Refine
Year of publication
Has Fulltext
- yes (123)
Is part of the Bibliography
- no (123)
Keywords
- LHC (7)
- ALICE (3)
- ALICE experiment (3)
- Hadron-Hadron Scattering (3)
- pp collisions (3)
- Beauty production (2)
- Breast cancer (2)
- Diagnostik (2)
- Früherkennung (2)
- Mammakarzinom (2)
- Nachsorge (2)
- Richtlinie (2)
- Single electrons (2)
- breast cancer (2)
- diagnosis (2)
- follow‑up (2)
- guideline (2)
- screening (2)
- 900 GeV (1)
- APP (1)
- Active middle ear implants (1)
- Atmospheric science (1)
- Auditory system (1)
- Australia (1)
- Bone conduction devices (1)
- Business strategy in drug development (1)
- C57BL/6J mice (1)
- C57BL/6N mice (1)
- CA1 (1)
- CABLE (1)
- COVID-19 (1)
- CVID (1)
- Cancer (1)
- Cancer stem cells (1)
- Cell biology (1)
- Charm physics (1)
- Chemical biology (1)
- Chocó rainforest (1)
- Climate change (1)
- Clinical variation (1)
- Cognitive impairment (1)
- Comparison with QCD (1)
- Consensus statement (1)
- Conservation biogeography (1)
- Deutsch (1)
- Digital breast tomosynthesis (DBT) (1)
- Digital mammography (1)
- Drug discovery (1)
- Drug therapy (1)
- EBV (1)
- Ecuador (1)
- Elderly (1)
- EnKS 3D (1)
- European Society for Immunodeficiencies (ESID) (1)
- Femtoscopy (1)
- Frailty (1)
- GRACE (1)
- GRX1-roGFP2 (1)
- General practitioners (1)
- Genetic wildlife monitoring (1)
- German PID-NET registry (1)
- Glucose metabolism (1)
- HBT (1)
- Hadron production (1)
- Hair sampling (1)
- Health policy (1)
- Heavy Ions (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-flavour production (1)
- Heavy-ion collisions (1)
- Hypertension (1)
- IgG substitution therapy (1)
- Inclusive spectra (1)
- Insulin secretion (1)
- Intensity interferometry (1)
- Jets (1)
- KCGS (1)
- LTER (1)
- Long‐term ecosystem research (1)
- Lure sticks (1)
- MACE (1)
- Mid-rapidity (1)
- Mitochondrial shuttles (1)
- Mixed hearing loss (1)
- Morphologie (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- NMDA IgA/IgM antibodies (1)
- NMDA antibody (1)
- Noninvasive genetic sampling (1)
- North China Plain (1)
- Nuclear modification factor (1)
- Oldest-old (1)
- PCR-GLOBWB (1)
- PID prevalence (1)
- PYTHIA (1)
- Pancreatic islet (1)
- Parkinson disease (1)
- Pb–Pb (1)
- Population-based screening (1)
- Proton–proton (1)
- RT-qPCR (1)
- Recall rate (1)
- Redox-sensitive GFP (1)
- Rehabilitation (1)
- Relativistic heavy ion physics (1)
- Research infrastructure (1)
- SARS-CoV-2 (1)
- Satzanalyse (1)
- Semantik (1)
- Single muons (1)
- Site networks (1)
- Stimulus-secretion coupling (1)
- Surgery (1)
- Syntax (1)
- Technical data (1)
- Transverse momentum (1)
- W3 (1)
- WGHM (1)
- aboveground biomass (1)
- atherosclerosis (1)
- biodiversity (1)
- cardiovascular disease (1)
- chemogenomic set (1)
- chronosequence (1)
- data assimilation (1)
- dentate gyrus (1)
- diabetic macular edema (1)
- diclofenac (1)
- drug discovery (1)
- druggable genome (1)
- epigenetics (1)
- fluocinolone acetonide (1)
- groundwater storage (1)
- hemodialysis (1)
- immunostaining (1)
- in situ hybridization (1)
- kidney disease (1)
- kinase inhibitor (1)
- laser microdissection (1)
- meta-analysis (1)
- miRNA (1)
- microdosing (1)
- neutralizing antibodies (1)
- next-generation sequencing (1)
- oral enzyme combination (1)
- osteoarthritis (1)
- phenotypic screening (1)
- primary immunodeficiency (PID) (1)
- protein kinase (1)
- randomized controlled trial (1)
- reassembly (1)
- registry for primary immunodeficiency (1)
- resilience (1)
- resistance (1)
- small molecules (1)
- spectra (1)
- spike protein (1)
- trees (1)
- understudied kinase (1)
- variants of concern (1)
- western blotting (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (78)
- Frankfurt Institute for Advanced Studies (FIAS) (65)
- Informatik (65)
- Medizin (28)
- Biodiversität und Klima Forschungszentrum (BiK-F) (5)
- Senckenbergische Naturforschende Gesellschaft (5)
- Biowissenschaften (4)
- Biochemie und Chemie (3)
- Exzellenzcluster Makromolekulare Komplexe (3)
- Institut für Ökologie, Evolution und Diversität (3)
Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.
