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Institute
- Theodor-Boveri-Institut für Biowissenschaften (99)
- Medizinische Klinik und Poliklinik II (38)
- Physikalisches Institut (34)
- Neurologische Klinik und Poliklinik (32)
- Medizinische Klinik und Poliklinik I (31)
- Institut für Psychologie (26)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (23)
- Institut für Anorganische Chemie (22)
- Rudolf-Virchow-Zentrum (22)
- Institut für Geographie und Geologie (21)
- Institut für Hygiene und Mikrobiologie (21)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (18)
- Institut für Organische Chemie (18)
- Institut für Virologie und Immunbiologie (18)
- Kinderklinik und Poliklinik (18)
- Institut für Molekulare Infektionsbiologie (16)
- Pathologisches Institut (16)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (14)
- Julius-von-Sachs-Institut für Biowissenschaften (13)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (13)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (13)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (13)
- Institut für Klinische Epidemiologie und Biometrie (11)
- Institut für Theoretische Physik und Astrophysik (10)
- Comprehensive Cancer Center Mainfranken (9)
- Institut für Humangenetik (9)
- Klinik und Poliklinik für Nuklearmedizin (9)
- Lehrstuhl für Orthopädie (9)
- Institut für Informatik (8)
- Klinik und Poliklinik für Strahlentherapie (8)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (8)
- Neurochirurgische Klinik und Poliklinik (8)
- Institut für Experimentelle Biomedizin (7)
- Institut für Pharmakologie und Toxikologie (7)
- Institut für Sportwissenschaft (7)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (7)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (6)
- Institut für Funktionsmaterialien und Biofabrikation (6)
- Institut für Klinische Neurobiologie (6)
- Institut für Pharmazie und Lebensmittelchemie (6)
- Institut für Physikalische und Theoretische Chemie (6)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (6)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (6)
- Frauenklinik und Poliklinik (5)
- Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen (5)
- Augenklinik und Poliklinik (4)
- Institut Mensch - Computer - Medien (4)
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- Klinik und Poliklinik für Anästhesiologie (ab 2004) (4)
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Sonstige beteiligte Institutionen
- Department of Hematology and Oncology, Sana Hospital Hof, Hof, Germany (1)
- Department of Laboratory Medicine and Medicine Huddinge, Karolinska Institutet and University Hospital, Stockholm, Sweden (1)
- Department of Medicine A, University Hospital of Münster, Münster, Germany (1)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (1)
- Interdisciplinary Center for Clinical Research (1)
- Johns Hopkins School of Medicine (1)
- University of Bari Medical School, Bari, Italy (1)
Selective serotonin reuptake inhibitors are among the most prescribed antidepressants. Fluoxetine is the lead molecule which exerts its therapeutic effects, at least in part, by promoting neuroplasticity through increased brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) signalling. It is unclear however, to which extent the neuroplastic effects of fluoxetine are solely mediated by the inhibition of the serotonin transporter (5-HTT). To answer this question, the effects of fluoxetine on neuroplasticity were analysed in both wild type (WT) and 5-Htt knock-out (KO) mice. Using Western blotting and RT-qPCR approaches, we showed that fluoxetine 10 µM activated BDNF/TrkB signalling pathways in both CD1 and C57BL/6J mouse primary cortical neurons. Interestingly, effects on BDNF signalling were observed in primary cortical neurons from both 5-Htt WT and KO mice. In addition, a 3-week in vivo fluoxetine treatment (15 mg/kg/d; i.p.) increased the expression of plasticity genes in brains of both 5-Htt WT and KO mice, and tended to equally enhance hippocampal cell proliferation in both genotypes, without reaching significance. Our results further suggest that fluoxetine-induced neuroplasticity does not solely depend on 5-HTT blockade, but might rely, at least in part, on 5-HTT-independent direct activation of TrkB.
We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.
Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.
Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.
Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
Honeybees (Apis mellifera) are threatened by numerous pathogens and parasites. To prevent infections they apply cooperative behavioral defenses, such as allo-grooming and hygiene, or they use antimicrobial plant resin. Resin is a chemically complex and highly variable mixture of many bioactive compounds. Bees collect the sticky material from different plant species and use it for nest construction and protection. Despite its importance for colony health, comparatively little is known about the precise origins and variability in resin spectra collected by honeybees. To identify the botanical resin sources of A. mellifera in Western Europe we chemically compared resin loads of individual foragers and tree resins. We further examined the resin intake of 25 colonies from five different apiaries to assess the effect of location on variation in the spectra of collected resin. Across all colonies and apiaries, seven distinct resin types were categorized according to their color and chemical composition. Matches between bee-collected resin and tree resin indicated that bees used poplar (Populus balsamifera, P. x canadensis), birch (Betula alba), horse chestnut (Aesculus hippocastanum) and coniferous trees (either Picea abies or Pinus sylvestris) as resin sources. Our data reveal that honeybees collect a comparatively broad and variable spectrum of resin sources, thus assuring protection against a variety of antagonists sensitive to different resins and/or compounds. We further unravel distinct preferences for specific resins and resin chemotypes, indicating that honeybees selectively search for bioactive resin compounds.
Background
The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.
Results
Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.
Conclusion
This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
Chronic alcohol use leads to specific neurobiological alterations in the dopaminergic brain reward system, which probably are leading to a reward deficiency syndrome in alcohol dependence. The purpose of our study was to examine the effects of such hypothesized neurobiological alterations on the behavioral level, and more precisely on the implicit and explicit reward learning. Alcohol users were classified as dependent drinkers (using the DSM-IV criteria), binge drinkers (using criteria of the USA National Institute on Alcohol Abuse and Alcoholism) or low-risk drinkers (following recommendations of the Scientific board of trustees of the German Health Ministry). The final sample (n = 94) consisted of 36 low-risk alcohol users, 37 binge drinkers and 21 abstinent alcohol dependent patients. Participants were administered a probabilistic implicit reward learning task and an explicit reward- and punishment-based trial-and-error-learning task. Alcohol dependent patients showed a lower performance in implicit and explicit reward learning than low risk drinkers. Binge drinkers learned less than low-risk drinkers in the implicit learning task. The results support the assumption that binge drinking and alcohol dependence are related to a chronic reward deficit. Binge drinking accompanied by implicit reward learning deficits could increase the risk for the development of an alcohol dependence.
Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384–402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.
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.
Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches.
A new strategy is demonstrated for the synthesis of warped, negatively curved, all‐sp\(^2\)‐carbon π‐scaffolds. Multifold C−C coupling reactions are used to transform a polyaromatic borinic acid into a saddle‐shaped polyaromatic hydrocarbon (2 ) bearing two heptagonal rings. Notably, this Schwarzite substructure is synthesized in only two steps from an unfunctionalized alkene. A highly warped structure of 2 was revealed by X‐ray crystallographic studies and pronounced flexibility of this π‐scaffold was ascertained by experimental and computational studies. Compound 2 exhibits excellent solubility, visible range absorption and fluorescence, and readily undergoes two reversible one‐electron oxidations at mild potentials.