - Mietchen, Daniel A1 - Hagedorn, Gregor A1 - Förstner, Konrad U. A1 - Kubke, M Fabiana A1 - Koltzenburg, Claudia A1 - Hahnel, Mark J. A1 - Penev, Lyubomir T1 - Wikis in scholarly publishing N2 - Scientific research is a process concerned with the creation, collective accumulation, contextualization, updating and maintenance of knowledge. Wikis provide an environment that allows to collectively accumulate, contextualize, update and maintain knowledge in a coherent and transparent fashion. Here, we examine the potential of wikis as platforms for scholarly publishing. In the hope to stimulate further discussion, the article itself was drafted on Species-ID – a wiki that hosts a prototype for wiki-based scholarly publishing – where it can be updated, expanded or otherwise improved. KW - Elektronisches Publizieren KW - wikis KW - scientific publishing KW - scholarly publishing KW - reputation KW - version control Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87770 ER - TY - JOUR A1 - Keller, Alexander A1 - Brandel, Annette A1 - Becker, Mira C. A1 - Balles, Rebecca A1 - Abdelmohsen, Usama Ramadan A1 - Ankenbrand, Markus J. A1 - Sickel, Wiebke T1 - Wild bees and their nests host Paenibacillus bacteria with functional potential of avail JF - Microbiome N2 - Background: In previous studies, the gram-positive firmicute genus Paenibacillus was found with significant abundances in nests of wild solitary bees. Paenibacillus larvae is well-known for beekeepers as a severe pathogen causing the fatal honey bee disease American foulbrood, and other members of the genus are either secondary invaders of European foulbrood or considered a threat to honey bees. We thus investigated whether Paenibacillus is a common bacterium associated with various wild bees and hence poses a latent threat to honey bees visiting the same flowers. Results: We collected 202 samples from 82 individuals or nests of 13 bee species at the same location and screened each for Paenibacillus using high-throughput sequencing-based 16S metabarcoding. We then isolated the identified strain Paenibacillus MBD-MB06 from a solitary bee nest and sequenced its genome. We did find conserved toxin genes and such encoding for chitin-binding proteins, yet none specifically related to foulbrood virulence or chitinases. Phylogenomic analysis revealed a closer relationship to strains of root-associated Paenibacillus rather than strains causing foulbrood or other accompanying diseases. We found anti-microbial evidence within the genome, confirmed by experimental bioassays with strong growth inhibition of selected fungi as well as gram-positive and gram-negative bacteria. Conclusions: The isolated wild bee associate Paenibacillus MBD-MB06 is a common, but irregularly occurring part of wild bee microbiomes, present on adult body surfaces and guts and within nests especially in megachilids. It was phylogenetically and functionally distinct from harmful members causing honey bee colony diseases, although it shared few conserved proteins putatively toxic to insects that might indicate ancestral predisposition for the evolution of insect pathogens within the group. By contrast, our strain showed anti-microbial capabilities and the genome further indicates abilities for chitin-binding and biofilm-forming, suggesting it is likely a useful associate to avoid fungal penetration of the bee cuticula and a beneficial inhabitant of nests to repress fungal threats in humid and nutrient-rich environments of wild bee nests. KW - 16S metabarcoding KW - American foulbrood KW - anti-microbial activit KW - bacterial genomics KW - bioassays KW - European foulbrood KW - Paenibacterin KW - phylogenomics KW - bee disease KW - pathogen vector Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177554 VL - 6 IS - 229 ER - TY - JOUR A1 - Fiore, Piera Filomena A1 - Vacca, Paola A1 - Tumino, Nicola A1 - Besi, Francesca A1 - Pelosi, Andrea A1 - Munari, Enrico A1 - Marconi, Marcella A1 - Caruana, Ignazio A1 - Pistoia, Vito A1 - Moretta, Lorenzo A1 - Azzarone, Bruno T1 - Wilms' tumor primary cells display potent immunoregulatory properties on NK cells and macrophages JF - Cancers N2 - The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm’s Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments. In this study, we stabilized four WT primary cultures expressing either a blastematous (CD56\(^+\)/CD133\(^−\)) or an epithelial (CD56\(^−\)/CD133\(^+\)) phenotype and investigated their interactions with innate immune cells, namely NK cells and monocytes. We show that cytokine-activated NK cells efficiently kill WT cells. However, after co-culture with WT primary cells, NK cells displayed an impaired cytotoxic activity, decreased production of IFNγ and expression of CD107a, DNAM-1 and NKp30. Analysis of the effects of the interaction between WT cells and monocytes revealed their polarization towards alternatively activated macrophages (M2) that, in turn, further impaired NK cell functions. In conclusion, we show that both WT blastematous and epithelial components may contribute directly and indirectly to a tumor immunosuppressive microenvironment that is likely to play a role in tumor progression. KW - Wilm's tumor KW - NK cells KW - macrophages KW - tumor microenvironment KW - Wilms' tumor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222981 SN - 2072-6694 VL - 13 IS - 2 ER - TY - JOUR A1 - Kuai, Yue A1 - Gong, Xin A1 - Ding, Liya A1 - Li, Fang A1 - Lei, Lizhen A1 - Gong, Yuqi A1 - Liu, Qingmeng