Objective: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets.
Methods: Islets were isolated from female C57BL/6J mice (J-islets), which lack functional NNT, and genetically close C57BL/6N mice (N-islets). Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures.
Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification.
Conclusion: These results drastically modify current views on NNT operation and mitochondrial function in pancreatic β-cells.
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
The physiological role of amyloid precursor protein (APP) has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and—at the behavioral level—hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus (DG) and area CA1 of the mouse hippocampus. We speculated that regional differences in APP expression could underlie these discrepancies and studied the expression of APP in both regions using immunostaining, in situ hybridization (ISH), and laser microdissection (LMD) in combination with quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. In sum, our results show that APP is approximately 1.7-fold higher expressed in pyramidal cells of Ammon’s horn than in granule cells of the DG. This regional difference in APP expression may explain why loss-of-function approaches using APP-deficient mice revealed a role for APP in Hebbian plasticity in area CA1, whereas this could not be shown in the DG of the same APP mutants.
Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.
Large-scale genetic census of an elusive carnivore, the European wildcat (Felis s. silvestris)
(2016)
The European wildcat, Felis silvestris silvestris, serves as a prominent target species for the reconnection of central European forest habitats. Monitoring of this species, however, appears difficult due to its elusive behaviour and the ease of confusion with domestic cats. Recently, evidence for multiple wildcat occurrences outside its known distribution has accumulated in several areas across Central Europe, questioning the validity of available distribution data for this species. Our aim was to assess the fine-scale distribution and genetic status of the wildcat in its central European distribution range. We compiled and analysed genetic samples from roadkills and hundreds of recent hair-trapping surveys and applied phylogenetic and genetic clustering methods to discriminate wild and domestic cats and identify population subdivision. 2220 individuals were confirmed as either wildcat (n = 1792) or domestic cat (n = 342), and the remaining 86 (3.9 %) were identified as hybrids between the two. Remarkably, genetic distinction of domestic cats, wildcats and their hybrids was only possible when taking into account the presence of two highly distinct genetic lineages of wildcats, with a suture zone in central Germany. 44 % of the individual wildcats where sampled outside the previously published distribution. Our analyses confirm a relatively continuous spatial presence of wildcats across large parts of the study area in contrast to previous analyses indicating a highly fragmented distribution. Our results suggest that wildcat conservation and management should take advantage of the higher than previously assumed dispersal potential of wildcats, which may use wildlife corridors very efficiently.
Global change effects on biodiversity and human wellbeing call for improved long-term environmental data as a basis for science, policy and decision making, including increased interoperability, multifunctionality, and harmonization. Based on the example of two global initiatives, the International Long-Term Ecological Research (ILTER) network and the Group on Earth Observations Biodiversity Observation Network (GEO BON), we propose merging the frameworks behind these initiatives, namely ecosystem integrity and essential biodiversity variables, to serve as an improved guideline for future site-based long-term research and monitoring in terrestrial, freshwater and coastal ecosystems. We derive a list of specific recommendations of what and how to measure at a monitoring site and call for an integration of sites into co-located site networks across individual monitoring initiatives, and centered on ecosystems. This facilitates the generation of linked comprehensive ecosystem monitoring data, supports synergies in the use of costly infrastructures, fosters cross-initiative research and provides a template for collaboration beyond the ILTER and GEO BON communities.