A1 - Tan, Huajiao A1 - Zhang, Xinxia A1 - Liu, Dongyu A1 - Ren, Guoping A1 - Pan, Hongyang A1 - Shi, Yaoyao A1 - Berberich-Siebelt, Friederike A1 - Ma, Zhengrong A1 - Zhou, Ren T1 - Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90 JF - Cell Communication and Signaling N2 - Background Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear. Methods Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation. Results WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro. Conclusion WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL. KW - WTAP KW - BCL6 KW - Hsp90 KW - complex KW - DLBCL Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230168 VL - 16 ER - TY - JOUR A1 - Weich, Alexander A1 - Rogoll, Dorothee A1 - Gawlas, Sophia A1 - Mayer, Lars A1 - Weich, Wolfgang A1 - Pongracz, Judit A1 - Kudlich, Theodor A1 - Meining, Alexander A1 - Scheurlen, Michael T1 - Wnt/β-catenin signaling regulates CXCR4 expression and [\(^{68}\)Ga] Pentixafor internalization in neuroendocrine tumor cells JF - Diagnostics N2 - Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a theragnostic target. Likewise, activation of Wnt/β-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. The NET cell lines BON-1, QGP-1, and MS-18 were exposed to Wnt inhibitors (5-aza-CdR, quercetin, and niclosamide) or the Wnt activator LiCl. The expressions of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western blot, and immunohistochemistry. The effects of Wnt modulators on uptake of the CXCR4 ligand [\(^{68}\)Ga] Pentixafor were measured. The Wnt activator LiCl induced upregulation of CXCR4 and Wnt target gene expression. Treatment with the Wnt inhibitors had opposite effects. LiCl significantly increased [\(^{68}\)Ga] Pentixafor uptake, while treatment with Wnt inhibitors decreased radiopeptide uptake. Wnt pathway modulation influences CXCR4 expression and function in NET cell lines. Wnt modulation might be a tool to enhance the efficacy of CXCR4-directed therapies in NET or to inhibit CXCR4-dependent proliferative signaling. The underlying mechanisms for the interaction of the Wnt pathway with CXCR4 expression and function have yet to be clarified. KW - neuroendocrine tumor KW - NET KW - Wnt KW - β-catenin KW - CXCR4 KW - [\(^{68}\)Ga] Pentixafor KW - BON-1 KW - QGP-1 KW - MS-18 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228914 SN - 2075-4418 VL - 11 IS - 2 ER - TY - JOUR A1 - Helfrich-Förster, C. A1 - Monecke, S. A1 - Spiousas, I. A1 - Hovestadt, T. A1 - Mitesser, O. A1 - Wehr, T. A. T1 - Women temporarily synchronize their menstrual cycles with the luminance and gravimetric cycles of the Moon JF - Science Advances N2 - Many species synchronize reproductive behavior with a particular phase of the lunar cycle to increase reproductive success. In humans, a lunar influence on reproductive behavior remains controversial, although the human menstrual cycle has a period close to that of the lunar cycle. Here, we analyzed long-term menstrual recordings of individual women with distinct methods for biological rhythm analysis. We show that women’s menstrual cycles with a period longer than 27 days were intermittently synchronous with the Moon’s luminance and/or gravimetric cycles. With age and upon exposure to artificial nocturnal light, menstrual cycles shortened and lost this synchrony. We hypothesize that in ancient times, human reproductive behavior was synchronous with the Moon but that our modern lifestyles have changed reproductive physiology and behavior. KW - moon KW - menstrual cycles Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231479 VL - 7 IS - 5 ER - TY - JOUR A1 - Keller, Daniela Barbara A1 - Schultz, Jörg T1 - Word Formation Is Aware of Morpheme Family Size N2 - Words are built from smaller meaning bearing parts, called morphemes. As one word can contain multiple morphemes, one morpheme can be present in different words. The number of distinct words a morpheme can be found in is its family size. Here we used Birth-Death-Innovation Models (BDIMs) to analyze the distribution of morpheme family sizes in English and German vocabulary over the last 200 years. Rather than just fitting to a probability distribution, these mechanistic models allow for the direct interpretation of identified parameters. Despite the complexity of language change, we indeed found that a specific variant of this pure stochastic model, the second order linear balanced BDIM, significantly fitted the observed distributions. In this model, birth and death rates are increased for smaller morpheme families. This finding indicates an influence of morpheme family sizes on vocabulary changes. This could be an effect of word formation, perception or both. On a more general level, we give an example on how mechanistic models can enable the identification of statistical trends in language change usually hidden by cultural influences. KW - linguistic morphology KW - language KW - death rates KW - psycholinguistics KW - chi square tests KW - vocabulary KW - birth rates KW - culture Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112848 ER - TY - JOUR A1 - Neuderth, Silke A1 - Schwarz, Betje A1 - Gerlich, Christian A1 - Schuler, Michael A1 - Markus, Miriam A1 - Bethge, Matthias T1 - Work-related medical rehabilitation in patients with musculoskeletal disorders: the protocol of a propensity score matched effectiveness study (EVA-WMR, DRKS00009780) JF - BMC Public Health N2 - Background Musculoskeletal disorders are one of the most important causes of work disability. Various rehabilitation services and return-to-work programs have been developed in order to reduce sickness absence and increase sustainable return-to-work. As the effects of conventional medical rehabilitation programs on sickness absence duration were shown to be slight, work-related medical rehabilitation programs have been developed and tested. While such studies proved the efficacy of work-related medical rehabilitation compared with conventional medical rehabilitation in well-conducted randomized controlled trials, its effectiveness under real-life conditions has yet to be proved. Methods/Design The cohort study will be performed under real-life conditions with two parallel groups. Participants will receive either a conventional or a work-related medical rehabilitation program. Propensity score matching will be used to identify controls that are comparable to treated work-related medical rehabilitation patients. Over a period of three months, about 18,000 insured patients with permission to undergo a musculoskeletal rehabilitation program will be contacted. Of these, 15,000 will receive a conventional and 3,000 a work-related medical rehabilitation. We expect a participation rate of 40 % at baseline. Patients will be aged 18 to 65 years and have chronic musculoskeletal disorders, usually back pain. The control group will receive a conventional medical rehabilitation program without any explicit focus on work, work ability and return to work in diagnostics and therapy. The intervention group will receive a work-related medical rehabilitation program that in addition to common rehabilitation treatments contains 11 to 25 h of work-related treatment modules. Follow-up data will be assessed three and ten months after patients’ discharge from the rehabilitation center. Additionally, department characteristics will be assessed and administrative data records used. The primary outcomes are sick leave duration, stable return to work and subjective work ability. Secondary outcomes cover several dimensions of health, functioning and coping strategies. Discussion This study will determine the relative effectiveness of a complex, newly implemented work-related rehabilitation strategy for patients with musculoskeletal disorders. KW - propensity score matching KW - work-related medical rehabilitation KW - effectiveness KW - work ability KW - return to work Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150015 VL - 16 IS - 804 ER - TY - JOUR A1 - Düking, Peter A1 - Giessing, Laura A1 - Frenkel, Marie Ottilie A1 - Koehler, Karsten A1 - Holmberg, Hans-Christer A1 - Sperlich, Billy T1 - Wrist-Worn Wearables for Monitoring Heart Rate and Energy Expenditure While Sitting or Performing Light-to-Vigorous Physical Activity: Validation Study JF - JMIR mhealth and uhealth N2 - Background: Physical activity reduces the incidences of noncommunicable diseases, obesity, and mortality, but an inactive lifestyle is becoming increasingly common. Innovative approaches to monitor and promote physical activity are warranted. While individual monitoring of physical activity aids in the design of effective interventions to enhance physical activity, a basic prerequisite is that the monitoring devices exhibit high validity. Objective: Our goal was to assess the validity of monitoring heart rate (HR) and energy expenditure (EE) while sitting or performing light-to-vigorous physical activity with 4 popular wrist-worn wearables (Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa). Methods: While wearing the 4 different wearables, 25 individuals performed 5 minutes each of sitting, walking, and running at different velocities (ie, 1.1 m/s, 1.9 m/s, 2.7 m/s, 3.6 m/s, and 4.1 m/s), as well as intermittent sprints. HR and EE were compared to common criterion measures: Polar-H7 chest belt for HR and indirect calorimetry for EE. Results: While monitoring HR at different exercise intensities, the standardized typical errors of the estimates were 0.09-0.62, 0.13-0.88, 0.62-1.24, and 0.47-1.94 for the Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, respectively. Depending on exercise intensity, the corresponding coefficients of variation were 0.9%-4.3%, 2.2%-6.7%, 2.9%-9.2%, and 4.1%-19.1%, respectively, for the 4 wearables. While monitoring EE at different exercise intensities, the standardized typical errors of the estimates were 0.34-1.84, 0.32-1.33, 0.46-4.86, and 0.41-1.65 for the Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, respectively. Depending on exercise intensity, the corresponding coefficients of variation were 13.5%-27.1%, 16.3%-28.0%, 15.9%-34.5%, and 8.0%-32.3%, respectively. Conclusions: The Apple Watch Series 4 provides the highest validity (ie, smallest error rates) when measuring HR while sitting or performing light-to-vigorous physical activity, followed by the Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, in that order. The Apple Watch Series 4 and Polar Vantage V are suitable for valid HR measurements at the intensities tested, but HR data provided by the Garmin Fenix 5 and Fitbit Versa should be interpreted with caution due to higher error rates at certain intensities. None of the 4 wrist-worn wearables should be employed to monitor EE at the intensities and durations tested." KW - cardiorespiratory fitness KW - innovation KW - smartwatch KW - technology KW - wearable KW - digital health Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229413 VL - 8 IS - 5 ER -