Purpose: To evaluate the efficacy of the virtual reality training simulator Eyesi to prepare surgeons for performing pars plana vitrectomies and its potential to predict the surgeons’ performance.
Methods: In a preparation phase, four participating vitreoretinal surgeons performed repeated simulator training with predefined tasks. If a surgeon was assigned to perform a vitrectomy for the management of complex retinal detachment after a surgical break of at least 60 hours it was randomly decided whether a warmup training on the simulator was required (n = 9) or not (n = 12). Performance at the simulator was measured using the built-in scoring metrics. The surgical performance was determined by two blinded observers who analyzed the video-recorded interventions. One of them repeated the analysis to check for intra-observer consistency. The surgical performance of the interventions with and without simulator training was compared. In addition, for the surgeries with simulator training, the simulator performance was compared to the performance in the operating room.
Results: Comparing each surgeon’s performance with and without warmup trainingshowed a significant effect of warmup training onto the final outcome in the operating room. For the surgeries that were preceeded by the warmup procedure, the performance at the simulator was compared with the operating room performance. We found that there is a significant relation. The governing factor of low scores in the simulator were iatrogenic retinal holes, bleedings and lens damage. Surgeons who caused minor damage in the simulation also performed well in the operating room.
Conclusions: Despite the large variation of conditions, the effect of a warmup training as well as a relation between the performance at the simulator and in the operating room was found with statistical significance. Simulator training is able to serve as a warmup to increase the average performance.
Purpose: There are little or no published data comparing the outcomes of ILUVIEN® (0.19 mg fluocinolone acetonide [FAc]) and OZURDEX® (0.7 mg dexamethasone [DEX]) implants in patients with diabetic macular edema (DME), and this case sought to compare their outcomes.
Methods: This case was extracted from a monocentric audit involving a pool of 25 patients (33 eyes) with DME and treated with a single FAc implant between October 2013 and December 2016. This case, a 61-year-old male with a pseudophakic lens, is from a patient that had received 4 intravitreal injections of a DEX implant prior to FAc implant and then was monitored for 3 years until re-treatment with a second FAc implant. Parameters measured included visual acuity (VA), central retinal thickness (CRT), and intraocular pressure (IOP).
Results: After the DEX implants, CRT transiently improved. In March 2014, the decision was taken to administer an FAc implant, and this led to a reduction in CRT below 300 µm (from a baseline of 748 µm), and this was sustained for 30 months. VA remained above 65 Early Treatment Diabetic Retinopathy Study letters to month 36, after which time a second FAc implant (in April 2017) was administered due to recurrence of edema and CRT decreased to below 300 µm and VA improved to 70 letters. Side effects included elevated IOP, which was effectively managed with IOP-lowering drops.
Conclusion: A single injection of FAc implant led to sustained improvements in CRT and VA that lasted for between 30 and 36 months, which is in contrast to the DEX implant where re-treatment was generally required within 6–7 months. After 36 months, re-treatment with the FAc implant again led to improved VA and CRT, and responses that were similar to those achieved with the first FAc implant.
Over recent decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes to an unprecedented extent. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g. irrigation, artificial dams, and water diversion) and at various scales (from a watershed to the globe). During the early 1990s, awareness of the potential for increased water scarcity led to the first detailed global water resource assessments. Shortly thereafter, in order to analyse the human perturbation on terrestrial water resources, the first generation of large-scale hydrological models (LHMs) was produced. However, at this early stage few models considered the interaction between terrestrial water fluxes and human activities, including water use and reservoir regulation, and even fewer models distinguished water use from surface water and groundwater resources. Since the early 2000s, a growing number of LHMs have incorporated human impacts on the hydrological cycle, yet the representation of human activities in hydrological models remains challenging. In this paper we provide a synthesis of progress in the development and application of human impact modelling in LHMs. We highlight a number of key challenges and discuss possible improvements in order to better represent the human–water interface in hydrological models.